Adjunctive Corticosteroids for Tuberculous Meningitis in HIV-infected Adults (The ACT HIV Trial)

• Status: Active, not recruiting
• Trial end date: 2022-05-01
• Target enrollment: 0
• Participant gender: All

Summary

The investigators will conduct a randomized, double blind, placebo controlled trial of adjunctive dexamethasone in the initial (6-8 weeks) treatment of tuberculous meningitis in Vietnamese adults. The trial will address a primary hypothesis in all enrolled patients, and a secondary hypothesis in a sub-group of enrolled patients who develop anti-tuberculosis drug-induced liver injury (DILI). The primary hypothesis is adjunctive dexamethasone increases survival from TBM in HIV co-infected adults. The secondary hypothesis is current guidelines for the management of anti-tuberculosis drug-induced liver injury in those with TBM result in the premature interruption of rifampicin and isoniazid (the critical active drugs in early therapy) and are thereby placing participants at risk of poor outcomes.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Oxford University Clinical Research Unit, Vietnam
• Collaborators: Cipto Mangunkusumo Hospital, Jakarta, Indonesia; Eijkman Oxford Clinical Research Unit, Indonesia; Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam; RSUP Persahabatan Hospital, Jakarta, Indonesia
• Treatments: BB 1101; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate

Criteria

Inclusion Criteria:

• Adult (18 years or older)

• HIV-infected

• Clinical diagnosis of TBM (≥5 days of meningitis symptoms, and CSF abnormalities) and anti-tuberculosis chemotherapy either planned or started by the attending physician

Note: Published diagnostic criteria will be applied to all enrolled participants at the end of the study when all mycobacterial culture results are available. The criteria will sub-divide all cases into definite, probable and possible TBM, and those with an alternative diagnosis.

Exclusion Criteria:

• An additional brain infection (other than TBM) confirmed or suspected: positive CSF Gram or India Ink stain; positive blood or CSF Cryptococcal antigen test; cerebral toxoplasmosis suspected and attending physician wants to give anti-toxoplasmosis treatment with anti-tuberculosis treatment

• More than 6 consecutive days of two or more drugs active against M. tuberculosis immediately before screening

• More than 3 consecutive days of any type of orally or intravenously administered corticosteroid immediately before randomisation

• Dexamethasone considered mandatory for any reason by the attending physician

• Dexamethasone considered to be contraindicated for any reason by the attending physician

• Previously been randomised into the trial for a prior episode of TBM

• Lack of consent from the participant or family member (if the participant is incapacitated by the disease)