title: Noninferiority of miltefosine versus meglumine antimoniate for cutaneous leishmaniasis in children.
abstract: BACKGROUND
  Children have a lower response rate to antimonial drugs and higher elimination rate of antimony (Sb) than adults. Oral miltefosine has not been evaluated for pediatric cutaneous leishmaniasis.
  
  
  METHODS
  A randomized, noninferiority clinical trial with masked evaluation was conducted at 3 locations in Colombia where Leishmania panamensis and Leishmania guyanensis predominated. One hundred sixteen children aged 2-12 years with parasitologically confirmed cutaneous leishmaniasis were randomized to directly observed treatment with meglumine antimoniate (20 mg Sb/kg/d for 20 days; intramuscular) (n = 58) or miltefosine (1.8-2.5 mg/kg/d for 28 days; by mouth) (n = 58). Primary outcome was treatment failure at or before week 26 after initiation of treatment. Miltefosine was noninferior if the proportion of treatment failures was ≤15% higher than achieved with meglumine antimoniate (1-sided test, α = .05).
  
  
  RESULTS
  Ninety-five percent of children (111/116) completed follow-up evaluation. By intention-to-treat analysis, failure rate was 17.2% (98% confidence interval [CI], 5.7%-28.7%) for miltefosine and 31% (98% CI, 16.9%-45.2%) for meglumine antimoniate. The difference between treatment groups was 13.8%, (98% CI, -4.5% to 32%) (P = .04). Adverse events were mild for both treatments.
  
  
  CONCLUSIONS
  Miltefosine is noninferior to meglumine antimoniate for treatment of pediatric cutaneous leishmaniasis caused by Leishmania (Viannia) species. Advantages of oral administration and low toxicity favor use of miltefosine in children.
  
  
  BACKGROUND
  NCT00487253.
authors.affiliation: Centro Internacional De Entrenamiento E Investigaciones Médicas (CIDEIM), Cali, Colombia.
authors.forename: Luisa Consuelo
authors.initials: LC
authors.lastname: Rubiano
authors.forename: María Consuelo
authors.initials: MC
authors.lastname: Miranda
authors.forename: Sandra
authors.initials: S
authors.lastname: Muvdi Arenas
authors.forename: Luz Mery
authors.initials: LM
authors.lastname: Montero
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodríguez-Barraquer
authors.forename: Daniel
authors.initials: D
authors.lastname: Garcerant
authors.forename: Martín
authors.initials: M
authors.lastname: Prager
authors.forename: Lyda
authors.initials: L
authors.lastname: Osorio
authors.forename: Maria Ximena
authors.initials: MX
authors.lastname: Rojas
authors.forename: Mauricio
authors.initials: M
authors.lastname: Pérez
authors.forename: Ruben Santiago
authors.initials: RS
authors.lastname: Nicholls
authors.forename: Nancy
authors.initials: N
authors.lastname: Gore Saravia
mesh_terms: D000284:Administration, Oral; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003105:Colombia; D005260:Female; D006801:Humans; D007891:Leishmania / Q000302:isolation & purification*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D008297:Male; D008536:Meglumine / Q000008:administration & dosage* / Q000009:adverse effects; D000077485:Meglumine Antimoniate; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D017211:Treatment Failure
chemical_list: D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D010767:Phosphorylcholine; C039128:miltefosine; D008536:Meglumine; D000077485:Meglumine Antimoniate