Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202310588244868 Date of Registration: 23/10/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Multimorbidity-associated emergency hospital admissions: a “screen and link” strategy to improve outcomes for high-risk patients in Malawi and Tanzania
Official scientific title Multimorbidity-associated emergency hospital admissions: a “screen and link” strategy to improve outcomes for high-risk patients in Malawi and Tanzania
Brief summary describing the background and objectives of the trial Background We will test an intervention that identifies and treats patients suffering from multiple diseases (multimorbidity) when they seek emergency care in Malawian and Tanzanian hospitals. This could improve early disease treatment (reducing death), and ensure better follow-up (preventing complications, disability, and hospital readmission). We have completed a study in these countries which shows the most common primary chronic diseases that cause multimorbidity are high blood pressure, diabetes and HIV infection. We know that improved control of these primary diseases reduces the risk of secondary complications such as strokes and heart attacks. Aim Our aim is that this intervention will improve survival and reduce the need for hospital readmissions for patients treated at the intervention hospitals. We will measure how well the intervention is being conducted at the hospitals by collecting data on how care has been delivered. We anticipate that our intervention will be more expensive to deliver than standard care and so will be collecting data on costs from participants and healthcare providers to guide policy makers on future implementation if the trial demonstrates benefit to patients.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) MULTILINK
Disease(s) or condition(s) being studied Cardiology,Circulatory System,Infections and Infestations,Kidney Disease,Nutritional, Metabolic, Endocrine
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Diagnosis / Prognosis
Anticipated trial start date 01/02/2024
Actual trial start date 02/12/2024
Anticipated date of last follow up 31/05/2025
Actual Last follow-up date 06/08/2025
Anticipated target sample size (number of participants) 3000
Actual target sample size (number of participants) 68
Recruitment status Stopped early/ terminated
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Baseline Period N/A 22 hospitals 9 months Standard care in the baseline period with a washout period after last patient recruited is discharged or dies. Recruited participants will receive enhanced diagnostics to determine presence and control of selected diseases (diabetes mellitus, hypertension and HIV-infection), including serum creatinine, at recruitment and subsequently at 90-day follow up clinic. Results of these enhanced tests will be made available to the patient and treating teams. 2090 Active-Treatment of Control Group
Experimental Group Period 2 Control and Intervention Arm N/A 22 sites, 2090 patients 9 months The cluster randomised control trial will evaluate a complex intervention comprising of six components; enhanced diagnostics, protocolised treatment recommendation, enhanced healthcare worker training, monthly outpatient clinic visits throughout the 3 month post discharge follow up period, enhanced linkage to community support and supporting self-management 2090
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Adults (≥18) acutely admitted to hospital with a medical presentation (unplanned admissions) • Diagnosed with ≥2 of diabetes mellitus, hypertension and HIV-infection. • Alive after two days of hospital admission OR well enough to be discharged from hospital within two days of admission • Lives within hospital catchment area • Participant likely to stay at their current home location for the next 3 months • Contactable on discharge by telephone (either directly or through a carer) • Surgical, obstetric or trauma hospital admission. • Presentation with suspected secondary complication of primary disease (e.g., stroke, myocardial infarction, end stage renal disease) • Participant refusal • Pregnancy • Detainees or prisoners • Planned medical admission for investigation 80 and over: 80+ Year,Adult: 18 Year(s)-44 Year(s),Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 120 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 01/08/2024 LSTM Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Pembroke Place Liverpool L3 5QA United Kingdom
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 10/09/2024 COMREC
Ethics Committee Address
Street address City Postal code Country
University of Malawi College of Medicine, Mahatma Gandhi Campus, Postgraduate Building Ground Floor, Blantyre Blantyre Malawi
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 31/10/2024 NIMR
Ethics Committee Address
Street address City Postal code Country
3 Barack Obama Drive, Dar es Salaam 9653 Tanzania
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 15/11/2024 CRERC Kilimanjaro Christian Medical College Research Ethics and Review Committee
Ethics Committee Address
Street address City Postal code Country
Kilimanjaro Christian Medical Centre Kilimanjaro PO Box 30 Tanzania
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 25/11/2024 Liverpool School of Tropical Medicine Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Pembroke Place Liverpool L3 5QA United Kingdom
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 21/05/2025 TMDA Tanzania Medicines and Medical Devices Authority
Ethics Committee Address
Street address City Postal code Country
Nelson Mandela Rd Dar es Salaam Tanzania Tanzania
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Secondary Outcome Secondary Clinical objective - Survival 90 days after index hospital admission. Outcome Measure - Disaggregated primary outcome measure. Participant alive at 90 days 90 days
Primary Outcome Primary Clinical Objective - Aggregated primary outcome measure consisting of survival and hospital re-admission data. Survival will be determined if the patient is alive 90 days after the date of index hospital admission. Hospital readmission will be determined if the participant required repeat all cause unplanned hospital admission within 90 days after index hospital admission. Admission will be defined as requirement for an overnight stay within a healthcare facility. 90 days after dates of index hospital admission
Secondary Outcome Secondary Clinical Objective - Prevalence of undiagnosed multimorbidity. Outcome Measures - Participants diagnosed with new multimorbid disease (≥2 of HIV, HTN or DM) from index admission Recruitment, 30, 60 and 90 days
Secondary Outcome Secondary Clinical Objective - Measures of disease control (e.g. blood pressure, HBA1c, HIV viraemia). Outcome Measures - Measurement of biological markers of disease control at enrolment and 90 day follow up. Hypertension (blood pressure), diabetes (HBA1c) and HIV (HIV viral load) Recruitment, 30, 60 and 90 days
Secondary Outcome Secondary Clinical Objective - Prevalence of new end-organ complications relevant to primary disease (e.g., stroke, myocardial infarction, chronic kidney disease). Outcome Measures - Presence or absence of new relevant clinically diagnosed secondary complications (e.g., stroke, myocardial infarction, chronic kidney disease), including cause of death where applicable Recruitment, 30, 60 and 90 days
Secondary Outcome Secondary Clinical Objective - Disability free survival at 90 days. Outcome Measures - Disability will be measured using the Washington Group Short Set on Functioning (18) at admission and subsequent follow up visits Recruitment, 30, 60 and 90 days
Secondary Outcome Secondary Health Economic Objective - Cost-effectiveness of intervention vs. control (using primary clinical outcome as an outcome as the effectiveness measure) from the societal perspective. Outcome Measures - Societal (i.e. health system plus patient) cost per additional person alive and not having had unplanned hospital readmission in intervention, versus standard care 90 days after date of index hospital admission with possible modelling over the lifetime horizon for a hypothetical patient cohort
Secondary Outcome Secondary Health Economic Objective - Patient costs in intervention vs control clusters. Outcome Measures - Mean and (separately) median cost per patient in intervention vs standard care (includes medical and non-medical out-of-pocket expenses for the patient and accompanying person/s) for the multimorbid conditions. Evaluated at 90 days after the date of index hospital admission by summing costs incurred during the index hospital stay, between discharge and 30 day follow up period, between 30 and 60 day followup
