1. Fixed-dose artesunate-amodiaquine combination vs chloroquine for treatment of uncomplicated blood stage P. vivax infection in the Brazilian amazon : an open-label randomized, controlled trial
- Author
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Ingrid Felger, Kim Vinicius Amaral Machado, Monica Costa Manso, Valerie Lameyre, Marly M. Marques, Marcus V. G. Lacerda, Andrea Kuehn, André Siqueira, José Luiz Fernandes Vieira, Belisa M. L. Magalhães, Aristóteles Comte de Alencar Filho, Gisely Cardoso de Melo, Aline Alencar, and Cláudio Tadeu Daniel-Ribeiro
- Subjects
Male ,Plasmodium vivax ,Kaplan-Meier Estimate ,Parasitemia ,law.invention ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Chloroquine ,Recurrence ,030212 general & internal medicine ,Treatment Failure ,Child ,biology ,Artesunate/amodiaquine ,Middle Aged ,Artemisinins ,Drug Combinations ,Infectious Diseases ,Treatment Outcome ,Child, Preschool ,Female ,Erratum ,geographic locations ,Brazil ,medicine.drug ,Microbiology (medical) ,Adult ,medicine.medical_specialty ,artesunate-amodiaquine ,Adolescent ,Genotype ,030231 tropical medicine ,malaria ,Malària ,Amodiaquine ,03 medical and health sciences ,Antimalarials ,Young Adult ,Internal medicine ,parasitic diseases ,Major Article ,medicine ,Malaria, Vivax ,Humans ,Adverse effect ,Aged ,Intention-to-treat analysis ,business.industry ,Infant ,randomized clinical trial ,biology.organism_classification ,Surgery ,Malaria ,chemistry ,Artesunate ,business - Abstract
Summary In the Brazilian Amazon, the artesunate–amodiaquine combination was more effective in preventing Plasmodium vivax recurrence. With a favorable safety profile, this antimalarial treatment proved to be a good first-line alternative. Chloroquine resistance is probably underestimated in the area., Background. Despite increasing evidence of the development of Plasmodium vivax chloroquine (CQ) resistance, there have been no trials comparing its efficacy with that of artemisinin-based combination therapies (ACTs) in Latin America. Methods. This randomized controlled trial compared the antischizontocidal efficacy and safety of a 3-day supervised treatment of the fixed-dose combination artesunate-amodiaquine Winthrop® (ASAQ) versus CQ for treatment of uncomplicated P. vivax infection in Manaus, Brazil. Patients were followed for 42 days. Primary endpoints were adequate clinical and parasitological responses (ACPR) rates at day 28. Genotype-adjustment was performed. Results. From 2012 to 2013, 380 patients were enrolled. In the per-protocol (PP) analysis, adjusted-ACPR was achieved in 100% (165/165) and 93.6% (161/172) of patients in the ASAQ and CQ arm (difference 6.4%, 95% CI 2.7%; 10.1%) at day 28 and in 97.4% (151/155) and 77.7% (129/166), respectively (difference 19.7%, 95% CI 12.9%; 26.5%), at day 42. Apart from ITT D28 assessment, superiority of ASAQ on ACPR was demonstrated. ASAQ presented faster clearance of parasitaemia and fever. Based on CQ blood level measurements, CQ resistance prevalence was estimated at 11.5% (95% CI: 7.5-17.3) up to day 42. At least one emergent adverse event (AE) was recorded for 79/190 (41x6%) in the ASAQ group and for 85/190 (44x7%) in the CQ group. Both treatments had similar safety profiles. Conclusions. ASAQ exhibited high efficacy against CQ resistant P. vivax and is an adequate alternative in the study area. Studies with an efficacious comparator, longer follow-up and genotype-adjustment can improve CQR characterization. Clinical Trials Registration. NCT01378286.
- Published
- 2017
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