ICMR-National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India
ICMR-National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India.
BMJ Open. 2022 Aug 29;12(8):e058606. doi: 10.1136/bmjopen-2021-058606.
Drug-resistant tuberculosis (DR-TB) is a global public health problem. Patients suffer for months if undiagnosed or treated inadequately, transmitting DR-TB in the community before succumbing to the disease. Early diagnosis, prompt treatment initiation and completion play a significant role in treatment success. However, extended regimens with injectable result in poor treatment adherence and outcomes. Our objective is to evaluate the effectiveness, safety and tolerability of various doses and duration of linezolid (LZD) in combination with bedaquiline (BDQ) and pretomanid (Pa) after 26 weeks of treatment in adults with pre-extensively drug-resistant or treatment intolerant/non-responsive multidrug-resistant pulmonary TB.
A multicentric, randomised pragmatic clinical trial in India will enrol participants in one of the three arms-control arm (arm 1): BDQ, Pa and LZD 600 mg daily for 26 weeks or intervention arms (arm 2): BDQ, Pa and LZD 600 mg for 9 weeks followed by 300 mg for 17 weeks or arm 3: BDQ, Pa and LZD 600 mg for 13 weeks followed by 300 mg for 13 weeks. The primary endpoint is the proportion of patients with favourable outcomes as sustained cure and treatment completion. The secondary endpoint is unfavourable outcomes, including deaths, treatment failure, toxicity/adverse events and lost to follow-up till 48 weeks post-treatment.
The study has been approved by the ethics committees of participating institutes and the National Institute for Research in TB. The trial results will help establish evidence towards a safe and effective dose of LZD that can be used in a fully, all-oral short course regimen for highly DR-TB patients. The results of this study will be shared with the National TB Elimination Programme of the country and the WHO guidelines development group through publications and dissemination meetings.
NCT05040126.
耐多药结核病（DR-TB）是一个全球性的公共卫生问题。如果未被诊断或治疗不当，患者将患病数月，并在死于该病之前在社区中传播 DR-TB。早期诊断、及时开始治疗并完成治疗对于治疗成功至关重要。然而，含有注射剂的延长方案会导致治疗依从性差和结局不佳。我们的目的是评估在 26 周治疗后，不同剂量和疗程的利奈唑胺（LZD）联合贝达喹啉（BDQ）和普托马尼（Pa）在治疗预广泛耐药或不耐受/无反应的耐多药肺结核成人患者中的有效性、安全性和耐受性。
一项在印度进行的多中心、随机实用临床试验将招募参与者进入以下三个试验组之一：对照组（第 1 组）：BDQ、Pa 和 LZD 600mg 每日治疗 26 周；或干预组（第 2 组）：BDQ、Pa 和 LZD 600mg 治疗 9 周，然后 300mg 治疗 17 周；或第 3 组：BDQ、Pa 和 LZD 600mg 治疗 13 周，然后 300mg 治疗 13 周。主要终点是具有良好结局（持续治愈和治疗完成）的患者比例。次要终点是不良结局，包括死亡、治疗失败、毒性/不良事件和治疗结束后 48 周失访。
该研究已获得参与机构的伦理委员会和国家结核病研究所的批准。研究结果将有助于确定 LZD 的安全有效剂量，该剂量可用于高度耐多药结核病患者的全口服短程方案。该研究结果将通过出版物和传播会议与该国的国家结核病消除计划和世卫组织指南制定小组共享。
NCT05040126。