Secondary Outcome Secondary Health Economic Objective - HRQoL measures (EQ5D-5L and visual analogue scale). Outcome Measures - Mean and separately median change in QALY per person calculated using the area under the curve methodology and summed by arm. Evaluated at 90 days after date of index hospital admission, using the utility scores obtained for each patient at initial, 30, 60 and 90 days to calculate area under the curve, with possible modellin
Secondary Outcome Secondary Health Economic Objective - Health system costs in intervention vs control. Outcome Measures - Estimated cost to health system of implementing intervention vs. standard care (includes medication, tests conducted, inpatient stay costs, staff costs, overheads such as electricity, water etc. and consumable costs). Cost modelling to esitmate annual cost per hospital of rolling out intervention
Secondary Outcome Intervention reach, effectiveness, adoption, fidelity and maintenance Longitudinal assessment throughout the trial
Secondary Outcome Determine and map care processes and patient pathways 90 days
Primary Outcome Principle Health Economic Outcome - Cost-utility of intervention vs.standard care (incremental cost per QALY gained compared to relevant thresholds expressed on the costeffectiveness acceptability curve) 90 days after date of index hospital admission with possible modelling over the lifetime horizon for a hypotherical patient cohort
Primary Outcome Principle Process Evaluation Objective - Understand under what context and through what mechanisms an enhanced diagnostic, protocolised treatment and patient centred care intervention will enhance integrated care for patients with multimorbidity and will modify patient outcomes in a cluster randomized trial in secondary care hospitals Outcome Measures - Explain ‘what worked for whom, in what condition and why’ with a focus on: Intervention fidelity and quality: What was implemented and how Change mechanism: How did the delivered intervention produce change Context: How did context affect implementation and outcomes 90 days
Secondary Outcome Secondary Clinical Objective - Hospital re-admission rate 90 days after index hospital admission. outcome Measures - Disaggregated primary outcome measure. Participant requires repeat hospital admission within 90 days 90 days
Secondary Outcome Secondary Process Evaluation Objective - To examine key secondary implementation outcomes including fidelity, acceptability, adoption, appropriateness, feasibility, and sustainability of the intervention. Outcome Measures - i. The extent to which the intervention is implemented as intended and whether any adaptations were made ii. Positive and negative effects of the intervention in the short and intermediate terms iii. Participation of the target population in the intervention iv. Extent of uptake of the intervention in hospital and community settings v. Sustainability of the intervention’s benefits Longitudinal assessment throughout the trial
Secondary Outcome Secondary Process Evaluation Objective - To assess how health system context at cluster/hospital and country level affect intervention fidelity and or outcomes. Outcome Measures - i. Organisation/integration of patient care (patient flow, NCD management, NCD treatment guidelines, clinical records, OPD service integration) ii. Availability of essential technologies and tools (monthly drug stock audit) iii. Human resources for health (dedicated staff for relevant NCDs and HIV, in post/staff vacancy levels) iv. Availability of core medicines (monthly drug stock audit) For i - ii at baseline, midline and endline. For iii-iv monthly staff and drug stick audits in intervention and control clusters.
Secondary Outcome Secondary Health Economic Objective - Cost utility of intervention vs. control (incremental cost per QALY gained compared to a range of relevant thresholds) from the societal perspective, measured at 90 days from hospital admission. Outcome Measures - Societal (i.e. health system and patient) cost per additional QALY gained in intervention, versus standard care 90 days after the date of hospital admission with the possible modelling over the lifetime horizon for a hypothetical patient cohort
Secondary Outcome Secondary Health Economic Objective - Investigation into the socioeconomic status of patients diagnosed with multimorbidity (pooled sample). Outcome measures - Participant data on household construction materials, water sources, sanitation access and ownership of various items will be used to construct a wealth index score using principle components analysis, that will be used to categorise households into wealth quintiles relative to the socioeconomic status in each country which will be obtained from the most recent Demographic and Health Survey analysis. Evaluated using data obtained during index hospital admission
Secondary Outcome Secondary Health Economic Objective - Cost effectiveness of intervention vs. control using the primary clinical outcome as effectiveness measure from the health system perspective - Outcome Measures - Health system cost per additional person alive and not having had unplanned hospital readmission in intervention, versus standard care Evaluated at 90 days after the date of index hospital admission, with the possible modelling over the lifetime horizon for a hypothetical patient cohort
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Chiradzulu District Hospital Kuunika Chiradzulu Malawi
Hai District Hospital Boma Ngombe Kilimanjaro Tanzania
Phalombe Hospital Phalombe Phalombe District Malawi
Mulanje Hospital Mulanje Mulanje Malawi
Thyolo Hospital Thyolo Thyolo District Malawi
Mwanza Hospital Mwanza Mwanza District Malawi
Ntcheu Hospital Ntcheu Ntcheu Districk Malawi
Balaka Hospital Balaka Balaka District Malawi
Machinga Hospital Machinga Machinga District Malawi
Chikwawa Hospital Chikwawa Chikwawa District Malawi
Nsanje Hospital Nsanje Nsanje District Malawi
St Joseph District Hospital St Joseph Soweto Tanzania
Kibosho Hospital Kibosho Kilimanjaro Tanzania
Marangu Lutheran Hospital Marangu Kilimanjaro Tanzania
Machame Lutheran Hospital Machame Kilimanjaro Tanzania
Huruma Catholic Diocese Hospital Huruma Kilimanjaro Tanzania
Tumbi Regional Referral Hospital Tumbi Dar es Salaam Tanzania
Temeke Regional Referral Hospital Temeke Dar es Salaam Tanzania
Mwananyamala Referral Regional Hospital Mwananyamala Dar es Salaam Tanzania
Amana Regional Referral Hospital Amana Dar es Salaam Tanzania
Kigamboni Health Centre Kigamboni Dar es Salaam Tanzania
Bagamoyo District Hospital Bagamoyo Dar es Salaam Tanzania
FUNDING SOURCES
Name of source Street address City Postal code Country
National Institute for Health and Care Research 15 Church Street Twickenham United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Liverpool School of Tropical Medicine Pembroke Place Liverpool L3 5QA United Kingdom Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Eve Worrall eve.worrall@lstmed.ac.uk +441517033759 Pembroke Place
City Postal code Country Position/Affiliation
Liverpool United Kingdom Co Chief Investigator
Role Name Email Phone Street address
Principal Investigator Felix Limbani felix.limbani@lstmed.ac.uk +441517059759 Queen Elizabeth Central Hospital
City Postal code Country Position/Affiliation
Blantyre Malawi Co Chief Investigator
Role Name Email Phone Street address
Principal Investigator Ben Morton ben.morton@lstmed.ac.uk +447033759 Pembroke Place
City Postal code Country Position/Affiliation
Liverpool United Kingdom Co Chief Investigator
Role Name Email Phone Street address
Public Enquiries Amy Smith amy.smith@lstmed.ac.uk +441517029575 Pembroke Place
City Postal code Country Position/Affiliation
Liverpool United Kingdom Programme Coordinator
Role Name Email Phone Street address
Scientific Enquiries Ben Morton ben.morton@lstmed.ac.uk +441517059759 Pembroke Place
City Postal code Country Position/Affiliation
Liverpool United Kingdom Co Chief Investigator
Role Name Email Phone Street address
Scientific Enquiries Matthew Rubach matthew.rubach@duke.edu +255718164044 KCMC
City Postal code Country Position/Affiliation
Kilimanjaro Tanzania CoInvestigator
Role Name Email Phone Street address
Scientific Enquiries Hendry Sawe hendry_sawe@yahoo.com +255754885658 Muhimbili
City Postal code Country Position/Affiliation
