Chlorproguanil-dapsone-artesunate versus artemether-lumefantrine: a randomized, double-blind phase III trial in African children and adolescents with uncomplicated Plasmodium falciparum malaria.

Zul Premji; Rich E Umeh; Seth Owusu-Agyei; Fabian Esamai; Emmanuel U Ezedinachi; Stephen Oguche; Steffen Borrmann; Akintunde Sowunmi; Stephan Duparc; Paula L Kirby; +6 more... Allan Pamba; Lynda Kellam; Robert Guiguemdé; Brian Greenwood ORCID logo; Stephen A Ward; Peter A Winstanley; (2009) Chlorproguanil-dapsone-artesunate versus artemether-lumefantrine: a randomized, double-blind phase III trial in African children and adolescents with uncomplicated Plasmodium falciparum malaria. PloS one, 4 (8). e6682-. ISSN 1932-6203 DOI: 10.1371/journal.pone.0006682
Copy

BACKGROUND: Chlorproguanil-dapsone-artesunate (CDA) was developed as an affordable, simple, fixed-dose artemisinin-based combination therapy for use in Africa. This trial was a randomized parallel-group, double-blind, double-dummy study to compare CDA and artemether-lumefantrine (AL) efficacy in uncomplicated Plasmodium falciparum malaria and further define the CDA safety profile, particularly its hematological safety in glucose-6-phosphate dehydrogenase (G6PD) -deficient patients. METHODS AND FINDINGS: The trial was conducted at medical centers at 11 sites in five African countries between June 2006 and August 2007. 1372 patients (> or =1 to <15 years old, median age 3 years) with acute uncomplicated P. falciparum malaria were randomized (2:1) to receive CDA 2/2.5/4 mg/kg once daily for three days (N = 914) or six-doses of AL over three days (N = 458). Non-inferiority of CDA versus AL for efficacy was evaluated in the Day 28 per-protocol (PP) population using parasitological cure (polymerase chain reaction [PCR]-corrected). Cure rates were 94.1% (703/747) for CDA and 97.4% (369/379) for AL (treatment difference -3.3%, 95%CI -5.6, -0.9). CDA was non-inferior to AL, but there was simultaneous superiority of AL (upper 95%CI limit <0). Adequate clinical and parasitological response at Day 28 (uncorrected for reinfection) was 79% (604/765) with CDA and 83% (315/381) with AL. In patients with a G6PD-deficient genotype (94/603 [16%] hemizygous males, 22/598 [4%] homozygous females), CDA had the propensity to cause severe and clinically concerning hemoglobin decreases: the mean hemoglobin nadir was 75 g/L (95%CI 71, 79) at Day 7 versus 97 g/L (95%CI 91, 102) for AL. There were three deaths, unrelated to study medication (two with CDA, one with AL). CONCLUSIONS: Although parasitologically effective at Day 28, the hemolytic potential of CDA in G6PD-deficient patients makes it unsuitable for use in a public health setting in Africa. TRIAL REGISTRATION: ClinicalTrials.Gov NCT00344006.


picture_as_pdf
pone.0006682.s002.pdf
subject
Published Version
Available under Creative Commons: 3.0

View Download

Atom BibTeX OpenURL ContextObject in Span Multiline CSV OpenURL ContextObject Dublin Core Dublin Core MPEG-21 DIDL EndNote HTML Citation JSON MARC (ASCII) MARC (ISO 2709) METS MODS RDF+N3 RDF+N-Triples RDF+XML RIOXX2 XML Reference Manager Refer Simple Metadata ASCII Citation EP3 XML
Export

Downloads