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

NCT04738812 | Completed Phase 3 DMC

• 1 other identifier: ANRS 12424 DATURA
• Study Type: interventional
• Target: 1,330
• Locations: 5 countries
• Sites: 5

Brief 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.

Conditions

Tuberculosis; HIV-1-infection; Immuno-Deficiency

Keywords

Tuberculosis; HIV-1; Mortality; Immuno-deficiency; Isoniazid; Rifampicin

Outcome Measures

Primary Outcomes (1)

• Rate of all causes death

  Number of deaths between the inclusion visit and week 48, divided by the total person-years of follow-up until week 48

  Up to 48 weeks

Secondary Outcomes (13)

• Rate of all causes death

  Up to 8 weeks

• Rate of all causes death

  Up to 24 weeks

• Rate of adverse events

  Up to 48 weeks

• Rate of AIDS-defining illnesses

  Up to 48 weeks

• Rate of paradoxical TB-associated IRIS

  Up to 14 weeks

Study Arms (2)

Intensified TB treatment

EXPERIMENTAL

* Increased doses of rifampicin (R) to 35±5 mg/kg daily and isoniazid (H) 10±2 mg/kg daily together with standard-dose of pyrazinamide (Z) 20-30 mg/kg daily + ethambutol (E) 15-20 mg/kg daily for 8 weeks (initial phase of TB treatment). * Prednisone 40 to 80 mg once a day (OD) according to weight bands for 2 weeks, followed by 20 to 40 mg OD according to weight bands for 2 weeks, then 10 to 20 mg OD according to weight bands for the last 2 weeks (total duration: 6 weeks). Because of the corticosteroid treatment, albendazole 400 mg OD will be given to participants for 3 days. * Continuation phase: 16 weeks of RH.

Drug: Intensified TB treatment (initial phase)

WHO standard TB treatment

ACTIVE COMPARATOR

* Standard-dose of R 8-12 mg/kg daily + H 4-6 mg/kg daily + Z 20-30 mg/kg daily + E 15-20 mg/kg daily for 8 weeks. * Continuation phase: 16 weeks of RH.

Drug: WHO standard TB treatment (initial phase)

Interventions

Intensified TB treatment (initial phase) DRUG

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.

Intensified TB treatment

WHO standard TB treatment (initial phase) DRUG

8 weeks of RHEZ with FDC.

WHO standard TB treatment

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient (and legally designed representative of minor patient) able to correctly understand the trial and to sign the informed consent
• Aged ≥ 15 years
• Confirmed HIV-1 infection as documented at any time prior to trial entry per national HIV testing procedures
• CD4 count ≤ 100 cells/μL
• Hospitalized for a newly diagnosed TB, defined by:
• Any positive Xpert® MTB/RIF specimen (sputum, urine, pus, other),
• Or a positive urine lipoarabinomannan (LAM) test,
• Or an abnormal chest X-ray compatible with active TB
• Initiation of TB drugs for more than 7 days
• History of TB treatment during the last 6 months
• Central neurological symptoms, including but not restrictive to TB meningitis
• Suspected TB pericarditis
• Documented Mycobacterium tuberculosis strain resistant to rifampicin using rapid molecular testing (Xpert® MTB/RIF)
• Any concomitant medication or known hypersensitivity contraindicating any component of the TB treatment
• HIV-2 co-infection

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• European Union: collaborator
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator

Study Sites (6)

National Center for HIV/AIDS, Dermatology and STD (NCHADS)

Phnom Penh, Cambodia

Location

Jamot Hospital

Yaoundé, Cameroon

Location

Ignace Deen Hospital

Conakry, Guinea

Location

MACHAVA Hospital

Maputo, Mozambique

Location

Mbarara Regional Referral hospital

Mbarara, Uganda

Location

University Teaching Hospital

Lusaka, Zambia

Location

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• BLANC François-Xavier, MD, PhD

  University Hospital of Nantes, France

  PRINCIPAL INVESTIGATOR

• LAUREILLARD Didier, MD

  University Hospital of Nimes, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: DATURA trial is a phase III, multicenter, two-arm, open-label, randomized superiority trial.

Study Record Dates

• First Submitted: February 1, 2021
• First Posted: February 4, 2021
• Study Start: April 21, 2022
• Primary Completion: November 12, 2025
• Study Completion: November 12, 2025
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be available after the princeps paper has been published and for at least 2 years.
• Access Criteria: After the analysis and publication of the trial results, a clear process for data access will be developed with the sponsor to ensure transparency and accountability of data requestors.

Locations

GU (1); CA (1); MO (1); UG (1); ZA (1)