HARVEST trial - improving outcomes from TB meningitis with high-dose oral rifampicin

Conditions

Tuberculous meningitis Infections and Infestations Tuberculous meningitis

Meya DB, Cresswell FV, Dai B, Engen N, Naidoo K, Ganiem AR, Imran D, Kabahubya M, Lessells RJ, Yunivita V, Estiasari R, Tugume L, Hlabisa B, Kurniawati MY, Sagita N, Kagimu E, Maharani K, Gakuru J, Gaharu MN, Mugabi T, Kimuda S, Namombwe S, Te Brake L, Aarnoutse R, Svensson EM, Bangdiwala AS, Namanda S, Bahr NC, Musubire AK, Moosa MYS, Hamers RL, Marais S, Boulware DR, van Crevel R, Ruslami R, HARVEST Trial Team.

2025-12-01

10.1056/nejmoa2502866

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

Julie Huynh, Chishala Chabala, Suvasini Sharma, Louise Choo, Varinder Singh et al. (31 authors)

BMJ Open2025-04-016 citations

10.1136/bmjopen-2024-088543

Experiences, challenges, gaps, and strategies for counselling persons presenting with advanced HIV-associated meningitis in Uganda.

Sadiq A, Kwizera R, Kiiza TK, Ayebare P, Ahimbisibwe C, Ndyetukira JF, Boulware DR, Meya DB.

2025-02-191 citations

10.1186/s12981-025-00705-z

A Phase 2A Trial of the Safety and Tolerability of Increased Dose Rifampicin and Adjunctive Linezolid, With or Without Aspirin, for Human Immunodeficiency Virus–Associated Tuberculous Meningitis: The LASER-TBM Trial

Angharad Davis, Sean Wasserman, Cari Stek, Mpumi Maxebengula, Chen Liang et al. (32 authors)

Clinical Infectious Diseases2022-12-0936 citations

10.1093/cid/ciac932

High dose oral rifampicin to improve survival from adult tuberculous meningitis: A randomised placebo-controlled double-blinded phase III trial (the HARVEST study).

Marais S, Cresswell FV, Hamers RL, Te Brake LHM, Ganiem AR, Imran D, Bangdiwala A, Martyn E, Kasibante J, Kagimu E, Musubire A, Maharani K, Estiasari R, Kusumaningrum A, Kusumadjayanti N, Yunivita V, Naidoo K, Lessells R, Moosa Y, Svensson EM, Huppler Hullsiek K, Aarnoutse RE, Boulware DR, van Crevel R, Ruslami R, Meya DB, Meya DB.

2019-01-0121 citations

10.12688/wellcomeopenres.15565.2

Interventions

Participants are allocated by chance to receive either: 1. Four oral rifampicin 300-mg capsules in addition to standard fixed-dose combination TB treatment 2. Standard fixed-dose combination TB trea

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. First episode TBM suspected by attending physician (>3 days of meningitis symptoms and CSF abnormalities) and anti-TB treatment planned 2. Age =18 years 3. Provision of written informed consent by participant or surrogate

Exclusion criteria

Exclusion criteria: 1. Presence of jaundice, known liver cirrhosis, or known elevated ALT >5x ULN 2. More than 5 doses of any TB treatment received within the previous 7 days 3. Known allergy to: isoniazid, rifampicin, ethambutol, or pyrazinamide 4. Known current/previous rifampicin-resistant M.tb infection 5. Additional active and confirmed CNS infection 6. Corticosteroids contraindicated 7. Cannot or unlikely to attend regular clinic visits 8. Pregnancy or breastfeeding 9. Known renal failure with eGFR <30 ml/min by Modification of Diet in Renal Disease (MDRD) Study equation 10. HIV Protease Inhibitor ongoing use

Design outcomes

Primary

Measure	Time frame
6-month survival	—

Secondary

Measure	Time frame
1. 12-month survival 2. Functional and neurocognitive outcomes measured using the following instruments: 2.1. Normalization of mental status with Glasgow coma scale score (GCS) of 15 and maintained for >2 days (among those with GCS 2 consecutive days 2.2. Functional outcomes assessed by Liverpool Outcome Score at month 6 (Appendix C) 2.3. Quantitative neurocognitive performance Z-scores (QNPZ-8) at 2 and 12 months (Uganda only). QNPZ-8 is derived from a test battery, which includes: 2.3.1. Grooved Pegboard test 2.3.2. Colour Trails 1 and 2 tests 2.3.3. WAIS-III Digit Symbol test 2.3.4. Finger Tapping test 2.3.5. WHO-UCLA Auditory Verbal Learning Test 2.3.6. Semantic Verbal Fluency test (category fluency) 3. Safety and tolerability endpoints: 3.1. Clinical AEs, grade 3-5 as classified by Division of AIDS (DAIDS) Toxicity Scale 3.2. Laboratory AEs, grade 3-5 as classified by DAIDS Toxicity Scale 3.3. All Serious AEs (SAEs) 3.4. Drug-induced liver injury (grade 3-5) § Alanine transaminase (ALT) or aspartate transaminase (AST) >5x upper limit of normal (ULN) 3.5. Discontinuation of TB treatment for >5 days in the first 8 weeks for any cause 4. Cumulative days of hospitalization (and re-hospitalization) 5. Incidence of re-hospitalization for neurologic deterioration 6. Incidence and management of drug-induced liver injury	—

Measure

Time frame

1. 12-month survival 2. Functional and neurocognitive outcomes measured using the following instruments: 2.1. Normalization of mental status with Glasgow coma scale score (GCS) of 15 and maintained for >2 days (among those with GCS 2 consecutive days 2.2. Functional outcomes assessed by Liverpool Outcome Score at month 6 (Appendix C) 2.3. Quantitative neurocognitive performance Z-scores (QNPZ-8) at 2 and 12 months (Uganda only). QNPZ-8 is derived from a test battery, which includes: 2.3.1. Grooved Pegboard test 2.3.2. Colour Trails 1 and 2 tests 2.3.3. WAIS-III Digit Symbol test 2.3.4. Finger Tapping test 2.3.5. WHO-UCLA Auditory Verbal Learning Test 2.3.6. Semantic Verbal Fluency test (category fluency) 3. Safety and tolerability endpoints: 3.1. Clinical AEs, grade 3-5 as classified by Division of AIDS (DAIDS) Toxicity Scale 3.2. Laboratory AEs, grade 3-5 as classified by DAIDS Toxicity Scale 3.3. All Serious AEs (SAEs) 3.4. Drug-induced liver injury (grade 3-5) § Alanine transaminase (ALT) or aspartate transaminase (AST) >5x upper limit of normal (ULN) 3.5. Discontinuation of TB treatment for >5 days in the first 8 weeks for any cause 4. Cumulative days of hospitalization (and re-hospitalization) 5. Incidence of re-hospitalization for neurologic deterioration 6. Incidence and management of drug-induced liver injury

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Countries

Indonesia, South Africa, Uganda

Outcome results

None listed