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PLoS Negl Trop Dis. 2014 Jan 16;8(1):e2613. doi: 10.1371/journal.pntd.0002613. eCollection 2014.

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

Author information

1
Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
2
Arba Minch Hospital, Regional Health Bureau of SNNP State, Arba Minch, Ethiopia.
3
Drugs for Neglected Diseases initiative (DNDi) Africa Regional Office, Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
4
University of Gondar, College of Medicine & Health Sciences, Gondar, Ethiopia.
5
Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands ; Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands.
6
MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.
7
Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
8
Royal Tropical Institute, KIT Biomedical Research, Amsterdam, The Netherlands.
9
Drugs for Neglected Diseases initiative (DNDi) Africa Regional Office, Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya ; Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
10
School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.

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.

PMID:
24454970
PMCID:
PMC3894173
DOI:
10.1371/journal.pntd.0002613
[Indexed for MEDLINE]
Free PMC Article

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