Three drug combinations for late-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Uganda.

Hdl Handle:
http://hdl.handle.net/10144/18264
Title:
Three drug combinations for late-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Uganda.
Authors:
Priotto, G; Fogg, C; Balasegaram, M; Erphas, O; Louga, A; Checchi, F; Ghabri, S; Piola, P
Journal:
PLoS Clinical Trials
Abstract:
OBJECTIVES: Our objective was to compare the efficacy and safety of three drug combinations for the treatment of late-stage human African trypanosomiasis caused by Trypanosoma brucei gambiense. DESIGN: This trial was a randomized, open-label, active control, parallel clinical trial comparing three arms. SETTING: The study took place at the Sleeping Sickness Treatment Center run by Médecins Sans Frontières at Omugo, Arua District, Uganda PARTICIPANTS: Stage 2 patients diagnosed in Northern Uganda were screened for inclusion and a total of 54 selected. INTERVENTIONS: Three drug combinations were given to randomly assigned patients: melarsoprol-nifurtimox (M+N), melarsoprol-eflornithine (M+E), and nifurtimox-eflornithine (N+E). Dosages were uniform: intravenous (IV) melarsoprol 1.8 mg/kg/d, daily for 10 d; IV eflornithine 400 mg/kg/d, every 6 h for 7 d; oral nifurtimox 15 (adults) or 20 (children <15 y) mg/kg/d, every 8 h for 10 d. Patients were followed up for 24 mo. OUTCOME MEASURES: Outcomes were cure rates and adverse events attributable to treatment. RESULTS: Randomization was performed on 54 patients before enrollment was suspended due to unacceptable toxicity in one of the three arms. Cure rates obtained with the intention to treat analysis were M+N 44.4%, M+E 78.9%, and N+E 94.1%, and were significantly higher with N+E (p = 0.003) and M+E (p = 0.045) than with M+N. Adverse events were less frequent and less severe with N+E, resulting in fewer treatment interruptions and no fatalities. Four patients died who were taking melarsoprol-nifurtimox and one who was taking melarsoprol-eflornithine. CONCLUSIONS: The N+E combination appears to be a promising first-line therapy that may improve treatment of sleeping sickness, although the results from this interrupted study do not permit conclusive interpretations. Larger studies are needed to continue the evaluation of this drug combination in the treatment of T. b. gambiense sleeping sickness.
Affiliation:
gpriotto@epicentre.msf.org
Issue Date:
2006
URI:
http://hdl.handle.net/10144/18264
DOI:
10.1371/journal.pctr.0010039
PubMed ID:
17160135
Language:
en
ISSN:
1555-5887
Appears in Collections:
Trypanosomiasis/Sleeping Sickness

Full metadata record

DC FieldValue Language
dc.contributor.authorPriotto, G-
dc.contributor.authorFogg, C-
dc.contributor.authorBalasegaram, M-
dc.contributor.authorErphas, O-
dc.contributor.authorLouga, A-
dc.contributor.authorChecchi, F-
dc.contributor.authorGhabri, S-
dc.contributor.authorPiola, P-
dc.date.accessioned2008-02-14T11:29:19Z-
dc.date.available2008-02-14T11:29:19Z-
dc.date.issued2006-
dc.identifier.citationThree drug combinations for late-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Uganda. 2006, 1 (8):e39notPLoS Clin Trialsen
dc.identifier.issn1555-5887-
dc.identifier.pmid17160135-
dc.identifier.doi10.1371/journal.pctr.0010039-
dc.identifier.urihttp://hdl.handle.net/10144/18264-
dc.description.abstractOBJECTIVES: Our objective was to compare the efficacy and safety of three drug combinations for the treatment of late-stage human African trypanosomiasis caused by Trypanosoma brucei gambiense. DESIGN: This trial was a randomized, open-label, active control, parallel clinical trial comparing three arms. SETTING: The study took place at the Sleeping Sickness Treatment Center run by Médecins Sans Frontières at Omugo, Arua District, Uganda PARTICIPANTS: Stage 2 patients diagnosed in Northern Uganda were screened for inclusion and a total of 54 selected. INTERVENTIONS: Three drug combinations were given to randomly assigned patients: melarsoprol-nifurtimox (M+N), melarsoprol-eflornithine (M+E), and nifurtimox-eflornithine (N+E). Dosages were uniform: intravenous (IV) melarsoprol 1.8 mg/kg/d, daily for 10 d; IV eflornithine 400 mg/kg/d, every 6 h for 7 d; oral nifurtimox 15 (adults) or 20 (children <15 y) mg/kg/d, every 8 h for 10 d. Patients were followed up for 24 mo. OUTCOME MEASURES: Outcomes were cure rates and adverse events attributable to treatment. RESULTS: Randomization was performed on 54 patients before enrollment was suspended due to unacceptable toxicity in one of the three arms. Cure rates obtained with the intention to treat analysis were M+N 44.4%, M+E 78.9%, and N+E 94.1%, and were significantly higher with N+E (p = 0.003) and M+E (p = 0.045) than with M+N. Adverse events were less frequent and less severe with N+E, resulting in fewer treatment interruptions and no fatalities. Four patients died who were taking melarsoprol-nifurtimox and one who was taking melarsoprol-eflornithine. CONCLUSIONS: The N+E combination appears to be a promising first-line therapy that may improve treatment of sleeping sickness, although the results from this interrupted study do not permit conclusive interpretations. Larger studies are needed to continue the evaluation of this drug combination in the treatment of T. b. gambiense sleeping sickness.en
dc.language.isoenen
dc.rightsArchived with thanks to PLoS clinical trialsen
dc.titleThree drug combinations for late-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Uganda.en
dc.contributor.departmentgpriotto@epicentre.msf.orgen
dc.identifier.journalPLoS Clinical Trialsen

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