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

Details

• Alternative Title:
  Trials
• Personal Author:
  Kwambai, Titus K. ; Dhabangi, Aggrey ; Idro, Richard ; Opoka, Robert ; Kariuki, Simon ; Samuels, Aaron M. ; Desai, Meghna ; van Hensbroek, Michael Boele ; John, Chandy C. ; Robberstad, Bjarne ; Wang, Duolao ; Phiri, Kamija ; ter Kuile, Feiko O.
• Description:
  Background
  
  Children hospitalised with severe anaemia in malaria endemic areas in Africa are at high risk of readmission or death within 6 months post-discharge. Currently, no strategy specifically addresses this period. In Malawi, 3 months of post-discharge malaria chemoprevention (PMC) with monthly treatment courses of artemether-lumefantrine given at discharge and at 1 and 2 months prevented 30% of all-cause readmissions by 6 months post-discharge. Another efficacy trial is needed before a policy of malaria chemoprevention can be considered for the post-discharge management of severe anaemia in children under 5 years of age living in malaria endemic areas.
  
  Objective
  
  We aim to determine if 3 months of PMC with monthly 3-day treatment courses of dihydroartemisinin-piperaquine is safe and superior to a single 3-day treatment course with artemether-lumefantrine provided as part of standard in-hospital care in reducing all-cause readmissions and deaths (composite primary endpoint) by 6 months in the post-discharge management of children less than 5 years of age admitted with severe anaemia of any or undetermined cause.
  
  Methods/design
  
  This is a multi-centre, two-arm, placebo-controlled, individually randomised trial in children under 5 years of age recently discharged following management for severe anaemia. Children in both arms will receive standard in-hospital care for severe anaemia and a 3-day course of artemether-lumefantrine at discharge. At 2 weeks after discharge, surviving children will be randomised to receive either 3-day courses of dihydroartemisinin-piperaquine at 2, 6 and 10 weeks or an identical placebo and followed for 26 weeks through passive case detection. The trial will be conducted in hospitals in malaria endemic areas in Kenya and Uganda. The study is designed to detect a 25% reduction in the incidence of all-cause readmissions or death (composite primary outcome) from 1152 to 864 per 1000 child years (power 80%, α = 0.05) and requires 520 children per arm (1040 total children).
  
  Results
  
  Participant recruitment started in May 2016 and is ongoing.
  
  Trial registration
  
  ClinicalTrials.gov, NCT02671175. Registered on 28 January 2016.
  
  Electronic supplementary material
  
  The online version of this article (10.1186/s13063-018-2972-1) contains supplementary material, which is available to authorized users.
  
  
• Subjects:
  Chemoprevention Cost-effectiveness Dihydroartemisinin-piperaquine Malaria Mortality Post-discharge Protocol Readmission Severe Anaemia Study Protocol
• Source:
  Trials. 19.
• Pubmed ID:
  30400934
• Pubmed Central ID:
  PMC6220494
• Document Type:
  Journal Article
• Funding:
  U01GH001646/ACL HHS/United States ; 234487/Norges Forskningsråd/ ; 1U01GH001646/Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention/
• Place as Subject:
  Kenya
• Volume:
  19
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:705444e719884c00da7d543e9cffda135ceaee26dcbb3e82b13d25eb053c3634
• Download URL:
  https://stacks.cdc.gov/view/cdc/60734/cdc_60734_DS1.pdf
• File Type:
  [PDF - 3.01 MB ]