TBTC Study 26: Weekly RFP/INH for 3 mo. vs. Daily INH for 9 mo. for the Treatment of LTBI - Full Text View

Sponsor:	Centers for Disease Control and Prevention
Collaborator:	Department of Veterans Affairs
Information provided by:	Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:	NCT00023452

Purpose

The objectives of this open-label Phase III clinical trial is to compare the effectiveness and tolerability of a three-month (12-dose) regimen of weekly rifapentine and isoniazid (3RPT/INH) to the effectiveness of a nine-month (270-dose)regimen of daily isoniazid (9INH) to prevent tuberculosis (TB) among high-risk tuberculin skin-test reactors, including children and HIV-infected persons, who require treatment of latent TB infection (TLI).

Condition	Intervention	Phase
Tuberculosis	Drug: Rifapentine + Isoniazid once weekly for 3 months Drug: Isoniazid daily for 9 months	Phase III

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	TBTC Study 26: Effectiveness and Tolerability of Weekly Rifapentine/Isoniazid for 3 Months Versus Daily Isoniazid for 9 Months for the Treatment of Latent Tuberculosis Infection

Resource links provided by NLM:

MedlinePlus related topics: Tuberculosis

Drug Information available for: Isoniazid Rifapentine Ftivazide

U.S. FDA Resources

Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:

Culture-confirmed tuberculosis in persons > 18 years old [ Time Frame: within 33 months of completion of LTBI therapy ] [ Designated as safety issue: No ]
Culture-confirmed or probable (clinical) tuberculosis in persons < 18 years old [ Time Frame: within 33 months of completion of LTBI therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Grade 3 or 4 drug-related toxicity [ Time Frame: during study therapy or within 60 days of the date of the last study dose ] [ Designated as safety issue: Yes ]
Death [ Time Frame: during study therapy or within 60 days of the date of the last study dose ] [ Designated as safety issue: Yes ]
Development of methadone withdrawal [ Time Frame: during study therapy or within 60 days of the date of the last study dose ] [ Designated as safety issue: Yes ]
Discontinuation of therapy for any reason [ Time Frame: during study therapy ] [ Designated as safety issue: Yes ]
Completion of the prescribed regimen [ Time Frame: within 33 months ] [ Designated as safety issue: Yes ]
Development of culture (+) TB among HIV-infected patients [ Time Frame: within 33 months of completion of LTBI therapy ] [ Designated as safety issue: No ]
Development of resistance to study medications in isolates during LTBI study therapy [ Time Frame: within 33 months ] [ Designated as safety issue: Yes ]
Discontinuation of study therapy due to AE [ Time Frame: during study therapy phase ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	8000
Study Start Date:	June 2002
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator INH daily for 9 mo.	Drug: Isoniazid daily for 9 months INH 300 mg daily self administered
B: Experimental RPT/INH weekly for 3 months given by DOT	Drug: Rifapentine + Isoniazid once weekly for 3 months Rifapentine 900 mg + INH 900 mg once weekly by DOT

Detailed Description:

The PRIMARY objective of this open-label Phase III clinical trial is to compare the effectiveness of a three-month (12-dose) regimen of weekly rifapentine and isoniazid (3RPT/INH) to the effectiveness of a nine-month (270-dose) regimen of daily isoniazid (9INH) to prevent tuberculosis (TB) among high-risk tuberculin skin-test reactors, including children and HIV-infected persons, who require treatment of latent TB infection (TLI). The 3RPT/INH regimen will be given under direct observation and the 9INH regimen will be self-administered.

SECONDARY Objectives:

Compare the rates of drug discontinuation due to adverse drug reactions associated with 3RPT/INH and 9INH.
Compare the rates of drug discontinuation for any reason associated with 3RPT/INH and 9INH.
Compare the rates of any grade 3, 4, or 5 drug toxicity associated with 3RPT/INH and 9INH.
Compare treatment completion rates of 3RPT/INH and 9INH. Compare the efficacy (i.e., among persons who complete study-phase therapy) of 3RPT/INH and 9INH.
Compare the effectiveness and tolerability of 3RPT/INH and 9INH in HIV-infected persons.
Compare the effectiveness and tolerability of 3RPT/INH and 9INH in children < 18 years old.
Compare the rates of methadone withdrawal associated with 3RPT/INH and 9INH among persons concomitantly receiving methadone.
Describe patterns of antibiotic resistance among M. tuberculosis isolates in patients who develop TB despite treatment of latent infection.

