NIH clinical trial of tuberculous meningitis drug regimen begins

Dec. 8, 2023
Six-month multidrug regimen being evaluated against standard treatment.

A trial of a new drug regimen to treat tuberculous meningitis (TBM) has started enrolling adults and adolescents in several countries where tuberculosis (TB) is prevalent.

The Improved Management with Antimicrobial Agents Isoniazid Rifampicin Linezolid for TBM (IMAGINE-TBM) trial will compare a six-month regimen of four drugs with the nine-month, standard-of-care regimen for TBM. The study aims to generate evidence that could improve treatment for people with TBM. IMAGINE-TBM is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and implemented through the NIAID-funded Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG).

Participants in the IMAGINE-TBM trial will be given either the investigational six-month regimen or a nine-month standard regimen. The six-month regimen will consist of high doses of rifampicin (35 mg/kg for 24 weeks) and isoniazid (15 mg/kg for the first two weeks, followed by 10 mg/kg for 22 weeks), in addition to linezolid (1200 mg) and pyrazinamide (25 mg/kg) for the first eight weeks of the treatment period. This regimen will be compared with the current standard of care, which consists of rifampicin (10-15 mg/kg, up to 900 mg/day), isoniazid (5 mg/kg), ethambutol (20 mg/kg), and pyrazinamide (25 mg/kg) for eight weeks, followed by rifampicin (10-15 mg/kg, up to 900 mg/day) and isoniazid (5 mg/kg) for the remainder of the treatment period. Over the course of the 48-week study period, the outcomes of the trial participants will be measured by assessing their clinical status, including their neurologic and functional abilities.

The trial will include 330 participants aged 15 years and older who have or are likely to have TBM based on signs and symptoms, including people living with and without HIV. Because pregnant women are eligible to enroll in this study with appropriate consent, a small number of pregnant women are expected to be included.

NIH release