Study protocol for a duration-randomized clinical trial to determine the optimal length of treatment for multidrug-resistant tuberculosis with a 5-drug regimen: The DRAMATIC trial

IF 2 3区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Contemporary clinical trials Pub Date : 2025-03-08 DOI:10.1016/j.cct.2025.107875

Pawandeep Kaur , Lelia H. Chaisson , Zana Wangari Kiragu , Praewpannarai Buddadhumaruk , Ariana F. Austin , Yilan Gao , Veronika J. Wirtz , Robert D. Arbeit , Krystle Bliss Fetalvero , Hoa Binh Nguyen , Nhung Viet Nguyen , Huy Ha , Kathleen Eisenach , Nicholas D. Walter , Carole D. Mitnick , Maria Tarcela S. Gler , Ha Phan , Payam Nahid , Patrick P.J. Phillips , C. Robert Horsburgh , Gustavo E. Velásquez

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引用次数: 0

Abstract

Background

Current guidelines for the treatment of multidrug-resistant/rifampin-resistant tuberculosis (MDR/RR-TB) are based on clinical trials evaluating fixed duration regimens. However, when a regimen succeeds, it remains unknown whether a shorter duration could yield the same results. Similarly, if a regimen fails, it is unclear whether extending the treatment could improve outcomes. Trials are needed to assess the relationship between various treatment durations and outcomes.

Methods/design

We designed a duration-randomized trial of treatment for fluoroquinolone-susceptible MDR/RR-TB. The DRAMATIC (Duration Randomized Anti-MDR-TB And Tailored Intervention Clinical) Trial is a multicenter, randomized, partially blinded, four-arm, phase 2 trial that examines an all oral, pyrazinamide-free regimen of bedaquiline, clofazimine, delamanid, linezolid, and levofloxacin, with administration of linezolid only in the initial 16 weeks of treatment. The four trial arms are treatment durations of 16, 24, 32 and 40 weeks. Randomization is stratified by “extensive” or “non-extensive” disease based on baseline smear (or Xpert) and cavitary status. The primary endpoint is relapse-free survival at week 76. The target sample size is 220. Participants are being enrolled in sites in the Philippines and Vietnam. The expected output will be an equation describing the relationship between treatment duration and the proportion of participants with relapse-free survival.

Discussion

This trial aims to demonstrate that a duration-response relationship can be described for the treatment of MDR/RR-TB by a duration-randomized trial.

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背景：目前治疗耐多药/耐利福平结核病（MDR/RR-TB）的指南是基于评估固定疗程方案的临床试验。然而，当一种治疗方案取得成功时，缩短疗程是否能取得同样的效果仍是未知数。同样，如果疗程失败，延长疗程是否能改善疗效也不清楚。需要进行试验来评估各种治疗持续时间与疗效之间的关系：我们设计了一项治疗氟喹诺酮敏感型 MDR/RR-TB 的疗程随机试验。DRAMATIC（Duration Randomized Anti-MDR-TB And Tailored Intervention Clinical）试验是一项多中心、随机、部分盲法、四臂、二期试验，研究了贝达喹啉、氯法齐明、地拉马尼、利奈唑烷和左氧氟沙星的全口服、不含吡嗪酰胺的治疗方案，仅在最初的16周治疗中使用利奈唑烷。四个试验组的治疗时间分别为 16、24、32 和 40 周。根据基线涂片（或 Xpert）和空洞状态，按 "广泛 "或 "非广泛 "疾病进行随机分层。主要终点是第76周的无复发生存率。目标样本量为 220 例。菲律宾和越南的研究机构正在招募参与者。预期结果将是描述治疗时间与无复发生存率之间关系的方程：本试验旨在证明，通过疗程随机试验可以描述 MDR/RR-TB 治疗的疗程-反应关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Contemporary clinical trials 医学-药学

CiteScore

3.70

自引率

4.50%

发文量

281

审稿时长

44 days

期刊介绍： Contemporary Clinical Trials is an international peer reviewed journal that publishes manuscripts pertaining to all aspects of clinical trials, including, but not limited to, design, conduct, analysis, regulation and ethics. Manuscripts submitted should appeal to a readership drawn from disciplines including medicine, biostatistics, epidemiology, computer science, management science, behavioural science, pharmaceutical science, and bioethics. Full-length papers and short communications not exceeding 1,500 words, as well as systemic reviews of clinical trials and methodologies will be published. Perspectives/commentaries on current issues and the impact of clinical trials on the practice of medicine and health policy are also welcome.