NCT04738812

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

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: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,330 (actual)
• Sponsor: ANRS, Emerging Infectious Diseases · Other Government
• Sex: All
• Age: 15 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Settings: 5 African (Cameroon, Guinea, Uganda, Zambia, Mozambique) and 1 South-East Asian (Cambodia) 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.

Conditions

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

Interventions

Type	Name	Description
DRUG	Intensified TB treatment (initial phase)	8 weeks of RHEZ with high dose of rifampicin (R) and isoniazid (H). Fixed dose combination (FDC) of RHZE with the addition of FDC of RH and single caps of R. 6 weeks of prednisone with tapering doses. 3 days of albendazole 400 mg.
DRUG	WHO standard TB treatment (initial phase)	8 weeks of RHEZ with FDC.

Timeline

• Start date: 2022-04-21
• Primary completion: 2025-11-12
• Completion: 2025-11-12
• First posted: 2021-02-04
• Last updated: 2025-12-22

Locations

6 sites across 6 countries: Cambodia, Cameroon, Guinea, Mozambique, Uganda, Zambia