 | Henk Dfh Schallig, Halidou Tinto, Patrick Sawa, Harparkash Kaur, Stephan Duparc, Deus S Ishengoma, Pascal Magnussen, Michael Alifrangis, Colin J Sutherland Randomised controlled trial of two sequential artemisinin-based combination therapy regimens to treat uncomplicated falciparum malaria in African children: a protocol to investigate safety, efficacy and adherence (Journal Article) In: BMJ Glob. Health, vol. 2, no. 3, pp. e000371, 2017, ISSN: 2059-7908. @article{Schallig2017-ux,
title = {Randomised controlled trial of two sequential artemisinin-based combination therapy regimens to treat uncomplicated falciparum malaria in African children: a protocol to investigate safety, efficacy and adherence},
author = {Henk Dfh Schallig and Halidou Tinto and Patrick Sawa and Harparkash Kaur and Stephan Duparc and Deus S Ishengoma and Pascal Magnussen and Michael Alifrangis and Colin J Sutherland},
doi = {10.1136/bmjgh-2017-000371},
issn = {2059-7908},
year = {2017},
date = {2017-08-01},
urldate = {2017-08-01},
journal = {BMJ Glob. Health},
volume = {2},
number = {3},
pages = {e000371},
abstract = {BACKGROUND: Management of uncomplicated Plasmodium falciparum
malaria relies on artemisinin-based combination therapies (ACTs).
These highly effective regimens have contributed to reductions in
malaria morbidity and mortality. However, artemisinin resistance
in Asia and changing parasite susceptibility to ACT in Africa
have now been well documented. Strategies that retain current ACT
as efficacious treatments are urgently needed. METHODS: We
present an open-label, randomised three-arm clinical trial
protocol in three African settings representative of varying
malaria epidemiology to investigate whether prolonged ACT-based
regimens using currently available formulations can eliminate
potentially resistant parasites. The protocol investigates
whether a sequential course of two licensed ACT in 1080 children
aged 6-120 months exhibits superior efficacy against acute P.
falciparum malaria and non-inferior safety compared with standard
single-course ACT given to 540 children. The primary endpoint is
PCR-corrected clinical and parasitological response at day 42 or
day 63 of follow-up. Persistence of PCR-detectable parasitaemia
at day 3 is analysed as a key covariate. Secondary endpoints
include gametocytaemia, occurrence of treatment-related adverse
events in the double-ACT versus single-ACT arms, carriage of
molecular markers of drug resistance, drug kinetics and patient
adherence to treatment. DISCUSSION: This protocol addresses
efficacy and safety of sequential ACT regimens in P. falciparum
malaria in Africa. The approach is designed to extend the useful
life of this class of antimalarials with maximal impact and
minimal delay, by deploying licensed medicines that could be
swiftly implemented as sequential double ACT by National Malaria
Control Programmes, before emerging drug resistance in Africa
becomes a major threat to public health.},
keywords = {malaria; randomised control trial},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Management of uncomplicated Plasmodium falciparum
malaria relies on artemisinin-based combination therapies (ACTs).
These highly effective regimens have contributed to reductions in
malaria morbidity and mortality. However, artemisinin resistance
in Asia and changing parasite susceptibility to ACT in Africa
have now been well documented. Strategies that retain current ACT
as efficacious treatments are urgently needed. METHODS: We
present an open-label, randomised three-arm clinical trial
protocol in three African settings representative of varying
malaria epidemiology to investigate whether prolonged ACT-based
regimens using currently available formulations can eliminate
potentially resistant parasites. The protocol investigates
whether a sequential course of two licensed ACT in 1080 children
aged 6-120 months exhibits superior efficacy against acute P.
falciparum malaria and non-inferior safety compared with standard
single-course ACT given to 540 children. The primary endpoint is
PCR-corrected clinical and parasitological response at day 42 or
day 63 of follow-up. Persistence of PCR-detectable parasitaemia
at day 3 is analysed as a key covariate. Secondary endpoints
include gametocytaemia, occurrence of treatment-related adverse
events in the double-ACT versus single-ACT arms, carriage of
molecular markers of drug resistance, drug kinetics and patient
adherence to treatment. DISCUSSION: This protocol addresses
efficacy and safety of sequential ACT regimens in P. falciparum
malaria in Africa. The approach is designed to extend the useful
life of this class of antimalarials with maximal impact and
minimal delay, by deploying licensed medicines that could be
swiftly implemented as sequential double ACT by National Malaria
Control Programmes, before emerging drug resistance in Africa
becomes a major threat to public health. |
