Short-course Rifamycin-based Regimens for Latent Tuberculosis in Patients With End-stage Kidney Disease
Primary Purpose
Latent Tuberculosis, Kidney Failure
Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Rifampicin plus Isoniazid
Rifapentine plus Isoniazid
Rifampicin alone
Sponsored by
About this trial
This is an interventional prevention trial for Latent Tuberculosis focused on measuring Tuberculosis, Rifamycins, Rifampicin, Rifapentine, Kidney failure
Eligibility Criteria
Inclusion Criteria:
- Age 18 years or older
- Stage 5 kidney disease (glomerular filtrate rate <15 mL/minute or under substitutive renal therapy
- Informed written consent
Exclusion Criteria:
- Prior allergy/intolerance to rifamycins or isoniazid
- Pregnancy or breastfeeding
- Pre-treatment transaminases (ALT and/or AST) >5-fold of normality titer
- Concomitant drugs contraindicated with rifamycins
- Having received rifamycins or isoniazid within the two previous weeks
- Weigh <32 Kgs
- Inability to understand the nature of the study or to give written consent
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Experimental
Arm Label
3-month Isoniazid plus Rifampicin
3-month Isoniazid plus Rifapentine
4-month Rifampicin
Arm Description
Daily isoniazid 300 mg plus rifampicin 600 mg for three months
Weekly isoniazid 900 mg plus rifapentine 900 mg for 12 weeks
Daily rifampicin 600 mg for four months
Outcomes
Primary Outcome Measures
Treatment completion
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
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
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
Number of participants who die while on the study, regardless of its relationship to the treatment assigned at randomization
Full Information
NCT ID
NCT05021731
First Posted
August 13, 2021
Last Updated
August 24, 2021
Sponsor
Miguel Santín
Collaborators
Institut d'Investigació Biomèdica de Bellvitge, Instituto de Salud Carlos III
1. Study Identification
Unique Protocol Identification Number
NCT05021731
Brief Title
Short-course Rifamycin-based Regimens for Latent Tuberculosis in Patients With End-stage Kidney Disease
Official Title
Comparison of 3-month Once-weekly Isoniazid Plus Rifapentine, 4-month Daily Rifampicin, and 3-month Daily Isoniazid Plus Rifampicin for the Treatment Latent Tuberculosis in Patients With End-stage Kidney Disease: A Randomised Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 1, 2022 (Anticipated)
Primary Completion Date
April 30, 2025 (Anticipated)
Study Completion Date
April 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Miguel Santín
Collaborators
Institut d'Investigació Biomèdica de Bellvitge, Instituto de Salud Carlos III
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Latent Tuberculosis, Kidney Failure
Keywords
Tuberculosis, Rifamycins, Rifampicin, Rifapentine, Kidney failure
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
225 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
3-month Isoniazid plus Rifampicin
Arm Type
Active Comparator
Arm Description
Daily isoniazid 300 mg plus rifampicin 600 mg for three months
Arm Title
3-month Isoniazid plus Rifapentine
Arm Type
Experimental
Arm Description
Weekly isoniazid 900 mg plus rifapentine 900 mg for 12 weeks
Arm Title
4-month Rifampicin
Arm Type
Experimental
Arm Description
Daily rifampicin 600 mg for four months
Intervention Type
Drug
Intervention Name(s)
Rifampicin plus Isoniazid
Intervention Description
Administration of rifampicin plus isoniazid for latent tuberculosis
Intervention Type
Drug
Intervention Name(s)
Rifapentine plus Isoniazid
Intervention Description
Administration of rifapentine plus isoniazid for latent tuberculosis
Intervention Type
Drug
Intervention Name(s)
Rifampicin alone
Intervention Description
Administration of rifampicin alone for latent tuberculosis
Primary Outcome Measure Information:
Title
Treatment completion
Description
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).
Time Frame
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.
Secondary Outcome Measure Information:
Title
Permanent discontinuation because of adverse events
Description
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).
Time Frame
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.
Title
Permanent discontinuation because of adverse events related to the treatment
Description
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).
Time Frame
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.
Title
Death
Description
Number of participants who die while on the study, regardless of its relationship to the treatment assigned at randomization
Time Frame
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18 years or older
Stage 5 kidney disease (glomerular filtrate rate <15 mL/minute or under substitutive renal therapy
Informed written consent
Exclusion Criteria:
Prior allergy/intolerance to rifamycins or isoniazid
Pregnancy or breastfeeding
Pre-treatment transaminases (ALT and/or AST) >5-fold of normality titer
Concomitant drugs contraindicated with rifamycins
Having received rifamycins or isoniazid within the two previous weeks
Weigh <32 Kgs
Inability to understand the nature of the study or to give written consent
12. IPD Sharing Statement
Citations:
PubMed Identifier
36269714
Citation
Santin M, Perez-Recio S, Grijota MD, Anibarro L, Barcala JM, De Souza-Galvao ML, Gijon P, Luque R, Sanchez F; RIFAKiD team trial. Comparison of three short-course rifamycin-based regimens for the prevention of tuberculosis in patients with end-stage kidney disease: Study protocol for a randomised clinical trial (RIFAKiD-TB trial). PLoS One. 2022 Oct 21;17(10):e0276387. doi: 10.1371/journal.pone.0276387. eCollection 2022.
Results Reference
derived
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Short-course Rifamycin-based Regimens for Latent Tuberculosis in Patients With End-stage Kidney Disease
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