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

• Status: Not yet recruiting
• Trial end date: 2024-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ANRS, Emerging Infectious Diseases; French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Collaborators: European and Developing Countries Clinical Trials Partnership (EDCTP); European Union

Criteria

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 3 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

• History of ART, unless if stopped for more than 1 year

• Current treatment with ART for more than 1 week

• Any contraindication to efavirenz and dolutegravir

• Severe associated diseases requiring specific treatment (including all specific AIDS defining illnesses other than TB and any severe sepsis)

• Impaired hepatic function with ALT (SGPT) > 5 times the upper limit of normal (ULN) value

• Creatinine clearance < 50 mL/min (according to the Cockcroft-Gault formula)

• Pregnancy or breastfeeding