Chlorproguanil-Dapsone-Artesunate versus Artemether-Lumefantrine: A Randomized, Double-Blind Phase III Trial in African Children and Adolescents with Uncomplicated Plasmodium falciparum Malaria
- Department for International Development
- 1 January 2009
- Document Type:
- Journal Article
- Greenwood, B., Premji, Z., Owusu-Agyei, S., Borrmann, S., Duparc, S. Pamba, A., Winstanley, P.A., Kirby, P.L., Esamai, F., Ezedinachi, E.U., Guiguemdé, R., Kellam, L., Oguche, S., Umeh, R.E., Ward, S.A, and Sowunmi, A.
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 haematological safety in glucose-6-phosphate dehydrogenase (G6PD) -deficient patients. Methods and Findings: The trial was conducted at medical centres at 11 sites in five African countries between June 2006 and August 2007. 1372 patients (≥1 to 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
Duparc, S.; Esamai, F.; Ezedinachi, E.U.; Greenwood, B.; Guiguemdé, R.; Kellam, L.; Kirby, P.L.; Oguche, S.; Borrmann, S.; Sowunmi, A.; Owusu-Agyei, S.; Pamba, A.; Premji, Z.; Umeh, R.E.; Ward, S.A; Winstanley, P.A. 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 (2009) 4 (8) e6682. [DOI: 10.1371/journal.pone.0006682]
Published: 1 January 2009
Document Type: Journal Article
Authors: Greenwood, B. Premji, Z. Owusu-Agyei, S. Borrmann, S. Duparc, S. Pamba, A. Winstanley, P.A. Kirby, P.L. Esamai, F. Ezedinachi, E.U. Guiguemdé, R. Kellam, L. Oguche, S. Umeh, R.E. Ward, S.A Sowunmi, A.