NCT04145258

Intensified Tuberculosis Treatment to Reduce the Mortality of Patients With Tuberculous Meningitis

Intensified Tuberculosis Treatment to Reduce the Mortality of HIV-infected and Uninfected Patients With Tuberculosis Meningitis: a Phase III Randomized Controlled Trial (Acronym: INTENSE-TBM)

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 768 (estimated)
• Sponsor: ANRS, Emerging Infectious Diseases · Other Government
• Sex: All
• Age: 15 Years
• Healthy volunteers: Not accepted

Summary

INTENSE-TBM is randomized controlled, phase III, multicenter, 2 x 2 factorial plan superiority trial assessing the efficacity of two interventions to reduce mortality from tuberculous meningitis (TBM) in adolescents and adults with or without HIV-infection in sub-Saharan Africa: * Intensified TBM treatment with high-dose rifampicin and linezolid, compared to WHO standard TBM treatment. * Aspirin, compared to not receiving aspirin. The trial will be open-label for anti-TB treatment and placebo-controlled for aspirin treatment.

Detailed description

Settings: Côte d'Ivoire, Madagascar, Uganda, South Africa. Follow-up: Participants will be followed up for 40 weeks. Sample size: 768 patients (192 in each arm). Primary analysis: We will use a Cox proportional hazard ratio model to compare intensified TB treatment with WHO standard TB treatment, and aspirin with placebo, adjusting for the initial stratification variables (trial country, HIV status, British Medical Research Council \|BMRC\] severity grade). The primary analysis will be conducted in the intention to treat population. Sub-studies: * The PK-PD sub-study will take place in the 4 participating countries, and involve 40 participants in total. * The Multi-Omics sub-study will only take place in South-Africa. It will involve 160 participants in this country. Participants in each sub-study will sign a specific informed consent.

Conditions

• Tuberculous Meningitis

Interventions

Type	Name	Description
DRUG	Aspirin	Two tablets of aspirin 100 mg per day from inclusion (D-0) to end of Week-8 (W-8)
DRUG	Placebo of aspirin	Two placebo tablets with the same appearance of aspirin 100 mg per day from inclusion (D-0) to end of Week-8 (W-8)
DRUG	WHO TBM treatment	2 months of (R-H-Z-E) + 7 months of (R-H)
DRUG	Intensified TBM treatment	2 months of (HDR-L-H-Z-E) + 7 months of (R-H), with HDR=high-dose rifampicin and L=linezolid

Timeline

• Start date: 2021-02-07
• Primary completion: 2025-09-01
• Completion: 2026-04-01
• First posted: 2019-10-30
• Last updated: 2024-01-22

Locations

13 sites across 4 countries: Côte d’Ivoire, Madagascar, South Africa, Uganda