CLINICAL TRIAL

FULL TITLE OF TRIAL AND ACRONYM

Intensified tuberculosis treatment with or without aspirin to reduce the mortality of tuberculous meningitis in HIV infected and uninfected patients: a phase III randomized controlled trial (INTENSE-TBM)

Clinicaltrials.gov identifier: NCT04145258

DESIGN

INTENSE-TBM is a randomized controlled, phase III, multicenter, 2 x 2 factorial plan superiority trial

SETTINGS

IVORY COAST . MADAGASCAR . SOUTH AFRICA . UGANDA

TRIAL HYPOTHESIS

The trial hypothesis is that intensifying TBM treatment and using aspirin during the first 8 weeks of TBM treatment will independently reduce mortality at month 9 (week 40).

PRIMARY OBJECTIVE

To assess the efficacy of two interventions to reduce mortality from TBM in adolescents and adults with or without HIV-infection in sub-Saharan Africa at month 9:

Intensified TBM treatment, compared to WHO standard TBM treatment
Aspirin, compared to not receiving aspirin (placebo)

TRIAL TREATMENTS

Participants will be randomized into 4 arms:

Arm 1: WHO standard TBM treatment + placebo
Arm 2: WHO standard TBM treatment + aspirin
Arm 3: Intensified TBM treatment + placebo
Arm 4: Intensified TBM treatment + aspirin

Standard WHO TBM treatment (arm 1 and 2):

Inclusion to end of month 2: rifampicin + isoniazid + ethambutol + pyrazinamide
Month 3 to month 9: rifampicin + isoniazid

Intensified TBM treatment (arm 3 and 4):

Inclusion to end of month 2: high dose rifampicin + high dose linezolid + isoniazid + ethambutol + pyrazinamide
Month 3 to month 9: rifampicin + isoniazid

Aspirin (arms 2 and 4):

Inclusion to end of month 2: aspirin

Placebo (arms 1 and 3):

Inclusion to end of month 2: placebo

INCLUSION CRITERIA

Age ≥ 15 years
TBM defined as “definite”, “probable” or “possible”, using the Tuberculosis Meningitis International Research Consortium criteria
Informed consent signed by the patient or by a relative

STUDY DURATION

Participants will be followed up for 9 months (exactly 40 weeks)