Falade C.O., Dada-Adegbola H.O., Ogunkunle O.O., Oguike M.C., Nash O., Ademowo O.G.
Evaluation of the comparative efficacy and safety of artemether- lumefantrine, artesunate-amodiaquine and artesunate-amodiaquine-chlorpheniramine (Artemoclo™) for the treatment of acute uncomplicated malaria in Nigerian children
Departments of Pharmacology, Therapeutics, University of Ibadan, Ibadan 200001, Nigeria; Departments of Medical Microbiology, Nigeria; Departments of Paediatrics, Nigeria; Institute for Advanced Medical Research and Training, College of Medicine, Costa Ri
Falade, C.O., Departments of Pharmacology, Therapeutics, University of Ibadan, Ibadan 200001, Nigeria, Institute for Advanced Medical Research and Training, College of Medicine, Costa Rica; Dada-Adegbola, H.O., Departments of Medical Microbiology, Nigeria; Ogunkunle, O.O., Departments of Paediatrics, Nigeria; Oguike, M.C., Immunology and Infection Department, London School of Tropical Medicine and Hygiene, London, United Kingdom; Nash, O., NABDA-Southwest Biotechnology Center of Excellence, University of Ibadan, Ibadan, Nigeria; Ademowo, O.G., Departments of Pharmacology, Therapeutics, University of Ibadan, Ibadan 200001, Nigeria, NABDA-Southwest Biotechnology Center of Excellence, University of Ibadan, Ibadan, Nigeria
Objective: To evaluate the comparative efficacy and safety of artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ) and artesunate-amodiaquine-chlorpheniramine (AQC) for the treatment of acute uncomplicated malaria among Southwest Nigerian children. Subjects and Methods: One hundred and sixty children aged 6 months to 14 years with acute uncomplicated malaria were randomized to AL (n = 53), ASAQ (n = 53), or AQC (n = 54). Enrollees were seen daily on days 0-3 and then on days 7, 14, 21, 28 and 42 for clinical and parasitological evaluations. Paired samples of genomic DNA at enrolment and at the time of recurrent parasitaemia were genotyped using nested PCR to distinguish between reinfection and recrudescence. Detailed haematological and biochemical evaluations were carried out in a subset of enrollees on days 0, 7 and 28 as part of a safety evaluation. Results: Of the 160 children, 144 (90%) completed the study. The mean fever clearance times and parasite clearance times for AL, ASAQ and AQC were comparable (p = 0.94 and p = 0.122, respectively). On day 14, the adequate clinical and parasitological response (ACPR) for AL and AQC was 100% and for ASAQ it was 90% (p = 0.39). The PCR-uncorrected results on days 28 and 42 and the ACPR-corrected results on day 42 were similar for all drugs (p = 0.62 and p = 0.56, respectively). AQC resulted in the best parasite clearance and haematological recovery on day 2 (p = 0.022 and p = 0.018, respectively). Biochemical parameters were not adversely affected by the three artemisinin-based combination therapies (ACTs) and these were well tolerated. Conclusion: The three ACTs were efficacious and safe, but AQC resulted in a better haematological recovery on day 2 and higher cure rates throughout the study period. © 2014 S. Karger AG, Basel.
amodiaquine; antimalarial agent; antipyretic analgesic agent; artemether plus benflumetol; artemocolo; artesunate; artesunate plus amodiaquine plus chlorpheniramine; bilirubin; chloroquine; genomic DNA; unclassified drug; amodiaquine; amodiaquine, artesunate drug combination; antimalarial agent; artemether; artemisinin derivative; benflumetol; chlorpheniramine; drug combination; ethanolamine derivative; fluorene derivative; alanine aminotransferase; amodiaquine plus artesunate; amodiaquine plus artesunate plus chlorpheniramine; antimalarial agent; artemether plus benflumetol; aspartate aminotransferase; creatinine; genomic DNA; abdominal pain; adolescent; adult; anorexia; article; bilirubin blood level; child; childhood disease; chill; comparative effectiveness; controlled study; convulsion; coughing; diarrhea; drug efficacy; drug fever; drug safety; drug withdrawal; female; follow up; genotype; headache; human; infant; irritability; major clinical study; malaria; male; multicenter study; Nigeria; open study; parasite clearance; parasitemia; polymerase chain reaction; randomized controlled trial; reinfection; rigor; side effect; vomiting; drug combination; genome; malaria; preschool child; alanine aminotransferase blood level; Article; aspartate aminotransferase blood level; chemotherapy induced emesis; comparative effectiveness; convalescence; creatinine blood level; drowsiness; drug induced headache; drug safety; evaluation study; fever; hematocrit; malaria falciparum; Nigerian; treatment outcome; Adolescent; Amodiaquine; Antimalarials; Artemisinins; Child; Child, Preschool; Chlorpheniramine; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluorenes; Genome, Protozoan; Humans; Infant; Malaria; Male; Nigeria; Polymerase Chain Reaction