Dar es Salaam Tanzania CoInvestigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Prior to the early termination of the planned parallel group cRCT in March 2025, only baseline data was collected for a small sample of 68 participants across 8 hospitals, with no intervention data to compare this to. Once this data has been cleaned and analysed in accordance with the project Statistical Analysis Plan and disseminated in accordance with the protocol, the data will be made available via an open access website; most likely the UK Data Service (https://datacatalogue.ukdataservice.ac.uk/#!?Search=&Rows=10&Sort=0&AccessFacet=Open) or another open access site. Study Protocol The data is expected to be shared within 12 months of the end of the Multilink programme, up to November 2026. Note: The research programme has an overall ‘the dissemination period’ of two years (up until November 2027), in agreement with the funder. Access to the data will be open with no restrictions on what or who can analyse it. For further information on the original analysis plan prior to the early termination of the trial, see GitHub link: https://github.com/mlw-stats/Multilink/tree/main/SAP
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 12/10/2023 Requested to provide a clear aim of the trial Test an intervention that identifies & treats patients suffering from multiple diseases (multimorbidity) when they seek emergency care in Malawian & Tanzanian hospitals. This could improve early disease treatment (reducing death), & ensure better follow-up (preventing complications, disability, and hospital readmission). We have completed a study in these countries which shows the most common primary chronic diseases that cause multimorbidity are high blood pressure, diabetes & HIV infection. Improved control of these primary diseases reduces the risk of secondary complications such as strokes & heart attacks. Hospitals will be randomised (not individual patients) to the intervention or to standard care. At all hospitals we will recruit patients admitted with these primary chronic diseases & offer point of care testing to measure disease control. This information will be provided to healthcare workers looking after the participants. At hospitals randomised to the intervention, this information will be used to inform treatment recommendations to manage these diseases. Treatment recommendations will be based on existing WHO & in-country guidelines & made during the hospital admission & subsequently in the outpatient clinic setting 1 & 2 two months later. We will offer enhanced healthcare worker education, enhanced patient education & linkage to community care at the intervention hospitals. These management strategies will not be offered at hospitals randomised to standard care. Our aim is that this intervention will improve survival & reduce the need for hospital readmissions for patients treated at the intervention hospitals. We will measure how well the intervention is being conducted at the hospitals by collecting data on how care has been delivered. We anticipate that our intervention will be more expensive to deliver than standard care and so will be collecting data on costs from participants and healthcare providers to guide policy makers on futureimplementation Our aim is that this intervention will improve survival and reduce the need for hospital readmissions for patients treated at the intervention hospitals. We will measure how well the intervention is being conducted at the hospitals by collecting data on how care has been delivered. We anticipate that our intervention will be more expensive to deliver than standard care and so will be collecting data on costs from participants and healthcare providers to guide policy makers on future implementation if the trial demonstrates benefit to patients.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 12/10/2023 Requested to provide a clear aim of the trial Our aim is that this intervention will improve survival and reduce the need for hospital readmissions for patients treated at the intervention hospitals. We will measure how well the intervention is being conducted at the hospitals by collecting data on how care has been delivered. We anticipate that our intervention will be more expensive to deliver than standard care and so will be collecting data on costs from participants and healthcare providers to guide policy makers on future implementation if the trial demonstrates benefit to patients. We will test an intervention that identifies and treats patients suffering from multiple diseases (multimorbidity) when they seek emergency care in Malawian and Tanzanian hospitals. This could improve early disease treatment (reducing death), and ensure better follow-up (preventing complications, disability, and hospital readmission). We have completed a study in these countries which shows the most common primary chronic diseases that cause multimorbidity are high blood pressure, diabetes and HIV infection. We know that improved control of these primary diseases reduces the risk of secondary complications such as strokes and heart attacks.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 19/10/2023 Background added as requested We will test an intervention that identifies and treats patients suffering from multiple diseases (multimorbidity) when they seek emergency care in Malawian and Tanzanian hospitals. This could improve early disease treatment (reducing death), and ensure better follow-up (preventing complications, disability, and hospital readmission). We have completed a study in these countries which shows the most common primary chronic diseases that cause multimorbidity are high blood pressure, diabetes and HIV infection. We know that improved control of these primary diseases reduces the risk of secondary complications such as strokes and heart attacks. Background We will test an intervention that identifies and treats patients suffering from multiple diseases (multimorbidity) when they seek emergency care in Malawian and Tanzanian hospitals. This could improve early disease treatment (reducing death), and ensure better follow-up (preventing complications, disability, and hospital readmission). We have completed a study in these countries which shows the most common primary chronic diseases that cause multimorbidity are high blood pressure, diabetes and HIV infection. We know that improved control of these primary diseases reduces the risk of secondary complications such as strokes and heart attacks. Aim Our aim is that this intervention will improve survival and reduce the need for hospital readmissions for patients treated at the intervention hospitals. We will measure how well the intervention is being conducted at the hospitals by collecting data on how care has been delivered. We anticipate that our intervention will be more expensive to deliver than standard care and so will be collecting data on costs from participants and healthcare providers to guide policy makers on future implementation if the trial demonstrates benefit to patients.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 13/12/2024 Trial start date was delayed due to ethical approval 02 Dec 2024
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Completion date 08/12/2025 The trial was terminated early due to changes to available funding and unanticipated recruitment shortages (see explanation above) on 6 August 2025. The Multilink Consortium research programme ended on 30 November 2025. 06 Aug 2025
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Final no of participants 08/12/2025 Prior to terminating the parallel group cRCT and pausing recruitment on 11/03/2025, 69 patients were screened and later followed up, of which 68 were eligible. This involved data collection for the observational baseline phase. No trial interventions were implemented for these participants. 68
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 15/04/2025 Trial has been paused due to a change in design. Not yet recruiting Stopped early/ terminated
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Inclusion criteria 08/12/2025 Clarified details on inclusion criteria as per protocol v4.0 on the parallel group cRCT design. • Adults (≥18) acutely admitted to hospital with a medical presentation. • Diagnosed with ≥2 of diabetes mellitus, hypertension and HIV-infection. • Adults (≥18) acutely admitted to hospital with a medical presentation (unplanned admissions) • Diagnosed with ≥2 of diabetes mellitus, hypertension and HIV-infection. • Alive after two days of hospital admission OR well enough to be discharged from hospital within two days of admission • Lives within hospital catchment area • Participant likely to stay at their current home location for the next 3 months • Contactable on discharge by telephone (either directly or through a carer)
