Field safety and effectiveness of new visceral leishmaniasis treatment regimens within public health facilities in Bihar, India.
BACKGROUND:In 2010, WHO recommended the use of new short-course treatment regimens in kala-azar elimination efforts for the Indian subcontinent. Although phase 3 studies have shown excellent results, there remains a lack of evidence on a wider treatment population and the safety and effectiveness of...
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ftdoajarticles:oai:doaj.org/article:27604aeab9ad4ef792e06c9f96aa4bb9 2023-05-15T15:17:12+02:00 Field safety and effectiveness of new visceral leishmaniasis treatment regimens within public health facilities in Bihar, India. Vishal Goyal Raman Mahajan Krishna Pandey Shambhu Nath Singh Ravi Shankar Singh Nathalie Strub-Wourgaft Fabiana Alves Vidya Nand Rabi Das Roshan Kamal Topno Bhawna Sharma Manica Balasegaram Caryn Bern Allen Hightower Suman Rijal Sally Ellis Temmy Sunyoto Sakib Burza Nines Lima Pradeep Das Jorge Alvar 2018-10-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006830 https://doaj.org/article/27604aeab9ad4ef792e06c9f96aa4bb9 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC6197645?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006830 https://doaj.org/article/27604aeab9ad4ef792e06c9f96aa4bb9 PLoS Neglected Tropical Diseases, Vol 12, Iss 10, p e0006830 (2018) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2018 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006830 2022-12-31T01:45:15Z BACKGROUND:In 2010, WHO recommended the use of new short-course treatment regimens in kala-azar elimination efforts for the Indian subcontinent. Although phase 3 studies have shown excellent results, there remains a lack of evidence on a wider treatment population and the safety and effectiveness of these regimens under field conditions. METHODS:This was an open label, prospective, non-randomized, non-comparative, multi-centric trial conducted within public health facilities in two highly endemic districts and a specialist referral centre in Bihar, India. Three treatment regimens were tested: single dose AmBisome (SDA), concomitant miltefosine and paromomycin (Milt+PM), and concomitant AmBisome and miltefosine (AmB+Milt). Patients with complicated disease or significant co-morbidities were treated in the SDA arm. Sample sizes were set at a minimum of 300 per arm, taking into account inter-site variation and an estimated failure risk of 5% with 5% precision. Outcomes of drug effectiveness and safety were measured at 6 months. The trial was prospectively registered with the Clinical Trials Registry India: CTRI/2012/08/002891. RESULTS:Out of 1,761 patients recruited, 50.6% (n = 891) received SDA, 20.3% (n = 358) AmB+Milt and 29.1% (n = 512) Milt+PM. In the ITT analysis, the final cure rates were SDA 91.4% (95% CI 89.3-93.1), AmB+Milt 88.8% (95% CI 85.1-91.9) and Milt+PM 96.9% (95% CI 95.0-98.2). In the complete case analysis, cure rates were SDA 95.5% (95% CI 93.9-96.8), AmB+Milt 95.5% (95% CI 92.7-97.5) and Milt+PM 99.6% (95% CI 98.6-99.9). All three regimens were safe, with 5 severe adverse events in the SDA arm, two of which were considered to be drug related. CONCLUSION:All regimens showed acceptable outcomes and safety profiles in a range of patients under field conditions. Phase IV field-based studies, although extremely rare for neglected tropical diseases, are good practice and an important step in validating the results of more restrictive hospital-based studies before widespread implementation, and in ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Indian Azar ENVELOPE(-63.733,-63.733,-64.983,-64.983) PLOS Neglected Tropical Diseases 12 10 e0006830 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Vishal Goyal Raman Mahajan Krishna Pandey Shambhu Nath Singh Ravi Shankar Singh Nathalie Strub-Wourgaft Fabiana Alves Vidya Nand Rabi Das Roshan Kamal Topno Bhawna Sharma Manica Balasegaram Caryn Bern Allen Hightower Suman Rijal Sally Ellis Temmy Sunyoto Sakib Burza Nines Lima Pradeep Das Jorge Alvar Field safety and effectiveness of new visceral leishmaniasis treatment regimens within public health facilities in Bihar, India. