title: In-hospital safety in field conditions of nifurtimox eflornithine combination therapy (NECT) for T. b. gambiense sleeping sickness.
abstract: BACKGROUND
  Trypanosoma brucei (T.b.) gambiense Human African trypanosomiasis (HAT; sleeping sickness) is a fatal disease. Until 2009, available treatments for 2(nd) stage HAT were complicated to use, expensive (eflornithine monotherapy), or toxic, and insufficiently effective in certain areas (melarsoprol). Recently, nifurtimox-eflornithine combination therapy (NECT) demonstrated good safety and efficacy in a randomised controlled trial (RCT) and was added to the World Health Organisation (WHO) essential medicines list (EML). Documentation of its safety profile in field conditions will support its wider use.
  
  
  METHODS
  In a multicentre, open label, single arm, phase IIIb study of the use of NECT for 2(nd) stage T.b. gambiense HAT, all patients admitted to the trial centres who fulfilled inclusion criteria were treated with NECT. The primary outcome was the proportion of patients discharged alive from hospital. Safety was further assessed based on treatment emergent adverse events (AEs) occurring during hospitalisation.
  
  
  RESULTS
  629 patients were treated in six HAT treatment facilities in the Democratic Republic of the Congo (DRC), including 100 children under 12, 14 pregnant and 33 breastfeeding women. The proportion of patients discharged alive after treatment completion was 98.4% (619/629; 95%CI [97.1%; 99.1%]). Of the 10 patients who died during hospitalisation, 8 presented in a bad or very bad health condition at baseline; one death was assessed as unlikely related to treatment. No major or unexpected safety concerns arose in any patient group. Most common AEs were gastro-intestinal (61%), general (46%), nervous system (mostly central; 34%) and metabolic disorders (26%). The overall safety profile was similar to previously published findings.
  
  
  CONCLUSIONS
  In field conditions and in a wider population, including children, NECT displayed a similar tolerability profile to that described in more stringent clinical trial conditions. The in-hospital safety was comparable to published results, and long term efficacy will be confirmed after 24 months follow-up.
  
  
  BACKGROUND
  The trial is registered at ClinicalTrials.gov, number NCT00906880.
authors.affiliation: Department of Medicines Research, Swiss Tropical and Public Health Institute, Basel, Switzerland.
authors.forename: Caecilia
authors.initials: C
authors.lastname: Schmid
authors.forename: Andrea
authors.initials: A
authors.lastname: Kuemmerle
authors.forename: Johannes
authors.initials: J
authors.lastname: Blum
authors.forename: Salah
authors.initials: S
authors.lastname: Ghabri
authors.forename: Victor
authors.initials: V
authors.lastname: Kande
authors.forename: Wilfried
authors.initials: W
authors.lastname: Mutombo
authors.forename: Medard
authors.initials: M
authors.lastname: Ilunga
authors.forename: Ismael
authors.initials: I
authors.lastname: Lumpungu
authors.forename: Sylvain
authors.initials: S
authors.lastname: Mutanda
authors.forename: Pathou
authors.initials: P
authors.lastname: Nganzobo
authors.forename: Digas
authors.initials: D
authors.lastname: Tete
authors.forename: Nono
authors.initials: N
authors.lastname: Mubwa
authors.forename: Mays
authors.initials: M
authors.lastname: Kisala
authors.forename: Severine
authors.initials: S
authors.lastname: Blesson
authors.forename: Olaf Valverde
authors.initials: OV
authors.lastname: Mordt
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015023:Democratic Republic of the Congo; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D000518:Eflornithine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006761:Hospitals; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009547:Nifurtimox / Q000008:administration & dosage* / Q000009:adverse effects; D011247:Pregnancy; D016019:Survival Analysis; D016896:Treatment Outcome; D014344:Trypanocidal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D014347:Trypanosoma brucei gambiense / Q000302:isolation & purification*; D014353:Trypanosomiasis, African / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D014344:Trypanocidal Agents; D009547:Nifurtimox; D000518:Eflornithine