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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/358

Title: Chlorproguanil-Dapsone-Artesunate versus Artemether-Lumefantrine: A Randomized, Double-Blind Phase III Trial in African Children and Adolescents with Uncomplicated Plasmodium falciparum Malaria
Authors: Premji, Zul
Umeh, Rich E.
Owusu-Agyei, Seth
Esamai, Fabian
Ezedinachi, Emmanuel U.
Oguche, Stephen
Borrmann, Steffen
Sowunmi, Akintunde
Duparc, Stephan
Kirby, Paula L.
Pamba, Allan
Kellam, Lynda
Guiguemde, Robert
Greenwood, Brian
Ward, Stephen A.
Winstanley, Peter A.
Issue Date: 19-Aug-2009
Series/Report no.: Vol.4;No.8;Pp 1-11
Abstract: Background: Chlorproguanil2dapsone2artesunate (CDA) was developed as an affordable, simple, fixed-dose artemisininbased combination therapy for use in Africa. This trial was a randomized parallel-group, double-blind, double-dummy study to compare CDA and artemether2lumefantrine (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 ($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, 20.9). 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
URI: http://hdl.handle.net/123456789/358
Appears in Collections:Paediatrics

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