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.: PACTR202303630742194 Date of Approval: 08/03/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Chemoprevention of malaria and other infectious disease in the post-discharge management of children with severe anaemia in Malawi, Kenya and Uganda
Official scientific title Dihydroartemisinin-piperaquine and azithromycin for the post-discharge management of children with severe anaemia in Malawi, Kenya and Uganda; A, multicentre, parallel-group, two-arm, randomised, double-blind superiority trial
Brief summary describing the background and objectives of the trial Background and rationale: Severe anaemia is associated with significant post-discharge morbidity and mortality in children in malaria-endemic Africa. A recent trial in areas with moderate to intense malaria transmission in Kenya and Uganda showed that three months of post-discharge malaria chemoprevention (PDMC) with monthly dihydroartemisinin-piperaquine (DP) in recently transfused children with severe anaemia prevented 35% of deaths or all-cause readmissions by six months post-discharge. The protective effect was restricted to the 3-month PDMC intervention period. PDMC-DP did not affect non-malarial causes of readmissions; 45% and 80% of the remaining readmissions and sick-child clinic visits (SCCV) were due to other causes. We hypothesise that the beneficial effect of PDMC can be boosted further by combining DP with azithromycin (AZ), a potent broad-spectrum antibiotic known to reduce all-cause mortality in African children. Primary objective: To determine if PDMC with four courses of monthly AZ treatment courses (given monthly) in combination with four months of weekly DP is superior to PDMC with weekly DP-alone in reducing non-malaria SCCV by six months post-discharge in children aged <5 years admitted with severe anaemia (Hb<5g/dl) who are ready to be discharged and are clinically stable and able to switch to oral medication.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PDMC II
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Diarrhoea, Respiratory tract infections,Malaria
Purpose of the trial Prevention
Anticipated trial start date 01/04/2023
Actual trial start date
Anticipated date of last follow up 01/09/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 958
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 Permuted block randomization Sealed opaque envelopes Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Azithromycin 10mg/kg bodyweight once a day for 3 days every month 3 months Broad spectrum antibiotic manufactured by Fosun Pharmaceutical, China (ZITMYC®, dispersible tablet) 479
Control Group Azithromycin Placebo 10mg/kg bodyweight (for active Azithromycin) once a day for 3 days every month 3 months Placebo Azithromycin dispersible tablets manufactured by Fosun Pharmaceuticals, China (dispersible tablet) 479 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Inclusion criteria for enrolment into pre-study screening period 1. Haemoglobin <5.0 g/dl or PCV < 15%, or requirement for blood transfusion for other clinical reasons on or during admission to the hospital 2. Aged less than 59.8 months 3. Body weight ≥5 kg 4. Resident in catchment area Inclusion criteria for enrolment: 1. Fulfilled the pre-study screening eligibility criteria 2. Aged < 59.8 months 3. Clinically stable, able to take oral medication 4. participant completed blood transfusion(s) or became clinically stable without transfusion 5. Able to feed (for breastfeeding children) or eat (for older children) 6. Absence of known cardiac problems 7. Provision of informed consent by parent or guardian Inclusion criteria for randomisation: 1. Fulfilled enrolment eligibility criteria and was enrolled during recent admission 2. Aged <60 months 3. Still clinically stable, able to take to oral medication, able to feed (for breastfeeding children) or eat (for older children) and able to sit unaided (for older children who were already able to do so prior to hospitalisation) Exclusion criteria for enrolment into pre-study screening period 1. Recognised specific other cause of severe anaemia (e.g. trauma, haematological malignancy, known bleeding disorder). 2. Known sickle cell disease. 3. Anticipated to reach the 5th birthday (60 months of age) within 1 week from enrolment (i.e. prior to randomization). 4. Child will reside for more than 25% of the 6 months study period (i.e. 6 weeks or more) outside of catchment area. 5. Hereditary polymorphisms, other than sickle cell disease, that are known to provide protection against severe forms of malaria 6. Cotrimoxazole prophylaxis (usually due to HIV infection or exposure) Exclusion criteria for enrolment: 1. Previous enrolment in the present study 2. Known hypersensitivity to study medication 3. Known sickle cell disease 4. Use or known need at the time of enrolment for concomitant prohibited medication during the 17 weeks intervention period 5. Ongoing or planned participation in another clinical trial 6. A known need at the time of enrolment for scheduled surgery during the subsequent course of the study (6 months from enrolment) 7. Suspected non-compliance with the follow-up schedule 8. Known heart conditions, or family history of congenital prolongation of the QTc interval. 