Tuberculous meningitis Infections and Infestations Tuberculous meningitis
Conditions
Interventions
Participants in this study will either be given the antibiotic medicines that are usually used to treat children with TB meningitis for 12 months (standard of care treatment) OR the higher dose medici
Sponsors
University College London
Eligibility
Sex/Gender
All
Age
29 Days to 18 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 22/08/2024: 1. Aged between 29 days and <18 years old 2. Weight =3 kg 3. Symptoms compatible with tuberculosis meningitis (TBM), including fever, vomiting, anorexia, listlessness and headache 4. Cerebrospinal fluid (CSF) result with abnormalities compatible with TBM (elevated cell count and/or protein with or without M. tuberculosis detected by microscopy or GeneXpert). Physician believes the child needs immediate initiation of anti-TB drugs. 5. Known (or pending confirmation of) HIV status 6. Parent/carer give informed, written consent 7. CSF sample processed for chemistry, microscopy, Ziehl–Nielsen or auramine stain and, mycobacterial culture (in process) and, where available, Xpert (Gene Xpert/Rif or Xpert Ultra) prior to commencing treatment. Where patients have already been started on ATT, pre-screening CSF results should be available. 8. Carer/parent can comply with the protocol requirements in the opinion of the site investigator 9. Home address accessible for visiting and intending to remain within the recruitment area for follow up period of at least 18 months _____ Previous inclusion criteria: 1. Aged between 29 days and 15 years 2. Weight =3 kg 3. Symptoms compatible with tuberculosis meningitis (TBM), including fever, vomiting, anorexia, listlessness and headache 4. Cerebrospinal fluid (CSF) result with abnormalities compatible with TBM (elevated cell count and/or protein with or without M. tuberculosis detected by microscopy or GeneXpert). Physician believes the child needs immediate initiation of anti-TB drugs. 5. Known (or pending confirmation of) HIV status 6. Parent/carer give informed, written consent 7. CSF sample processed for chemistry, microscopy, Ziehl–Nielsen or auramine stain and, mycobacterial culture (in process) and, where available, Xpert (Gene Xpert/Rif or Xpert Ultra) prior to commencing treatment. Where patients have already been started on ATT, pre-screening CSF results should be available. 8. Carer/parent can comply with the protocol requirements in the opinion of the site investigator 9. Home address accessible for visiting and intending to remain within the recruitment area for follow up period of at least 18 months
Exclusion criteria
Exclusion criteria: 1. Recent contact (last 12 months) with known or suspected rifampicin-resistant TB 2. Proven drug resistance to rifampicin in the child 3. On ATT for >7 days 4. Severely moribund - high risk of death within 24 hours 5. History or presence of known allergy or other contraindication to any of the following: 5.1. First-line anti-tuberculosis drugs 5.2. Corticosteroids 5.3. Aspirin 6. Pregnancy 7. History of gastrointestinal (GI) bleeding or bleeding diathesis 8. Active clinical infection with influenza or varicella 9. Grade 4 liver toxicity or other contraindications for taking part in the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The two randomisations have individual primary outcome measures. Randomisation 1 (standard of care treatment versus test treatment): 1. All-cause mortality at 48 weeks, reported by the site investigators and captured via case report forms (CRFs) Randomisation 2 (aspirin versus placebo): 1. Neurodevelopment at 48 weeks, assessed using a Modified Rankin score (MRS), captured on a CRF using the standardised MRS measure | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Neurodevelopment at 24 and 48 weeks, assessed using a Modified Rankin score (MRS), captured on a case report form (CRF) using the standardised MRS measure (for randomisation 1) 2. All-cause mortality at 72 weeks, reported by the site investigators and captured via CRFs 3. Clinical or microbiological relapse of TBM and/or TB disease at other sites by 72 weeks, reported by the site investigators following up the participants and captured via CRFs 4. Any new grade 3 or grade 4 clinical or laboratory adverse events, and adverse events of any grade, leading to treatment modification, evaluated and reported by the site investigators using the Division of AIDS (DAIDS) toxicity table throughout the study 5. Other specific adverse events, evaluated and reported by the site investigators using the DAIDs toxicity table throughout the study: 5.1. Any gastrointestinal bleeding (any grade) 5.2. Drug-induced liver injury (DILI) of Grade 2 or more 5.3. Development of obstructive hydrocephalus 6. Acquired drug resistance, evaluated and reported by the site investigators using a blood test at screening, randomisation and optionally (if from a local practice) at study days 1 and 2 7. Non-adherence to treatment, evaluated and reported by the site investigators using standardised questionnaires and pill counts at days 1, 7 and 14, and weeks 4, 8, 16, 24, 36, 48 and 72 8. Suppressed HIV viral load and CD4 cell count in HIV-infected children, assessed using a blood test at the baseline and at 24, 48 and 72 weeks | — |
Countries
India, Uganda, Viet Nam, Zambia, Zimbabwe
Contacts
Public ContactAnna Griffiths
Outcome results
None listed