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Exclusion criteria 08/12/2025 Clarified details on exclusion criteria as per protocol v4.0. • Surgical, obstetric or trauma hospital admission. • Presentation with suspected secondary complication of primary disease (e.g., stroke, myocardial infarction, end stage renal disease) • Participant refusal • Surgical, obstetric or trauma hospital admission. • Presentation with suspected secondary complication of primary disease (e.g., stroke, myocardial infarction, end stage renal disease) • Participant refusal • Pregnancy • Detainees or prisoners • Planned medical admission for investigation
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 04/10/2024 Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied. Control Group, Baseline Period , N/A 22 hospitals , 9 months, Standard care in the baseline period with a washout period after last patient recruited is discharged or dies. Recruited participants will receive enhanced diagnostics to determine presence and control of selected diseases (diabetes mellitus, hypertension and HIV-infection), including serum creatinine, at recruitment and subsequently at 90-day follow up clinic. Results of these enhanced tests will be made available to the patient and treating teams. , 2090, Active-Treatment of Control Group
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 04/10/2024 Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied. Experimental Group, Period 2 Control and Intervention Arm , N/A 22 sites, 2090 patients , 9 months , The cluster randomised control trial will evaluate a complex intervention comprising of six components; enhanced diagnostics, protocolised treatment recommendation, enhanced healthcare worker training, monthly outpatient clinic visits throughout the 3 month post discharge follow up period, enhanced linkage to community support and supporting self-management , 2090,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 04/10/2024 Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied. Control Group, Standard care, N/A 10 hospitals, n=150 per hospital, 90 days, Standard care at the treating hospital. Recruited participants will receive enhanced diagnostics to determine presence and control of selected diseases (diabetes mellitus, hypertension and HIV-infection), including serum creatinine, at recruitment and subsequently at 90-day follow up clinic. Results of these enhanced tests will be made available to the patient and treating teams. , 1500, Active-Treatment of Control Group Control Group, Baseline Period , N/A 22 hospitals , 6 months , Standard care in the baseline period with a washout period after last patient recruited is discharged or dies. Recruited participants will receive enhanced diagnostics to determine presence and control of selected diseases (diabetes mellitus, hypertension and HIV-infection), including serum creatinine, at recruitment and subsequently at 90-day follow up clinic. Results of these enhanced tests will be made available to the patient and treating teams. , 2090, Active-Treatment of Control Group
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 04/10/2024 Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied. Experimental Group, Screen and link, N/A 10 hospitals, n=150/site, 90 days, 1. Enhanced diagnostics to assess presence and control of diabetes, hypertension and HIV 2. Protocolised treatment recommendation based on WHO and relevant national treatment guidelines; informed by disease control; and renal function (serum creatinine). 3. Enhanced training for healthcare workers to promote/facilitate adoption of enhanced diagnostics and acceptance of protocolised treatment 4. Outpatient clinic visits one and two months after hospital discharge to monitor and titrate treatment for improved disease control. 5. Enhanced linkage to community support (which we will also aim to train/strengthen) and other services 6. Supporting self-management (including improved health literacy and empowerment for patients to take control of their conditions) , 1500, Experimental Group, Period 2 Control and Intervention Arm , N/A 22 sites, 2090 patients , 9 months , 1. Enhanced diagnostics to assess presence and control of diabetes, hypertension and HIV 2. Protocolised treatment recommendation based on WHO and relevant national treatment guidelines; informed by disease control; and renal function (serum creatinine). 3. Enhanced training for healthcare workers to promote/facilitate adoption of enhanced diagnostics and acceptance of protocolised treatment 4. Outpatient clinic visits one and two months after hospital discharge to monitor and titrate treatment for improved disease control. 5. Enhanced linkage to community support (which we will also aim to train/strengthen) and other services 6. Supporting self-management (including improved health literacy and empowerment for patients to take control of their conditions) , 2090,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 04/10/2024 Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied. Control Group, Control and Intervention Period , n/a , 9 months , c, 2090, Active-Treatment of Control Group
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 04/10/2024 Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied. Control Group, Control and Intervention Period , n/a , 9 months , c, 2090, Active-Treatment of Control Group Control Group, Control and Intervention Period , n/a , 9 months , The cluster randomised control trial will evaluate a complex intervention comprising of six components; enhanced diagnostics, protocolised treatment recommendation, enhanced healthcare worker training, monthly outpatient clinic visits throughout the 3 month post discharge follow up period, enhanced linkage to community support and supporting self-management , 2090, Active-Treatment of Control Group
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 04/10/2024 Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficinetly powered trial. After several internal discussions, and expert advice from statisticains, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfcatory solution. We therefore identified an alterantive trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied. Control Group, Control and Intervention Period , n/a , 9 months , The cluster randomised control trial will evaluate a complex intervention comprising of six components; enhanced diagnostics, protocolised treatment recommendation, enhanced healthcare worker training, monthly outpatient clinic visits throughout the 3 month post discharge follow up period, enhanced linkage to community support and supporting self-management , 2090, Active-Treatment of Control Group
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Survival 90 days after index hospital admission. Outcome Measure - Disaggregated primary outcome measure. Participant alive at 90 days, 90 days Secondary Outcome, Secondary Clinical objective - Survival 90 days after index hospital admission. Outcome Measure - Disaggregated primary outcome measure. Participant alive at 90 days, 90 days
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficinetly powered trial. After several internal discussions, and expert advice from statisticains, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfcatory solution. We therefore identified an alterantive trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied. Primary Outcome, To compare hospital re-admission free survival 90 days after index admission between intervention and standard cluster arms. Outcome Measure- Aggregated primary outcome measure consisting of survival and hospital re-admission data. Survival will be determined if the patient is alive 90 days after the date of index hospital admission. Hospital readmission will be determined if the participant required repeat all cause unplanned hospital admission within 90 days after index hospital admission. Admission will be defined as requirement for an overnight stay within a healthcare facility. , 90 days after dates of index hospital admission Primary Outcome, Aggregated primary outcome measure consisting of survival and hospital re-admission data. Survival will be determined if the patient is alive 90 days after the date of index hospital admission. Hospital readmission will be determined if the participant required repeat all cause unplanned hospital admission within 90 days after index hospital admission. Admission will be defined as requirement for an overnight stay within a healthcare facility. , 90 days after dates of index hospital admission
