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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
372
Given for 2 months
Given for 2 months
Given for 2 months
Given for 6 months
Given for 6 months
Tapering dose of dexamethasone or prednisolone upto 8 weeks
Standard dose for 4 months after the initial treatment with high dose
2 months
7-10 months as per TB program guidelines
ICMR- National Institute for Research in Tuberculosis
Chennai, Tamil Nadu, India
Mortality rate
Between two groups
Time frame: 12 months
Disability rate
Measured by Modified Rankin scale. A score of 0 to 2 will be considered as no disability and 3-5 will be considered as disability. 0 - no symptoms ; 5 - severe disability
Time frame: 12 months
Mortality rate
Time frame: 12 months
Disability rate
Measured by Modified Rankin scale. A score of 0 to 2 will be considered as no disability and 3-5 will be considered as disability. 0 - no symptoms ; 5 - severe disability
Time frame: 24 months
Maximum Plasma Concentration [Cmax] of high dose rifampicin, isoniazid, pyrazinamide and moxifloxacin (Subset of patients)
Plasma Cmax, cerebrospinal fluid \[CSF\] Cmax, and plasma/CSF Cmax ratio
Time frame: Between week 1 & 2
Time for maximal concentration of high dose rifampicin, isoniazid, pyrazinamide and moxifloxacin (Subset of patients)
Plasma Tmax, cerebrospinal fluid \[CSF\] Tmax, and plasma/CSF Tmax ratio
Time frame: Between week 1 & 2
Area Under the Curve (AUC) of high dose rifampicin, isoniazid, pyrazinamide and moxifloxacin (Subset of patients)
Plasma Tmax, cerebrospinal fluid \[CSF\] Tmax, and plasma/CSF Tmax ratio
Time frame: Between week 1 & 2
Grade 3 & 4 adverse events
Comparison of the number of participants who develop Grade 3 or Grade 4 adverse events (according to Division of AIDS (DAIDS) criteria) during treatment. Grade 1 - mild event ; Grade 2 - moderate event; Grade 3- severe event ;Grade 4 - potentially life-threatening
Time frame: 12 months
Grade 3 & 4 adverse events
Comparison of the number of participants who develop Grade 3 or Grade 4 adverse events (according to Division of AIDS (DAIDS) criteria) during treatment. Grade 1 - mild event ; Grade 2 - moderate event; Grade 3- severe event ;Grade 4 - potentially life-threatening
Time frame: 24 months
Quality of life (QoL) in both the arms and change in QoL during the follow up
Using WHO Short form -36 (SF-36), a questionnaire to assess health related outcomes
Time frame: 6,12 & 24 months
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