A new drug regimen trial targeting tuberculous meningitis (TBM) has commenced enrollment in multiple tuberculosis (TB)-prevalent countries. The Improved Management with Antimicrobial Agents Isoniazid Rifampicin Linezolid for TBM (IMAGINE-TBM) trial, spearheaded by the National Institute of Allergy and Infectious Diseases (NIAID) and executed through the NIAID-funded Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG), aims to revolutionize treatment methodologies for TBM.
TBM, accountable for a fatality rate of 25-50% in affected adults and often leading to lasting impairments, arises from the Mycobacterium tuberculosis bacterium. Unlike the more common pulmonary TB affecting the lungs, TBM infects the brain and spinal cord’s surrounding membranes (meninges), resulting in meningitis and potentially causing brain pressure elevation, stroke, and, frequently, neurological damage or fatality. Roughly a quarter of the global population harbours latent TB, with up to 10% progressing to active infection. Within this group, up to 5% develop TBM. Although TB cases are infrequent in the United States, individuals with HIV face a heightened risk of fatal outcomes, surpassing a 50% fatality rate. Despite its severity, there remains a gap in understanding optimal treatments for TBM compared to pulmonary TB.
The IMAGINE-TBM trial will assign participants to either a new six-month drug regimen or the established nine-month standard regimen. The investigational regimen comprises intensified doses of rifampicin and isoniazid, along with linezolid and pyrazinamide during the initial eight weeks, contrasted with the current standard involving multiple drugs for a specified period. Outcomes will be tracked over 48 weeks, assessing participants’ clinical, neurological, and functional statuses.
Encompassing 330 participants aged 15 and above, including those with or without HIV, the trial will also include a small cohort of pregnant women with appropriate consent. This trial offers a significant opportunity to explore treatment options for high-risk groups like adolescent children and pregnant women, where limited data exists on the use of certain medications.
The challenge in reaching patients affected by this rare form of TB and the complexities in diagnosis highlight the importance of this study. Leveraging ACTG’s robust clinical research infrastructure in TB and HIV prevalent regions, this trial aims to unveil a potentially more efficient treatment for TBM, potentially saving lives and mitigating neurological impairments.
