Determination of Adequate Tuberculosis Regimen in Patients Hospitalized With HIV-associated Severe Immune Suppression
NCT ID: NCT04738812
Last Updated: 2025-12-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE3
1330 participants
INTERVENTIONAL
2022-04-21
2025-11-12
Brief Summary
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* 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.
Detailed Description
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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
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
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.
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.
WHO standard TB treatment (initial phase)
8 weeks of RHEZ with FDC.
Interventions
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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.
WHO standard TB treatment (initial phase)
8 weeks of RHEZ with FDC.
Eligibility Criteria
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Inclusion Criteria
* 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
15 Years
ALL
No
Sponsors
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European Union
OTHER
European and Developing Countries Clinical Trials Partnership (EDCTP)
OTHER_GOV
ANRS, Emerging Infectious Diseases
OTHER_GOV
Responsible Party
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Principal Investigators
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BLANC François-Xavier, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
University Hospital of Nantes, France
LAUREILLARD Didier, MD
Role: PRINCIPAL_INVESTIGATOR
University Hospital of Nimes, France
Locations
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National Center for HIV/AIDS, Dermatology and STD (NCHADS)
Phnom Penh, , Cambodia
Jamot Hospital
Yaoundé, , Cameroon
Ignace Deen Hospital
Conakry, , Guinea
MACHAVA Hospital
Maputo, , Mozambique
Mbarara Regional Referral hospital
Mbarara, , Uganda
University Teaching Hospital
Lusaka, , Zambia
Countries
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Other Identifiers
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ANRS 12424 DATURA
Identifier Type: -
Identifier Source: org_study_id