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 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202411682724094 Date of Registration: 05/11/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Post-discharge Malaria Chemoprevention Implementation Trial in Benin ( PDMC-SL)
Official scientific title Delivery Strategies for Malaria Chemoprevention in the Post-discharge Management of Children Hospitalised With Severe Anaemia or Severe Malaria: a Cluster Randomised Controlled Implementation Trial in Benin
Brief summary describing the background and objectives of the trial In June 2022, the World Health Organization (WHO) recommended PDMC for the post-discharge management of children with severe anaemia (Post-discharge malaria chemoprevention, PDMC) in settings with moderate to high perennial malaria transmission to reduce hospital readmissions and deaths after discharge. However, there is no obvious delivery platform for PDMC, unlike for intermittent preventive treatment in infants (IPTi) or pregnant women (IPTp). Furthermore, a potential limitation of PDMC is adherence to the 3-day dosing regimen, which is provided monthly three times after discharge. Therefore, implementation research is urgently needed to support the introduction and scale-up of PDMC. The proposed research aims to conduct implementation trials in Benin, co-designed with national stakeholders, to evaluate different delivery strategies for optimizing health system delivery of PDMC drugs and adherence to PDMC. This chemoprevention strategy is effective in reducing hospital readmissions and deaths after discharge. However, there is no clear delivery platform for PDMC, and adherence to the 3-day dosing regimen, provided monthly three times after discharge, is a potential limitation. The current trial will provide evidence-based data on acceptability, feasibility, and cost-effectiveness to aid decision-makers. The evidence generated will be used to support the effective implementation and scale-up of PDMC in high malaria-endemic areas such as Benin.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PDMCSL
Disease(s) or condition(s) being studied Infections and Infestations,Paediatrics
Sub-Disease(s) or condition(s) being studied Malaria,Severe anaemia and severe malaria
Purpose of the trial Prevention
Anticipated trial start date 01/11/2024
Actual trial start date
Anticipated date of last follow up 01/06/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 648
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
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 Simple randomization using a randomization table created by a computer software program 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
Experimental Group Delivery strategy A 9 doses of dihydroartemisinin-piperaquine, administered as three 3-day treatment courses, each spaced one month apart 14 weeks post-discharge All PDMC drugs will be given to the caregivers at discharge with the CHW support through monthly home visits to remind the caregiver to administrate the PDMC drugs 216
Experimental Group Delivery strategy B 9 doses of dihydroartemisinin-piperaquine, administered as three 3-day treatment courses, each spaced one month apart 14 weeks post-discharge All PDMC drugs will be given by the community health worker (CHW) to deliver to the caregivers at home, with a SMS/phone reminder from the qualified community health officers (ASCQ) to the CHW to deliver the drug 216
Control Group Delivery strategy control 9 doses of dihydroartemisinin-piperaquine, administered as three 3-day treatment courses, each spaced one month apart 14 week post-discharge All PDMC drug given to the caregivers at discharge with no other adherence support approaches 216 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
- Aged below 10 years of both sexes - Hospitalised with severe anaemia or severe malaria (Initially hospitalised with haemoglobin below 5.0 g/dl or PCV below 15%, or requirement for blood transfusion for other clinical reasons on or during admission to the hospital, or severe malaria, defined as a requirement for parenteral artesunate in the opinion of the treating clinician and the presence of microscopy or RDT confirmed Plasmodium infection) - Recognised specific other causes of severe anaemia (i.e., trauma, haematological malignancy, known bleeding disorders, such as haemophilia) - Sickle cell anaemia/sickle cell disease - Body weight below 5 kg Child: 6 Year-12 Year,Infant: 13 Month(s)-24 Month(s),Preschool Child: 2 Year-5 Year 6 Month(s) 9 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 04/10/2024 Comite d Ethique de la Recherche de l Institut des Sciences Biomedicales Appliquees CER ISBA
Ethics Committee Address
Street address City Postal code Country
