Effectiveness and safety of shortened intensive treatment for children with tuberculous meningitis (SURE): a protocol for a phase 3 randomised controlled trial evaluating 6 months of antituberculosis therapy and 8 weeks of aspirin in Asian and African children with tuberculous meningitis

作者：Julie Huynh, Chishala Chabala, Suvasini Sharma, Louise Choo, Varinder Singh, Naveen Sankhyan, Hilda Mujuru, Nhung Nguyen, Tung Huu Trinh, Phan Hữu Phúc, Nguyen Viet Nhung, Kafula Lisa Nkole, Titiksha Sirari, Constantine Mutata, Eleni Frangou, Anna Griffiths, Eric Wobudeya, Caitlin Muller, Sierra Santana, Evelyne Kestelyn, Lam Van Nguyen, Thanh Hung Nguyen, Dai Q. Tran, James A. Seddon, Anna Turkova, Susan Abarca-Salazar, Ron Basuroy, Guy Thwaites, Angela M. Crook, Suzanne T. Anderson, Diana M. Gibb · 发表于：BMJ Open · 年份：2025 · DOI：10.1136/bmjopen-2024-088543 · 被引用次数：13 · 研究领域：Infectious Diseases and Tuberculosis、Tuberculosis Research and Epidemiology、Bacterial Infections and Vaccines

INTRODUCTION: Childhood tuberculous meningitis (TBM) is a devastating disease. The long-standing WHO recommendation for treatment is 2 months of intensive phase with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E), followed by 10 months of isoniazid and rifampicin. In 2022, WHO released a conditional recommendation that 6 months of intensified antituberculosis therapy (ATT) could be used as an alternative for drug-susceptible TBM. However, this has never been evaluated in a randomised clinical trial. Trials evaluating ATT shortening regimens using high-dose rifampicin and drugs with better central nervous system penetration alongside adjuvant anti-inflammatory therapy are needed to improve outcomes. METHODS AND ANALYSIS: ningitis (SURE) trial is a phase 3, randomised, partially blinded, factorial trial being conducted in Asia (India and Vietnam) and Africa (Uganda, Zambia and Zimbabwe). It is coordinated by the Medical Research Council Clinical Trial Unit at University College London (MRCCTU at UCL). 400 children (aged 29 days to <18 years) with clinically diagnosed TBM will be randomised, using a factorial design, to either a 24-week intensified regimen (isoniazid (20 mg/kg), rifampicin (30 mg/kg), pyrazinamide (40 mg/kg) and levofloxacin (20 mg/kg)) or the standard 48-week ATT regimen and 8 weeks of high-dose aspirin or placebo. The primary outcome for the first randomisation is all-cause mortality, and for the second randomisation is the paediatric modif...