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
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 rel...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2025-04-01
|
| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/15/4/e088543.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850272677768462336 |
|---|---|
| author | Varinder Singh Naveen Sankhyan Diana M Gibb Guy E Thwaites Hilda Mujuru James A Seddon Nitya Wadhwa Angela Crook Evelyne Kestelyn Julie Huynh Suzanne T Anderson Nhung Nguyen Thanh Nguyen Anna Turkova Kafula Lisa Nkole Elena Frangou Nguyen Viet Nhung Godfrey Musoro Chishala Chabala Kusum Nathoo Ennie Chidziva Moses Chitsamatanga Suvasini Sharma Phuc Huu Phan Louise Choo Tung Huu Trinh Titiksha Sirari Constantine Mutata Anna Griffiths Eric Wobudeya Caitlin Muller Sierra Santana Lam Van Nguyen Dai Tran Susan Abarca-Salazar Robin Basu-Roy Sibusiswe Wesa Vivian Mumbrio Misheck Phiri Joyce Chipili Lungu Christina Zulu Kriti Nautiyal Kamal Singhal Joshua Choga Secrecy Gondo Adam Gregory Yogesh Kumar Tiwari Mutsa Bwakura Diksha Shafiq Ngoc Lam Hong Bao Shepard Mudzingwa Nancy Nabukeera |
| author_facet | Varinder Singh Naveen Sankhyan Diana M Gibb Guy E Thwaites Hilda Mujuru James A Seddon Nitya Wadhwa Angela Crook Evelyne Kestelyn Julie Huynh Suzanne T Anderson Nhung Nguyen Thanh Nguyen Anna Turkova Kafula Lisa Nkole Elena Frangou Nguyen Viet Nhung Godfrey Musoro Chishala Chabala Kusum Nathoo Ennie Chidziva Moses Chitsamatanga Suvasini Sharma Phuc Huu Phan Louise Choo Tung Huu Trinh Titiksha Sirari Constantine Mutata Anna Griffiths Eric Wobudeya Caitlin Muller Sierra Santana Lam Van Nguyen Dai Tran Susan Abarca-Salazar Robin Basu-Roy Sibusiswe Wesa Vivian Mumbrio Misheck Phiri Joyce Chipili Lungu Christina Zulu Kriti Nautiyal Kamal Singhal Joshua Choga Secrecy Gondo Adam Gregory Yogesh Kumar Tiwari Mutsa Bwakura Diksha Shafiq Ngoc Lam Hong Bao Shepard Mudzingwa Nancy Nabukeera |
| collection | DOAJ |
| description | 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 The Shortened Intensive Therapy for Children with Tuberculous Meningitis (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 modified Rankin Scale (mRS), both at 48 weeks. Nested substudies include pharmacokinetics, pharmacogenetics, pathophysiology, diagnostics and prognostic biomarkers, in-depth neurodevelopmental outcomes, MRI and health economics.Ethics and dissemination Local ethics committees at all participating study sites and respective regulators approved the SURE protocol. Ethics approval was also obtained from UCL, UK (14935/001). Informed consent from parents/carers and assent from age-appropriate children are required for all participants. Results will be published in international peer-reviewed journals, and appropriate media will be used to summarise results for patients and their families and policymakers.Trial registration ISRCTN40829906 (registered 13 November 2018). |
| format | Article |
| id | doaj-art-c39ba71972c6428ebd413cacd0f9b935 |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-c39ba71972c6428ebd413cacd0f9b9352025-08-20T01:51:42ZengBMJ Publishing GroupBMJ Open2044-60552025-04-0115410.1136/bmjopen-2024-088543Effectiveness 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 Varinder Singh0Naveen Sankhyan1Diana M Gibb2Guy E Thwaites3Hilda Mujuru4James A Seddon5Nitya WadhwaAngela Crook6Evelyne Kestelyn7Julie Huynh8Suzanne T Anderson9Nhung Nguyen10Thanh Nguyen11Anna Turkova12Kafula Lisa Nkole13Elena Frangou14Nguyen Viet Nhung15Godfrey MusoroChishala Chabala16Kusum NathooEnnie ChidzivaMoses ChitsamatangaSuvasini Sharma17Phuc Huu Phan18Louise Choo19Tung Huu Trinh20Titiksha Sirari21Constantine Mutata22Anna Griffiths23Eric Wobudeya24Caitlin Muller25Sierra Santana26Lam Van Nguyen27Dai Tran28Susan Abarca-Salazar29Robin Basu-Roy30Sibusiswe WesaVivian MumbrioMisheck PhiriJoyce Chipili LunguChristina ZuluKriti NautiyalKamal SinghalJoshua ChogaSecrecy GondoAdam GregoryYogesh Kumar TiwariMutsa BwakuraDiksha ShafiqNgoc Lam Hong BaoShepard MudzingwaNancy NabukeeraLady Hardinge Medical College and Associated Kalawati Saran Children`s Hospital, New Delhi, IndiaDepartment of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaMRC Clinical Trials Unit at UCL, London, UKOxford University Clinical Research Unit, Ho Chi Minh City, Ho Chi Minh, VietnamUniversity of Zimbabwe Clinical Research Centre, Harare, ZimbabweDepartment of Infectious Disease, Imperial College London, London, UKMRC Clinical Trials Unit at UCL, London, UKOxford University Clinical Research Unit, Ho Chi Minh City, Ho Chi Minh, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, Ho Chi Minh, VietnamMRC Clinical Trials Unit at UCL, London, UKDepartment of Paediatrics, Pham Ngoc Thach Hospital, Ho Chi Minh City, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, Ho Chi Minh, VietnamMRC Clinical Trials Unit at UCL, London, UKUniversity Teaching Hospitals-Children`s Hospital, Lusaka, ZambiaMRC Clinical Trials Unit at UCL, London, UKThe National Lung Hospital, Hanoi, VietnamDepartment of Paediatrics, University of Zambia, Lusaka, ZambiaLady Hardinge Medical College and Associated Kalawati Saran Children`s Hospital, New Delhi, IndiaPaediatric Intensive Care, Vietnam National Children’s Hospital, Hanoi, VietnamMRC Clinical Trials Unit at UCL, London, UKChildren’s Hospital 2, Ho Chi Minh City, VietnamDepartment of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaUniversity of Zimbabwe Clinical Research Centre, Harare, ZimbabweMRC Clinical Trials Unit at UCL, London, UKMakerere University—John Hopkins University Research Collaboration, Kampala, UgandaMRC Clinical Trials Unit at UCL, London, UKMRC Clinical Trials Unit at UCL, London, UKCenter for Tropical Diseases, Vietnam National Children`s Hospital, Hanoi, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, Ho Chi Minh, VietnamMRC Clinical Trials Unit at UCL, London, UKBlizard Institute, Queen Mary University of London, London, UKIntroduction 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 The Shortened Intensive Therapy for Children with Tuberculous Meningitis (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 modified Rankin Scale (mRS), both at 48 weeks. Nested substudies include pharmacokinetics, pharmacogenetics, pathophysiology, diagnostics and prognostic biomarkers, in-depth neurodevelopmental outcomes, MRI and health economics.Ethics and dissemination Local ethics committees at all participating study sites and respective regulators approved the SURE protocol. Ethics approval was also obtained from UCL, UK (14935/001). Informed consent from parents/carers and assent from age-appropriate children are required for all participants. Results will be published in international peer-reviewed journals, and appropriate media will be used to summarise results for patients and their families and policymakers.Trial registration ISRCTN40829906 (registered 13 November 2018).https://bmjopen.bmj.com/content/15/4/e088543.full |
| spellingShingle | Varinder Singh Naveen Sankhyan Diana M Gibb Guy E Thwaites Hilda Mujuru James A Seddon Nitya Wadhwa Angela Crook Evelyne Kestelyn Julie Huynh Suzanne T Anderson Nhung Nguyen Thanh Nguyen Anna Turkova Kafula Lisa Nkole Elena Frangou Nguyen Viet Nhung Godfrey Musoro Chishala Chabala Kusum Nathoo Ennie Chidziva Moses Chitsamatanga Suvasini Sharma Phuc Huu Phan Louise Choo Tung Huu Trinh Titiksha Sirari Constantine Mutata Anna Griffiths Eric Wobudeya Caitlin Muller Sierra Santana Lam Van Nguyen Dai Tran Susan Abarca-Salazar Robin Basu-Roy Sibusiswe Wesa Vivian Mumbrio Misheck Phiri Joyce Chipili Lungu Christina Zulu Kriti Nautiyal Kamal Singhal Joshua Choga Secrecy Gondo Adam Gregory Yogesh Kumar Tiwari Mutsa Bwakura Diksha Shafiq Ngoc Lam Hong Bao Shepard Mudzingwa Nancy Nabukeera 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 BMJ Open |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://bmjopen.bmj.com/content/15/4/e088543.full |
| work_keys_str_mv | AT effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT varindersingh effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT naveensankhyan effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT dianamgibb effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT guyethwaites effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT hildamujuru effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT jamesaseddon effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT nityawadhwa effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT angelacrook effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT evelynekestelyn effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT juliehuynh effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT suzannetanderson effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT nhungnguyen effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT thanhnguyen effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT annaturkova effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT kafulalisankole effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT elenafrangou effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT nguyenvietnhung effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT godfreymusoro effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT chishalachabala effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT kusumnathoo effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT enniechidziva effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT moseschitsamatanga effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT suvasinisharma effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT phuchuuphan effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT louisechoo effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT tunghuutrinh effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT titikshasirari effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT constantinemutata effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT annagriffiths effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT ericwobudeya effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT caitlinmuller effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT sierrasantana effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT lamvannguyen effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT daitran effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT susanabarcasalazar effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT robinbasuroy effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT sibusiswewesa effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT vivianmumbrio effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT misheckphiri effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT joycechipililungu effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT christinazulu effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT kritinautiyal effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT kamalsinghal effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT joshuachoga effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT secrecygondo effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT adamgregory effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT yogeshkumartiwari effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT mutsabwakura effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT dikshashafiq effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT ngoclamhongbao effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT shepardmudzingwa effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis AT nancynabukeera effectivenessandsafetyofshortenedintensivetreatmentforchildrenwithtuberculousmeningitissureaprotocolforaphase3randomisedcontrolledtrialevaluating6monthsofantituberculosistherapyand8weeksofaspirininasianandafricanchildrenwithtuberculousmeningitis |