Comparison of 3-month Once-weekly Isoniazid Plus Rifapentine, 4-month Daily Rifampicin, and 3-month Daily Isoniazid Plus Rifampicin for the Treatment Latent Tuberculosis in Patients With End-stage Kidney Disease: A Randomised Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 225
- 主要终点
- Treatment completion
研究概览
简要总结
Objective To determine if treatment completion with a 4-month rifampin (4R) or 3-month rifapentine (P) + isoniazid (H) weekly for 12 weeks (3HP) regimens is better than with a 3-month (3HR) regimen for treatment of latent tuberculosis (TB) infection (LTBI) in patients with end stage kidney disease.
Methods Design: Multicenter, prospective, parallel-group, open-label, controlled clinical trial.
Study population: All adult patients with ESKD in who treatment for LTBI is prescribed at 7 hospitals.
Interventions: Patients who accept participation, will be randomly assigned to one of the 3 arms: 3HR (control) (90 doses), 4R (120 doses) or 3HP (12 doses).
Outcome: Proportion of participants who discontinue permanently the assigned treatment. Follow-up: Periodic assessment for permanent or temporary discontinuation, and adverse events of the assigned treatment.
Sample size: 225 subjects (75 per arm) will be needed to demonstrate, if exists, a 0.16 decrease in permanent discontinuation rates in the experimental arms (4R and 3HP) with respect to the control arm (3HR), with α= 0.025, β= 0.20, and 5% expected losses, and assuming a 0.25 proportion of permanent discontinuation in the control.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older
- •Stage 5 kidney disease (glomerular filtrate rate <15 mL/minute or under substitutive renal therapy
- •Informed written consent
排除标准
- •Prior allergy/intolerance to rifamycins or isoniazid
- •Pregnancy or breastfeeding
- •Pre-treatment transaminases (ALT and/or AST) >5-fold of normality titer
- •Concomitant drugs contraindicated with rifamycins
- •Having received rifamycins or isoniazid within the two previous weeks
- •Weigh <32 Kgs
- •Inability to understand the nature of the study or to give written consent
研究组 & 干预措施
3-month Isoniazid plus Rifampicin
Daily isoniazid 300 mg plus rifampicin 600 mg for three months
干预措施: Rifampicin plus Isoniazid (Drug)
3-month Isoniazid plus Rifapentine
Weekly isoniazid 900 mg plus rifapentine 900 mg for 12 weeks
干预措施: Rifapentine plus Isoniazid (Drug)
4-month Rifampicin
Daily rifampicin 600 mg for four months
干预措施: Rifampicin alone (Drug)
结局指标
主要结局
Treatment completion
时间窗: From date of randomization until the date of completion of the assigned treatment, or date of lost to follow-up, or date of death, whichever came first, assessed up to 16 weeks for the 3HR arm, 14 weeks for the 3HP arm, and 20 weeks for the 4R arm.
Proportion of participants who complete the treatment assigned at randomization, defined as: 1) 90 doses within a maximum of 16 weeks, without interruptions longer than 2 weeks, and no more than in 2 occasions, for 3HR (control arm); 2) 12 doses within a maximum of 14 weeks, without interruptions longer than 10 days, for 3HP (experimental arm 1), and 3) 120 doses within a maximum of 20 weeks, without interruptions longer than 2 weeks, and no more than in two occasions, for 4R (experimental arm 2).
次要结局
- Permanent discontinuation because of adverse events(From date of randomization until the date of completion of the assigned treatment, or date of lost to follow-up, or date of death, whichever came first, assessed up to 16 weeks for the 3HR arm, 14 weeks for the 3HP arm, and 20 weeks for the 4R arm.)
- Death(From date of randomization until four weeks after completing the assigned treatment, or lost to follow-up, assessed up to 17 weeks for the 3HR arm, 15 weeks for the 3HP arm, and 21 weeks for the 4R arm.)
- Permanent discontinuation because of adverse events related to the treatment(From date of randomization until the date of completion of the assigned treatment, or date of lost to follow-up, or date of death, whichever came first, assessed up to 16 weeks for the 3HR arm, 14 weeks for the 3HP arm, and 20 weeks for the 4R arm.)
研究者
Miguel Santín
Senior consultant in infectious diseases
Hospital Universitari de Bellvitge