title: A simplified intravenous artesunate regimen for severe malaria.
abstract: BACKGROUND
  We compared a conventional empirically derived regimen with a simplified regimen for parenteral artesunate in severe malaria.
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled comparison to assess the noninferiority of a simplified 3-dose regimen (given at 0, 24, and 48 hours) compared with the conventional 5-dose regimen of intravenous artesunate (given at 0, 12, 24, 48, and 72 hours) in African children with Plasmodium falciparum malaria with a prespecified delta of 0.2. The total dose of artesunate in each group was 12 mg/kg. The primary end point was the proportion of children clearing ≥ 99% of their admission parasitemia at 24 hours. Safety data, secondary efficacy end points, and pharmacokinetics were also analyzed.
  
  
  RESULTS
  In 171 children (per protocol), 78% of the recipients (95% confidence interval [CI], 69%-87%) in the 3-dose group achieved ≥ 99% parasite clearance 24 hours after the start of treatment, compared with 85% (95% CI, 77%-93%) of those receiving the conventional regimen (treatment difference, -7.2%; 95% CI, -18.9% to 4.4%). Dihydroartemisinin was cleared slightly more slowly in those children receiving the higher 3-dose regimen (7.4 vs 8.8 L/h for a 13-kg child; P 5 .008).
  
  
  CONCLUSIONS
  Pharmacodynamic analysis suggests that 3 doses of artesunate were not inferior to 5 doses for the treatment of severe malaria in children.
  
  
  BACKGROUND
  NCT00522132.
authors.affiliation: Institut für Tropenmedizin, Universität Tübingen, Germany.
authors.forename: Peter Gottfried
authors.initials: PG
authors.lastname: Kremsner
authors.forename: Terrie
authors.initials: T
authors.lastname: Taylor
authors.forename: Saadou
authors.initials: S
authors.lastname: Issifou
authors.forename: Maryvonne
authors.initials: M
authors.lastname: Kombila
authors.forename: Yamikani
authors.initials: Y
authors.lastname: Chimalizeni
authors.forename: Kondwana
authors.initials: K
authors.lastname: Kawaza
authors.forename: Marielle K
authors.initials: MK
authors.lastname: Bouyou Akotet
authors.forename: Mattias
authors.initials: M
authors.lastname: Duscha
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mordmüller
authors.forename: Katrin
authors.initials: K
authors.lastname: Kösters
authors.forename: Alexander
authors.initials: A
authors.lastname: Humberg
authors.forename: R Scott
authors.initials: RS
authors.lastname: Miller
authors.forename: Peter
authors.initials: P
authors.lastname: Weina
authors.forename: Stephan
authors.initials: S
authors.lastname: Duparc
authors.forename: Jörg
authors.initials: J
authors.lastname: Möhrle
authors.forename: Jürgen F J
authors.initials: JF
authors.lastname: Kun
authors.forename: Tim
authors.initials: T
authors.lastname: Planche
authors.forename: Paktiya
authors.initials: P
authors.lastname: Teja-Isavadharm
authors.forename: Julie Anne
authors.initials: JA
authors.lastname: Simpson
authors.forename: Carsten
authors.initials: C
authors.lastname: Köhler
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Krishna
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy*; D008297:Male; D059208:Parasite Load; D018512:Parasitemia / Q000188:drug therapy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; C039060:artenimol