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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-10-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC6197645?pdf=render |
| _version_ | 1828496050452692992 |
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| 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 |
| collection | DOAJ |
| 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 this case contributed to national level policy change in India. TRIAL REGISTRATION:Clinical trial is registered at Clinical trial registry of India (CTRI/2012/08/002891, Registered on 16/08/2012, Trial Registered Prospectively). |
| first_indexed | 2024-12-11T12:23:12Z |
| format | Article |
| id | doaj.art-27604aeab9ad4ef792e06c9f96aa4bb9 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-11T12:23:12Z |
| publishDate | 2018-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-27604aeab9ad4ef792e06c9f96aa4bb92022-12-22T01:07:29ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352018-10-011210e000683010.1371/journal.pntd.0006830Field safety and effectiveness of new visceral leishmaniasis treatment regimens within public health facilities in Bihar, India.Vishal GoyalRaman MahajanKrishna PandeyShambhu Nath SinghRavi Shankar SinghNathalie Strub-WourgaftFabiana AlvesVidya Nand Rabi DasRoshan Kamal TopnoBhawna SharmaManica BalasegaramCaryn BernAllen HightowerSuman RijalSally EllisTemmy SunyotoSakib BurzaNines LimaPradeep DasJorge AlvarBACKGROUND: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 this case contributed to national level policy change in India. TRIAL REGISTRATION:Clinical trial is registered at Clinical trial registry of India (CTRI/2012/08/002891, Registered on 16/08/2012, Trial Registered Prospectively).http://europepmc.org/articles/PMC6197645?pdf=render |
| spellingShingle | 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. PLoS Neglected Tropical Diseases |
| title | 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_short | 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 |
| url | http://europepmc.org/articles/PMC6197645?pdf=render |
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