Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study.
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-10-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC2964291?pdf=render |
| _version_ | 1818503697979670528 |
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| author | Ahmed M Musa Brima Younis Ahmed Fadlalla Catherine Royce Manica Balasegaram Monique Wasunna Asrat Hailu Tansy Edwards Raymond Omollo Mahmoud Mudawi Gilbert Kokwaro Ahmed El-Hassan Eltahir Khalil |
| author_facet | Ahmed M Musa Brima Younis Ahmed Fadlalla Catherine Royce Manica Balasegaram Monique Wasunna Asrat Hailu Tansy Edwards Raymond Omollo Mahmoud Mudawi Gilbert Kokwaro Ahmed El-Hassan Eltahir Khalil |
| author_sort | Ahmed M Musa |
| collection | DOAJ |
| description | 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.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.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).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. |
| first_indexed | 2024-12-10T21:27:27Z |
| format | Article |
| id | doaj.art-391462a9ef5a4d678b54f969996a7060 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-10T21:27:27Z |
| publishDate | 2010-10-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-391462a9ef5a4d678b54f969996a70602022-12-22T01:32:56ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352010-10-01410e85510.1371/journal.pntd.0000855Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study.Ahmed M MusaBrima YounisAhmed FadlallaCatherine RoyceManica BalasegaramMonique WasunnaAsrat HailuTansy EdwardsRaymond OmolloMahmoud MudawiGilbert KokwaroAhmed El-HassanEltahir KhalilA 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.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.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).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.http://europepmc.org/articles/PMC2964291?pdf=render |
| spellingShingle | Ahmed M Musa Brima Younis Ahmed Fadlalla Catherine Royce Manica Balasegaram Monique Wasunna Asrat Hailu Tansy Edwards Raymond Omollo Mahmoud Mudawi Gilbert Kokwaro Ahmed El-Hassan Eltahir Khalil Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. PLoS Neglected Tropical Diseases |
| title | Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. |
| title_full | Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. |
| title_fullStr | Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. |
| title_full_unstemmed | Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. |
| title_short | Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. |
| title_sort | paromomycin for the treatment of visceral leishmaniasis in sudan a randomized open label dose finding study |
| url | http://europepmc.org/articles/PMC2964291?pdf=render |
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