title: Artesunate-amodiaquine fixed dose combination for the treatment of Plasmodium falciparum malaria in India.
abstract: BACKGROUND
  Artemisinin-based combination therapy (ACT) has been recommended for the treatment of falciparum malaria by the World Health Organization. Though India has already switched to ACT for treating falciparum malaria, there is need to have multiple options of alternative forms of ACT. A randomized trial was conducted to assess the safety and efficacy of the fixed dose combination of artesunate-amodiaquine (ASAQ) and amodiaquine (AQ) for the treatment of uncomplicated falciparum malaria for the first time in India. The study sites are located in malaria-endemic, chloroquine-resistant areas.
  
  
  METHODS
  This was an open label, randomized trial conducted at two sites in India from January 2007 to January 2008. Patients between six months and 60 years of age having Plasmodium falciparum mono-infection were randomly allocated to ASAQ and AQ arms. The primary endpoint was 28-day PCR-corrected parasitological cure rate.
  
  
  RESULTS
  Three hundred patients were enrolled at two participating centres, Ranchi, Jharkhand and Rourkela, Odisha. Two patients in AQ arm had early treatment failure while there was no early treatment failure in ASAQ arm. Late treatment failures were seen in 13 and 12 patients in ASAQ and AQ arms, respectively. The PCR-corrected cure rates in intent-to-treat population were 97.51% (94.6-99.1%) in ASAQ and 88.65% (81.3-93.9%) in AQ arms. In per-protocol population, they were 97.47% (94.2-99.2%) and 88.30% (80-94%) in ASAQ and AQ arms respectively. Seven serious adverse events (SAEs) were reported in five patients, of which two were reported as related to the treatment. All SAEs resolved without sequel.
  
  
  CONCLUSIONS
  The fixed dose combination of ASAQ was found to be efficacious and safe treatment for P. falciparum malaria. Amodiaquine also showed acceptable efficacy, making it a suitable partner of artesunate. The combination could prove to be a viable option in case India opts for fixed dose combination ACT.
  
  
  BACKGROUND
  ISRCTN84408319.
authors.affiliation: National Institute of Malaria Research, Sector 8, Dwarka, New Delhi 110077, India.
authors.forename: Anupkumar R
authors.initials: AR
authors.lastname: Anvikar
authors.forename: Bhawna
authors.initials: B
authors.lastname: Sharma
authors.forename: Bhartendu H
authors.initials: BH
authors.lastname: Shahi
authors.forename: Prajesh K
authors.initials: PK
authors.lastname: Tyagi
authors.forename: Tarit K
authors.initials: TK
authors.lastname: Bose
authors.forename: Surya K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Prakriti
authors.initials: P
authors.lastname: Srivastava
authors.forename: Bina
authors.initials: B
authors.lastname: Srivastava
authors.forename: Jean R
authors.initials: JR
authors.lastname: Kiechel
authors.forename: Aditya P
authors.initials: AP
authors.lastname: Dash
authors.forename: Neena
authors.initials: N
authors.lastname: Valecha
mesh_terms: D000293:Adolescent; D000328:Adult; D000655:Amodiaquine / Q000008:administration & dosage* / Q000009:adverse effects*; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects*; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000235:genetics / Q000302:isolation & purification; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007194:India; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D016054:DNA, Protozoan; D004338:Drug Combinations; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine