Ultra Curto (Ultra Short) TB Prevention Therapy

Sponsor

Johns Hopkins University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04703075

Collaborator

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

500

Enrollment

Locations

Arms

33.3

Anticipated Duration (Months)

250

Patients Per Site

7.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis	Drug: Rifapentine 600 mg and INH 300 mg Drug: Rifapentine 900 mg and INH 900 mg	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Mar 24, 2022

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Number of participants who complete treatment with >90% adherence [2 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 99 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fundacao de Medicina Tropical Doutor Heitor	Manaus	AM	Brazil	69040-000
2	NAPDOT	Rio De Janeiro	RJ	Brazil	22450-221

Sponsors and Collaborators

Johns Hopkins University
National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Principal Investigator: Richard Chaisson, MD, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Johns Hopkins University

ClinicalTrials.gov Identifier:

NCT04703075

Other Study ID Numbers:

IRB00284317
U01AI152961

First Posted:

Jan 11, 2021

Last Update Posted:

Apr 22, 2022

Last Verified:

Apr 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Tuberculosis

Rifapentine

Rifampin

Study Results

No Results Posted as of Apr 22, 2022