Damien Foundation, Niamey, Niamey, Niger.
National Hospital of Niamey, Niamey, Niger.
Int J Infect Dis. 2023 Aug;133:78-81. doi: 10.1016/j.ijid.2023.05.002. Epub 2023 May 5.
High-dose rifampicin (R) and isoniazid (H) are known to be safe but were not yet combined in a single regimen. The primary objective of the TRIple-DOse RE-treatment (TRIDORE) study is to determine whether a 6-month firstline regimen with triple dose of both R and H (intervention arm; 6RHZE) is non-inferior in terms of safety compared to a normal-dose regimen (6RHZE) in previously treated patients with R-susceptible (Rs) recurrent tuberculosis (TB).
DESIGN/METHODS: TRIDORE is an ongoing pragmatic open-label multi-stage randomized clinical trial.
Between March 2021 and February 2022, 127 consenting patients were randomly assigned to either the intervention or control arm: 62 and 65 were treated with 6RHZE and 6RHZE, respectively. Of 127, 111 (87.4%) were male and the median age (interquartile range) was 37 (30-48) years. The median body mass index at enrollment was 18.1 (16.3-19.7) kg/m. Drugrelated severe adverse events (AEs) (grade III-V) were significantly more frequent when 6RHZE was used (5/62 vs 0/65, P = 0.03, difference weighted for site 8% [95% confidence interval: 1.0,14.3]). The Data and Safety Monitoring Board recommended publishing our interim safety data analysis.
We show that the combination of triple-dose R with triple-dose H in a re-treatment regimen for patients with Rs-TB causes excess drug-related AEs.
高剂量利福平（R）和异烟肼（H）已被证实安全，但尚未联合用于单一方案。TRIDORE 研究的主要目的是确定在先前接受过敏感型利福平（Rs）复发性结核病（TB）治疗的患者中，使用两种药物的三联剂量（干预组；6RHZE）的 6 个月一线方案在安全性方面是否不劣于常规剂量方案（6RHZE）。
设计/方法：TRIDORE 是一项正在进行的实用开放性多阶段随机临床试验。
在 2021 年 3 月至 2022 年 2 月期间，有 127 名同意参与的患者被随机分配至干预组或对照组：分别有 62 名和 65 名患者接受 6RHZE 和 6RHZE 治疗。在 127 名患者中，111 名（87.4%）为男性，中位年龄（四分位间距）为 37（30-48）岁。入组时的中位体质指数（BMI）为 18.1（16.3-19.7）kg/m。使用 6RHZE 时，药物相关严重不良事件（AE）（3-5 级）明显更为常见（5/62 比 0/65，P=0.03，按站点加权差异为 8%[95%置信区间：1.0，14.3]）。数据和安全监测委员会建议公布我们的临时安全性数据分析。
我们表明，在 Rs-TB 患者的再治疗方案中，将 R 与 H 的三联剂量联合使用会导致药物相关不良事件增加。
