%0 Journal Article
%T Field safety and effectiveness of new visceral leishmaniasis treatment regimens within public health facilities in Bihar, India
%A Allen Hightower
%A Bhawna Sharma
%A Caryn Bern
%A Fabiana Alves
%A Jorge Alvar
%A Krishna Pandey
%A Manica Balasegaram
%A Nathalie Strub-Wourgaft
%A Nines Lima
%A Pradeep Das
%A Raman Mahajan
%A Ravi Shankar Singh
%A Roshan Kamal Topno
%A Sakib Burza
%A Sally Ellis
%A Shambhu Nath Singh
%A Suman Rijal
%A Temmy Sunyoto
%A Vidya Nand Rabi Das
%A Vishal Goyal
%J -
%D 2018
%R 10.1371/journal.pntd.0006830
%X 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每93.1), AmB+Milt 88.8% (95% CI 85.1每91.9) and Milt+PM 96.9% (95% CI 95.0每98.2). In the complete case analysis, cure rates were SDA 95.5% (95% CI 93.9每96.8), AmB+Milt 95.5% (95% CI 92.7每97.5) and Milt+PM 99.6% (95% CI 98.6每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)
%K Drug therapy
%K India
%K Adverse events
%K Drug research and development
%K Anemia
%K Amphotericin
%K Kala-azar
%K Leishmaniasis
%U https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006830