Clinical trial NCT05917340: Intensified Short Course Regimen for TBM in Adults
Official title: Comparative Evaluation of Intensified Short Course Regimen and Standard Regimen for Adults TB Meningitis : an Open-label Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Tuberculous Meningitis
Lead sponsor: Indian Council of Medical Research
Sponsor class: OTHER_GOV
Collaborators: name: All India Institute of Medical Sciences, Jodhpur
name: Christian Medical College, Vellore, India
name: Jawaharlal Institute of Postgraduate Medical Education & Research
name: North Eastern Indira Gandhi Regional Institute of Health ans Medical Sciences
name: Madras Medical College
name: Rural Development Trust Hospital
First posted: 2023-06-23
Enrollment: 372
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: Inclusion Criteria:

A patient will be eligible for entry to the trial if ALL of the following conditions are satisfied

1. Adults (\> 18 years) with or without HIV infection
2. Possible, probable or definite TBM according to Lancet consensus diagnostic criteria
3. Willing to give written informed consent
4. Is willing to have an HIV test.
5. Residing within 100 km of the study sites
6. Express willingness to attend the treatment centre for supervised treatment
7. Express willingness to adhere to the trial procedures and follow-up schedule.
8. Agrees to use effective barrier contraception during the period of the treatment in case of female participants

Exclusion Criteria:

Patients will not be eligible for the trial if they meet ANY of the following criteria

1. Known current/previous drug resistance to ATT (Rifampicin, INH, FQ)\*\*
2. Concurrent or known diagnosis any other meningitis such as bacterial, viral, and fungal.
3. 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.
4. 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
5. 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.
6. pregnant or lactating women
7. 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.
8. 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.

Primary outcomes:
measure: Mortality rate
timeFrame: 12 months
measure: Disability rate
timeFrame: 12 months
measure: Mortality rate
timeFrame: 12 months
measure: Disability rate
timeFrame: 24 months
Secondary outcomes:
measure: Maximum Plasma Concentration [Cmax] of high dose rifampicin, isoniazid, pyrazinamide and moxifloxacin (Subset of patients)
timeFrame: Between week 1 & 2
measure: Time for maximal concentration of high dose rifampicin, isoniazid, pyrazinamide and moxifloxacin (Subset of patients)
timeFrame: Between week 1 & 2
measure: Area Under the Curve (AUC) of high dose rifampicin, isoniazid, pyrazinamide and moxifloxacin (Subset of patients)
timeFrame: Between week 1 & 2
measure: Grade 3 & 4 adverse events
timeFrame: 12 months
measure: Grade 3 & 4 adverse events
timeFrame: 24 months
measure: Quality of life (QoL) in both the arms and change in QoL during the follow up
timeFrame: 6,12 & 24 months
Other outcomes:
Locations:
city: Chennai
country: India
facility: ICMR- National Institute for Research in Tuberculosis
state: Tamil Nadu
Study officials:
References: