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Clin Infect Dis. 2017 Jan 15;64(2):166-174. doi: 10.1093/cid/ciw706. Epub 2016 Oct 20.

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 information

1
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, andre.siqueira@ini.fiocruz.br amsiqueira@gmail.com.
2
Universidade do Estado do Amazonas, Manaus.
3
Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro.
4
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado.
5
Universidade Federal do Amazonas, Manaus, Brazil.
6
ISGlobal, Barcelona Center for International Health Research (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
7
Swiss Tropical and Public Health Institute, Basel, Switzerland.
8
Universidade Federal do Pará, Belém, Brazil.
9
Access to Medicines Department, Sanofi , Paris, France.
10
Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, and.
11
Instituto Leônidas e Maria Deane, Fundação Oswaldo Cruz, Manaus, Brazil.

Erratum in

Abstract

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.

KEYWORDS:

Plasmodium vivax ; artesunate-amodiaquine.; chloroquine; malaria; randomized clinical trial

PMID:
27988484
PMCID:
PMC5215218
DOI:
10.1093/cid/ciw706
[Indexed for MEDLINE]
Free PMC Article

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