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:In 2010, WHO recommended the use of new short-course treatment regimens in kala-azar elimination efforts for the Indian subcontinent. Although phase 3 studies have shown excellent results, there remains a lack of evidence on a wider treatment population and the safety and effectiveness of these regimens under field conditions. METHODS:This was an open label, prospective, non-randomized, non-comparative, multi-centric trial conducted within public health facilities in two highly endemic districts and a specialist referral centre in Bihar, India. Three treatment regimens were tested: single dose AmBisome (SDA), concomitant miltefosine and paromomycin (Milt+PM), and concomitant AmBisome and miltefosine (AmB+Milt). Patients with complicated disease or significant co-morbidities were treated in the SDA arm. Sample sizes were set at a minimum of 300 per arm, taking into account inter-site variation and an estimated failure risk of 5% with 5% precision. Outcomes of drug effectiveness and safety were measured at 6 months. The trial was prospectively registered with the Clinical Trials Registry India: CTRI/2012/08/002891. RESULTS:Out of 1,761 patients recruited, 50.6% (n = 891) received SDA, 20.3% (n = 358) AmB+Milt and 29.1% (n = 512) Milt+PM. In the ITT analysis, the final cure rates were SDA 91.4% (95% CI 89.3-93.1), AmB+Milt 88.8% (95% CI 85.1-91.9) and Milt+PM 96.9% (95% CI 95.0-98.2). In the complete case analysis, cure rates were SDA 95.5% (95% CI 93.9-96.8), AmB+Milt 95.5% (95% CI 92.7-97.5) and Milt+PM 99.6% (95% CI 98.6-99.9). All three regimens were safe, with 5 severe adverse events in the SDA arm, two of which were considered to be drug related. CONCLUSION:All regimens showed acceptable outcomes and safety profiles in a range of patients under field conditions. Phase IV field-based studies, although extremely rare for neglected tropical diseases, are good practice and an important step in validating the results of more restrictive hospital-based studies before widespread implementation, and in ... |
format |
Article in Journal/Newspaper |
author |
Vishal Goyal Raman Mahajan Krishna Pandey Shambhu Nath Singh Ravi Shankar Singh Nathalie Strub-Wourgaft Fabiana Alves Vidya Nand Rabi Das Roshan Kamal Topno Bhawna Sharma Manica Balasegaram Caryn Bern Allen Hightower Suman Rijal Sally Ellis Temmy Sunyoto Sakib Burza Nines Lima Pradeep Das Jorge Alvar |
author_facet |
Vishal Goyal Raman Mahajan Krishna Pandey Shambhu Nath Singh Ravi Shankar Singh Nathalie Strub-Wourgaft Fabiana Alves Vidya Nand Rabi Das Roshan Kamal Topno Bhawna Sharma Manica Balasegaram Caryn Bern Allen Hightower Suman Rijal Sally Ellis Temmy Sunyoto Sakib Burza Nines Lima Pradeep Das Jorge Alvar |
author_sort |
Vishal Goyal |
title |
Field safety and effectiveness of new visceral leishmaniasis treatment regimens within public health facilities in Bihar, India. |
title_short |
Field safety and effectiveness of new visceral leishmaniasis treatment regimens within public health facilities in Bihar, India. |
title_full |
Field safety and effectiveness of new visceral leishmaniasis treatment regimens within public health facilities in Bihar, India. |
title_fullStr |
Field safety and effectiveness of new visceral leishmaniasis treatment regimens within public health facilities in Bihar, India. |
title_full_unstemmed |
Field safety and effectiveness of new visceral leishmaniasis treatment regimens within public health facilities in Bihar, India. |
title_sort |
field safety and effectiveness of new visceral leishmaniasis treatment regimens within public health facilities in bihar, india. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2018 |
url |
https://doi.org/10.1371/journal.pntd.0006830 https://doaj.org/article/27604aeab9ad4ef792e06c9f96aa4bb9 |
long_lat |
ENVELOPE(-63.733,-63.733,-64.983,-64.983) |
geographic |
Arctic Indian Azar |
geographic_facet |
Arctic Indian Azar |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 12, Iss 10, p e0006830 (2018) |
op_relation |
http://europepmc.org/articles/PMC6197645?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006830 https://doaj.org/article/27604aeab9ad4ef792e06c9f96aa4bb9 |
op_doi |
https://doi.org/10.1371/journal.pntd.0006830 |
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PLOS Neglected Tropical Diseases |
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12 |
container_issue |
10 |
container_start_page |
e0006830 |
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