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

Kidney Failure Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05021731
• Other study ID #: PI21/00444
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: April 20, 2024
• Est. completion date: April 30, 2025

Study information

• Verified date: March 2024
• Source: Hospital Universitari de Bellvitge
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 225
• Est. completion date: April 30, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Kidney Diseases
• Kidney Failure
• Kidney Failure, Chronic
• Latent Tuberculosis
• Renal Insufficiency
• Tuberculosis

Intervention

Drug:
• Rifampicin plus Isoniazid
Administration of rifampicin plus isoniazid for latent tuberculosis
• Rifapentine plus Isoniazid
Administration of rifapentine plus isoniazid for latent tuberculosis
• Rifampicin alone
Administration of rifampicin alone for latent tuberculosis

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Miguel Santín	Institut d'Investigació Biomèdica de Bellvitge, Instituto de Salud Carlos III

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	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	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).	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	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).	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	Death	Number of participants who die while on the study, regardless of its relationship to the treatment assigned at randomization	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.