Post-discharge Malaria Chemoprevention(PMC) Study
PMC
Malaria Chemoprevention With Monthly Treatment With Dihydroartemisinin-piperaquine for the Post-discharge Management of Severe Anaemia in Children Aged Less Than 5 Years in Uganda and Kenya: A Two-arm Randomised Placebo Controlled Trial
4 other identifiers
interventional
1,049
2 countries
9
Brief Summary
This study evaluates the efficacy and safety of 3 months of malaria chemoprevention post-discharge using dihydroartemisinin piperaquine (DHA-P) in children under 5 years of age admitted with severe anemia. One half will receive monthly DHA-P and the other half placebo.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started May 2016
Typical duration for phase_3
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 28, 2016
CompletedFirst Posted
Study publicly available on registry
February 2, 2016
CompletedStudy Start
First participant enrolled
May 20, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 24, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
December 12, 2018
CompletedJune 4, 2020
June 1, 2020
2.4 years
January 28, 2016
June 2, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
All-cause deaths or all-cause re-admissions by 26 weeks from randomization (composite primary outcome).
Primary outcome
6 months
Secondary Outcomes (24)
Readmission due to severe malaria (defined as any treatment with parenteral quinine or artesunate, or presence of severe anaemia and treatment with oral antimalarials) by 26 weeks from randomization
26 weeks from randomization
All-cause readmission by 26 weeks from randomization
26 weeks from randomization
Readmissions due to severe anaemia (defined as Haemoglobin (Hb) <5g/dL or packed-cell volume (PCV) <15% or requirement for blood transfusion based on other clinical indication)by 26 weeks from randomization
26 weeks from randomization
Readmission due to severe malarial anaemia (severe anaemia plus parenteral or oral antimalarial treatment)by 26 weeks from randomization
26 from randomization
Readmission due to severe anaemia or severe malaria (composite outcome)by 26 weeks from randomization
26 weeks from randomization
- +19 more secondary outcomes
Study Arms (2)
dihydroartemisinin-piperaquine
ACTIVE COMPARATORdihydroartemisinin-piperaquine (3-day treatment courses, given 2, 6, and 10 weeks after enrollment)
dihydroartemisinin-piperaquine Placebo
PLACEBO COMPARATORPlacebo comparator (matching tablets containing no active ingredients)
Interventions
Children in both arms will receive standard in-hospital care for severe anaemia (blood transfusion, often combined with quinine or artesunate IV/IM). All children will then receive a 3-day course of AL (whether they initially had malaria or not), which will be started in-hospital as soon as they are able to take oral medication, and will be completed at home after discharge. At 2 weeks after enrolment surviving children will be randomized to receive either a standard 3-day courses of dihydroartemisinin-piperaquine (Eurartesim®, Sigma Tau, Italy) or an identical placebo regimen at 2, 6 and 10 weeks after enrolment.
Children will receive standard in-hospital care for severe anaemia (blood transfusion, often combined with quinine or artesunate IV/IM). All children will then receive a 3-day course of AL (whether they initially had malaria or not), which will be started in-hospital as soon as they are able to take oral medication, and will be completed at home after discharge. At 2 weeks after enrolment surviving children will be randomized to receive either a standard 3-day courses of dihydroartemisinin-piperaquine (Eurartesim®, Sigma Tau, Italy) or an identical placebo regimen at 2, 6 and 10 weeks after enrolment.
Eligibility Criteria
You may qualify if:
- Pre-study screening
- Haemoglobin \<5.0 g/dl or PCV \< 15%, or requirement for blood transfusion for other clinical reasons on or during admission to the hospital
- Aged less than 59.5 months
- Body weight \>5 kg
- Resident in catchment area Enrolment in study(t=0)
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- Fulfilled the pre-study screening eligibility criteria
- Aged \< 59.5 months
- Clinically stable, able to take oral medication
- Subject completed blood transfusion(s) or became clinically stable without transfusion
- Able to feed (for breastfeeding children) or eat (for older children)
- Absence of know cardiac problems
- Provision of informed consent by parent or guardian Randomisation (t=2 weeks)
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- Fulfilled enrolment eligibility criteria and was enrolled during recent admission
- +2 more criteria
You may not qualify if:
- Pre-study screening
- Recognised specific other cause of severe anaemia (e.g. trauma, haematological malignancy, known bleeding disorder)
- Known sickle cell disease
- Anticipated to reach the 5th birthday (60 months of age) within 2 weeks from enrolment (i.e. prior to randomization)
- Child will reside for more than 25%of the 6 months study period (i.e. 6 weeks or more) outside of catchment area Enrolment in study (t=0)
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- Previous enrolment in the present study
- Known hypersensitivity to study drug
- Sickle cell disease
- Use or known need at the time of enrolment for concomitant prohibited medication during the 14 weeks PMC treatment period.
