2R2: Higher Dose Rifampin for 2 Months vs Standard Dose Rifampin for Latent TB: a 3-arm Randomized Trial.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,368
- 试验地点
- 10
- 主要终点
- Treatment completion (taking 80% of doses within 120% of allowed time)
研究概览
简要总结
Rationale:
Shorter regimens of high dose daily rifampin may be safe, and as effective as the standard rifampin regimen when taken for 4 months to treat latent TB (LTBI). However, there is insufficient evidence on the optimal dose of rifampin that has similar efficacy as the standard 4-month rifampin regimen without jeopardizing safety or affecting completion rates.
Objectives:
The general purpose of this study is to determine if rifampin at double or triple the standard dose for 2 months is as safe and effective as the standard dose of rifampin when taken for 4 months to treat latent tuberculosis (TB).
Treatment:
Persons who need treatment for latent TB, will be given rifampin, either at the standard dose (10mg/kg/day) for 4 months (control arm); or at double dose (20mg/kg/day) for 2 months (intervention arm 1); or at triple dose (30mg/kg/day) for 2 months (intervention arm 2).
Design:
This is 1:1:1 randomized, phase 2b, partially blind, controlled trial. The two higher doses (intervention arms) will be administered double-blind: participants and providers will be aware of the duration of their regimen, but they will both remain blinded to the specific dose (i.e. 20 or 30 mg/kg/day) for those randomized to 2-months regimens. All members of the same household of a patient with newly diagnosed active pulmonary TB will be randomized together (i.e. cluster randomized).
Population and setting:
Adults and children aged 10 years and above, who have latent TB infection and are recommended by their doctor to take treatment for latent TB can participate in the study.
The planned number of persons with latent TB to recruit is about 1359 in total (or about 453 for each of the three arms).
The study will take place in 6 sites: four in Canada (Calgary, Edmonton, Montreal and Vancouver), one in Indonesia (Bandung) and one in Viet Nam (1 clinic in Ho Chi Min City and 3 clinics in Ha Noi).
Outcomes:
Primary outcomes are: 1) Treatment completion and 2) Safety (i.e. grade 3-5 adverse events).
Secondary outcomes are: 1) Safety (i.e. grade 1-2 adverse events) and 2) Efficacy (i.e. rates of active TB in the 26 months post-randomization). More information on how outcomes are defined is provided in the detailed description below.
详细描述
Additional information extracted from study protocol is provided below:
Study duration:
The study started in September 2019. Enrollment has started in all study sites and is planned to last until end of 2022. At each site, study will last until 26 months after the last randomization in that site.
Study procedures:
The treatment should be given at the time of randomization; participants will be followed for the duration of treatment (i.e. 2-4 months), and for 2 years after treatments is finished.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
This is a partially double-blinded trial. Participation in control arm will be open label while participation in the two intervention arms will be double-blinded.
入排标准
- 年龄范围
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults, and children aged 10 and older who weigh at least 25kg.
- •Evidence of latent TB infection: positive tuberculin skin test (5mm or greater or 10mm or greater, based on National guidelines) or positive interferon gamma release assay.
- •Eligible to take latent TB treatment according to Canadian guidelines in the Canadian sites, and according to World Health Organization (WHO) guidelines in the international sites (this includes household contacts, other contacts, HIV infected, other causes of immune suppression, fibronodular disease on chest-x ray (CXR), or other indication).
排除标准
- •Children aged 0-9 and children aged 10 or older who weigh less than 25kg
- •Pregnancy
- •Baseline AST or ALT that is at least 3 times higher than upper limit of normal
- •Baseline Grade 3-4 abnormalities of hematological tests (WBC, platelets or hemoglobin).
- •Prior treatment for latent or active TB.
- •Rifampin contra-indicated - due to potential drug interactions that are considered too important, or difficult to manage, by health care provider; or due to history of allergy/ hypersensitivity to rifampin, rifabutin or rifapentine.
- •Household contacts of index TB patients with confirmed, or suspected rifampin resistant TB.
研究组 & 干预措施
Intervention Arm 2
Two months of daily self-administered rifampin at 30 mg/Kg (maximum 1800 mg/day).
干预措施: Rifampin triple dose (Drug)
Intervention Arm 1
Two months of daily self-administered rifampin at 20 mg/kg (maximum 1200 mg/day).
干预措施: Rifampin double dose (Drug)
Control Arm
Four months of daily self-administered rifampin at a dose of 10mg per kg per day (maximum 600mg per day).
干预措施: Rifampin standard dose (Drug)
结局指标
主要结局
Treatment completion (taking 80% of doses within 120% of allowed time)
时间窗: 2 months from randomization for participants in the two intervention arms and 4 months for the control arm.
Completion will be defined as taking 80% of doses within 120% of allowed time (48 doses within 72 days for the two-month regimens, and 96 doses within 144 days for the 4-month regimen).
Safety measured by Grade 3 to 5 adverse events
时间窗: 2 months plus 2 weeks in the intervention arms; 4 months plus 2 weeks in the control arm.
Grade 3 to 5 adverse events (and Grade 1-2 rash) which result in permanent discontinuation of the study drug, and that are considered probably or possibly related to the study drug by the majority of a three-member independent and blinded Adverse Events panel.
次要结局
- Safety measured by Grade 1 to 2 adverse events(2 months plus 2 weeks in the intervention arms; 4 months plus 2 weeks in the control arm.)
- Efficacy measured during follow-up visits and telephone calls(26 months from randomization in all arms.)
研究者
Dick Menzies
Senior Investigator at Research Institute of McGill University Health Center
McGill University Health Centre/Research Institute of the McGill University Health Centre