The endTB observational study protocol: treatment of MDR-TB with bedaquiline or delamanid containing regimens

Abstract

Background At a time when programs were struggling to design effective regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB), the marketing authorization of bedaquiline and delamanid was a critical development in the MDR-TB treatment landscape. However, despite their availability for routine programmatic use, the uptake of these drugs has remained slow; concerns included a lack of evidence on safety and efficacy and the need to protect the new drugs from the development of acquired resistance. As part of the endTB Project, we aimed to address these barriers by generating evidence on safety and efficacy of bedaquiline or delamanid based MDR-TB regimens. Methods This is a protocol for a multi-center prospective cohort study to enroll 2600 patients from April 2015 through September 2018 in 17 countries. The protocol describes inclusion of patients started on treatment with bedaquiline- or delamanid- containing regimens under routine care, who consented to participate in the endTB observational study. Patient follow-up was according to routine monitoring schedules recommended for patients receiving bedaquiline or delamanid as implemented at each endTB site. Therefore, no additional tests were performed as a part of the study. Data were to be collected in a customized, open-source electronic medical record (EMR) system developed as a part of the endTB Project across all 17 countries. Discussion The endTB observational study will generate evidence on safety and efficacy of bedaquiline- and delamanid-containing regimens in a large, extremely heterogeneous group of MDR-TB patients, from 17 epidemiologically diverse countries. The systematic, prospective data collection of repeated effectiveness and safety measures, and analyses performed on these data, will improve the quality of evidence available to inform MDR-TB treatment and policy decisions. Further, the resources available to countries through implementation of the endTB project will have permitted countries to: gain experience with the use of these drugs in MDR-TB regimens, improve local capacity to record and report adverse events (pharmacovigilance), and enhance significantly the body of data available for safety evaluation of these drugs and other novel treatments. Trial registration This study was registered on 24 August 2017 at clincaltrials.gov (Registration number: NCT03259269). Electronic supplementary material The online version of this article (10.1186/s12879-019-4378-4) contains supplementary material, which is available to authorized users.

Culture Conversion in Patients Treated with Bedaquiline and/or Delamanid. A Prospective Multicountry Study

“…The endTB Observational Study (NCT02754765) comprises a prospective cohort of patients with rifampin resistant (RR)/MDR-TB who were treated with BDQ and/or DLM, (31)…”

Refining MDR-TB treatment regimens for ultra short therapy (TB-TRUST): study protocol for a randomized controlled trial

“…At present, a number of studies of shorter regimen for MDR-TB including MDR-END [ 21 ], endTB [ 22 ] and so on are carried out. The trends of MDR-TB treatment are short-term and full oral.…”

“…As a full-oral shorter regimen, without introducing bedaquiline is regrettably. Bedaquiline-containing regimens have achieved high conversion and success rates of MDR- and XDR-TB trials in published studies [ 8 , 26 , 27 ] and it is a popular and important agent in recent shorter regimen trials [ 22 ]. However, most Chinese patients cannot afford bedaquiline due to the high price and different medical insurance reimbursement ratio, which has affected its promotion in China.…”

World Health Organization recommendations on the treatment of drug-resistant tuberculosis, 2020 update

“…For this PICO question the data were derived from the EndTB observational study [ 40 ], with the overall dataset comprising a total of 1094 patients from 13 countries [ 40 ]. These countries are Armenia, Bangladesh, Belarus, Democratic People's Republic of Korea, Ethiopia, Georgia, Indonesia, Kazakhstan, Kenya, Lesotho, Myanmar, Pakistan and Peru.…”