title: Randomized non-inferiority and safety trial of dihydroartemisin-piperaquine and artesunate-amodiaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Cameroonian children.
abstract: BACKGROUND
  Artemether-lumefantrine and artesunate-amodiaquine are first-line treatment for uncomplicated malaria in Cameroon. No study has yet compared the efficacy of these drugs following the WHO recommended 42-day follow-up period. The goal of this study was to compare the clinical efficacy, tolerability and safety of artesunate-amodiaquine (ASAQ), artemether-lumefantrine (AL) and dihydroartemisinin piperaquine (DHAP) among children aged less than ten years in two malaria-endemic ecological regions of Cameroon.
  
  
  METHODS
  A three-arm, randomized, controlled, non-inferiority trial was conducted among children of either gender aged six months (>5 kg) to ten years (n = 720) with acute uncomplicated Plasmodium falciparum infection. Parents/guardians of children provided consent prior to randomization to receive ASAQ, DHAP or AL in the ratio of 2:2:1, respectively. Treatment outcome was assessed based on standard WHO 2003 classification after 42 days of follow-up. The primary outcome was PCR-corrected day-42 cure rates. The non-inferiority, one-sided, lower limit asymptotic 97.5% confidence interval (CI) on the difference in PCR-corrected cure rates of ASAQ and DHAP when compared to AL was accepted if the lower limit of the CI was greater than -10%. Secondary outcomes were parasite and fever clearances and day 7 haemoglobin changes.
  
  
  RESULTS
  PCR-corrected PP cure rates of 96.7, 98.1 and 96.3, respectively, for AL, ASAQ and DHAP was observed. The lower bound of the one-sided 97.5% CI calculated around the difference between day-42 cure rate point estimates in AL and ASAQ groups, AL and DHAP groups were, -6% and -4% respectively. There were no statistical significant differences in parasite or fever clearance times between treatments, although fever clearance pattern was different between ASAQ and DHAP. No statistical significant differences were observed in the occurrence of adverse events among treatment groups.
  
  
  CONCLUSIONS
  ASAQ and DHAP are considered safe and tolerable and are not inferior to AL in the treatment of uncomplicated P. falciparum malaria in Cameroonian children.
  
  
  BACKGROUND
  NCT01845701.
authors.forename: Akindeh M
authors.initials: AM
authors.lastname: Nji
authors.forename: Innocent M
authors.initials: IM
authors.lastname: Ali
authors.forename: Marcel N
authors.initials: MN
authors.lastname: Moyeh
authors.forename: Eric-Oliver
authors.initials: EO
authors.lastname: Ngongang
authors.forename: Aristide M
authors.initials: AM
authors.lastname: Ekollo
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Chedjou
authors.forename: Valentine N
authors.initials: VN
authors.lastname: Ndikum
authors.forename: Marie S
authors.initials: MS
authors.lastname: Evehe
authors.forename: Guenter
authors.initials: G
authors.lastname: Froeschl
authors.forename: Christian
authors.initials: C
authors.lastname: Heumann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mansmann
authors.forename: Olumide
authors.initials: O
authors.lastname: Ogundahunsi
authors.affiliation: The Biotechnology Centre, University of Yaoundé I, Yaoundé, Cameroon. wfmbacham@prd-college.eu.
authors.forename: Wilfred F
authors.initials: WF
authors.lastname: Mbacham
mesh_terms: D000655:Amodiaquine / Q000009:adverse effects / Q000627:therapeutic use*; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use*; D002163:Cameroon; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions; D004983:Ethanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D005449:Fluorenes / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D010879:Piperazines
chemical_list: D000655:Amodiaquine; D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D011804:Quinolines; C515299:amodiaquine, artesunate drug combination; C039060:artenimol; C034759:piperaquine; D010879:Piperazines