新型短期结核病治疗方案的2C期临床试验：TBTC研究38/CRUSH-TB设计

IF 1.9 3区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Contemporary clinical trials Pub Date : 2025-09-05 DOI:10.1016/j.cct.2025.108075

Ekaterina V. Kurbatova , Kelly E. Dooley , Wendy Carr , Jason E. Stout , Eric L. Nuermberger , Patrick P.J. Phillips , Nigel A. Scott , Caryn M. Upton , Elisa Ignatius , Michelle Haas , Nicholas D. Walter , Rita M. Traxler , Nicole E. Brown , Rosanna Boyd , Kia E. Bryant , Meredith G. Dixon , Rada Savic , Christie Eichberg , Anneke Hesseling , Charles Bark , Daniel W. Fitzgerald

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引用次数: 0

摘要

临床前和临床研究数据显示，联合使用贝达喹啉（B或BDQ）、莫西沙星(M)和吡嗪酰胺(Z)，即BMZ，具有有效的抗菌活性，可能缩短药物敏感肺结核的治疗时间。方法/设计：我们描述了结核试验联盟（TBTC） Study 38/CRUSH-TB （NCT05766267）的设计，这是一项开放标签的多中心国际随机对照2C期试验，比较了两个4个月的方案，BMZ +利法布汀（Rb）（2BMZRb/2BMRb）或BMZ + delamanid (D或DLM) (2BMZD/2BMD)，与标准的6个月异烟肼、利福平、吡嗪酰胺和乙胺丁醇（HRZE）。所有药物每周7天在直接观察下使用，每周至少5天。288名参与者，年龄≥12 岁，新诊断为痰涂片阳性或Xpert MTB/RIF （Ultra）阳性药敏肺结核，将按1:1:1随机分配接受BMZRb、BMZD或HRZE治疗。受试者将被随访至随机化后78 周，或最后一名受试者完成随机化后52 周，以先到者为准。主要终点是液体培养基中痰培养阴性的时间。次要终点包括持续治愈、安全性以及其他分枝杆菌学、药代动力学和药效学结果。这个试验有一个适应性设计，其中可以添加新的手臂。讨论：本试验测试了四个月的以bmz为基础的Rb或D方案是否可以缩短培养消极情绪的时间，同时对参与者来说是安全和可容忍的。研究设计是自适应的，允许在新药物可用时进行额外的研究。这项试验的发现可能对个人和项目层面的药物敏感肺结核临床管理具有重要意义。试验注册IND号：158058。IND发起人：美国疾病控制与预防中心。临床试验:govIdentifier: NCT05766267。2023年3月13日注册：https://classic.Clinicaltrials: gov/ct2/show/NCT05766267。

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Phase 2C clinical trial of novel short-course regimens for the treatment of pulmonary tuberculosis: TBTC study 38/CRUSH-TB design

Introduction

Preclinical and clinical study data show that combining bedaquiline (B or BDQ), moxifloxacin (M), and pyrazinamide (Z), known as BMZ, has potent antimicrobial activity that might shorten treatment duration for drug-susceptible pulmonary tuberculosis.

Methods/Design

We describe the design of Tuberculosis Trials Consortium (TBTC) Study 38/CRUSH-TB (NCT05766267), an open-label multicenter international randomized controlled phase 2C trial that compares two four-month regimens, BMZ plus rifabutin (Rb) (2BMZRb/2BMRb) or BMZ plus delamanid (D or DLM) (2BMZD/2BMD), with standard 6-months isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE). All drugs are administered seven days per week, under direct observation, at least five days per week. A total of 288 participants, aged ≥12 years, newly diagnosed with sputum smear-positive or Xpert MTB/RIF (Ultra)-positive drug-susceptible pulmonary tuberculosis, will be randomized 1:1:1 to receive BMZRb, BMZD, or HRZE. Participants are followed until 78 weeks post-randomization, or until the last enrolled participant completes 52 weeks post-randomization, whichever comes first. The primary endpoint is time to sputum culture negative in liquid media. Secondary endpoints include sustained cure, safety, and additional mycobacteriology and pharmacokinetic and pharmacodynamic outcomes. This trial has an adaptive design, wherein new arms can be added.

Discussion

This trial tests the hypothesis whether four-month BMZ-based regimens with Rb or D can shorten time to culture negativity while being safe and tolerable for participants. The study design is adaptive, allowing for additional study arms as new drugs become available. Findings from this trial might have important implications for clinically managing drug-susceptible pulmonary tuberculosis at individual and programmatic levels.

Trial registration

IND Number: 158058.

IND Sponsor: U.S. Centers for Disease Control and Prevention.

ClinicalTrials.gov Identifier: NCT05766267. Registered 13 March 2023, https://classic.clinicaltrials.gov/ct2/show/NCT05766267.

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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.