9. Taking other medicinal products that are known to prolong the QTc interval Exclusion criteria for randomisation: 1. Used AZ since enrolment 2. Use or known need at the time of randomisation for concomitant prohibited medication during the 16 weeks PDMC treatment period. 3. Enrolled, or known agreement to enrol into another clinical trial involving ongoing or scheduled treatment with medicinal products during the course of the study (6 months from enrolment) 4. A known need at the time of randomisation for scheduled surgery during the subsequent course of the study (6 months from enrolment) 5. Suspected non-compliance with the follow-up schedule 6. Withdrawal of consent since enrolment Infant: 1 Month-23 Month,Preschool Child: 2 Year-5 Year 4 Month(s) 59 Month(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 23/12/2022 KEMRI Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
OFF MBAGATHI ROAD Nairobi 00200 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 29/08/2022 Makerere University School of Medicine Research and Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Kampala Kampala 7072 Uganda
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 05/09/2022 National Health Science Research Committee
Ethics Committee Address
Street address City Postal code Country
Lilongwe Lilongwe 30377 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 17/10/2022 Regional Committee for Medical and Health Research Ethics
Ethics Committee Address
Street address City Postal code Country
Blindern Oslo NO-0318 Norway
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Non-malaria sick-child clinic visits (SCCV) by 26 weeks from randomization By 26 weeks from randomization
Secondary Outcome All-cause sick-child clinic visits by 26 weeks from randomization By 26 weeks from randomization
Secondary Outcome Readmission due to severe disease other than severe anaemia and severe malaria by 26 weeks from randomization By 26 weeks from randomization
Secondary Outcome Readmissions due to severe anaemia (defined as Hb <5g/dL or PCV <15% or requirement for blood transfusion based on other clinical indication) by 26 weeks from randomization By 26 weeks from randomization
Secondary Outcome All-cause hospital readmission by 26 weeks from randomization By 26 weeks from randomization
Secondary Outcome All-cause mortality by 26 weeks from randomization By 26 weeks from randomization
Secondary Outcome Serious adverse events, excluding primary and secondary efficacy outcomes, by 26 weeks from randomization By 26 weeks from randomization
Secondary Outcome Serious adverse events within 7 days after the start of each course of azithromycin, excluding primary and secondary efficacy outcomes. Within 7 days after the start of each course of azithromycin
Secondary Outcome Non-severe adverse events by 26 weeks from randomization By 26 weeks from randomization
Secondary Outcome Non-severe adverse events within 7 days after start of each course of azithromycin Within within 7 days after start of each course of azithromycin
Secondary Outcome QTc prolongation measured by electro cardiogram (ECG) 4-6 hours after 3rd dose of each course of azithromycin 4-6 hours after 3rd dose of each course of azithromycin
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Zomba Central Hospital M3 Blantyre Road Zomba Malawi
Kamuzu Central Hospital Mzimba Road Lilongwe Malawi
Jinja Regional Referral Hospital Jinja Jinja Uganda
Kitgum General Hospital Kitgum Kitgum Uganda
Jaramogi Oginga Odinga Teaching and Referral Hospital Kisumu Kisumu Kenya
Busia County Referral Hospital Busia Busia Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
European and Developing Countries Clinical Trials Partnership Anna van Saksenlaan The Hague 51 - 2593 Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Training and Research Unit of Excellence 1 Kufa Road Blantyre Malawi Non-for-profit Research Organisation
COLLABORATORS
Name Street address City Postal code Country
Dr Richard Idro Kampala Kampala Uganda
Prof Feiko ter Kuile Pembroke Place Liverpool L3 5QA United Kingdom
Dr Robert Opoka Kampala Kampala Uganda
Prof Bjarne Robberstad Bergen Bergen 5020 Norway
Prof Michael Boele van Hensbroek Meibergdreef 9 Amsterdam 1105 AZ Netherlands
Prof Paolo Denti Rondebosch Cape Town 7701 South Africa
Dr Simon Kariuki Kisumu Kisumu Kenya
Dr Aggrey Dhabangi Kampala Kampala Uganda
Dr Roeland Wassman Rondebosch Cape Town South Africa
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Kamija Phiri director@true.mw +265999957048 1 Kufa Road
City Postal code Country Position/Affiliation
Blantyre Malawi Director
Role Name Email Phone Street address
Public Enquiries Kamija Phiri director@true.mw +265999957048 1 Kufa Road
City Postal code Country Position/Affiliation
Blantyre Malawi Director
Role Name Email Phone Street address
Scientific Enquiries Kamija Phiri director@true.mw +265999957048 1 Kufa Road
City Postal code Country Position/Affiliation
Blantyre Malawi Director
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual data that underlie the results reported in scientific articles after deidentification Statistical Analysis Plan,Study Protocol Beginning 3 months and ending 5 years following article(s) publication Data will be provided to researchers who provide a methodological sound proposal
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