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

Titus K. Kwambai, Aggrey Dhabangi, Richard Idro, Robert Opoka, Simon Kariuki, Aaron M. Samuels, Meghna Desai, Michael Boele Van Hensbroek, Chandy John, Bjarne Robberstad, Duolao Wang, Kamija Phiri, Feiko O. Ter Kuile

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number610
JournalTrials
Volume19
Issue number1
DOIs
StatePublished - Nov 6 2018
Externally publishedYes

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dihydroartemisinin
Uganda
Kenya
Chemoprevention
Malaria
Anemia
Placebos
Malawi
Hospitalized Child
piperaquine

Keywords

  • Chemoprevention
  • Cost-effectiveness
  • Dihydroartemisinin-piperaquine
  • Malaria
  • Mortality
  • Post-discharge
  • Protocol
  • Readmission
  • Severe anaemia

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology (medical)

Cite this

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. / Kwambai, Titus K.; Dhabangi, Aggrey; Idro, Richard; Opoka, Robert; Kariuki, Simon; Samuels, Aaron M.; Desai, Meghna; Van Hensbroek, Michael Boele; John, Chandy; Robberstad, Bjarne; Wang, Duolao; Phiri, Kamija; Ter Kuile, Feiko O.

In: Trials, Vol. 19, No. 1, 610, 06.11.2018.

Research output: Contribution to journalArticle

Kwambai, Titus K. ; Dhabangi, Aggrey ; Idro, Richard ; Opoka, Robert ; Kariuki, Simon ; Samuels, Aaron M. ; Desai, Meghna ; Van Hensbroek, Michael Boele ; John, Chandy ; Robberstad, Bjarne ; Wang, Duolao ; Phiri, Kamija ; Ter Kuile, Feiko O. / 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. In: Trials. 2018 ; Vol. 19, No. 1.
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abstract = "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.",
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T1 - 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

T2 - Study protocol for a multi-centre, two-arm, randomised, placebo-controlled, superiority trial

AU - Kwambai, Titus K.

AU - Dhabangi, Aggrey

AU - Idro, Richard

AU - Opoka, Robert

AU - Kariuki, Simon

AU - Samuels, Aaron M.

AU - Desai, Meghna

AU - Van Hensbroek, Michael Boele

AU - John, Chandy

AU - Robberstad, Bjarne

AU - Wang, Duolao

AU - Phiri, Kamija

AU - Ter Kuile, Feiko O.

PY - 2018/11/6

Y1 - 2018/11/6

N2 - 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.

AB - 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.

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KW - Cost-effectiveness

KW - Dihydroartemisinin-piperaquine

KW - Malaria

KW - Mortality

KW - Post-discharge

KW - Protocol

KW - Readmission

KW - Severe anaemia

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