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Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial.

Abstract：

BACKGROUND:Anti-leishmanial drug regimens that include a single dose AmBisome could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown. METHODOLOGY:A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC) at 6 months. Symptomatic patients with parasitologically-confirmed, non-severe VL, received a single dose of AmBisome 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1-5, 14, and 21. If interim analyses, evaluated 30 days after the start of treatment following 40 or 80 patients, showed the single dose gave significantly poorer parasite clearance than multiple doses at the 5% significance level, the single dose was increased by 2·5 mg/kg. In a sub-set of patients, parasite clearance was measured by quantitative reverse transcriptase (qRT) PCR. PRINCIPAL FINDINGS:The trial was terminated after the third interim analysis because of low efficacy of both regimens. Based on the intention-to-treat population, DC was 85% (95%CI 73-93%), 40% (95%CI 19-64%), and 58% (95%CI 41-73%) in patients treated with multiple doses (n = 63), and single doses of 7·5 (n = 21) or 10 mg/kg (n = 40), respectively. qRT-PCR suggested superior parasite clearance with multiple doses as early as day 3. Safety data accorded with the drug label. CONCLUSIONS:The tested AmBisome regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified. TRIALS REGISTRATION:www.clinicaltrials.govNCT00832208.

journal_name

PLoS Negl Trop Dis

journal_title

PLoS neglected tropical diseases

authors

Khalil EA,Weldegebreal T,Younis BM,Omollo R,Musa AM,Hailu W,Abuzaid AA,Dorlo TP,Hurissa Z,Yifru S,Haleke W,Smith PG,Ellis S,Balasegaram M,EL-Hassan AM,Schoone GJ,Wasunna M,Kimutai R,Edwards T,Hailu A

doi

10.1371/journal.pntd.0002613

subject

Has Abstract

pub_date

2014-01-16 00:00:00

pages

e2613

issue

eissn

1935-2727

issn

1935-2735

pii

PNTD-D-13-00632

journal_volume

pub_type

杂志文章,多中心研究,随机对照试验

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Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial.