Clinical trial NCT05021731: 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
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Latent Tuberculosis
Kidney Failure
Keywords: Tuberculosis
Rifamycins
Rifampicin
Rifapentine
Kidney failure
Lead sponsor: Hospital Universitari de Bellvitge
Sponsor class: OTHER
Collaborators: name: Institut d'Investigació Biomèdica de Bellvitge
name: Instituto de Salud Carlos III
First posted: 2021-08-25
Enrollment: 225
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Treatment completion
timeFrame: 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:
measure: Permanent discontinuation because of adverse events
timeFrame: 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.
measure: Permanent discontinuation because of adverse events related to the treatment
timeFrame: 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.
measure: Death
timeFrame: 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.
Other outcomes:
Locations:
Study officials:
References:
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.