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The increasing burden of drug-resistant tuberculosis (TB) is a major public health concern, and effective strategies need to be planned to prevent its emergence and transmission. Private healthcare centres and pharmacies are the first point of healthcare access in many low- and middle-income countries. The prevalence of resistance to second-line anti-TB drugs, especially fluoroquinolones, is high in some countries with a high TB burden. In these countries, second-line anti-TB drugs, such as fluoroquinolones, amoxicillin-clavulanate and injectable agents such as amikacin, are often available as over-the-counter drugs, often taken as self-medication and used for other indications. Stringent policies and effective implementation need to be in place for preventing the inappropriate use of these drugs to prevent the emergence of drug resistance. [ABSTRACT FROM AUTHOR]

Background: Despite several incremental improvements in the management of tuberculous meningitis (TBM), the mortality rates remain high. In spite of national and international guidelines, variation in the choice, dose, and duration of drugs exist between countries and clinicians. We propose to evaluate a shorter and more effective regimen containing agents with augmented intracerebral drug exposure and anti-inflammatory approaches to improve disability-free survival among patients with TBM. Our strategy incorporates the various developments in the field of TBM over the last two decades and only few trials have evaluated a composite of these strategies in the overall outcomes of TBM. Methods: An open label, parallel arms, randomized controlled superiority trial will be conducted among 372 participants across 6 sites in India. Eligible participants will be randomly allocated in 1:1:1 ratio into one of the three arms. The intervention arm consists of 2 months of high-dose rifampicin (25 mg/kg), moxifloxacin (400 mg), pyrazinamide, isoniazid, aspirin (150 mg), and steroids followed by rifampicin, isoniazid, and pyrazinamide for 4 months. The second intervention arm includes all the drugs as per the first arm except aspirin and the patients in the control arm will receive treatment according to the National TB Elimination Program guidelines. All participants will be followed up for 1 year after the treatment. Discussion: Current WHO regimens have agents with poor central nervous system drug exposure and is too long. It does not reflect the accumulating evidence in the field. We propose a comprehensive clinical trial incorporating the emerging evidence accrued over the last two decades to shorten the duration and improve the treatment outcomes. This multi-centric trial may generate crucial evidence with policy and practice implications in the treatment of TBM. Trial registration: Clinical Trial Registry India CTRI/2023/05/053314. Registered on 31 May 2023 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=ODYzMzg=&Enc=&userName=CTRI/2023/05/053314). ClinicalTrials.gov NCT05917340. Registered on 6 August 2023 (https://classic.clinicaltrials.gov/ct2/show/NCT05917340). Protocol version: Version 1.3 dated 12 July 2023. [ABSTRACT FROM AUTHOR]

Background: Despite several incremental improvements in the management of tuberculous meningitis (TBM), the mortality rates remain high. In spite of national and international guidelines, variation in the choice, dose, and duration of drugs exist between countries and clinicians. We propose to evaluate a shorter and more effective regimen containing agents with augmented intracerebral drug exposure and anti-inflammatory approaches to improve disability-free survival among patients with TBM. Our strategy incorporates the various developments in the field of TBM over the last two decades and only few trials have evaluated a composite of these strategies in the overall outcomes of TBM. Methods: An open label, parallel arms, randomized controlled superiority trial will be conducted among 372 participants across 6 sites in India. Eligible participants will be randomly allocated in 1:1:1 ratio into one of the three arms. The intervention arm consists of 2 months of high-dose rifampicin (25 mg/kg), moxifloxacin (400 mg), pyrazinamide, isoniazid, aspirin (150 mg), and steroids followed by rifampicin, isoniazid, and pyrazinamide for 4 months. The second intervention arm includes all the drugs as per the first arm except aspirin and the patients in the control arm will receive treatment according to the National TB Elimination Program guidelines. All participants will be followed up for 1 year after the treatment. Discussion: Current WHO regimens have agents with poor central nervous system drug exposure and is too long. It does not reflect the accumulating evidence in the field. We propose a comprehensive clinical trial incorporating the emerging evidence accrued over the last two decades to shorten the duration and improve the treatment outcomes. This multi-centric trial may generate crucial evidence with policy and practice implications in the treatment of TBM. Trial registration: Clinical Trial Registry India CTRI/2023/05/053314. Registered on 31 May 2023 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=ODYzMzg=&Enc=&userName=CTRI/2023/05/053314). ClinicalTrials.gov NCT05917340. Registered on 6 August 2023 (https://classic.clinicaltrials.gov/ct2/show/NCT05917340). Protocol version: Version 1.3 dated 12 July 2023. [ABSTRACT FROM AUTHOR]