Field safety and effectiveness of new visceral leishmaniasis treatment regimens within public health facilities in Bihar, India

Autor: Goyal, Vishal, Mahajan, Raman, Pandey, Krishna, Singh, Shambhu Nath, Singh, Ravi Shankar, Strub-Wourgaft, Nathalie, Alves, Fabiana, Rabi Das, Vidya Nand, Topno, Roshan Kamal, Sharma, Bhawna, Balasegaram, Manica, Bern, Caryn, Hightower, Allen, Rijal, Suman, Ellis, Sally, Sunyoto, Temmy, Burza, Sakib, Lima, Nines, Das, Pradeep, Alvar, Jorge
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
Paromomycin
Geographical Locations
Zoonoses
Medicine and Health Sciences
Prospective Studies
Amphotericin
Child
Leishmaniasis
Aged
80 and over
Pharmaceutics
Antimicrobials
lcsh:Public aspects of medicine
Drugs
Anemia
Hematology
Middle Aged
Infectious Diseases
Treatment Outcome
Research Design
Child
Preschool
Leishmaniasis
Visceral
Drug Therapy
Combination
Female
Research Article
Neglected Tropical Diseases
Adult
lcsh:Arctic medicine. Tropical medicine
Asia
Drug Research and Development
Adolescent
Drug-Related Side Effects and Adverse Reactions
lcsh:RC955-962
Clinical Research Design
Phosphorylcholine
Antiprotozoal Agents
India
Mycology
Research and Analysis Methods
Microbiology
Kala-Azar
Young Adult
Drug Therapy
Microbial Control
Amphotericin B
parasitic diseases
Parasitic Diseases
Humans
Aged
Pharmacology
Antifungals
Protozoan Infections
Biology and Life Sciences
lcsh:RA1-1270
Tropical Diseases
People and Places
Adverse Events
Zdroj: PLoS Neglected Tropical Diseases
PLoS Neglected Tropical Diseases, Vol 12, Iss 10, p e0006830 (2018)
ISSN: 1935-2735
1935-2727
Popis: 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).
Author summary Treatment is one of key strategies for visceral leishmaniasis control and elimination. Historically a number of monotherapy drugs for VL treatment were used in India including pentavalent antimonials, amphotericin B deoxycholate (AmB), and miltefosine (MF). With the limited number of drugs available there was a need to preserve existing drugs and to develop shorter and safer treatment regimens. Three short-course combination regimen including AmBisome, miltefosine and paromomycin have been evaluated in a phase III clinical trial conducted in India (2008–2010). All showed an excellent safety profile and an efficacy of at least 97% in controlled conditions. 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 within national program settings. This study was implemented in field conditions with treatment provided by government doctors, providing further evidence for scaling up new regimens in national program contexts within the public health sector and contributing to national policy change in India.
Databáze: OpenAIRE
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