Eligibility

Ages Eligible for Study:	2 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

INCLUSION criteria:

Males or nonpregnant, non-nursing females > 2 years old.
Tuberculin (PPD) skin test reactors at high risk for developing TB but without evidence of active TB. High-risk reactors are defined as:
1. Household and other close contacts of persons with culture-confirmed TB who are TST-positive as part of a contact investigation conducted within two years of the date of enrollment. Close contact is defined as > 4 hours in a shared airspace during a one-week period. Among close contacts, a positive TST is defined as > 5 mm induration after 5 TU of PPD placed intradermally using the Mantoux technique.
2. TST converters--converting from a documented negative to positive TST within a two-year period. This is defined as persons with a tuberculin skin test of > 10 mm within two years of a nonreactive test or persons with an increase of > 10 mm within a two-year period.
3. HIV-seropositive, TST positive (> 5 mm induration) persons.
4. Persons with > 2 cm2 of pulmonary parenchymal fibrosis on chest X-ray, no prior history of TB treatment, > 5 mm induration on TST, and 3 sputum cultures negative for M. tuberculosis on final report.
HIV-seropositive close contacts of persons with culture-confirmed TB, regardless of TST status. In addition, HIV-seropositive close contacts of persons with culture-confirmed TB who have a documented history of completing an adequate course of treatment for active TB or latent TB infection, are also eligible.
Willing to provide signed informed consent, or parental consent and participant assent.

EXCLUSION criteria:

Current confirmed culture-positive or clinical TB
Suspected TB (as defined by the site investigator)
Tuberculosis resistant to isoniazid or rifampin in the source case
A history of treatment for > 14 consecutive days with a rifamycin or > 30 consecutive days with INH during the previous 2 years.
A documented history of a completing an adequate course of treatment for active TB or latent TB infection in a person who is HIV-seronegative.
History of sensitivity/intolerance to isoniazid or rifamycins
Serum aminotransferase aspartate (AST, SGOT) > 5x upper limit of normal among persons in whom AST is determined
Pregnant or nursing females
Persons currently receiving or planning to receive HIV-1 protease inhibitors or nonnucleoside reverse transcriptase inhibitors in the first 90 days after enrollment.
Weight < 10.0 kg

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00023452

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Locations

United States, Arkansas
Central Arkansas Veterans Health System
Little Rock, Arkansas, United States, 72205
United States, California
LA County/USC Medical Center
Los Angeles, California, United States, 90033
University of California, San Francisco
San Francisco, California, United States, 94110
UCSD Medical Center
San Diego, California, United States, 92103
United States, Colorado
Denver Department of Public Health and Hospitals
Denver, Colorado, United States, 80204
United States, District of Columbia
Washington, D.C. VAMC
Washington, District of Columbia, United States, 20422
United States, Georgia
Emory University, Department of Medicine
Atlanta, Georgia, United States, 30303
United States, Illinois
Hines VA Medical Center
Hines, Illinois, United States, 60141
Chicago VA Medical Center (Lakeside)
Chicago, Illinois, United States, 60611
United States, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21287-0003
United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
United States, New Jersey
New Jersey Medical School
Newark, New Jersey, United States, 07107-3001
United States, New York
Columbia University/Presbyterian Medical Center
New York, New York, United States, 10032
Harlem Hospital Center
New York, New York, United States, 10037
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 34222
Carolinas Medical Center
Charlotte, North Carolina, United States, 28203
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
Audi L. Murphy VA Hospital
San Antonio, Texas, United States, 78284
Michael Debakey Veterans Affairs Medical Center
Houston, Texas, United States, 77009
University of North Texas Health Science Center
Fort Worth, Texas, United States, 76107-2699
United States, Washington
Seattle King County Health Department
Seattle, Washington, United States, 98104
Brazil
Universidade Federal do Rio de Janeiro
Rio de Janeiro, Brazil, cep: 21941.590
Canada, British Columbia
University of British Columbia
Vancouver, British Columbia, Canada, Canada V5Z 4R4
Canada, Manitoba
University of Manitoba
Winnipeg, Manitoba, Canada, CANADA R3A 1R8
Canada, Quebec
Montreal Chest Institute McGill University
Montreal, Quebec, Canada, H2X 2P4Pq Canada
Spain
Agencia de Salut Publica
Barcelona, Spain, 08023

Sponsors and Collaborators

Centers for Disease Control and Prevention

Department of Veterans Affairs

Investigators

Study Director:	Elsa Villarino, MD, MPH	Centers for Disease Control and Prevention
Study Chair:	Timothy Sterling, MD	Vanderbilt University

More Information

Additional Information:

(Click here for more information about the Tuberculosis Trials Consortium(TBTC) This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Division of TB Elimination, NCHHSTP, CCID, CDC ( Dr. M. Elsa Villarino, TBTC Team Leader, CHSRB )
Study ID Numbers:	CDC-NCHSTP-3041, TBTC Study 26
Study First Received:	September 6, 2001
Last Updated:	July 27, 2009
ClinicalTrials.gov Identifier:	NCT00023452 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Centers for Disease Control and Prevention:

Latent TB infection

Additional relevant MeSH terms:

Bacterial Infections
Antimetabolites
Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Antilipemic Agents
Rifapentine
Actinomycetales Infections
Pharmacologic Actions
Antibiotics, Antitubercular

Anti-Bacterial Agents
Gram-Positive Bacterial Infections
Therapeutic Uses
Mycobacterium Infections
Tuberculosis
Antitubercular Agents
Fatty Acid Synthesis Inhibitors
Leprostatic Agents
Isoniazid

ClinicalTrials.gov processed this record on November 30, 2009