Standard versus sequential anti-tubercular treatment in patients with tuberculous meningitis: a randomized controlled trial

Abstract

Abstract Background To compare the safety and efficacy of sequential anti-tubercular treatment (ATT) regimen with the standard regimen in tuberculous meningitis (TBM). Methods This single-centre, open-label, parallel group randomized controlled trial was conducted from May 2017 to June 2019 in India. Treatment-naïve patients with TBM fulfilling the inclusion criteria were randomized to four drug ATT regimens (rifampicin, isoniazid, ethambutol and pyrazinamide) administered either simultaneously (standard arm) or one after another (sequential arm) in a 1 : 1 ratio. The primary endpoint was drug-induced hepatitis (DIH) and the secondary endpoints were in-hospital death and disability at 3 and 6 months using a modified Rankin Scale. Results A total of 97 patients with TBM were recruited; 15 did not meet the inclusion criteria and 2 refused to participate. The median age of the patients was 26 y (range 15–75) and 37 (46.2%) were males. The patients in the sequential arm had fewer cases of DIH (20% vs 42.5%; p=0.03). The patients in the sequential arm had lower in-hospital mortality (2.5% vs 17.5%; p=0.025) and better 6-month outcomes (25.0% vs 50.0%; p=0.02) compared with the standard arm. Conclusions Sequential ATT was associated with a lower frequency of DIH, lower in-hospital mortality and better 6-month outcome. Trial registration Clinical Trials Registry of India (ctri.nic.in) identifier: REF/2016/09/012214/CTRI/2017/10/010072.