Autor/a:
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Siqueira, André Machado; Alencar, Aline; Melo, Gisely Cardoso de; Magalhaes, Belisa M. L.; Machado, Kim; Alencar Filho, Aristóteles C.; Kuehn, Andrea; Marques, Marly M.; Costa Manso, Monica; Felger, Ingrid; Vieira, José L. F.; Lameyre, Valerie; Daniel-Ribeiro, Claudio T.; Lacerda, Marcus Vinícius Guimarães
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Abstract:
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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(R) (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. |