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Primary Outcome, Aggregated primary outcome measure consisting of survival and hospital re-admission data. Survival will be determined if the patient is alive 90 days after the date of index hospital admission. Hospital readmission will be determined if the participant required repeat all cause unplanned hospital admission within 90 days after index hospital admission. Admission will be defined as requirement for an overnight stay within a healthcare facility. , 90 days after dates of index hospital admission Primary Outcome, Primary Clinical Objective - Aggregated primary outcome measure consisting of survival and hospital re-admission data. Survival will be determined if the patient is alive 90 days after the date of index hospital admission. Hospital readmission will be determined if the participant required repeat all cause unplanned hospital admission within 90 days after index hospital admission. Admission will be defined as requirement for an overnight stay within a healthcare facility. , 90 days after dates of index hospital admission
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Prevalence of undiagnosed multimorbidity. Outcome Measures - Participants diagnosed with new multimorbid disease (≥2 of HIV, HTN or DM) from index admission, Recruitment, 30, 60 and 90 days Secondary Outcome, Secondary Clinical Objective - Prevalence of undiagnosed multimorbidity. Outcome Measures - Participants diagnosed with new multimorbid disease (≥2 of HIV, HTN or DM) from index admission, Recruitment, 30, 60 and 90 days
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Measures of disease control (e.g. blood pressure, HBA1c, HIV viraemia). Outcome Measures - Measurement of biological markers of disease control at enrolment and 90 day follow up. Hypertension (blood pressure), diabetes (HBA1c) and HIV (HIV viral load), Recruitment, 30, 60 and 90 days Secondary Outcome, Secondary Clinical Objective - Measures of disease control (e.g. blood pressure, HBA1c, HIV viraemia). Outcome Measures - Measurement of biological markers of disease control at enrolment and 90 day follow up. Hypertension (blood pressure), diabetes (HBA1c) and HIV (HIV viral load), Recruitment, 30, 60 and 90 days
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Prevalence of new end-organ complications relevant to primary disease (e.g., stroke, myocardial infarction, chronic kidney disease). Outcome Measures - Presence or absence of new relevant clinically diagnosed secondary complications (e.g., stroke, myocardial infarction, chronic kidney disease), including cause of death where applicable, Recruitment, 30, 60 and 90 days Secondary Outcome, Secondary Clinical Objective - Prevalence of new end-organ complications relevant to primary disease (e.g., stroke, myocardial infarction, chronic kidney disease). Outcome Measures - Presence or absence of new relevant clinically diagnosed secondary complications (e.g., stroke, myocardial infarction, chronic kidney disease), including cause of death where applicable, Recruitment, 30, 60 and 90 days
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 "Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied" Secondary Outcome, Disability free survival at 90 days. Outcome Measures - Disability will be measured using the Washington Group Short Set on Functioning (12) at admission and subsequent follow up visits, Recruitment, 30, 60 and 90 days Secondary Outcome, Disability free survival at 90 days. Outcome Measures - Disability will be measured using the Washington Group Short Set on Functioning (18) at admission and subsequent follow up visits, Recruitment, 30, 60 and 90 days
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Disability free survival at 90 days. Outcome Measures - Disability will be measured using the Washington Group Short Set on Functioning (18) at admission and subsequent follow up visits, Recruitment, 30, 60 and 90 days Secondary Outcome, Secondary Clinical Objective - Disability free survival at 90 days. Outcome Measures - Disability will be measured using the Washington Group Short Set on Functioning (18) at admission and subsequent follow up visits, Recruitment, 30, 60 and 90 days
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Cost-effectiveness of intervention vs. control (using primary clinical outcome as an outcome) from the societal perspective. Outcome Measures - Cost per additional person alive and not having had unplanned hospital readmission in intervention, versus control arm, 90 days after date of index hospital admission Secondary Outcome, Cost-effectiveness of intervention vs. control (using primary clinical outcome as an outcome) from the societal perspective. Outcome Measures - Societal (i.e. health system plus patient) cost per additional person alive and not having had unplanned hospital readmission in intervention, versus standard care, 90 days after date of index hospital admission with possible modelling over the lifetime horizon for a hypothetical patient cohort
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Cost-effectiveness of intervention vs. control (using primary clinical outcome as an outcome) from the societal perspective. Outcome Measures - Societal (i.e. health system plus patient) cost per additional person alive and not having had unplanned hospital readmission in intervention, versus standard care, 90 days after date of index hospital admission with possible modelling over the lifetime horizon for a hypothetical patient cohort Secondary Outcome, Secondary Health Economic Objective - Cost-effectiveness of intervention vs. control (using primary clinical outcome as an outcome) from the societal perspective. Outcome Measures - Societal (i.e. health system plus patient) cost per additional person alive and not having had unplanned hospital readmission in intervention, versus standard care, 90 days after date of index hospital admission with possible modelling over the lifetime horizon for a hypothetical patient cohort
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Secondary Health Economic Objective - Cost-effectiveness of intervention vs. control (using primary clinical outcome as an outcome) from the societal perspective. Outcome Measures - Societal (i.e. health system plus patient) cost per additional person alive and not having had unplanned hospital readmission in intervention, versus standard care, 90 days after date of index hospital admission with possible modelling over the lifetime horizon for a hypothetical patient cohort Secondary Outcome, Secondary Health Economic Objective - Cost-effectiveness of intervention vs. control (using primary clinical outcome as an outcome as the effectiveness measure) from the societal perspective. Outcome Measures - Societal (i.e. health system plus patient) cost per additional person alive and not having had unplanned hospital readmission in intervention, versus standard care, 90 days after date of index hospital admission with possible modelling over the lifetime horizon for a hypothetical patient cohort
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Patient costs and catastrophic health expenditure. Outcome Measures - (i) Mean/median cost per patient by arm and (ii) proportion of patients whose costs are catastrophic (i.e. % of patients where costs > to 10% annual income the previous year) per arm , 90 days after date of index hospital admission Secondary Outcome, Patient costs in intervention vs control clusters. Outcome Measures - Mean and (separately) median cost per patient in intervention vs standard care (includes medical and non-medical out-of-pocket expenses for the patient and accompanying person/s) for the multimorbid conditions., Evaluated at 90 days after the date of index hospital admission by summing costs incurred during the index hospital stay, between discharge and 30 day follow up period, between 30 and 60 day followup
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Patient costs in intervention vs control clusters. Outcome Measures - Mean and (separately) median cost per patient in intervention vs standard care (includes medical and non-medical out-of-pocket expenses for the patient and accompanying person/s) for the multimorbid conditions., Evaluated at 90 days after the date of index hospital admission by summing costs incurred during the index hospital stay, between discharge and 30 day follow up period, between 30 and 60 day followup Secondary Outcome, Secondary Health Economic Objective - Patient costs in intervention vs control clusters. Outcome Measures - Mean and (separately) median cost per patient in intervention vs standard care (includes medical and non-medical out-of-pocket expenses for the patient and accompanying person/s) for the multimorbid conditions., Evaluated at 90 days after the date of index hospital admission by summing costs incurred during the index hospital stay, between discharge and 30 day follow up period, between 30 and 60 day followup
