Chlorproguanil-dapsone-artesunate versus chlorproguanil-dapsone: a randomized, double-blind, phase III trial in African children, adolescents, and adults with uncomplicated Plasmodium falciparum malaria.
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 (>or= 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 >or= 40 g/L or >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.
Tiono
Alfred B
AB
Centre National de Recherche et de Formation sur le Paludisme, Ministère de la Santé, Ouagadougou, Burkina Faso. t.alfred@fasonet.bf
Dicko
Alassane
A
Ndububa
Dennis A
DA
Agbenyega
Tsiri
T
Pitmang
Simon
S
Awobusuyi
Jacob
J
Pamba
Allan
A
Duparc
Stephan
S
Goh
Li-Ean
LE
Harrell
Emma
E
Carter
Nick
N
Ward
Stephen A
SA
Greenwood
Brian
B
Winstanley
Peter A
PA
D000293:Adolescent; D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D003622:Dapsone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005953:Glycogen Storage Disease Type I / Q000235:genetics; D006461:Hemolysis; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D010963:Plasmodium falciparum / Q000235:genetics; D002727:Proguanil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors
D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; C007030:chlorproguanil; D003622:Dapsone; D002727:Proguanil