Using adalimumab to improve survival in HIV 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
This study is testing if adding a medication called adalimumab to the usual treatment can help HIV patients with tuberculosis meningitis live longer and stay safe.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 130 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | ANRS, Emerging Infectious Diseases Government |
| Drugs / interventions | adalimumab |
| Locations | 3 sites (Rio de Janeiro and 2 other locations) |
| Trial ID | NCT05590455 on ClinicalTrials.gov |
What this trial studies
This phase II clinical trial evaluates the effect of adding adalimumab, a tumor necrosis factor inhibitor, to the standard treatment regimen for HIV-infected adults diagnosed with tuberculosis meningitis. Participants will be randomized to receive either standard treatment with anti-tuberculosis drugs and corticosteroids or the same treatment plus adalimumab. The trial aims to assess the impact on 3-month mortality and safety across three countries: Brazil, Mozambique, and Zambia. The study will also monitor the initial severity of the condition using the British Medical Research Council score to stratify randomization.
Who should consider this trial
Good fit: Ideal candidates include HIV-1 infected adults aged 18 and older who are ART-naïve or have discontinued ART for at least 6 months and have been diagnosed with tuberculosis meningitis.
Not a fit: Patients with other neurological infections, HIV-2 infection, or those who have contraindications to the study drugs may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly reduce mortality rates in HIV patients suffering from tuberculosis meningitis.
How similar studies have performed: While the use of TNF inhibitors in other contexts has shown promise, this specific approach in HIV patients with tuberculosis meningitis is novel and has not been extensively tested.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Criteria: * 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
Where this trial is running
Rio de Janeiro and 2 other locations
- Laboratory of clinical research on STD/AIDS - IPEC/FIOCRUZ — Rio de Janeiro, Brazil (Recruiting)
- Instituto Nacional de Saude — Maputo, Mozambique (Not_yet_recruiting)
- Adult Infectious Diseases Centre, University Teaching Hospital — Lusaka, Zambia (Not_yet_recruiting)
Study contacts
- Principal investigator: Nathalie DE CASTRO, MD — AP-HP, Hôpital Saint-Louis
- Study coordinator: Vanessa MACHAULT, PhD
- Email: vanessa.machault@u-bordeaux.fr
- Phone: +335 57 57 57 63
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.