Paromomycin for the Treatment of Visceral Leishmaniasis in Sudan: A Randomized, Open-Label, Dose-Finding Study


Musa, AM; Younis, B; Fadlalla, A; Royce, C; Balasegaram, M; Wasunna, M; Hailu, A; Edwards, T; Omollo, R; Mudawi, M; Kokwaro, G; el-Hassan, A; Khalil, E; (2010) Paromomycin for the Treatment of Visceral Leishmaniasis in Sudan: A Randomized, Open-Label, Dose-Finding Study. PLoS neglected tropical diseases, 4 (10). ISSN 1935-2727 DOI: https://doi.org/10.1371/journal.pntd.0000855

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Abstract

Background: A recent study has shown that treatment of visceral leishmaniasis (VL) with the standard dose of 15 mg/kg/day of paromomycin sulphate (PM) for 21 days was not efficacious in patients in Sudan. We therefore decided to test the efficacy of paramomycin for a longer treatment duration (15 mg/kg/day for 28 days) and at the higher dose of 20 mg/kg/day for 21 days. Methods: This randomized, open-label, dose-finding, phase II study assessed the two above high-dose PM treatment regimens. Patients with clinical features and positive bone-marrow aspirates for VL were enrolled. All patients received their assigned courses of PM intramuscularly and adverse events were monitored. Parasite clearance in bone-marrow aspirates was tested by microscopy at end of treatment (EOT, primary efficacy endpoint), 3 months (in patients who were not clinically well) and 6 months after EOT (secondary efficacy endpoint). Pharmacokinetic data were obtained from a subset of patients weighing over 30 kg. Findings: 42 patients (21 per group) aged between 4 and 60 years were enrolled. At EOT, 85% of patients (95% confidence interval [CI]: 63.7% to 97.0%) in the 20 mg/kg/day group and 90% of patients (95% CI: 69.6% to 98.8%) in the 15 mg/kg/day group had parasite clearance. Six months after treatment, efficacy was 80.0% (95% CI: 56.3% to 94.3%) and 81.0% (95% CI: 58.1% to 94.6%) in the 20 mg/kg/day and 15 mg/kg/day groups, respectively. There were no serious adverse events. Pharmacokinetic profiles suggested a difference between the two doses, although numbers of patients recruited were too few to make it significant (n = 3 and n = 6 in the 20 mg/kg/day and 15 mg/kg/day groups, respectively). Conclusion: Data suggest that both high dose regimens were more efficacious than the standard 15 mg/kg/day PM for 21 days and could be further evaluated in phase III studies in East Africa.

Item Type: Article
Keywords: SODIUM STIBOGLUCONATE, INJECTABLE PAROMOMYCIN, AMINOSIDINE, INDIA, BIHAR, DRUG, Adolescent, Adult, Antiprotozoal Agents, administration & dosage, adverse effects, pharmacokinetics, Bone Marrow, parasitology, Child, Child, Preschool, Female, Humans, Injections, Intramuscular, Leishmania donovani, isolation & purification, Leishmaniasis, Visceral, drug therapy, Male, Microscopy, Middle Aged, Paromomycin, administration & dosage, adverse effects, pharmacokinetics, Sudan, Time Factors, Treatment Outcome, Young Adult
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Leishmaniasis Group
Neglected Tropical Diseases Network
Tropical Epidemiology Group
PubMed ID: 21049063
Web of Science ID: 283559600023
URI: http://researchonline.lshtm.ac.uk/id/eprint/1586

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