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, HRQoL measures (EQ5D-5L and visual analogue scale). Outcome Measures - Mean/median change in QALY per person per arm, 90 days after date of index hospital admission Secondary Outcome, HRQoL measures (EQ5D-5L and visual analogue scale). Outcome Measures - Mean and separately median change in QALY per person calculated using the area under the curve methodology and summed by arm. , Evaluated at 90 days after date of index hospital admission, using the utility scores obtained for each patient at initial, 30, 60 and 90 days to calculate area under the curve, with possible modellin
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, HRQoL measures (EQ5D-5L and visual analogue scale). Outcome Measures - Mean and separately median change in QALY per person calculated using the area under the curve methodology and summed by arm. , Evaluated at 90 days after date of index hospital admission, using the utility scores obtained for each patient at initial, 30, 60 and 90 days to calculate area under the curve, with possible modellin Secondary Outcome, Secondary Health Economic Objective - HRQoL measures (EQ5D-5L and visual analogue scale). Outcome Measures - Mean and separately median change in QALY per person calculated using the area under the curve methodology and summed by arm. , Evaluated at 90 days after date of index hospital admission, using the utility scores obtained for each patient at initial, 30, 60 and 90 days to calculate area under the curve, with possible modellin
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Health system costs. Outcome Measures - Estimated cost to health system of implementing intervention , 90 days after date of index hospital admission Secondary Outcome, Health system costs in intervention vs control. Outcome Measures - Estimated cost to health system of implementing intervention vs. standard care (includes medication, tests conducted, inpatient stay costs, staff costs, overheads such as electricity, water etc. and consumable costs)., Cost modelling to esitmate annual cost per hospital of rolling out intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Health system costs in intervention vs control. Outcome Measures - Estimated cost to health system of implementing intervention vs. standard care (includes medication, tests conducted, inpatient stay costs, staff costs, overheads such as electricity, water etc. and consumable costs)., Cost modelling to esitmate annual cost per hospital of rolling out intervention Secondary Outcome, Secondary Health Economic Objective - Health system costs in intervention vs control. Outcome Measures - Estimated cost to health system of implementing intervention vs. standard care (includes medication, tests conducted, inpatient stay costs, staff costs, overheads such as electricity, water etc. and consumable costs)., Cost modelling to esitmate annual cost per hospital of rolling out intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 "Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied" Primary Outcome, Determine cost utility and cost effectiveness of the intervention Outcome Measures - Cost-utility of intervention vs. control (incremental cost per QALY averted compared to relevant thresholds expressed on the cost-effectiveness acceptability curve) , 90 days after date of index hospital admission Primary Outcome, Principle Health Economic Outcome - Cost-utility of intervention vs.standard care (incremental cost per QALY gained compared to relevant thresholds expressed on the costeffectiveness acceptability curve), 90 days after date of index hospital admission with possible modelling over the lifetime horizon for a hypotherical patient cohort
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 "Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied" Primary Outcome, Understand under what context and through what mechanisms an enhanced diagnostic, protocolised treatment and patient centred care intervention will enhance integrated care for patients with multimorbidity and will modify patient outcomes in a cluster randomized trial in secondary care hospitals Outcome Measures - Explain ‘what worked for whom, in what condition and why’ with a focus on: Intervention fidelity and quality: What was implemented and how Change mechanism: How did the delivered intervention produce change Context: How did context affect implementation and outcomes , 90 days Primary Outcome, Principle Process Evaluation Objective - Understand under what context and through what mechanisms an enhanced diagnostic, protocolised treatment and patient centred care intervention will enhance integrated care for patients with multimorbidity and will modify patient outcomes in a cluster randomized trial in secondary care hospitals Outcome Measures - Explain ‘what worked for whom, in what condition and why’ with a focus on: Intervention fidelity and quality: What was implemented and how Change mechanism: How did the delivered intervention produce change Context: How did context affect implementation and outcomes , 90 days
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Hospital re-admission rate 90 days after index hospital admission. outcome Measures - Disaggregated primary outcome measure. Participant requires repeat hospital admission within 90 days, 90 days Secondary Outcome, Secondary Clinical Objective - Hospital re-admission rate 90 days after index hospital admission. outcome Measures - Disaggregated primary outcome measure. Participant requires repeat hospital admission within 90 days, 90 days
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, To examine key secondary implementation outcomes including fidelity, acceptability, adoption, appropriateness, feasibility, and sustainability of the intervention. Outcome Measures - i. The extent to which the intervention is implemented as intended and whether any adaptations were made ii. Positive and negative effects of the intervention in the short and intermediate terms iii. Participation of the target population in the intervention iv. Extent of uptake of the intervention in hospital and community settings v. Sustainability of the intervention’s benefits , Longitudinal assessment throughout the trial Secondary Outcome, Secondary Process Evaluation Objective - To examine key secondary implementation outcomes including fidelity, acceptability, adoption, appropriateness, feasibility, and sustainability of the intervention. Outcome Measures - i. The extent to which the intervention is implemented as intended and whether any adaptations were made ii. Positive and negative effects of the intervention in the short and intermediate terms iii. Participation of the target population in the intervention iv. Extent of uptake of the intervention in hospital and community settings v. Sustainability of the intervention’s benefits , Longitudinal assessment throughout the trial
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, To assess how health system context at cluster/hospital and country level affect intervention fidelity and or outcomes. Outcome Measures - i. Organisation/integration of patient care (patient flow, NCD management, NCD treatment guidelines, clinical records, OPD service integration) ii. Availability of essential technologies and tools (monthly drug stock audit) iii. Human resources for health (dedicated staff for relevant NCDs and HIV, in post/staff vacancy levels) iv. Availability of core medicines (monthly drug stock audit) , At baseline, midline and endline Secondary Outcome, To assess how health system context at cluster/hospital and country level affect intervention fidelity and or outcomes. Outcome Measures - i. Organisation/integration of patient care (patient flow, NCD management, NCD treatment guidelines, clinical records, OPD service integration) ii. Availability of essential technologies and tools (monthly drug stock audit) iii. Human resources for health (dedicated staff for relevant NCDs and HIV, in post/staff vacancy levels) iv. Availability of core medicines (monthly drug stock audit) , For i - ii at baseline, midline and endline. For iii-iv monthly staff and drug stick audits in intervention and control clusters.
