Ultra Curto (Ultra Short) TB Prevention Therapy

Safety and Tolerability of Ultra-short Course Rifapentine and Isoniazid (1HP) for Prevention of Tuberculosis in HIV-Uninfected Individuals

To compare treatment success (adherence and completion of treatment) and safety of 1HP with 3HP in HIV-uninfected adults and adolescents at increased risk of TB.

Study Overview

• Status: Active, not recruiting
• Conditions: Tuberculosis
• Intervention / Treatment: Drug: Rifapentine 600 mg and INH 300 mg; Drug: Rifapentine 900 mg and INH 900 mg

Detailed Description

Tuberculosis (TB) is the leading infectious killer globally and a major cause of illness and suffering. The World Health Organization has prioritized TB preventive therapy (TPT) for people with latent TB infection (LTBI) as a key strategy for controlling the epidemic. Prevention of TB with isoniazid preventive therapy (IPT) is effective and reduces morbidity and mortality, and has been the mainstay of TB prevention for decades. But for an intervention with an excellent evidence of efficacy, global uptake has been abysmal. Completion rates for IPT when it is administered are poor (Gillespie 2008; Durovni 2010), with a large proportion of patients unable to complete treatment (McClintock 2017; Sterling 2011). While uptake is influenced by a variety of factors, a critical element has been the duration of IPT, with adherence falling sharply over time in clinical trials and practice. Shorter course regimens have a much higher completion rate and are more acceptable to patients, clinicians, and programs.

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Beatriz Kohler; Phone Number: 410-614-3812; Email: bkohler@jhmi.edu
• Study Contact Backup: Name: Richard Chaisson, MD; Phone Number: 4109551755; Email: rchaiss@jhmi.edu

Study Locations

• Brazil
  • AM
    • Manaus, AM, Brazil, 69040-000
      • Fundacao de Medicina Tropical Doutor Heitor
  • RJ
    • Rio De Janeiro, RJ, Brazil, 22450-221
      • NAPDOT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Positive tuberculin skin test or interferon-gamma release assay (IGRA) test and
• Household contact of an infectious TB case within previous 90 days, defined as sleeping at least once in a residence with a person diagnosed with pulmonary TB, or
• Documented conversion of Tuberculin skin test (TST)/IGRA from negative to positive within 2 years

Exclusion Criteria:

• Documented HIV infection
• Evidence of active tuberculosis on clinical exam or chest x-ray
• Known intolerance of any study drug
• Treatment for active or latent TB in the past for more than 14 days
• Known close contact to someone with INH or rifampin resistant TB
• Active liver disease or Aspartate aminotransferase(AST)/Alanine transaminase (ALT) >3 times upper limit of normal (ULN)
• Neutropenia (ANC <1000)
• Peripheral neuropathy >Grade 1 by DAIDS Grading Table
• Pregnant or breastfeeding. Women of childbearing potential must agree to use non-hormonal contraception during study treatment.
• Weight <40 kg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rifapentine 600 mg and Isoniazid 300 mg; Participants will receive Rifapentine 600 mg daily and isoniazid (INH) 300 mg daily for 4 weeks.	Drug: Rifapentine 600 mg and INH 300 mg; Participants will receive Rifapentine 600 mg and INH 300 mg
Active Comparator: Rifapentine 900 mg and Isoniazid 900 mg; Participants will receive Rifapentine 900 mg and isoniazid 900 mg weekly for 12 weeks.	Drug: Rifapentine 900 mg and INH 900 mg; Participants will receive Rifapentine 900 mg and INH 900mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who complete treatment with >90% adherence	To compare treatment success (completion of treatment with >90% adherence) of 1HP with 3HP in HIV-uninfected adults and adolescents at increased risk of TB.	2 years

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Richard Chaisson, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2022
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: January 7, 2021
• First Submitted That Met QC Criteria: January 7, 2021
• First Posted (Actual): January 11, 2021

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifapentine; Rifampin
• Other Study ID Numbers: IRB00284317; U01AI152961 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No