Chlorproguanil-Dapsone-Artesunate versus Chlorproguanil-Dapsone: A Randomized, Double-Blind, Phase III Trial in African Children, Adolescents, and Adults with Uncomplicated Plasmodium falciparum Malaria


Tiono, AB; Dicko, A; Ndububa, DA; Agbenyega, T; Pitmang, S; Awobusuyi, J; Pamba, A; Duparc, S; Goh, LE; Harrell, E; Carter, N; Ward, SA; Greenwood, B; Winstanley, PA; (2009) Chlorproguanil-Dapsone-Artesunate versus Chlorproguanil-Dapsone: A Randomized, Double-Blind, Phase III Trial in African Children, Adolescents, and Adults with Uncomplicated Plasmodium falciparum Malaria. The American journal of tropical medicine and hygiene, 81 (6). pp. 969-978. ISSN 0002-9637 DOI: https://doi.org/10.4269/ajtmh.2009.09-0351

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Abstract

This multi-center, randomized, parallel-group, double-blind, double-dummy study compared the efficacy and safety of chlorproguanil-dapsone-artesunate (CDA) and chlorproguanil-dapsone (CPG-DDS) in the treatment of falciparum malaria in Africa (Burkina Faso, Ghana, Mali, Nigeria). Six hundred patients (>= 1 year of age) received CDA 2.0/2.5/4.0 mg/kg, and 292 CPG-DDS 2.0/2.5 mg/kg, once daily for 3 days. Day 28 parasitologic cure rate (polymerase chain reaction [PCR]-corrected, per-protocol population) was 89.1% (416/467) for CDA, non-inferior but also superior to CPG-DDS, 83.0% (176/212) (treatment difference 6.1%; 95% confidence interval [CI] 0.3, 11.9). Glucose-6-phosphate dehydrogenase (G6PD) genotype was available for 844/892 (95%) patients. Occurrences of a composite hemoglobin safety endpoint (hemoglobin drop >= 40 g/L or >= 40% versus baseline, hemoglobin < 50 g/L, or blood transfusion) were CDA 13/44 (30%), CPG-DDS 7/24 (29%) in G6PD-deficient patients versus CDA 4/448 (< 1%), CPG-DDS 6/221 (3%) in G6PD-normal patients. No deaths occurred. CDA was more efficacious than CPG-DDS. However, the hemolytic potential in G6PD-deficient patients does not Support further development of CDA.

Item Type: Article
Keywords: artemether-lumefantrine, glucose-6-phosphate-dehydrogenase deficiency, combination therapy, plus artesunate, open-label, drug, efficacy, transmission, mutations, parasites, Adolescent, Adult, Africa South of the Sahara, epidemiology, Animals, Antimalarials, administration & dosage, therapeutic use, Artemisinins, administration & dosage, therapeutic use, Child, Child, Preschool, Chloroguanide, administration & dosage, adverse effects, analogs & derivatives, therapeutic use, Dapsone, administration & dosage, adverse effects, therapeutic use, Double-Blind Method, Drug Therapy, Combination, Female, Glycogen Storage Disease Type I, genetics, Hemolysis, Humans, Malaria, Falciparum, drug therapy, Male, Plasmodium falciparum, genetics, Time Factors
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Research Centre: Malaria Centre
Centre for Maternal, Reproductive and Child Health (MARCH)
PubMed ID: 19996424
Web of Science ID: 272709600008
URI: http://researchonline.lshtm.ac.uk/id/eprint/4322

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