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, To assess how health system context at cluster/hospital and country level affect intervention fidelity and or outcomes. Outcome Measures - i. Organisation/integration of patient care (patient flow, NCD management, NCD treatment guidelines, clinical records, OPD service integration) ii. Availability of essential technologies and tools (monthly drug stock audit) iii. Human resources for health (dedicated staff for relevant NCDs and HIV, in post/staff vacancy levels) iv. Availability of core medicines (monthly drug stock audit) , For i - ii at baseline, midline and endline. For iii-iv monthly staff and drug stick audits in intervention and control clusters. Secondary Outcome, Secondary Process Evaluation Objective - To assess how health system context at cluster/hospital and country level affect intervention fidelity and or outcomes. Outcome Measures - i. Organisation/integration of patient care (patient flow, NCD management, NCD treatment guidelines, clinical records, OPD service integration) ii. Availability of essential technologies and tools (monthly drug stock audit) iii. Human resources for health (dedicated staff for relevant NCDs and HIV, in post/staff vacancy levels) iv. Availability of core medicines (monthly drug stock audit) , For i - ii at baseline, midline and endline. For iii-iv monthly staff and drug stick audits in intervention and control clusters.
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Cost utility of intervention vs. control (incremental cost per QALY gained compared to a range of relevant thresholds) from the societal perspective, measured at 90 days from hospital admission. Outcome Measures - Societal (i.e. health system and patient) cost per additional QALY gained in intervention, versus standard care, 90 days after the date of hospital admission with the possible modelling over the lifetime horizon for a hypothetical patient cohort
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Cost utility of intervention vs. control (incremental cost per QALY gained compared to a range of relevant thresholds) from the societal perspective, measured at 90 days from hospital admission. Outcome Measures - Societal (i.e. health system and patient) cost per additional QALY gained in intervention, versus standard care, 90 days after the date of hospital admission with the possible modelling over the lifetime horizon for a hypothetical patient cohort Secondary Outcome, Secondary Health Economic Objective - Cost utility of intervention vs. control (incremental cost per QALY gained compared to a range of relevant thresholds) from the societal perspective, measured at 90 days from hospital admission. Outcome Measures - Societal (i.e. health system and patient) cost per additional QALY gained in intervention, versus standard care, 90 days after the date of hospital admission with the possible modelling over the lifetime horizon for a hypothetical patient cohort
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Investigation into the socioeconomic status of patients diagnosed with multimorbidity (pooled sample). Outcome measures - Participant data on household construction materials, water sources, sanitation access and ownership of various items will be used to construct a wealth index score using principle components analysis, that will be used to categorise households into wealth quintiles relative to the socioeconomic status in each country which will be obtained from the most recent Demographic and Health Survey analysis., Evaluated using data obtained during index hospital admission
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Investigation into the socioeconomic status of patients diagnosed with multimorbidity (pooled sample). Outcome measures - Participant data on household construction materials, water sources, sanitation access and ownership of various items will be used to construct a wealth index score using principle components analysis, that will be used to categorise households into wealth quintiles relative to the socioeconomic status in each country which will be obtained from the most recent Demographic and Health Survey analysis., Evaluated using data obtained during index hospital admission Secondary Outcome, Secondary Health Economic Objective - Investigation into the socioeconomic status of patients diagnosed with multimorbidity (pooled sample). Outcome measures - Participant data on household construction materials, water sources, sanitation access and ownership of various items will be used to construct a wealth index score using principle components analysis, that will be used to categorise households into wealth quintiles relative to the socioeconomic status in each country which will be obtained from the most recent Demographic and Health Survey analysis., Evaluated using data obtained during index hospital admission
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" Secondary Outcome, Secondary Health Economic Objective - Cost effectiveness of intervention vs. control using the primary clinical outcome as effectiveness measure from the health system perspective - Outcome Measures - Health system cost per additional person alive and not having had unplanned hospital readmission in intervention, versus standard care, Evaluated at 90 days after the date of index hospital admission, with the possible modelling over the lifetime horizon for a hypothetical patient cohort
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site confirmed Phalombe Hospital , Phalombe, Phalombe District , , Malawi
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site confirmed Mulanje Hospital , Mulanje, Mulanje, , Malawi
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site confirmed Thyolo Hospital , Thyolo , Thyolo District , , Malawi
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site confirmed Mwanza Hospital, Mwanza, Mwanza District, , Malawi
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site confirmed Ntcheu Hospital, Ntcheu, Ntcheu Districk , , Malawi
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site confirmed Balaka Hospital, Balaka , Balaka District , , Malawi
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site confirmed Machinga Hospital , Machinga, Machinga District , , Malawi
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site confirmed Chikwawa Hospital, Chikwawa, Chikwawa District , , Malawi
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site confirmed Nsanje Hospital, Nsanje, Nsanje District , , Malawi
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site confirmed St Joseph District Hospital, St Joseph, Soweto , , Tanzania
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site confirmed Kibosho Hospital , Kibosho , Kilimanjaro, , Tanzania
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site Confirmed Marangu Lutheran Hospital, Marangu, Kilimanjaro, , Tanzania
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site Confirmed TPC Hospital, TPC, Kilimanjaro, , Tanzania
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site Confirmed TPC Hospital, TPC, Kilimanjaro, , Tanzania Machame Lutheran Hospital, Machame , Kilimanjaro, , Tanzania
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site Confirmed Huruma Catholic Diocese Hospital , Huruma, Kilimanjaro, , Tanzania
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site Confirmed Tumbi Regional Referral Hospital, Tumbi, Dar es Salaam , , Tanzania
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site Confirmed Temeke Regional Referral Hospital, Temeke, Dar es Salaam, , Tanzania
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site Confirmed Mwananyamala Referral Regional Hospital, Mwananyamala, Dar es Salaam, , Tanzania
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site Confirmed Amana Regional Referral Hospital, Amana, Dar es Salaam, , Tanzania
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site Confirmed Kigamboni Health Centre, Kigamboni, Dar es Salaam, , Tanzania
