Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, South Korea.
Trials. 2022 Aug 17;23(1):666. doi: 10.1186/s13063-022-06631-z.
The standard treatment regimen for drug-sensitive tuberculosis (TB), comprising four companion drugs, requires a minimum duration of 6 months, and this lengthy treatment leads to poor adherence and increased toxicity. To improve rates of adherence, reduce adverse events, and lower costs, a simplified and shortened treatment regimen is warranted.
This study is a multicenter, open-label randomized clinical trial of non-inferiority design that compares a new regimen with the conventional regimen for drug-sensitive pulmonary TB. The investigational group will use a regimen of high-dose rifampicin (30 mg/kg/day) with isoniazid and pyrazinamide, and the treatment will be maintained for 12 weeks after the achievement of negative conversion of sputum culture. The control group will be treated for 6 months with a World Health Organization-endorsed regimen consisting of isoniazid, rifampicin (10 mg/kg/day), ethambutol, and pyrazinamide. The primary endpoint is the proportion of unfavorable outcomes at 18 months after randomization. Secondary outcomes include time to unfavorable treatment outcome, time to culture conversion on liquid medium, treatment success rate at the end of treatment, proportion of recurrence at 18 months after randomization, time to recurrence after treatment completion, and adverse events of grade 3 or higher during the treatment. We predict a 10% unfavorable outcome for the control group, and 0% difference from the investigational group. Based on 80% verification power and a 2.5% one-sided significance level for a non-inferiority margin of 6%, 393 participants per group are required. Considering the 15% dropout rate, a total of 926 participants (463 in each group) will be recruited.
This study will inform on the feasibility of the treatment regimen using high-dose rifampicin with a shortened and individualized treatment duration for pulmonary TB.
ClinicalTrials.gov NCT04485156 . Registered on July 24, 2020.
标准的药敏结核病（TB）治疗方案包括四种联合用药，需要至少 6 个月的疗程，这种漫长的治疗导致患者的依从性差，毒性增加。为了提高依从性、减少不良事件和降低成本，需要简化和缩短治疗方案。
这是一项多中心、开放标签、非劣效性设计的随机临床试验，比较了新方案和传统方案治疗药敏性肺结核的效果。实验组将使用高剂量利福平（30mg/kg/天）联合异烟肼和吡嗪酰胺，痰培养转阴后治疗持续 12 周。对照组将按照世界卫生组织推荐的方案治疗 6 个月，方案包括异烟肼、利福平（10mg/kg/天）、乙胺丁醇和吡嗪酰胺。主要终点是随机分组后 18 个月不良结局的比例。次要结局包括不良治疗结局的时间、液体培养基培养转换时间、治疗结束时的治疗成功率、随机分组后 18 个月的复发比例、治疗完成后复发的时间、以及治疗期间 3 级或以上的不良事件。我们预测对照组的不良结局为 10%，实验组与对照组的差异为 0%。基于 80%的验证效能和 2.5%的单侧显著性水平，非劣效性边界为 6%，每组需要 393 名参与者。考虑到 15%的脱落率，共需要招募 926 名参与者（每组 463 名）。
本研究将为使用高剂量利福平治疗肺结核并缩短个体化治疗时间的方案可行性提供信息。
ClinicalTrials.gov NCT04485156。于 2020 年 7 月 24 日注册。
