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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
Miguel Santín
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Latent Tuberculosis focused on measuring Tuberculosis, Rifamycins, Rifampicin, Rifapentine, Kidney failure

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age 18 years or older
  2. Stage 5 kidney disease (glomerular filtrate rate <15 mL/minute or under substitutive renal therapy
  3. Informed written consent

Exclusion Criteria:

  1. Prior allergy/intolerance to rifamycins or isoniazid
  2. Pregnancy or breastfeeding
  3. Pre-treatment transaminases (ALT and/or AST) >5-fold of normality titer
  4. Concomitant drugs contraindicated with rifamycins
  5. Having received rifamycins or isoniazid within the two previous weeks
  6. Weigh <32 Kgs
  7. 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

    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
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    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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