부산대학교 도서관

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 Author Summary: Visceral leishmaniasis is a potentially fatal disease which affects 0.2–0.4 million people every year, principally in South-East Asia, Latin America or Eastern Africa. Currently the safest drug in use is AmBisome®, which cures 90% of patients in India at 5 mg/kg, and is even more effective at higher doses (10 mg/kg) or in combination with miltefosine or paromomycin. These regimens have been shown to be equally cost-effective in India. However, the drug requires a cold chain for storage and reconstitution prior to injection. Although it is licensed for use in eastern Africa, in practice it is mainly used as a second-line treatment. A small study carried out in Kenya indicated that a higher dose is necessary in eastern Africa in contrast to Asia. This study aimed to determine the minimum single dose that is safe and effective for treatment of eastern African VL patients so as to be used in simplified treatment regimens. However, the tested regimens were found to be ineffective, and an optimal single dose that could potentially be used in simplified treatment regimens was not identified. [ABSTRACT FROM AUTHOR]