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/10/2024 Site Confirmed Bagamoyo District Hospital, Bagamoyo, Dar es Salaam, , Tanzania
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 08/12/2025 Updated approval of revised v.4 protocol TRUE, LSTM Research Ethics Committee , Pembroke Place , Liverpool, L3 5QA, United Kingdom, , 04 Oct 2023, +447029396, lstmrec@lstmed.ac.uk, 26931_25883_4737.pdf TRUE, LSTM Research Ethics Committee , Pembroke Place , Liverpool, L3 5QA, United Kingdom, , 01 Aug 2024, +447029396, lstmrec@lstmed.ac.uk, 26931_25883_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 12/10/2023 Malawi ethics approval pending FALSE, COMREC, University of Malawi College of Medicine, Mahatma Gandhi Campus, Postgraduate Building Ground Floor,, Blantyre, Blantyre , Malawi, 25 Oct 2023, , +2651874377, mandal@medcol.mw,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" FALSE, COMREC, University of Malawi College of Medicine, Mahatma Gandhi Campus, Postgraduate Building Ground Floor,, Blantyre, Blantyre , Malawi, 25 Oct 2023, , +2651874377, mandal@medcol.mw, FALSE, COMREC, University of Malawi College of Medicine, Mahatma Gandhi Campus, Postgraduate Building Ground Floor,, Blantyre, Blantyre , Malawi, 25 Oct 2023, , +2651874377, mandal@medcol.mw, 26931_25889_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" FALSE, COMREC, University of Malawi College of Medicine, Mahatma Gandhi Campus, Postgraduate Building Ground Floor,, Blantyre, Blantyre , Malawi, 25 Oct 2023, , +2651874377, mandal@medcol.mw, 26931_25889_4737.pdf TRUE, COMREC, University of Malawi College of Medicine, Mahatma Gandhi Campus, Postgraduate Building Ground Floor,, Blantyre, Blantyre , Malawi, 25 Oct 2023, 10 Sep 2024, +2651874377, mandal@medcol.mw, 26931_25889_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 12/10/2023 Tanzania ethics approval pending FALSE, NIMR, 3 Barack Obama Drive,, Dar es Salaam, 9653, Tanzania, 25 Oct 2023, , +255222121400, hq@nimr.or.tz,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 08/12/2025 Updated approval of revised v.4 protocol FALSE, NIMR, 3 Barack Obama Drive,, Dar es Salaam, 9653, Tanzania, 25 Oct 2023, , +255222121400, hq@nimr.or.tz, TRUE, NIMR, 3 Barack Obama Drive,, Dar es Salaam, 9653, Tanzania, 25 Oct 2023, 31 Oct 2024, +255222121400, hq@nimr.or.tz, 26931_25890_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 13/10/2023 KCMC institutional ethics application FALSE, CRERC, Kilimanjaro Christian Medical Centre, Kilimanjaro, PO Box 30, Tanzania, 25 Oct 2023, , +255272754377, kcmcadmin@kcmc.ac.tz,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 08/12/2025 Updated approval of revised v.4 protocol FALSE, CRERC, Kilimanjaro Christian Medical Centre, Kilimanjaro, PO Box 30, Tanzania, 25 Oct 2023, , +255272754377, kcmcadmin@kcmc.ac.tz, TRUE, CRERC Kilimanjaro Christian Medical College Research Ethics and Review Committee, Kilimanjaro Christian Medical Centre, Kilimanjaro, PO Box 30, Tanzania, 25 Oct 2023, 15 Nov 2024, +255272754377, kcmcadmin@kcmc.ac.tz, 26931_25894_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" TRUE, Liverpool School of Tropical Medicine Research Ethics Committee, Pembroke Place , Liverpool, L3 5QA, United Kingdom, , 01 Aug 2024, +447029396, lstmrec@lstmed.ac.uk, 26931_30072_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 08/12/2025 FULL ethics approval confirmed after receiving in-country ethics approvals TRUE, Liverpool School of Tropical Medicine Research Ethics Committee, Pembroke Place , Liverpool, L3 5QA, United Kingdom, , 01 Aug 2024, +447029396, lstmrec@lstmed.ac.uk, 26931_30072_4737.pdf TRUE, Liverpool School of Tropical Medicine Research Ethics Committee, Pembroke Place , Liverpool, L3 5QA, United Kingdom, , 25 Nov 2024, +447029396, lstmrec@lstmed.ac.uk, 26931_30072_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 04/10/2024 """Our analysis revealed that the intracluster-correlation coefficient (ICC) and other key parameters were such the original sample size proposed at grant development may not be adequate to yield a sufficiently powered trial. After several internal discussions, and expert advice from statisticians, triallists and epidemiologists with experience in cluster randomised trials over a period of months we held a meeting with our Trial Steering Committee in April 2024 to highlight the issues and propose some options. The TSC commended our work but noted that none of the options identified (which would be possible to complete within current time and budget) were satisfactory and directed us to find a more satisfactory solution. We therefore identified an alternative trial design which would provide additional statistical power even under pessimistic (but possible) assumptions about key parameters. This new design was presented to our DSMB in June 2024 who endorsed the new study design and agreed it was robust and appropriate. We further communicated to the TSC who were also satisfied""" FALSE, TMDA, Nelson Mandela Rd, Dar es Salaam , Tanzania, Tanzania, 29 Oct 2023, , +255222450512, info@tmda.go.tz,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 08/12/2025 Updated REGULATORY approval of revised v.4 protocol for TANZANIA (Note: trial was never opened in Tanzania) FALSE, TMDA, Nelson Mandela Rd, Dar es Salaam , Tanzania, Tanzania, 29 Oct 2023, , +255222450512, info@tmda.go.tz, TRUE, TMDA Tanzania Medicines and Medical Devices Authority, Nelson Mandela Rd, Dar es Salaam , Tanzania, Tanzania, 29 Oct 2023, 21 May 2025, +255222450512, info@tmda.go.tz, 26931_30073_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 08/12/2025 Updated REGULATORY approval of revised v.4 protocol for TANZANIA (Note: trial was never opened in Tanzania) TRUE, MUHAS Muhimbili University of Health and Allied Sciences, P.O box 65001, MUHAS, Dar es Salaam, 12101, United Republic of Tanzania, , 22 Nov 2024, +255752360543, vc@muhas.ac.tz, 26931_35581_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 12/10/2023 Representative from Tanzania Scientific Enquiries, Matthew , Rubach, Prof., matthew.rubach@duke.edu, , +255718164044, KCMC , Kilimanjaro, , Tanzania, CoInvestigator
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 12/10/2023 Representative for Tanzania Scientific Enquiries, Hendry , Sawe, Dr., hendry_sawe@yahoo.com, , +255754885658, Muhimbili , Dar es Salaam , , Tanzania, CoInvestigator
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 08/12/2025 Since the last update to the registry, discussions have been held about how to manage and share the data that was collected before the parallel group cRCT was discontinued. n/a Prior to the early termination of the planned parallel group cRCT in March 2025, only baseline data was collected for a small sample of 68 participants across 8 hospitals, with no intervention data to compare this to. Once this data has been cleaned and analysed in accordance with the project Statistical Analysis Plan and disseminated in accordance with the protocol, the data will be made available via an open access website; most likely the UK Data Service (https://datacatalogue.ukdataservice.ac.uk/#!?Search=&Rows=10&Sort=0&AccessFacet=Open) or another open access site.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD-Sharing time frame 08/12/2025 Answer updated in line with the latest developments to the study and dissemination plan. n/a The data is expected to be shared within 12 months of the end of the Multilink programme, up to November 2026. Note: The research programme has an overall ‘the dissemination period’ of two years (up until November 2027), in agreement with the funder.
Section Name Field Name Date Reason Old Value Updated Value
Reporting Key access criteria 08/12/2025 Answer updated in line with the latest developments to the study and dissemination plan. n/a Access to the data will be open with no restrictions on what or who can analyse it. For further information on the original analysis plan prior to the early termination of the trial, see GitHub link: https://github.com/mlw-stats/Multilink/tree/main/SAP