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

NCT05021731 | Not Yet Recruiting Phase 4

• 1 other identifier: PI21/00444
• Study Type: interventional
• Target: 225
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Latent Tuberculosis; Kidney Failure

Keywords

Tuberculosis; Rifamycins; Rifampicin; Rifapentine; Kidney failure

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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.

• 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.

• 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.

Study Arms (3)

3-month Isoniazid plus Rifampicin

ACTIVE COMPARATOR

Daily isoniazid 300 mg plus rifampicin 600 mg for three months

Drug: Rifampicin plus Isoniazid

3-month Isoniazid plus Rifapentine

EXPERIMENTAL

Weekly isoniazid 900 mg plus rifapentine 900 mg for 12 weeks

Drug: Rifapentine plus Isoniazid

4-month Rifampicin

EXPERIMENTAL

Daily rifampicin 600 mg for four months

Drug: Rifampicin alone

Interventions

Rifampicin plus Isoniazid DRUG

Administration of rifampicin plus isoniazid for latent tuberculosis

3-month Isoniazid plus Rifampicin

Rifapentine plus Isoniazid DRUG

Administration of rifapentine plus isoniazid for latent tuberculosis

3-month Isoniazid plus Rifapentine

Rifampicin alone DRUG

Administration of rifampicin alone for latent tuberculosis

4-month Rifampicin

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Miguel Santín: lead
• Institut d'Investigació Biomèdica de Bellvitge: collaborator
• Instituto de Salud Carlos III: collaborator

Related Publications (1)

• 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.

  PMID: 36269714 DERIVED

MeSH Terms

Conditions

Latent Tuberculosis; Renal Insufficiency; Tuberculosis

Interventions

Rifampin; Isoniazid; rifapentine

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior consultant in infectious diseases

Study Record Dates

• First Submitted: August 13, 2021
• First Posted: August 25, 2021
• Study Start: April 20, 2024
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: March 15, 2024

Record last verified: 2024-03