Determination of Adequate Tuberculosis Regimen in Patients Hospitalized With HIV-associated Severe Immune Suppression — DATURA  

Tuberculosis Clinical Trial

Official title: ANRS 12424: Determination of Adequate Tuberculosis Regimen in Adults and Adolescents Hospitalized With HIV-associated Severe Immune Suppression (CD4 ≤ 100 Cells/µL): the DATURA Trial.

Status Recruiting

Clinical Trial Summary

DATURA trial is a phase III, multicenter, two-arm, open-label, randomized superiority trial to compare the efficacy and the safety of an intensified tuberculosis (TB) regimen versus standard TB treatment in HIV-infected adults and adolescents hospitalized for TB with CD4 ≤ 100 cells/μL over 48 weeks:

• Intensified TB treatment regimen: increased doses of rifampicin and isoniazid together with standard-dose of pyrazinamide and ethambutol for 8 weeks in addition to prednisone for 6 weeks and albendazole for 3 days

• WHO standard TB treatment regimen.

The continuation phase of TB treatment will be identical in the two arms: 4 months of rifampicin and isoniazid at standard doses.

Clinical Trial Description

Settings: 4 African (Cameroon, Guinea, Uganda, Zambia) and 2 South-East Asian (Cambodia, Vietnam) countries.

Sample size : 1330 patients (665 in each arm). Follow-up : 48 weeks after entry in the trial (TB treatment initiation).

All participants will initiate antiretroviral therapy (ART) 2 weeks after starting TB treatment. In each country, the chosen ART regimen will be the same in both arms. According to the first-line regimen recommended in each country, the ART combination will be TDF/3TC/EFV 600 mg, or TDF/3TC + double-dose DTG.

The primary objective is to estimate the impact of an intensified initial phase of TB treatment on mortality at 48 weeks among HIV-infected adults and adolescents hospitalized for TB with CD4 ≤ 100 cells/μL in comparison with standard TB treatment.

The secondary objectives are to estimate the impact of an intensified initial phase of TB treatment, in comparison with the standard TB regimen, on:

• Mortality at weeks 8 and 24

• Adverse events, including

• All grade 3 and 4 events

• Selected grade 2 events of interest

• Drug-related adverse events

• AIDS-defining illnesses

• Paradoxical TB-associated immune reconstitution inflammatory syndrome (IRIS)

• TB treatment success

• TB recurrence

• ART response in terms of virological success and immunological response

• Adherence to TB treatment and ART

• Peak plasma concentrations of rifampicin and isoniazid (and its N-acetyl-metabolite) at day 3, day 7 and week 2

• Plasma concentrations of efavirenz and dolutegravir at week 4 (i.e. 2 weeks after the onset of ART).

A pharmacokinetic sub-study of rifampicin and isoniazid will be carried out in 72 voluntary patients (6 patients/arm/country) at the second week of the main study. ;

Related Conditions & MeSH terms

• HIV-1-infection
• Immuno-Deficiency
• Immunologic Deficiency Syndromes
• Tuberculosis

• NCT number: NCT04738812
• Study type: Interventional
• Source: ANRS, Emerging Infectious Diseases
• Contact: BLANC François-Xavier, MD, PhD
• Phone: +33 240 165 545
• Email: xavier.blanc@chu-nantes.fr
• Status: Recruiting
• Phase: Phase 3
• Start date: April 21, 2022
• Completion date: March 2025