Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial.
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.A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design,...
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ftdoajarticles:oai:doaj.org/article:0ca5beabc05445dca399343829a7a798 2023-05-15T15:12:17+02:00 Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial. Eltahir A G Khalil Teklu Weldegebreal Brima M Younis Raymond Omollo Ahmed M Musa Workagegnehu Hailu Abuzaid A Abuzaid Thomas P C Dorlo Zewdu Hurissa Sisay Yifru William Haleke Peter G Smith Sally Ellis Manica Balasegaram Ahmed M EL-Hassan Gerard J Schoone Monique Wasunna Robert Kimutai Tansy Edwards Asrat Hailu 2014-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002613 https://doaj.org/article/0ca5beabc05445dca399343829a7a798 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3894173?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002613 https://doaj.org/article/0ca5beabc05445dca399343829a7a798 PLoS Neglected Tropical Diseases, Vol 8, Iss 1, p e2613 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002613 2022-12-31T08:43:52Z 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.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.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.The tested AmBisome regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified.www.clinicaltrials.govNCT00832208. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 8 1 e2613 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Eltahir A G Khalil Teklu Weldegebreal Brima M Younis Raymond Omollo Ahmed M Musa Workagegnehu Hailu Abuzaid A Abuzaid Thomas P C Dorlo Zewdu Hurissa Sisay Yifru William Haleke Peter G Smith Sally Ellis Manica Balasegaram Ahmed M EL-Hassan Gerard J Schoone Monique Wasunna Robert Kimutai Tansy Edwards Asrat Hailu Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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.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.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.The tested AmBisome regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified.www.clinicaltrials.govNCT00832208. |
format |
Article in Journal/Newspaper |
author |
Eltahir A G Khalil Teklu Weldegebreal Brima M Younis Raymond Omollo Ahmed M Musa Workagegnehu Hailu Abuzaid A Abuzaid Thomas P C Dorlo Zewdu Hurissa Sisay Yifru William Haleke Peter G Smith Sally Ellis Manica Balasegaram Ahmed M EL-Hassan Gerard J Schoone Monique Wasunna Robert Kimutai Tansy Edwards Asrat Hailu |
author_facet |
Eltahir A G Khalil Teklu Weldegebreal Brima M Younis Raymond Omollo Ahmed M Musa Workagegnehu Hailu Abuzaid A Abuzaid Thomas P C Dorlo Zewdu Hurissa Sisay Yifru William Haleke Peter G Smith Sally Ellis Manica Balasegaram Ahmed M EL-Hassan Gerard J Schoone Monique Wasunna Robert Kimutai Tansy Edwards Asrat Hailu |
author_sort |
Eltahir A G Khalil |
title |
Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial. |
title_short |
Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial. |
title_full |
Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial. |
title_fullStr |
Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial. |
title_full_unstemmed |
Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial. |
title_sort |
safety and efficacy of single dose versus multiple doses of ambisome for treatment of visceral leishmaniasis in eastern africa: a randomised trial. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0002613 https://doaj.org/article/0ca5beabc05445dca399343829a7a798 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 1, p e2613 (2014) |
op_relation |
http://europepmc.org/articles/PMC3894173?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002613 https://doaj.org/article/0ca5beabc05445dca399343829a7a798 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002613 |
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PLoS Neglected Tropical Diseases |
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e2613 |
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