TuberculosisPhase 3DATURANCT04738812
Determination of Adequate Tuberculosis Regimen in Patients Hospitalized With HIV-associated Severe Immune Suppression
A Phase 3 study testing Intensified TB treatment (initial phase) and WHO standard TB treatment (initial phase) in people with Tuberculosis and HIV-1-infection, run by ANRS, Emerging Infectious Diseases at 6 sites in 6 countries.
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… Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Tuberculosis, HIV-1-infection, Immuno-Deficiency
- What is being tested?
- Intensified TB treatment (initial phase) and WHO standard TB treatment (initial phase)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,330 participants
- Where
- 6 sitesin 6 countries
- Study dates
- 21 Apr 2022to 12 Nov 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- HIV-2 co-infection
- Current treatment with ART containing protease inhibitors
- Any contraindication to efavirenz and dolutegravir
- Severe associated diseases requiring corticosteroids or for which corticosteroids are contra-indicated
- Impaired hepatic function with ALT (SGPT) > 5 times the upper limit of normal (ULN) value
- Creatinine clearance < 30 mL/min/1.73m2 (according to either the MDRD or the CKD-EPI formula)
- Pregnancy or breastfeeding
Trial locations and contacts
6 sites in 6 countries.
6 sites in 6 countries
Cambodia1 site
National Center for HIV/AIDS, Dermatology and STD (NCHADS)
Phnom Penh
About this study
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.
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.
Read the 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
- Being tested
- Intensified TB treatment (initial phase), WHO standard TB treatment (initial phase)
- Keywords
- Tuberculosis, HIV-1, Mortality, Immuno-deficiency, Isoniazid, Rifampicin
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
WHO standard TB treatment (initial phase)Drug
8 weeks of RHEZ with FDC.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: WHO standard TB treatment (initial phase) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 48 weeks
Secondary outcomes (13)
Rate of all causes death
Death for any cause at week 8 will be calculated as the number of deaths between the inclusion visit and week 24, divided by the total person-years of follow-up during the same period
Measured: Up to 8 weeks
Rate of all causes death
Death for any cause at week 24 will be calculated as the number of deaths between the inclusion visit and week 24, divided by the total person-years of follow-up during the same period
Measured: Up to 24 weeks
Rate of adverse events
Number of serious adverse events, all grade 3-4 adverse events (using the DAIDS tables), and any grade 2 adverse events of interest (e.g., hepatotoxicity, rash, peripheral neuropathy, thrombocytopenia, neuropsychiatric disorders), between the inclusion visit and week 48, divided by the total person-years of follow-up during that period
Measured: Up to 48 weeks
Rate of AIDS-defining illnesses
Number of AIDS-defining illnesses according to the WHO clinical staging table
Measured: Up to 48 weeks
Rate of paradoxical TB-associated IRIS
Number of paradoxical TB-associated IRIS according to the definition of the international network for the study of HIV-associated (INSHI) consensus case definition
Measured: Up to 14 weeks
Rate of TB treatment success
The percentage of patients with TB success will be calculated as the number of patients who are cured or who have completed TB treatment, as defined by WHO, divided by the total number of randomized patients
Measured: Up to 24 weeks
Rate of TB recurrence
The number of patients with TB recurrence divided by the total number of randomized patients with TB treatment success at week 24
Measured: Up to 48 weeks
Rate of virological success
The percentage will be calculated as the number of patients with HIV RNA <50 copies/mL divided by the total number of randomized patients.
Measured: Week 24
Rate of virological success
The percentage will be calculated as the number of patients with HIV RNA <50 copies/mL divided by the total number of randomized patients.
Measured: Week 48
Adherence to TB and ART treatment
The proportion of days with perfect adherence divided by the total number of days of treatment
Measured: up to 24 weeks
Immunological response
The mean CD4 cell count gain (with 95% confidence interval) will be calculated as the difference of CD4 cell count between pre-inclusion and week 48
Measured: Up to 48 weeks
Plasma concentrations of rifampicin and isoniazid
Determined 2 hours after the TB drugs intake at day 3, day 7 and week 2 in a subset of 20 patients per arm per country
Measured: Up to 2 weeks
Plasma concentrations of efavirenz and dolutegravir
Determined 12 hours after the drugs intake at week 4 (i.e. 2 weeks after the onset of ART) in a subset of 60 patients per arm for efavirenz and 60 patients per arm for dolutegravir
Measured: Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2021
- Study start21 Apr 2022
- Primary completion12 Nov 2025
- Study completion12 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- DATURA trial is a phase III, multicenter, two-arm, open-label, randomized superiority trial.
- Masking
- None (open label)
- Enrolment
- 1,330 participants (actual)
Sponsor and investigators
- Lead sponsor
- ANRS, Emerging Infectious Diseases
- Sponsor type
- Other government
- Collaborators
- European Union, European and Developing Countries Clinical Trials Partnership (EDCTP)
- Responsible party
- Sponsor
- Investigators
- BLANC François-Xavier, MD, PhD, Principal investigator, University Hospital of Nantes, FranceLAUREILLARD Didier, MD, Principal investigator, University Hospital of Nimes, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04738812
- Sponsor's protocol ID
- ANRS 12424 DATURA
- Acronym
- DATURA
- Status last verified
- Dec 2025
- First submitted
- 1 Feb 2021
- Last updated
- 22 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All coded IPD will be available upon researchers request.