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

December 16, 2025 updated by: ANRS, Emerging Infectious Diseases

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1330

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Cambodia
      • Phnom Penh, Cambodia
        • National Center for HIV/AIDS, Dermatology and STD (NCHADS)
  • Cameroon
      • Yaoundé, Cameroon
        • Jamot Hospital
  • Guinea
      • Conakry, Guinea
        • Ignace Deen Hospital
  • Mozambique
      • Maputo, Mozambique
        • MACHAVA Hospital
  • Uganda
      • Mbarara, Uganda
        • Mbarara Regional Referral Hospital
  • Zambia
      • Lusaka, Zambia
        • University Teaching Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

11 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

INCLUSION CRITERIA

  • 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

EXCLUSION CRITERA

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Intensified TB treatment
  • 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)

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.
Active Comparator: WHO standard TB treatment
  • 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)
8 weeks of RHEZ with FDC.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Rate of all causes death
Time Frame: Up to 48 weeks
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Rate of all causes death
Time Frame: Up to 8 weeks
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
Up to 8 weeks
Rate of all causes death
Time Frame: Up to 24 weeks
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
Up to 24 weeks
Rate of adverse events
Time Frame: Up to 48 weeks
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
Up to 48 weeks
Rate of AIDS-defining illnesses
Time Frame: Up to 48 weeks
Number of AIDS-defining illnesses according to the WHO clinical staging table
Up to 48 weeks
Rate of paradoxical TB-associated IRIS
Time Frame: Up to 14 weeks
Number of paradoxical TB-associated IRIS according to the definition of the international network for the study of HIV-associated (INSHI) consensus case definition
Up to 14 weeks
Rate of TB treatment success
Time Frame: Up to 24 weeks
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
Up to 24 weeks
Rate of TB recurrence
Time Frame: Up to 48 weeks
The number of patients with TB recurrence divided by the total number of randomized patients with TB treatment success at week 24
Up to 48 weeks
Rate of virological success
Time Frame: Week 24
The percentage will be calculated as the number of patients with HIV RNA <50 copies/mL divided by the total number of randomized patients.
Week 24
Rate of virological success
Time Frame: Week 48
The percentage will be calculated as the number of patients with HIV RNA <50 copies/mL divided by the total number of randomized patients.
Week 48
Adherence to TB and ART treatment
Time Frame: up to 24 weeks
The proportion of days with perfect adherence divided by the total number of days of treatment
up to 24 weeks
Immunological response
Time Frame: Up to 48 weeks
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
Up to 48 weeks
Plasma concentrations of rifampicin and isoniazid
Time Frame: Up to 2 weeks
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
Up to 2 weeks
Plasma concentrations of efavirenz and dolutegravir
Time Frame: Week 4
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
Week 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ANRS, Emerging Infectious Diseases

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
European and Developing Countries Clinical Trials Partnership (EDCTP)
European Union

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: BLANC François-Xavier, MD, PhD, University Hospital of Nantes, France
  • Principal Investigator: LAUREILLARD Didier, MD, University Hospital of Nimes, France

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 21, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 12, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 12, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 1, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 1, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 4, 2021

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 22, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 16, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ANRS 12424 DATURA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All coded IPD will be available upon researchers request.

IPD Sharing Time Frame

Data will be available after the princeps paper has been published and for at least 2 years.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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