A Randomized Double Blind Placebo Controlled Trial of Rifapentine and Isoniazid for Prevention of Tuberculosis in People With Diabetes
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 3,000
- 试验地点
- 4
- 主要终点
- First diagnosis of TB
研究概览
简要总结
Diabetes mellitus (DM) increases susceptibility to Tuberculosis (TB) and worsens TB patient outcomes. The number of patients with combined TB and DM now outnumbers that of combined TB and HIV and it has been estimated that 15-30% of TB disease may be attributable to diabetes globally. This may be expected to rise substantially as DM prevalence increases. Treatment of Latent TB Infection (LTBI) in this population will likely have a significant clinical benefit. Similar to HIV-infected individuals, those with DM might benefit from therapy to prevent the development of TB disease. Current international guidelines do not recommend LTBI management in people with DM, but this is because no studies have examined the risk-benefit ratio of such an intervention. To date, no RCTs have been conducted to investigate the efficacy and safety of preventive treatment of LTBI in DM patients. Based on evidence on effectiveness, safety, and treatment completion rates, 3HP has been selected as the regimen of choice for this study of African people living with DM. People living with DM will be randomized to 3HP or placebo to determine the efficacy of 3HP in the prevention of TB disease in this population. PROTID's preventive treatment of LTBI among people with DM will generate the first solid evidence to support or refute the use of preventive treatment against TB in people with DM.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Enrolled in diabetes care with a history of DM and current use of anti-diabetic medication ('known DM'); OR in the absence of anti-diabetic medication an HbA1c of =6.5% (48 mmol/mol) or a fasting venous plasma glucose of =7.0 mmol (126 mg/dl). For those with no previously known DM a repeat test above the diagnostic cut-point is required to confirm the diagnosis ('new DM')
- •Adult (18 years or older)
- •Diagnosed with LTBI, defined as a positive IGRA test or TST reactivity =10 mm
- •Voluntarily signed Informed Consent Form
- •If sexually active, willing to use an effective contraceptive method for the duration of preventive therapy.
排除标准
- •Weight <45 kg
- •Previous TB disease, defined as either bacteriologically confirmed or clinically diagnosed and treated
- •Treatment with a rifamycin medication or isoniazid in the previous 2 years.
- •Diagnosis of probable or definite TB during screening
- •Confirmed HIV-infection or receiving antiretroviral treatment
- •Liver dysfunction, defined as serum aspartate aminotransferase (AST) level 5 times the upper limit of normal
- •Pregnant or planning to become pregnant in the next 3 months, or lactating
- •Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation
- •Other conditions inapplicable for participation in this study, such as likely to fail to adhere to study commitment or to complete the whole study, at the discretion of the site investigator
研究组 & 干预措施
Isoniazid and Rifapentine (INH-RPT)
Participants in intervention arm will receive an oral combination of rifapentine (RPT, 900 mg) and isoniazid (INH, 900 mg), once-weekly for 12 weeks.
干预措施: Isoniazid and Rifapentine (INH-RPT) (Drug)
Control
Participants in the control arm will receive placebo once weekly for 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
First diagnosis of TB
时间窗: Through study completion, median of 33 months follow-up
The primary outcome will compare the rate of occurrence of TB disease (defined as definite or probable TB) in treatment and control groups. Definite TB disease will be confirmed by a culture or Xpert positive result for M. tuberculosis. Probable TB will be diagnosed according to an algorithm that takes into account symptoms, chest x-ray reading, sputum smear, histology and verbal autopsy results.
次要结局
- Occurrence of possible, probable or definite TB disease(At least 24 months post randomisation)
- Occurrence of an adverse event(From randomisation to 60 days after end of study treatment)
- Treatment completion(Defined as > 11 of 12 doses of treatment over no more than 16 weeks.)
- All-cause mortality(At least 24 months post randomisation)
- Occurrence of possible, probable, or definite TB, or death(At least 24 months post randomisation)
研究者
Dr. Nyanda Elias Ntinginya
Director, NIMR - Mbeya Medical Research Centre
National Institute for Medical Research, Tanzania