Ultra Curto (Ultra Short) TB Prevention Therapy

Johns Hopkins University

Status and phase: Completed; Phase 4

Conditions: Tuberculosis

Treatments: Drug: Rifapentine 900 mg and INH 900 mg; Drug: Rifapentine 600 mg and INH 300 mg

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT04703075

U01AI152961 (U.S. NIH Grant/Contract)

IRB00284317

Details and patient eligibility

About

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.

Full 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.

Enrollment: 531 patients

Sex: All

Ages: 15 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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531 participants in 2 patient groups

Arm A: 1HP

Experimental group

Description:

Participants will receive Rifapentine 600 mg daily and isoniazid (INH) 300 mg daily for 4 weeks.

Treatment:

Drug: Rifapentine 600 mg and INH 300 mg

Arm B: 3HP

Active Comparator group

Description:

Participants will receive Rifapentine 900 mg and isoniazid 900 mg weekly for 12 weeks.

Treatment:

Drug: Rifapentine 900 mg and INH 900 mg