Short-course Rifamycin-based Regimens for Latent Tuberculosis in Patients With End-stage Kidney Disease
Study Details
Study Description
Brief Summary
Objective To determine if treatment completion with a 4-month rifampin (4R) or 3-month rifapentine (P) + isoniazid (H) weekly for 12 weeks (3HP) regimens is better than with a 3-month (3HR) regimen for treatment of latent tuberculosis (TB) infection (LTBI) in patients with end stage kidney disease.
Methods Design: Multicenter, prospective, parallel-group, open-label, controlled clinical trial.
Study population: All adult patients with ESKD in who treatment for LTBI is prescribed at 7 hospitals.
Interventions: Patients who accept participation, will be randomly assigned to one of the 3 arms: 3HR (control) (90 doses), 4R (120 doses) or 3HP (12 doses).
Outcome: Proportion of participants who discontinue permanently the assigned treatment. Follow-up: Periodic assessment for permanent or temporary discontinuation, and adverse events of the assigned treatment.
Sample size: 225 subjects (75 per arm) will be needed to demonstrate, if exists, a 0.16 decrease in permanent discontinuation rates in the experimental arms (4R and 3HP) with respect to the control arm (3HR), with α= 0.025, β= 0.20, and 5% expected losses, and assuming a 0.25 proportion of permanent discontinuation in the control.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Active Comparator: 3-month Isoniazid plus Rifampicin Daily isoniazid 300 mg plus rifampicin 600 mg for three months |
Drug: Rifampicin plus Isoniazid
Administration of rifampicin plus isoniazid for latent tuberculosis
|
Experimental: 3-month Isoniazid plus Rifapentine Weekly isoniazid 900 mg plus rifapentine 900 mg for 12 weeks |
Drug: Rifapentine plus Isoniazid
Administration of rifapentine plus isoniazid for latent tuberculosis
|
Experimental: 4-month Rifampicin Daily rifampicin 600 mg for four months |
Drug: Rifampicin alone
Administration of rifampicin alone for latent tuberculosis
|
Outcome Measures
Primary Outcome Measures
- Treatment completion [From date of randomization until the date of completion of the assigned treatment, or date of lost to follow-up, or date of death, whichever came first, assessed up to 16 weeks for the 3HR arm, 14 weeks for the 3HP arm, and 20 weeks for the 4R arm.]
Proportion of participants who complete the treatment assigned at randomization, defined as: 1) 90 doses within a maximum of 16 weeks, without interruptions longer than 2 weeks, and no more than in 2 occasions, for 3HR (control arm); 2) 12 doses within a maximum of 14 weeks, without interruptions longer than 10 days, for 3HP (experimental arm 1), and 3) 120 doses within a maximum of 20 weeks, without interruptions longer than 2 weeks, and no more than in two occasions, for 4R (experimental arm 2).
Secondary Outcome Measures
- Permanent discontinuation because of adverse events [From date of randomization until the date of completion of the assigned treatment, or date of lost to follow-up, or date of death, whichever came first, assessed up to 16 weeks for the 3HR arm, 14 weeks for the 3HP arm, and 20 weeks for the 4R arm.]
Proportion of participants who permanently discontinue the treatment assigned, because of adverse events, regardless the relationship of the event/s to the study treatment. Permanent discontinuation defined as: 1) not completion of 90 doses within a maximum of 16 weeks, without interruptions longer than 2 weeks, and no more than in 2 occasions, for 3HR (control arm); 2) not completion 12 doses within a maximum of 14 weeks, without interruptions longer than 10 days, for 3HP (experimental arm 1), and 3) not completion of 120 doses within a maximum of 20 weeks, without interruptions longer than 2 weeks, and no more than in two occasions, for 4R (experimental arm 2).
- Permanent discontinuation because of adverse events related to the treatment [From date of randomization until the date of completion of the assigned treatment, or date of lost to follow-up, or date of death, whichever came first, assessed up to 16 weeks for the 3HR arm, 14 weeks for the 3HP arm, and 20 weeks for the 4R arm.]
Proportion of participants who permanently discontinue the treatment assigned, because of adverse events related to he study treatment Permanent discontinuation defined as: 1) not completion of 90 doses within a maximum of 16 weeks, without interruptions longer than 2 weeks, and no more than in 2 occasions, for 3HR (control arm); 2) not completion 12 doses within a maximum of 14 weeks, without interruptions longer than 10 days, for 3HP (experimental arm 1), and 3) not completion of 120 doses within a maximum of 20 weeks, without interruptions longer than 2 weeks, and no more than in two occasions, for 4R (experimental arm 2).
- Death [From date of randomization until four weeks after completing the assigned treatment, or lost to follow-up, assessed up to 17 weeks for the 3HR arm, 15 weeks for the 3HP arm, and 21 weeks for the 4R arm.]
Number of participants who die while on the study, regardless of its relationship to the treatment assigned at randomization
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age 18 years or older
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Stage 5 kidney disease (glomerular filtrate rate <15 mL/minute or under substitutive renal therapy
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Informed written consent
Exclusion Criteria:
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Prior allergy/intolerance to rifamycins or isoniazid
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Pregnancy or breastfeeding
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Pre-treatment transaminases (ALT and/or AST) >5-fold of normality titer
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Concomitant drugs contraindicated with rifamycins
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Having received rifamycins or isoniazid within the two previous weeks
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Weigh <32 Kgs
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Inability to understand the nature of the study or to give written consent
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Miguel Santín
- Institut d'Investigació Biomèdica de Bellvitge
- Instituto de Salud Carlos III
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PI21/00444