Shortening TB Treatment With Optimised Rifampicin-Based Therapy and Disease Stratification: A Pragmatic Phase 3 Double-Blind Placebo-Controlled Randomised Trial (RIFAstrat)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 1,000
- 主要终点
- Proportion of participants with an unfavourable efficacy outcome (treatment failure, recurrence or re-treatment for poor treatment response) through week 48 in the intention to treat population.
研究概览
简要总结
RIFAstrat is a Phase 3, double-blind, placebo-controlled, non-inferiority trial to compare the 6-month standard treatment for DS-TB with a 4-month optimised- rifampicin based regimen provided to individuals with limited disease severity.
详细描述
RIFAstrat is a Phase 3, double-blind, placebo-controlled, non-inferiority trial to compare the 6-month standard treatment for DS-TB with a 4-month optimised-rifampicin based regimen provided to individuals with limited disease severity.
Participants are eligible for the study if they are ≥12 years old with newly diagnosed rifampicin-susceptible pulmonary TB confirmed by rapid molecular testing (Xpert MTB/RIF or ultra) with a limited disease phenotype, defined as a cycle threshold on sputum Xpert MTB/RIF or Ultra corresponding to 'medium' or below for bacterial burden at screening. Broad eligibility criteria allow for enrolment of people living with HIV, diabetes, other common comorbidities.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 12 years and over
- •Clinical and/or radiological evidence of pulmonary TB
- •At least one sputum specimen positive for M. tuberculosis by Xpert MTB/RIF or Ultra within 30 days of screening confirming rifampicin-sensitive TB
- •Have limited TB disease defined as having a cycle threshold on sputum Xpert MTB/RIF or Ultra corresponding to 'medium' or below for bacterial burden at screening (where results from more than one test are available at screening, eligibility will be determined by the highest grade)
- •Documentation of HIV status from a validated test performed within 30 days of screening or known to be HIV-positive
- •Well enough to be treated as an outpatient
排除标准
- •Received more than 7 days treatment for index TB episode
- •Previous treatment for active TB disease in past 12 months
- •M. tuberculosis with known resistance to rifampicin or isoniazid
- •Weight < 30 kg at screening
- •Sick with one or more WHO 'danger signs' at screening (respiratory rate > 30 breaths per minute, temperature > 39 ˚C, heart rate > 120 bpm, inability to walk unaided)
- •Suspected or confirmed extra-pulmonary TB involving the central nervous system, bones, joints, abdomen, and/or pericardium (coexistent pleural or lymph node TB are not exclusions)
- •For participants living with HIV:
- •Urinary lipoarabinomannan test positive at screening
- •Requires protease inhibitor-based antiretroviral therapy, and/or long acting antiretrovirals cabotegravir/rilpivirine
- •For participants of child-bearing potential: currently pregnant or not currently pregnant but unwilling to practice an effective method of contraception during study drug treatment
- •Clinical evidence of acute hepatitis or advanced chronic liver disease (e.g. jaundice, signs of portal hypertension)
- •Known end stage renal failure
- •Active malignancy not in remission or had systemic chemotherapy within 2 years (except for non-melanomatous skin cancer)
- •Contraindication to study medications because of known allergy or intolerance or unavoidable drug-drug interaction
- •Other medical conditions, that, in the investigator's judgment, make study participation not in the individual's best interest
- •Inability to attend follow up visits
研究组 & 干预措施
16-Week Regimen (Standard of Care Treatment + 600 mg of Rifampicin daily)
Optimised regimen consisting of rifampicin at 20 mg/kg and isoniazid for 4 months (16 weeks), plus pyrazinamide and ethambutol for the first 2 months (2R20HZE/2R20H). Delivered as local standard of care (RHZE) plus 600mg (2 additional tablets) of rifampicin.
干预措施: Extra 600mg of Rifampicin (Drug)
24-Week Regimen (Standard of Care Treatment) + Placebo for 16 weeks
The standard treatment regimen for DS-TB (rifampicin at 10 mg/kg and isoniazid for 6 months, plus pyrazinamide and ethambutol for the first 2 months; 2RHZE/4RH), with additional placebo for the first 4 months (16 weeks).
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of participants with an unfavourable efficacy outcome (treatment failure, recurrence or re-treatment for poor treatment response) through week 48 in the intention to treat population.
时间窗: From enrollment through to Week 48.
次要结局
- Death(72 weeks)
- Treatment-emergent adverse events(14 days after end of randomised treatment)
- Proportion of participants experiencing symptoms of interest during assigned treatment (tolerability)(14 days after end of randomised treatment)
- Proportion of participants temporarily discontinuing assigned treatment (tolerability)(14 days after end of randomised treatement)
- Proportion of participants permanently discontinuing assigned treatment (tolerability)(14 days after end of randomised treatment)
- Percentage of treatment doses taken (adherence)(48 weeks)
- Total Time on Treatment(72 weeks)
- Proportion of participants with acquired (post-baseline) drug resistance(72 weeks)
- Scores on 5-level EQ-5D questionnaire(72 weeks)
- Catastrophic costs and cost-effectiveness ratios, calculated using the adapted WHO patient costs survey(72 weeks)
- Respiratory disability measured by Medical Research Council (MRC) Dyspnea scale(72 weeks)