RecruitingPhase 2NCT05590455

Tnf Inhibitors to Reduce Mortality in HIV-1 Infected PAtients With Tuberculosis meNIngitis

ANRS 12404 TIMPANI: Tnf Inhibitors to Reduce Mortality in HIV-1 Infected PAtients With Tuberculosis meNIngitis: a Phase II, Multicenter, Randomized Clinical Trial

Sponsor

ANRS, Emerging Infectious Diseases

Enrollment

130 participants

Start Date

Apr 11, 2023

Study Type

INTERVENTIONAL

Conditions

HIV I Infection Tuberculous Meningitis

Summary

Randomized phase II clinical trial which aims to assess the impact on 3-month mortality and safety of adding adalimumab to standard treatment (anti-tuberculosis drugs and corticosteroids) in HIV patients with tuberculosis meningitis in 3 countries (Brazil, Mozambique, and Zambia).

Eligibility

Min Age: 18 Years

Inclusion Criteria5

Age ≥18 years
HIV-1 infection
Definite or probable tuberculosis meningitis
Standard tuberculosis meningitis treatment ≤3 days: anti TB drugs at standard doses and high-dose dexamethasone as per WHO guidelines
Signed informed consent form by patient or relative.

Exclusion Criteria14

Other concomitant neurological infection, i.e. toxoplasmosis, cryptococcosis, progressive multifocal leukoencephalopathy, bacterial meningitis, neuro-syphilis
Asymptomatic positive cryptococcal antigen in serum
HBsAg positive or anti hepatitis C virus antibodies positive
Alanine transaminase (ALT)\>5 ULN
Rifampicin-resistant TB detected by GeneXpert MTB/RIF Ultra
History of previous TB treatment in patients with GeneXpert MTB/RIF Ultra negative or unavailable
Current use of drugs contraindicated with study drugs and that cannot be safely stopped
Allergy to study drugs or any of their components
Uncontrolled opportunistic infection
Moderate to severe cardiac insufficiency (NYHA classes III / IV)
Any condition which might, in the investigator's opinion, compromise the safety of treatment and/or patient's adherence to study procedures
For women of childbearing age: 1) Pregnancy or breastfeeding; 2) Refusal to use effective contraception to be discussed with the investigator
Subjects participating in another clinical trial evaluating therapies and including an exclusion period that is still in force during the screening phase
Person under guardianship, or deprived of freedom by a judicial or administrative decision

Interventions

DRUGAdalimumab Injection

one sub-cutaneous injection, every 2 weeks for 10 weeks (total 6 injections), started as soon as possible during the first 3 days of antituberculosis treatment and high-dose steroids