Institut des Sciences Biomedicales Appliquees ISBA Cotonou 00229 Benin
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Number of children with incomplete adherence to 9 doses of PDMC by the end of week 14 post-discharge Adherence to the PDMC strategy: Proportion of children with incomplete adherence to 9 doses of PDMC (three courses of 3-day treatments 3x3=9) i.e. the number of children who do not receive the total of 9 doses of PDMC tablets by the end of week 14 after discharge out of the total sample size. Time Frame: Administration of PDMC courses at 2, 6 and 10 weeks post discharge
Secondary Outcome Number of children readmitted to hospital from all-cause and malaria-specific by the end of week 14 post-discharge Incidence of all-cause and malaria-specific readmissions by the end of week 14 after discharge, i.e. the number of children readmitted for malaria by the end of week 14 after discharge out of the total sample size. Time Frame: 14 weeks post discharge
Secondary Outcome Number of sick-child clinic visits from all-cause and malaria-specific by the end of week 14 post-discharge Proportion of all-cause and malaria-specific sick-child clinic visits by the end of week 14 after discharge, i.e. the number of children who visit the hospital for any cause or due to malaria by the end of week 14 after discharge out of the total of sample size. Time Frame: 14 weeks post discharge
Secondary Outcome Number of children who die within 14 weeks post-discharge Incidence of all-cause mortality of children by the end of week 14 after discharge, i.e. the number of children who die within 14 weeks of discharge out of the total sample size. Time Frame: 14 weeks post discharge
Secondary Outcome Number of serious adverse events following PDMC administration within 14 weeks post-discharge Safety of PDMC strategy: Proportion of serious adverse events occurring after discharge to 14 weeks post-discharge, i.e. the number of children presenting serious adverse events by the end of week 14 after discharge out of the total sample size. Time Frame: 14 weeks post discharge
Secondary Outcome Cost per Disability adjusted life years (DALY) averted for each intervention versus control arm DALYs will be determined at the individual level and calculated based on the standard method used by the 2010 Global Burden of Disease Study (and using disability weights and life expectancies at age of death from the most recent WHO life tables). The total number of DALYs will be calculated by adding the DALYs for each individual who receives the intervention/s. The cost per DALY averted for each intervention will be compared against published country-specific willingness-to-pay thresholds to assess cost-effectiveness Time Frame: 14 weeks post discharge
Secondary Outcome Stakeholder perceptions of the feasibility on the delivery strategy with adherence supports Health providers, managers, health community workers, and policy stakeholders; perceptions regarding the feasibility of the delivery strategy and adherence support by assessing barriers and constraints through focus group discussions and key in-depth interviews. Time Frame: Within 6 month following the benning of trial
Secondary Outcome Stakeholder acceptability of the regimen of the PDMC strategy and perception of caregiver acceptability and adherence Health providers, managers, health community workers, and policy stakeholders acceptability regarding the acceptability of the regimen and the perception of the caregivers acceptability and adherence. Acceptability theory will draw on Sekhon’s constructs of acceptability - - affective attitude (general feelings about the intervention), burden (perceptions of effort needed to take part), ethicality (fit with their value system), intervention coherence (understanding of the intervention and how it works), opportunity costs (what must be given up in order to participate), perceived effectiveness (perceptions of the intervention’s ability to achieve its aim), and self-efficacy (feeling that they can do what they need to do to take part) and unintended consequences Time Frame: Within 6 month following the benning of trial
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Lagune Mother and Child University Hospital Centre Ganhi Cotonou 00229 Benin
Goho Departmental Hospital Centre Route place Goho Abomey 00229 Benin
FUNDING SOURCES
Name of source Street address City Postal code Country
The Global Health European and Developing Countries Clinical Trials Partnership EDCTP 3 Joint Undertaking and its members Anna van Saksenlaan 51 2593 HW The Hague The Netherlands Hague Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Institut de Recherche Clinique du Benin Route de hopital de zone Abomey-Calavi AbomeyCalavi 00229 Benin Not for-profit Organization
COLLABORATORS
Name Street address City Postal code Country
Liverpool School of Tropical Medicine Pembroke Place, Liverpool L3 5QA Liverpool United Kingdom
Kenya Medical Research Institute P.O. Box 1578 Kisumu 40100 Kisumu Kenya
Epicentre 14-34 Avenue Jean Jaures 75019 Paris Paris 75019 France
Institut de Recherche pour le Developpement MERIT UMR126 4 avenue de l Observatoire Paris 75006 France
Training Research Unit of Excellence 1 Kufa Road, Mandala Blantyre Malawi
Centers for Disease Control and Prevention P.O. Box 1578, Kisumu 40100. Kisumu Kenya
Makerere University College of Health Sciences P.O. Box 7072 Kampala Uganda. Kampala Uganda
CONTACT PEOPLE
Role Name Email Phone Street address
Scientific Enquiries Manfred Accrombessi accrombessimanfred@gmail.com +22966033138 Route de hopital de zone
City Postal code Country Position/Affiliation
Abomey Calavi Benin Country PI
Role Name Email Phone Street address
Principal Investigator Jenny Hill jenny.hill@lstmed.ac.uk +441517053216 Pembroke Place, Liverpool L3 5QA, UK
City Postal code Country Position/Affiliation
Liverpool United Kingdom Chief investigator
Role Name Email Phone Street address
Public Enquiries Achille Massougbodji massougbodjiachille@yahoo.fr +22996807027 Route de hopital de zone
City Postal code Country Position/Affiliation
Abomey Calavi 00229 Benin Director IRCB
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes De-identified individual participant data collected during the trial will be shared at 1 year after article publication with no end date. Pseudonymised data will be available to other researchers for further analysis, participant to ethical approval, the terms of the original participant consent and agreement on its use according to prevailing laws on intellectual property rights at partner institutes. Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol The data will be shared once the publication is accepted by a journal 1. An independent IDDO Data Access Committee (DAC) 2. A contributor-controlled process – where the data contributor assesses each data access application that requests the re-use of their data
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://www.iddo.org/data-sharing/contributing-data 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 22/10/2024 Request from reviewer The proposed research aims to conduct implementation trials in Benin, co-designed with national stakeholders, to evaluate different delivery strategies for optimizing health system delivery of post-discharge malaria chemoprevention (PDMC) drugs and adherence to PDMC. This chemoprevention strategy is effective in reducing hospital readmissions and deaths after discharge. However, there is no clear delivery platform for PDMC, and adherence to the 3-day dosing regimen, provided monthly three times after discharge, is a potential limitation. The current trial will provide evidence-based data on acceptability, feasibility, and cost-effectiveness to aid decision-makers. The evidence generated will be used to support the effective implementation and scale-up of PDMC in high malaria-endemic areas such as Benin. In June 2022, the World Health Organization (WHO) recommended PDMC for the post-discharge management of children with severe anaemia (Post-discharge malaria chemoprevention, PDMC) in settings with moderate to high perennial malaria transmission to reduce hospital readmissions and deaths after discharge. However, there is no obvious delivery platform for PDMC, unlike for intermittent preventive treatment in infants (IPTi) or pregnant women (IPTp). Furthermore, a potential limitation of PDMC is adherence to the 3-day dosing regimen, which is provided monthly three times after discharge. Therefore, implementation research is urgently needed to support the introduction and scale-up of PDMC. The proposed research aims to conduct implementation trials in Benin, co-designed with national stakeholders, to evaluate different delivery strategies for optimizing health system delivery of PDMC drugs and adherence to PDMC. This chemoprevention strategy is effective in reducing hospital readmissions and deaths after discharge. However, there is no clear delivery platform for PDMC, and adherence to the 3-day dosing regimen, provided monthly three times after discharge, is a potential limitation. The current trial will provide evidence-based data on acceptability, feasibility, and cost-effectiveness to aid decision-makers. The evidence generated will be used to support the effective implementation and scale-up of PDMC in high malaria-endemic areas such as Benin.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Target no of participants 22/10/2024 Sample size has been recalculated to take into account cluster effect 636 648
