Short-course Rifamycin-based Regimens for Latent Tuberculosis in Patients With End-stage Kidney Disease

Sponsor
Miguel Santín (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05021731
Collaborator
Institut d'Investigació Biomèdica de Bellvitge (Other), Instituto de Salud Carlos III (Other)
225
3
37

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
  • Drug: Rifampicin plus Isoniazid
  • Drug: Rifapentine plus Isoniazid
  • Drug: Rifampicin alone
Phase 4

Study Design

Study Type:
Interventional
Anticipated Enrollment :
225 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
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
Anticipated Study Start Date :
Apr 1, 2022
Anticipated Primary Completion Date :
Apr 30, 2025
Anticipated Study Completion Date :
Apr 30, 2025

Arms and Interventions

Arm Intervention/Treatment
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

  1. 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

  1. 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).

  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).

  3. 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

Ages Eligible for Study:
18 Years to 85 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

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.
Responsible Party:
Miguel Santín, Senior consultant in infectious diseases, Hospital Universitari de Bellvitge
ClinicalTrials.gov Identifier:
NCT05021731
Other Study ID Numbers:
  • PI21/00444
First Posted:
Aug 25, 2021
Last Update Posted:
Aug 25, 2021
Last Verified:
Aug 1, 2021
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
Keywords provided by Miguel Santín, Senior consultant in infectious diseases, Hospital Universitari de Bellvitge
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 25, 2021