Clinical trial NCT04703075: Ultra Curto (Ultra Short) TB Prevention Therapy
Official title: Safety and Tolerability of Ultra-short Course Rifapentine and Isoniazid (1HP) for Prevention of Tuberculosis in HIV-Uninfected Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Tuberculosis
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2021-01-11
Enrollment: 500
Sex: ALL
Minimum age (years): 15
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm A (n=250): Experimental arm. Rifapentine 600 mg daily and isoniazid 300 mg daily for 4 weeks.

Arm B (n=250): Control arm. Rifapentine 900 mg and isoniazid 900 mg weekly for 12 weeks.
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants who complete treatment with >90% adherence
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Manaus
country: Brazil
facility: Fundacao de Medicina Tropical Doutor Heitor
state: AM
city: Rio De Janeiro
country: Brazil
facility: NAPDOT
state: RJ
Study officials:
affiliation: Johns Hopkins University
name: Richard Chaisson, MD
role: PRINCIPAL_INVESTIGATOR
References: