title: 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.
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.
  
  
  BACKGROUND
  NCT01378286.
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, andre.siqueira@ini.fiocruz.br amsiqueira@gmail.com.|Universidade do Estado do Amazonas, Manaus.|Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro.
authors.forename: Andre M
authors.initials: AM
authors.lastname: Siqueira
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado.|Universidade do Estado do Amazonas, Manaus.
authors.forename: Aline C
authors.initials: AC
authors.lastname: Alencar
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado.|Universidade do Estado do Amazonas, Manaus.
authors.forename: Gisely C
authors.initials: GC
authors.lastname: Melo
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado.|Universidade do Estado do Amazonas, Manaus.
authors.forename: Belisa L
authors.initials: BL
authors.lastname: Magalhaes
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado.
authors.forename: Kim
authors.initials: K
authors.lastname: Machado
authors.affiliation: Universidade Federal do Amazonas, Manaus, Brazil.
authors.forename: Aristóteles C
authors.initials: AC
authors.lastname: Alencar Filho
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado.|ISGlobal, Barcelona Center for International Health Research (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kuehn
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado.
authors.forename: Marly M
authors.initials: MM
authors.lastname: Marques
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado.
authors.forename: Monica Costa
authors.initials: MC
authors.lastname: Manso
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Felger
authors.affiliation: Universidade Federal do Pará, Belém, Brazil.
authors.forename: José L F
authors.initials: JL
authors.lastname: Vieira
authors.affiliation: Access to Medicines Department, Sanofi , Paris, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Lameyre
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, and.
authors.forename: Claudio T
authors.initials: CT
authors.lastname: Daniel-Ribeiro
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado.|Universidade do Estado do Amazonas, Manaus.|Instituto Leônidas e Maria Deane, Fundação Oswaldo Cruz, Manaus, Brazil.
authors.forename: Marcus V G
authors.initials: MV
authors.lastname: Lacerda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000655:Amodiaquine / Q000008:administration & dosage*; D000962:Antimalarials / Q000008:administration & dosage*; D037621:Artemisinins / Q000008:administration & dosage*; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000008:administration & dosage*; D004338:Drug Combinations; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000469:parasitology* / Q000635:transmission; D008297:Male; D008875:Middle Aged; D018512:Parasitemia / Q000188:drug therapy* / Q000469:parasitology*; D010966:Plasmodium vivax / Q000187:drug effects* / Q000235:genetics; D012008:Recurrence; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine; D002738:Chloroquine
keywords: 
  Plasmodium vivax
  ; artesunate-amodiaquine.; chloroquine; malaria; randomized clinical trial