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

Miguel Santín

Status and phase: Not yet enrolling; Phase 4

Conditions: Kidney Failure; Latent Tuberculosis

Treatments: Drug: Rifampicin alone; Drug: Rifampicin plus Isoniazid; Drug: Rifapentine plus Isoniazid

Study type: Interventional

Funder types: Other

Identifiers

NCT05021731

PI21/00444

Details and patient eligibility

About

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.

Enrollment: 225 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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225 participants in 3 patient groups

3-month Isoniazid plus Rifampicin

Active Comparator group

Description:

Daily isoniazid 300 mg plus rifampicin 600 mg for three months

Treatment:

Drug: Rifampicin plus Isoniazid

3-month Isoniazid plus Rifapentine

Experimental group

Description:

Weekly isoniazid 900 mg plus rifapentine 900 mg for 12 weeks

Treatment:

Drug: Rifapentine plus Isoniazid

4-month Rifampicin

Experimental group

Description:

Daily rifampicin 600 mg for four months

Treatment:

Drug: Rifampicin alone