Novel Triple-dose Tuberculosis Retreatment Regimen: How to Overcome Resistance Without Creating More in Niger
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 370
- 试验地点
- 1
- 主要终点
- STAGE 1:number of patients with any grade 3-5 Adverse Event (AE) during treatment, assessed as probably or definitely related to TB treatment
研究概览
简要总结
To determine if a high-dose first-line regimen is non-inferior (non-inferiority margin 10%) in terms of safety to the same regimen at regular dosing, in previously treated patients with rifampicin-susceptible recurrent Tuberculosis (TB).
详细描述
Stage 1: This is a pragmatic open-label multi-stage randomized clinical trial. Potential participants will be screened and enrolled in Damien Foundation (DF) clinics participating in the trial.
First we will perform a two-arm study with 6EHRZ as control arm and 6EH³R³Z as intervention arm. If at interim analysis the intervention arm is not considered to be non-inferior to the control arm, the intervention stops and enrolment will continue in a an adapted intervention arm and the control arm (6EHRZ). Otherwise, enrolment continues to 6EHRZ and 6EH³R³Z.
Observational study (stage 2): The DSMB members agreed due to safety concerns to continuing the study as a cohort with only the control arm. The control regimen will remain the same (6EHRZ).
As per routine practice, during treatment patients are in daily contact with the direct observed therapy (DOT) supervisor and minimally monthly clinic visits are scheduled for monitoring of safety and treatment response.
Additionally, liver function tests will be performed at fixed intervals during treatment. Six month and one year after treatment completion or cure the patient will be checked for relapse with systematic sputum acid-fast bacilli (AFB)-microscopy and TB culture.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Providers in the TB clinics and lab technicians in the Niger clinics and labs will not be blinded to the prescribed regimen. However, lab technicians working in the Institute of Tropical Medicine (ITM) lab will be blinded to the prescribed regimen. Also the statistician will be blinded to the prescribed regimen until the first interim analysis is completed.
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All newly registered patients with smear-positive recurrent pulmonary TB
- •Adults as well as children (no age limit)
- •Able and willing to provide written informed consent
- •Added for stage 2: lives within 5 km of a health facility with a medical doctor
排除标准
- •All patients with TB initially resistant to rifampicin on Xpert MTB/RIF testing
- •Patients transferred to a health facility not supported by the Damien Foundation
- •Patients previously enrolled in the trial, and with another episode of rifampicin-susceptible TB during the study period
- •Those with grade III elevation of liver function tests at baseline, or with clinically active liver disease at screening
- •Pregnant or breastfeeding woman
- •HIV co-infected patients requiring treatment with a protease inhibitor
研究组 & 干预措施
6EH³R3Z
(Rifampicin (R)/ Isoniazid (H) / Pyrazinamide (Z)/Ethambutol (E)) 6-month high-dose treatment; New high-dose isoniazid / high-dose rifampicin retreatment regimen (6EH³R3Z) - that includes triple-dose rifampicin (R3; 30 mg/kg), and triple-dose isoniazid (H3; 15 mg/kg), complemented with pyrazinamide (Z) and ethambutol (E).
干预措施: 6EH³R³Z (Drug)
6EHRZ
Standard of care: 6-month 6RHZE regimen with dose combination tablets (one tablet: 150 mg R + 75 mg H + 400 mg Z + 275mg E)
干预措施: 6EHRZ (Drug)
结局指标
主要结局
STAGE 1:number of patients with any grade 3-5 Adverse Event (AE) during treatment, assessed as probably or definitely related to TB treatment
时间窗: 18 months
STAGE 2: Describe bacterial effectiveness
时间窗: 18 months
for stage 2 participants of the trial
STAGE 2: Describe acquired resistance
时间窗: 18 months
for stage 2 participants of the trial
次要结局
- STAGE 2:number of participants with any TB treatment change due to drug-induced hepatoxicity(18 months)
- STAGE 2:number of participants with any TB treatment change due to AE(18 months)
- STAGE 2:number of participants with any grade 3-5 AE(18 months)
- STAGE 2:number of participants with any Serious Adverse Event (SAE)(18 months)
- STAGE 1:number of participants with any TB treatment change due to AE(18 months)
- STAGE 1:number of participants with any grade 3-5 AE(18 months)
- number of participants with stable (without reversion) SSM conversion(2 months)
- STAGE 1: number of previously treated patients with H-monoresistance and H-polyresistance, rifampicin (RMP) resistance missed by Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF)(18 months)
- STAGE 1: Programmatical effectiveness:number of participants with treatment success divided by number of participants with failure, death, or Lost to follow-up (LTFU)(6 months, 18 months)
- STAGE 1: Clinical effectiveness: number of participants with treatment success, divided by number of participants with failure or death(6 months, 18 months)
- STAGE 1:Bacteriological effectiveness : number of participants with treatment success, divided by number of participants with failure(6 months, 18 months)
- STAGE 2:Bacteriological effectiveness : number of participants with treatment success, divided by number of participants with failure(6 months, 18 months)
- STAGE 1:number of participants with any TB treatment change due to drug-induced hepatoxicity(18 months)
- STAGE 2: number of participants with acquired resistance, to Isoniazid (INH) and/or RMP(6 months, 18 months)
- STAGE 1: number of participants with drug-induced hepatotoxicity(18 months)
- STAGE 1:number of participants with any Serious Adverse Event (SAE)(18 months)
- STAGE 2: number of participants with drug-induced hepatotoxicity(18 months)