title: Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia.
abstract: BACKGROUND
  Safety surveillance of widely used artemisinin-based combination therapy (ACT) is essential, but tolerability data in the over five years age group are largely anecdotal.
  
  
  METHODS
  Two open-label, randomized trials were conducted in Nimba County, Liberia: i) the main tolerability trial with 1,000 Plasmodium falciparum malaria patients aged over five years (Study-T), and, ii) an efficacy trial with a secondary objective of collecting tolerability data among 300 children age six to 59 months (Study-E). In both studies patients were randomized to fixed-dose artesunate-amodiaquine (ASAQ Winthrop®) or artemether-lumefantrine (AL, Coartem®), respectively. Clinical- and laboratory-adverse events (AEs) were recorded until day 28.
  
  
  RESULTS
  Study-T: most patients experienced at least one AE. Severe AEs were few, primarily asymptomatic blood system disorders or increased liver enzyme values. No treatment or study discontinuation occurred. Mild or moderate fatigue (39.8% vs 16.3%, p < 0.001), vomiting (7.1% vs 1.6%, p < 0.001), nausea (3.2% vs 1.0%, p = 0.01), and anaemia (14.9% vs 9.8%, p = 0.01) were more frequently recorded in the ASAQ versus AL arm. Study-E: mild or moderate AEs were common, including anaemia, fatigue, vomiting or diarrhoea. The few severe events were asymptomatic blood system disorders and four clinical events (pneumonia, malaria, vomiting and stomatitis).
  
  
  CONCLUSIONS
  Both ASAQ and AL were well tolerated in patients of all age groups. No unexpected AEs occurred. Certain mild or moderate AEs were more frequent in the ASAQ arm. Standardised safety surveillance should continue for all forms of ACT.
  
  
  BACKGROUND
  The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN40020296, ISRCTN51688713, (http://www.controlled-trials.com).
authors.forename: Birgit
authors.initials: B
authors.lastname: Schramm
authors.forename: Parastou
authors.initials: P
authors.lastname: Valeh
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Baudin
authors.forename: Charles S
authors.initials: CS
authors.lastname: Mazinda
authors.forename: Richard
authors.initials: R
authors.lastname: Smith
authors.forename: Loretxu
authors.initials: L
authors.lastname: Pinoges
authors.forename: Timothy
authors.initials: T
authors.lastname: Sundaygar
authors.forename: Yah M
authors.initials: YM
authors.lastname: Zolia
authors.forename: Joel J
authors.initials: JJ
authors.lastname: Jones
authors.forename: Eric
authors.initials: E
authors.lastname: Comte
authors.forename: Arnaud
authors.initials: A
authors.lastname: Bruneel
authors.forename: Michel
authors.initials: M
authors.lastname: Branger
authors.forename: Vincent
authors.initials: V
authors.lastname: Jullien
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Carn
authors.forename: Jean-René
authors.initials: JR
authors.lastname: Kiechel
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ashley
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Guérin
mesh_terms: D000293:Adolescent; D000328:Adult; 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; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004983:Ethanolamines / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005449:Fluorenes / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine