PROJECT

Comparative evaluation of intensified short course regimen and standard regimen for adults TB meningitis : an open label randomized controlled trial (INSHORT trial)

August 2024 - September 2028

Objectives:

To compare the intensified short-course ATT with standard ATT regimen in reducing composite outcome (mortality and disability) and compare pharmacokinetic parameters between the two groups

Study Overview:

Patients with brain TB have higher mortality and multiple complications, even with adequate treatment. There is a need for a stronger regimen that reduces death. We aim to test a newer, shorter, and intensified regimen to see if this can significantly reduce death and disability among these patients. About 370 participants from six hospitals in India will be randomly assigned to one of three groups. Two groups will receive a shorter, stronger treatment that includes higher doses of some medicines, while the third group will receive the standard treatment. Participants will be followed for up to 2 years to assess treatment effectiveness and monitor safety.

Study Approach:

The trial is an open-label randomised controlled trial with a sample size of 372 being conducted across 6 sites in India. Eligible participants are randomly allocated in 1:1:1 ratio into either one of the two intervention arms or the control arm. Participants in the intervention arms receive high-dose rifampicin (25mg/kg), moxifloxacin with or without aspirin, and HZ during the intensive phase, followed by 4HRZ in the continuation phase. A modified intention-to-treat analysis and a Per Protocol (PP) analysis will be conducted at 12 and 24 months after treatment initiation.

Expected Public Health Impact:

The INSHORT trial holds immense translational potential as the largest multi-centric clinical trial ever conducted in India among patients with TB meningitis. Given the current TBM regimen’s several drawbacks, if the study regimen proves beneficial, it will have policy implications for both national and global TBM treatment Full protocol of the trial can be accessed here : https://shorturl.at/UjBZr