Médecins sans Frontières, 10 Furnival Street, London, EC4A1AB, UK.
Burnet Institute, 85 Commercial Rd, Melbourne, VIC, 3004, Australia.
Trials. 2022 Jun 13;23(1):484. doi: 10.1186/s13063-022-06331-8.
Globally rifampicin-resistant tuberculosis disease affects around 460,000 people each year. Currently recommended regimens are 9-24 months duration, have poor efficacy and carry significant toxicity. A shorter, less toxic and more efficacious regimen would improve outcomes for people with rifampicin-resistant tuberculosis.
TB-PRACTECAL is an open-label, randomised, controlled, phase II/III non-inferiority trial evaluating the safety and efficacy of 24-week regimens containing bedaquiline and pretomanid to treat rifampicin-resistant tuberculosis. Conducted in Uzbekistan, South Africa and Belarus, patients aged 15 and above with rifampicin-resistant pulmonary tuberculosis and requiring a new course of therapy were eligible for inclusion irrespective of HIV status. In the first stage, equivalent to a phase IIB trial, patients were randomly assigned one of four regimens, stratified by site. Investigational regimens include oral bedaquiline, pretomanid and linezolid. Additionally, two of the regimens also included moxifloxacin (arm 1) and clofazimine (arm 2) respectively. Treatment was administered under direct observation for 24 weeks in investigational arms and 36 to 96 weeks in the standard of care arm. The second stage of the study was equivalent to a phase III trial, investigating the safety and efficacy of the most promising regimen/s. The primary outcome was the percentage of unfavourable outcomes at 72 weeks post-randomisation. This was a composite of early treatment discontinuation, treatment failure, recurrence, lost-to-follow-up and death. The study is being conducted in accordance with ICH-GCP and full ethical approval was obtained from Médecins sans Frontières ethical review board, London School of Hygiene and Tropical Medicine ethical review board as well as ERBs and regulatory authorities at each site.
TB-PRACTECAL is an ambitious trial using adaptive design to accelerate regimen assessment and bring novel treatments that are effective and safe to patients quicker. The trial took a patient-centred approach, adapting to best practice guidelines throughout recruitment. The implementation faced significant challenges from the COVID-19 pandemic. The trial was terminated early for efficacy on the advice of the DSMB and will report on data collected up to the end of recruitment and, additionally, the planned final analysis at 72 weeks after the end of recruitment.
Clinicaltrials.gov NCT02589782. Registered on 28 October 2015.
全球每年有大约 46 万人患有利福平耐药结核病。目前推荐的方案持续 9-24 个月，疗效差且毒性大。更短、毒性更小且更有效的方案将改善耐利福平结核病患者的预后。
TB-PRACTECAL 是一项开放性标签、随机、对照、二期/三期非劣效性试验，评估贝达喹啉和普托马尼德治疗耐利福平肺结核的 24 周方案的安全性和疗效。该试验在乌兹别克斯坦、南非和白俄罗斯进行，纳入年龄在 15 岁及以上、患有耐利福平肺结核且需要新疗程治疗的患者，无论 HIV 状态如何，均符合入组条件。在第一阶段，相当于 2B 期试验，患者根据地点分层随机分配到四个方案之一。研究方案包括口服贝达喹啉、普托马尼德和利奈唑胺。此外，两个方案还分别包括莫西沙星（方案 1）和氯法齐明（方案 2）。在研究方案中，患者接受为期 24 周的直接观察治疗，在标准治疗方案中接受 36-96 周的治疗。该研究的第二阶段相当于三期试验，研究最有前途的方案/方案的安全性和疗效。主要结局为随机分组后 72 周时不良结局的百分比。这是早期治疗终止、治疗失败、复发、失访和死亡的综合结果。该研究符合 ICH-GCP 标准，伦敦卫生与热带医学院伦理审查委员会、无国界医生组织伦理审查委员会以及每个地点的伦理委员会和监管机构均已获得充分的伦理批准。
TB-PRACTECAL 是一项雄心勃勃的试验，采用适应性设计来加速方案评估，并更快地为患者带来有效且安全的新治疗方法。该试验采用以患者为中心的方法，在整个招募过程中适应最佳实践指南。该试验受到 COVID-19 大流行的严重挑战。在数据监测委员会的建议下，该试验因疗效而提前终止，将报告截止招募结束时收集的数据，此外还将报告计划在招募结束后 72 周时的最终分析数据。
Clinicaltrials.gov NCT02589782。注册于 2015 年 10 月 28 日。
