PMID- 23209861
OWN - NLM
STAT- MEDLINE
DCOM- 20130405
LR  - 20211021
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 6
IP  - 11
DP  - 2012
TI  - In-hospital safety in field conditions of nifurtimox eflornithine combination 
      therapy (NECT) for T. b. gambiense sleeping sickness.
PG  - e1920
LID - 10.1371/journal.pntd.0001920 [doi]
LID - e1920
AB  - 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. METHODOLOGY: 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. PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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. REGISTRATION: The trial is registered at ClinicalTrials.gov, 
      number NCT00906880.
FAU - Schmid, Caecilia
AU  - Schmid C
AD  - Department of Medicines Research, Swiss Tropical and Public Health Institute, 
      Basel, Switzerland.
FAU - Kuemmerle, Andrea
AU  - Kuemmerle A
FAU - Blum, Johannes
AU  - Blum J
FAU - Ghabri, Salah
AU  - Ghabri S
FAU - Kande, Victor
AU  - Kande V
FAU - Mutombo, Wilfried
AU  - Mutombo W
FAU - Ilunga, Medard
AU  - Ilunga M
FAU - Lumpungu, Ismael
AU  - Lumpungu I
FAU - Mutanda, Sylvain
AU  - Mutanda S
FAU - Nganzobo, Pathou
AU  - Nganzobo P
FAU - Tete, Digas
AU  - Tete D
FAU - Mubwa, Nono
AU  - Mubwa N
FAU - Kisala, Mays
AU  - Kisala M
FAU - Blesson, Severine
AU  - Blesson S
FAU - Mordt, Olaf Valverde
AU  - Mordt OV
LA  - eng
SI  - ClinicalTrials.gov/NCT00906880
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20121129
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Trypanocidal Agents)
RN  - M84I3K7C2O (Nifurtimox)
RN  - ZQN1G5V6SR (Eflornithine)
SB  - IM
CIN - Estimating and Mapping the Population at Risk of Sleeping Sickness .
CIN - Identification of Compounds with Anti-Proliferative Activity against Trypanosoma 
      brucei brucei Strain 427 by a Whole Cell Viability Based HTS Campaign.
CIN - Human African Trypanosomiasis Diagnosis in First-Line Health Services of Endemic 
      Countries, a Systematic Review .
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - Democratic Republic of the Congo
MH  - Drug Therapy, Combination/adverse effects/*methods
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology
MH  - Eflornithine/*administration & dosage/adverse effects
MH  - Female
MH  - Hospitals
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Middle Aged
MH  - Nifurtimox/*administration & dosage/adverse effects
MH  - Pregnancy
MH  - Survival Analysis
MH  - Treatment Outcome
MH  - Trypanocidal Agents/*administration & dosage/adverse effects
MH  - Trypanosoma brucei gambiense/*isolation & purification
MH  - Trypanosomiasis, African/*drug therapy
MH  - Young Adult
PMC - PMC3510081
COIS- The authors have declared that no competing interests exist.
EDAT- 2012/12/05 06:00
MHDA- 2013/04/06 06:00
PMCR- 2012/11/29
CRDT- 2012/12/05 06:00
PHST- 2012/05/03 00:00 [received]
PHST- 2012/10/11 00:00 [accepted]
PHST- 2012/12/05 06:00 [entrez]
PHST- 2012/12/05 06:00 [pubmed]
PHST- 2013/04/06 06:00 [medline]
PHST- 2012/11/29 00:00 [pmc-release]
AID - PNTD-D-12-00537 [pii]
AID - 10.1371/journal.pntd.0001920 [doi]
PST - ppublish
SO  - PLoS Negl Trop Dis. 2012;6(11):e1920. doi: 10.1371/journal.pntd.0001920. Epub 
      2012 Nov 29.