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

NCT03100786 · Status: COMPLETED · Phase: PHASE3 · Type: INTERVENTIONAL · Enrollment: 702

Last updated 2025-06-17

No results posted yet for this study

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.

Conditions

  • Tuberculosis
  • Tuberculous Meningitis
  • Drug-Induced Liver Injury

Interventions

DRUG

Dexamethasone

Active treatment with dexamethasone from randomisation (IV followed by oral according to disease severity at the start of treatment): Dexamethasone for intravenous injection and dexamethasone for oral ingestion

OTHER

Placebo

Treatment with matched placebo: Standard saline for intravenous injection and placebo oral tablets containing cellulose

Sponsors & Collaborators

  • Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam

    collaborator OTHER

  • Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

    collaborator OTHER

  • Oxford University Clinical Research Unit, Vietnam

    lead OTHER

Principal Investigators

  • Guy Thwaites, MD · University of Oxford, UK

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2018-02-12
Primary Completion
2023-03-09
Completion
2024-03-09

Countries

  • Vietnam

Study Locations

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Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03100786 on ClinicalTrials.gov