- Ongoing or planned participation in another clinical trial involving ongoing or scheduled treatment with prohibited medicinal products or active follow-up during the course of the study (6 months from enrolment)
- A known need at the time of enrolment for scheduled surgery during the subsequent course of the study (6 months from enrolment)
- Suspected non-compliance with the follow-up schedule
- Know heart conditions, or family history of congenital prolongation of the QTc interval.
- Taking medicinal products that are known to prolong the QTc interval Randomisation (t=2 weeks)
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Liverpool School of Tropical Medicinelead
- The Research Council of Norwaycollaborator
- Kenya Medical Research Institutecollaborator
- Makerere Universitycollaborator
Study Sites (9)
Homa Bay County Referral Hospital
Homa Bay, Homa Bay County, 40100, Kenya
Migori County Referral Hospital
Migori, Migori County, 40400, Kenya
Siaya County Referral Hospital
Siaya, Siaya County, 40100, Kenya
Jaramogi Oginga Odinga Teaching and Referral Hospital
Kisumu, Kenya
Hoima Regional Referral Hospital
Hoima, Uganda
Jinja Regional Referral Hospital
Jinja, Uganda
Kamuli Mission Hospital
Kamuli, Uganda
Masaka Regional Referral Hospital
Masaka, Uganda
Mubende Regional Referral Hospital:
Mubende, Uganda
Related Publications (2)
Kwambai TK, Dhabangi A, Idro R, Opoka R, Watson V, Kariuki S, Kuya NA, Onyango ED, Otieno K, Samuels AM, Desai MR, Boele van Hensbroek M, Wang D, John CC, Robberstad B, Phiri KS, Ter Kuile FO. Malaria Chemoprevention in the Postdischarge Management of Severe Anemia. N Engl J Med. 2020 Dec 3;383(23):2242-2254. doi: 10.1056/NEJMoa2002820.
PMID: 33264546DERIVEDKwambai TK, Dhabangi A, Idro R, Opoka R, Kariuki S, Samuels AM, Desai M, van Hensbroek MB, John CC, Robberstad B, Wang D, Phiri K, Ter Kuile FO. Malaria chemoprevention with monthly dihydroartemisinin-piperaquine for the post-discharge management of severe anaemia in children aged less than 5 years in Uganda and Kenya: study protocol for a multi-centre, two-arm, randomised, placebo-controlled, superiority trial. Trials. 2018 Nov 6;19(1):610. doi: 10.1186/s13063-018-2972-1.
PMID: 30400934DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Dr Titus K Kwambai, MSc
Liverpool School of Tropical Medicine
- PRINCIPAL INVESTIGATOR
Dr Simon K Kariuki, PhD
Kenya Medical Research Institute
- PRINCIPAL INVESTIGATOR
Dr Richard IDRO, PhD
Makerere University
- PRINCIPAL INVESTIGATOR
Dr Robert Opoka, M.Med
Makerere University
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 28, 2016
First Posted
February 2, 2016
Study Start
May 20, 2016
Primary Completion
October 24, 2018
Study Completion
December 12, 2018
Last Updated
June 4, 2020
Record last verified: 2020-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- 3 months after publication of this Article
- Access Criteria
- Proposals should be directed to feiko.terkuile@lstmed.ac.uk and Bjarne.Robberstad@uib.no; to gain access, data requesters will need to sign a data access agreement, and the de-identified database will be transferred electronically
All individual-participant data collected during this trial will be stored in a public data repository after de-identification. Data and documents, including the study protocol, and the statistical analysis plan, will be made available and access to data provided when a proposal has been approved by the investigators, after consideration of overlap between the proposal and any ongoing efforts. Data will be available beginning at three months after publication of this Article.