Comparative Evaluation of Intensified Short Course Regimen and Standard Regimen for Adults TB Meningitis : an Open-label Randomized Controlled Trial

Indian Council of Medical Research1 个研究点分布在 1 个国家目标入组 372 人开始时间: 2024年3月最近更新: 2023年12月21日

适应症

干预措施

试验速览

阶段: 3 期
状态: 尚未招募
发起方: Indian Council of Medical Research
入组人数: 372
试验地点: 1
主要终点: Mortality rate

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Tuberculous meningitis (TBM) is the most lethal form of extra pulmonary tuberculosis. This devastating disease kills almost a third of its sufferers and disables a significant proportion of the survivors. TBM poses one of the most difficult diagnostic and therapeutic challenges in modern clinical practice. High-quality robust clinical trials have made a considerable contribution to the treatment of pulmonary tuberculosis in the last four decades. However, evidence from such clinical trials is lacking in TBM and the treatment remains uncertain. There is a significant variation in the choice, dose and duration of drugs between countries, institutions and clinicians. Investigators propose a multi-centric open-label clinical trial to assess the efficacy of short-course anti-TB drugs with high dose rifampicin, and moxifloxacin along with conventional anti-TB drugs and adjuvant therapy with aspirin and corticosteroids. Controls will receive standard treatment as per national guidelines for TBM. The investigators also aim to assess the safety and tolerability of high-dose Rifampicin and Moxifloxacin and the Pharmacodynamics and Pharmacokinetics parameters of ATT (Rifampicin, INH, Moxifloxacin and Pyrazinamide) in CSF between the two groups

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

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

•A patient will be eligible for entry to the trial if ALL of the following conditions are satisfied
•Adults (> 18 years) with or without HIV infection
•Possible, probable or definite TBM according to Lancet consensus diagnostic criteria
•Willing to give written informed consent
•Is willing to have an HIV test.
•Residing within 100 km of the study sites
•Express willingness to attend the treatment centre for supervised treatment
•Express willingness to adhere to the trial procedures and follow-up schedule.
•Agrees to use effective barrier contraception during the period of the treatment in case of female participants

排除标准

•Patients will not be eligible for the trial if they meet ANY of the following criteria
•Known current/previous drug resistance to ATT (Rifampicin, INH, FQ)**
•Concurrent or known diagnosis any other meningitis such as bacterial, viral, and fungal.
•Currently having an uncontrolled cardiac arrhythmia or ECG abnormalities which are contradiction for the administration of moxifloxacin including prolonged QTc. QTc value define as >450 ms in males and >460 ms in females measured in lead II or V5 on a standard 12-lead ECG.
•Has clinical icterus or hepatic impairment characterized by serum bilirubin level above the normal laboratory reference range with abnormal liver enzymes, or isolated alanine aminotransferase (ALT) and/ or aspartate aminotransferase (AST) levels above 5 times the upper limit of the normal laboratory reference range
•Previous history of anti-TB treatment, If any, should not exceed one month in the past and not more than 7 days in the preceding one month.
•pregnant or lactating women
•rapid clinical deterioration or very sick and moribund during the screening process, renal failure, liver disease or any condition (social or medical) that in the opinion of the investigator would make trial participation unreliable or unsafe.
•Has a known allergy to any of the drugs proposed to be used in the trial regimen
•All participants with Rifampicin resistance will be excluded at baseline from the study. Participants with H, FQ and Z resistance identified from MGIT results done at baseline will be referred back to NTEP for appropriate management and their numbers will be compensated.