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Inclusion criteria 22/10/2024 Request from reviewer Aged below 10 years of both sexes Hospitalised with severe anaemia or severe malaria: Initially hospitalised with haemoglobin below 5.0 g/dl or PCV below 15%, or requirement for blood transfusion for other clinical reasons on or during admission to the hospital, or severe malaria, defined as a requirement for parenteral artesunate in the opinion of the treating clinician and the presence of microscopy or RDT confirmed Plasmodium infection - Aged below 10 years of both sexes - Hospitalised with severe anaemia or severe malaria (Initially hospitalised with haemoglobin below 5.0 g/dl or PCV below 15%, or requirement for blood transfusion for other clinical reasons on or during admission to the hospital, or severe malaria, defined as a requirement for parenteral artesunate in the opinion of the treating clinician and the presence of microscopy or RDT confirmed Plasmodium infection)
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Exclusion criteria 22/10/2024 Request from reviewer Recognised specific other causes of severe anaemia (i.e., trauma, haematological malignancy, known bleeding disorders, such as haemophilia) Sickle cell anaemia/sickle cell disease Body weight below 5 kg - Recognised specific other causes of severe anaemia (i.e., trauma, haematological malignancy, known bleeding disorders, such as haemophilia) - Sickle cell anaemia/sickle cell disease - Body weight below 5 kg
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 28/10/2024 Re-estimation of the sample size taking into account the cluster effect Experimental Group, Delivery strategy A, 9 doses of dihydroartemisinin-piperaquine, administered as three 3-day treatment courses, each spaced one month apart, 14 weeks post-discharge, All PDMC drugs will be given to the caregivers at discharge with the CHW support through monthly home visits to remind the caregiver to administrate the PDMC drugs, 216,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 28/10/2024 Re.estimation of sample size to take into account the cluster effect Experimental Group, Delivery strategy B, 9 doses of dihydroartemisinin-piperaquine, administered as three 3-day treatment courses, each spaced one month apart, 14 weeks post-discharge, All PDMC drugs will be given by the community health worker (CHW) to deliver to the caregivers at home, with a SMS/phone reminder from the qualified community health officers (ASCQ) to the CHW to deliver the drug, 212, Experimental Group, Delivery strategy B, 9 doses of dihydroartemisinin-piperaquine, administered as three 3-day treatment courses, each spaced one month apart, 14 weeks post-discharge, All PDMC drugs will be given by the community health worker (CHW) to deliver to the caregivers at home, with a SMS/phone reminder from the qualified community health officers (ASCQ) to the CHW to deliver the drug, 216,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 28/10/2024 Re.estimation of sample size to take into account the cluster effect Control Group, Delivery strategy control, 9 doses of dihydroartemisinin-piperaquine, administered as three 3-day treatment courses, each spaced one month apart, 14 week post-discharge, All PDMC drug given to the caregivers at discharge with no other adherence support approaches, 212, Active-Treatment of Control Group Control Group, Delivery strategy control, 9 doses of dihydroartemisinin-piperaquine, administered as three 3-day treatment courses, each spaced one month apart, 14 week post-discharge, All PDMC drug given to the caregivers at discharge with no other adherence support approaches, 216, Active-Treatment of Control Group
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 22/10/2024 We received the formal approval today (22/10/2024) FALSE, Comite d Ethique de la Recherche de l Institut des Sciences Biomedicales Appliquees CER ISBA, Institut des Sciences Biomedicales Appliquees ISBA, Cotonou, 00229, Benin, 29 Jul 2024, , 0022996685110, cer_isba@yahoo.fr, TRUE, Comite d Ethique de la Recherche de l Institut des Sciences Biomedicales Appliquees CER ISBA, Institut des Sciences Biomedicales Appliquees ISBA, Cotonou, 00229, Benin, 29 Jul 2024, 04 Oct 2024, 0022996685110, cer_isba@yahoo.fr, 31962_30097_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 22/10/2024 Request from reviewer All IPD that underlie results in a publication De-identified individual participant data collected during the trial will be shared at 1 year after article publication with no end date. Pseudonymised data will be available to other researchers for further analysis, participant to ethical approval, the terms of the original participant consent and agreement on its use according to prevailing laws on intellectual property rights at partner institutes.