Overview

Leukotriene A4 Hydrolase Stratified Trial of Adjunctive Corticosteroids for HIV-uninfected Adults With Tuberculous Meningitis

Status:
Recruiting

Trial end date:
2022-10-01

Target enrollment:

Participant gender:

Summary

The primary objective is to determine whether Leukotriene A4 hydrolase (LTA4H) genotype, defined at randomisation, determines dexamethasone's clinical effectiveness when added to the first 6-8 weeks of anti-tuberculosis treatment of TBM. The investigators will conduct a LTA4H genotype stratified, parallel group, randomised, double blind, placebo-controlled multi-centre Phase III non-inferiority trial evaluating dexamethasone versus placebo for 6-8 weeks in addition to standard anti-tuberculosis drugs. The investigators will take a hybrid trial-design approach which assumes a modest harm of dexamethasone and aims to prove non-inferiority of placebo first but also allows claiming superiority of placebo in case dexamethasone causes substantial harm. Moreover, as it is possible that harm of dexamethasone only applies to the LTA4H CC genotype, the trial will allow dropping the CT group at an interim analysis but continue randomization of the CC group. In making this assessment the investigators not only determine whether dexamethasone influences survival and the incidence of new neurological events (the primary endpoint), but also whether it influences disability assessed by the modified Rankin score 12 months after the start of treatment. The secondary objective is to investigate alternative management strategies in a subset of patients who develop drug-induced liver injury that will enable the safe continuation of rifampicin and isoniazid therapy whenever possible.

Phase:

Phase 3

Details

Lead Sponsor:

Oxford University Clinical Research Unit, Vietnam

Collaborators:

Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam

Treatments:

BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate