Assessment of the Safety, Tolerability, and Effectiveness of Rifapentine Given Daily for LTBI

Summary

This study is conducted to compare the safety and effectiveness of a novel short 6-week regimen of daily rifapentine (6wP, experimental arm) with a comparator arm of 12-16 weeks of rifamycin-based treatment (standard of care, control arm) of latent M. tuberculosis infection (LTBI).

This trial is conducted among persons who are at increased risk of progression to tuberculosis (TB) and require treatment of LTBI. The study will be conducted in low, medium and high TB incidence settings that have treatment of LTBI as their standard of care and offer 12-16 week rifamycin-based therapy as standard of care.

The hypothesis of this study is that the safety and effectiveness of the experimental treatment (6wP arm) is non-inferior to a comparator arm of 12-16 weeks of rifamycin-based treatment of LTBI (control arm).

Participants are enrolled and randomly assigned to one of the two study arms: experimental 6wP or control. The comparator (control) arm's treatment regimens include 12 weeks of once-weekly isoniazid (INH) and rifapentine (3HP), 12 weeks of daily INH and rifampin (3HR), and 16 weeks of daily rifampin (4R). A total of 560 participants per arm (1,120 total) for the evaluation of safety and 1,700 participants per arm (3,400 total) for the evaluation of effectiveness will be enrolled, given treatment as per randomization assignment, and followed for 24 months from the date of enrollment.

After completion of data collection, statistical analyses will be conducted to compare proportions of drug discontinuation due to adverse drug reaction (ADR) and proportions of newly diagnosed tuberculosis between 6wP and control arm.

Conditions

• Latent Tuberculosis

Interventions

DRUG

Rifapentine daily for 6 weeks

600 mg of Rifapentine (RPT) given once daily (o.d., omni die) for 6 weeks (6wP).

DRUG

Rifapentine and Isoniazid weekly for 12 weeks

Rifapentine (RPT) 900 mg and isoniazid (INH) 900 mg given once-weekly for 12 weeks (3HP).\* \*Dose adjustments based on patient's weight will be made according to ATS/CDC/IDSA guidelines. RPT 900 mg once-weekly for persons weighing \> 50 kg. For persons weighing \< 50 kg, the following doses will be given: weight \> 25-32 kg - RPT 600 mg; weight \> 32-50 kg - RPT 750 mg; + INH 15 mg/kg (round up to nearest 50 or 100 mg; 900 mg max).

DRUG

Rifampin and Isoniazid daily for 12 weeks

Rifampin (RIF) 600 mg and Isoniazid (INH) 300 mg given once-daily for 12 weeks (3HR)\*. \*Dose adjustments based on patient's weight will be made according to ATS/CDC/IDSA guidelines. RIF 600 mg daily for persons weighing \> 50 kg. For persons weighing \< 50 kg, give 10 mg/kg daily; round up to nearest 50 or 100 mg; + INH 5 mg/kg daily (rounded up to nearest 50 or 100 mg; 300 mg max).

DRUG

Rifampin daily for 16 weeks

Rifampin (RIF) 600 mg given once-daily for 16 weeks (4R).\* \*Dose adjustments based on patient's weight will be made according to ATS/CDC/IDSA guidelines. RIF 600 mg daily for persons weighing \> 50 kg. For persons weighing \< 50 kg, 10 mg/kg daily; round up to nearest 50 or 100 mg.

Sponsors & Collaborators

• Centers for Disease Control and Prevention

  lead FED

Principal Investigators

• Timothy Sterling, MD · Vanderbilt University Medical Center

• Robert Belknap, MD · Denver Public Health (USA)

• Amber Robinson, PhD · Centers for Disease Control and Prevention

• Rosanna M Boyd, PhD · Centers for Disease Control (USA)

• Dick Menzies, MD · McGill University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-08-01

Primary Completion

2029-12-31

Completion

2029-12-31

FDA Drug

Yes

Countries

• United States
• Australia
• Benin
• Canada
• Haiti
• South Africa
• Uganda
• Vietnam

Study Locations