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

Last updated: February 18, 2025
Sponsor: ANRS, Emerging Infectious Diseases
Overall Status: Active - Not Recruiting

Phase

3

Condition

Hiv

Hiv Infections

Lung Disease

Treatment

Intensified TB treatment (initial phase)

WHO standard TB treatment (initial phase)

Clinical Study ID

NCT04738812
ANRS 12424 DATURA
  • Ages > 15
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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 Design

Total Participants: 1330
Treatment Group(s): 2
Primary Treatment: Intensified TB treatment (initial phase)
Phase: 3
Study Start date:
April 21, 2022
Estimated Completion Date:
December 31, 2025

Study 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.

Connect with a study center

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

    Phnom Penh,
    Cambodia

    Site Not Available

  • Jamot Hospital

    Yaoundé,
    Cameroon

    Site Not Available

  • Ignace Deen Hospital

    Conakry,
    Guinea

    Site Not Available

  • MACHAVA Hospital

    Maputo,
    Mozambique

    Site Not Available

  • Mbarara Regional Referral hospital

    Mbarara,
    Uganda

    Site Not Available

  • Pham Ngoc Thach Hospital

    Ho Chi Minh City,
    Vietnam

    Site Not Available

  • University Teaching Hospital

    Lusaka,
    Zambia

    Site Not Available

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