title: Comparison of azithromycin plus chloroquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in children in Africa: a randomized, open-label study.
abstract: BACKGROUND
  This randomized, open-label study was conducted to establish the non-inferiority of a combination of azithromycin (AZ) and chloroquine (CQ) to artemether-lumefantrine (AL) for treatment of uncomplicated malaria in children from six sites in sub-Saharan Africa.
  
  
  METHODS
  Children with uncomplicated Plasmodium falciparum malaria between six and 59 months of age were randomized 1:1 to either AZCQ (30 mg/kg AZ + 10 mg/kg CQ base) or AL per prescribing information for three days (Days 0, 1, 2). Each site could enrol in the study population once the treatment of uncomplicated malaria in five children five to 12 years of age was deemed to be effective and well tolerated. The primary efficacy evaluation was the proportion of subjects in both the modified intent-to-treat (MITT) and per-protocol (PP) populations with an adequate clinical and parasitological response (PCR corrected) at Day 28. Non-inferiority was concluded if the lower bound of the 95% confidence interval comparing the two groups was 10 percentage points or greater.
  
  
  RESULTS
  A total of 255 children were enrolled in the efficacy analysis (AZCQ, n = 124; AL, n = 131). The PCR corrected clearance rates were 89% (AZCQ) versus 98% (AL) for MITT, a difference of -9.10 (95% confidence interval; -16.02, -2.18) and 93% (AZCQ) versus 99% (AL) for PP, a difference of -6.08 (-12.10, -0.05). Early and late treatment failures were more common in subjects receiving AZCQ. Adverse events were more common in subjects treated with AZCQ. Drug concentrations obtained at specified time points following AZCQ administration had a large coefficient of variation partially due to sparse sampling with sample collection time window.
  
  
  CONCLUSIONS
  In this study, non-inferiority of AZCQ to AL was not demonstrated.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00677833 .
authors.affiliation: Novartis, Cambridge, MA, USA. richa.chandra@novartis.com.
authors.forename: Richa
authors.initials: R
authors.lastname: Chandra
authors.affiliation: Navrongo Health Research Centre, Ghana Health Service War Memorial Hospital, Navrongo, Ghana. patansah@hotmail.com.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ansah
authors.affiliation: Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali. isagara@icermali.org.
authors.forename: Issaka
authors.initials: I
authors.lastname: Sagara
authors.affiliation: Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso. alisie.crsn@fasonet.bf.
authors.forename: Ali
authors.initials: A
authors.lastname: Sie
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso. t.alfred@fasonet.bf.
authors.forename: Alfred B
authors.initials: AB
authors.lastname: Tiono
authors.affiliation: Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali. adjimde@icermali.org.
authors.forename: Abdoulaye A
authors.initials: AA
authors.lastname: Djimde
authors.affiliation: Global Research and Development, Pfizer Inc, 445 Eastern Point Road, Groton, CT, 06340, USA. Qinying.zhao@pfizer.com.
authors.forename: Qinying
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Global Research and Development, Pfizer Inc, 445 Eastern Point Road, Groton, CT, 06340, USA. Jeffery.Robbins@pfizer.com.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Robbins
authors.affiliation: Institut Pasteur de Côte d' Ivoire, Unité de Paludologie, Abidjan, Côte d'Ivoire. louis.penali@wwarn.org.
authors.forename: Louis K
authors.initials: LK
authors.lastname: Penali
authors.affiliation: Walter Reed Project, Centre for Clinical Research, Kenya Medical Research Institute, Kisumu, Kenya. bernhards.ogutu@usamru-k.org.
authors.forename: Bernhards
authors.initials: B
authors.lastname: Ogutu
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D000962:Antimalarials / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017963:Azithromycin / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004338:Drug Combinations; D004983:Ethanolamines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology*; D008297:Male
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D017963:Azithromycin; D002738:Chloroquine