SURE: Short intensive treatment for children with tuberculous meningitis

Phase 3

• Conditions: Tuberculous meningitis; Infections and Infestations

• Registration Number: ISRCTN40829906
• Lead Sponsor: niversity College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-11-13
• Last Update Posted: 2 September 2024
• Study Completion: 2026-03-30

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 369

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

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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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The two randomisations have individual primary outcome measures.<br>Randomisation 1 (standard of care treatment versus test treatment):<br>1. All-cause mortality at 48 weeks, reported by the site investigators and captured via case report forms (CRFs)<br>Randomisation 2 (aspirin versus placebo):<br>1. Neurodevelopment at 48 weeks, assessed using a Modified Rankin score (MRS), captured on a CRF using the standardised MRS measure