Study 33: Adherence to Latent Tuberculosis Infection Treatment 3HP SAT Versus 3HP DOT (iAdhere)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Centers for Disease Control and Prevention
Sponsor:
Information provided by (Responsible Party):
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT01582711
First received: February 10, 2012
Last updated: October 10, 2012
Last verified: October 2012
  Purpose

The study is an open label, multicenter, randomized (three arms: DOT (standard control), SAT, SAT with SMS reminders) controlled clinical trial. The trial is conducted in patients diagnosed with latent tuberculosis infection (LTBI) who are recommended for treatment. The primary objective is to evaluate adherence to a three-month (12-dose) regimen of weekly rifapentine and isoniazid (3RPT/INH) given by directly observed therapy (DOT) compared to self-administered therapy (SAT). The secondary objectives:

  • To compare the treatment completion rates between participants randomized to SAT without reminders versus SAT with weekly SMS reminders
  • To evaluate the timing of doses and patterns of adherence to once weekly RPT/INH among participants who complete treatment and those who discontinue therapy prior to completion.
  • To determine the availability and acceptability of using SMS reminders among all patients consenting to participate in the study.
  • To determine the toxicity and tolerability by comparing the rates of any drug-related grade 3 or 4 adverse events or death between the DOT arm and the SAT arms (both combined and individually)
  • To compare the frequency, timing, and causes for failure to complete treatment between the DOT arm and the SAT arms
  • To collect patient-specific cost data related to the 3 treatment arms
  • To describe the pattern of antituberculosis drug resistance among Mycobacterium tuberculosis strains cultured from participants who develop active TB.

Condition Intervention Phase
Latent Tuberculosis Infection
Behavioral: Self Administered Therapy (SAT)
Behavioral: SMS reminders
Drug: isoniazid and rifapentine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: TBTC Study 33. An Evaluation of Adherence to Latent Tuberculosis Infection (LTBI) Treatment With 12 Doses of Once Weekly Rifapentine (RPT) and Isoniazid (INH) Given as Self-administered (SAT) Versus Directly-observed Therapy (DOT): iAdhere.

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Treatment completion rate. [ Time Frame: Up to 16 weeks from start of treatment. ] [ Designated as safety issue: No ]
    Treatment completion rates between participants randomized to DOT vs SAT without reminders and DOT versus SAT with weekly SMS reminders. Treatment completion is defined as taking at least 90% of the doses (11/12 doses of each drug) within 16 weeks of treatment initiation.


Secondary Outcome Measures:
  • Treatment completion rates between the DOT arm and the SAT arm with SMS reminders [ Time Frame: Up to 16 weeks from start of treatment. ] [ Designated as safety issue: No ]
  • Treatment completion rates between the DOT arm and the SAT arm without SMS reminders. [ Time Frame: Up to 16 weeks from start of treatment. ] [ Designated as safety issue: No ]
  • Treatment completion rates between the SAT arm with SMS reminders and the SAT arm without SMS reminders. [ Time Frame: Up to 16 weeks from start of treatment. ] [ Designated as safety issue: No ]
  • Rates of treatment discontinuation by category. [ Time Frame: Up to 16 weeks from start of treatment. ] [ Designated as safety issue: No ]

    Categories of treatment discontinuation include:

    • due to adverse events
    • due to patient choice
    • due to inability to locate patient
    • other

  • Rates of SMS reminders utilization. [ Time Frame: Up to 16 weeks from start of treatment. ] [ Designated as safety issue: No ]
  • Rates of any drug-related grade 3, 4, or 5 adverse events between the DOT arm and the SAT arms (both combined and individually) [ Time Frame: Up to 20 weeks from start of treatment. ] [ Designated as safety issue: Yes ]
  • Rates and timing of treatment discontinuations between the DOT arm and the SAT arms (both combined and individually). [ Time Frame: Up to 16 weeks from start of treatment. ] [ Designated as safety issue: Yes ]

    This includes discontinuations due to:

    • non-adherence
    • any adverse event (AE)
    • a diagnosis of active TB
    • other reasons

  • Cost of treatment (in USD or QALY) associated with adverse events between the DOT arm and the SAT arms (both combined and individually). [ Time Frame: Up to 20 weeks from start of treatment. ] [ Designated as safety issue: No ]
  • Rates of antituberculosis drug resistance among Mycobacterium tuberculosis strains cultured from patients who develop active TB between the DOT arm and the SAT arms (both combined and individually). [ Time Frame: up to 2 years from start of treatment. ] [ Designated as safety issue: No ]

Estimated Enrollment: 1000
Study Start Date: September 2012
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 3HP Directly Observed Therapy (DOT)
900mg of isoniazid plus 900mg of rifapentine given weekly for 3 months (12 weeks, 12 doses) under Directly Observed Therapy (DOT)
Drug: isoniazid and rifapentine
rifapentine (PRIFTIN, RPT) 900 mg and isoniazid (INH) 900mg, once-weekly, for 12 weeks (12 doses)
Other Names:
  • PRIFTIN
  • RPT
  • P
  • INH
  • I
Experimental: 3HP Self Administered Therapy (SAT)
900mg of isoniazid plus 900mg of rifapentine given weekly for 3 months (12 weeks, 12 doses) as patient Self Administered Therapy (SAT)
Behavioral: Self Administered Therapy (SAT)
Self Administered Therapy (SAT)
Other Name: SAT
Drug: isoniazid and rifapentine
rifapentine (PRIFTIN, RPT) 900 mg and isoniazid (INH) 900mg, once-weekly, for 12 weeks (12 doses)
Other Names:
  • PRIFTIN
  • RPT
  • P
  • INH
  • I
Experimental: 3HP SAT with SMS Reminders
900mg of isoniazid plus 900mg of rifapentine given weekly for 3 months (12 weeks, 12 doses) as patient Self Administered Therapy (SAT). In addition, patient receives phone Short Message Service (SMS) reminders weekly.
Behavioral: Self Administered Therapy (SAT)
Self Administered Therapy (SAT)
Other Name: SAT
Behavioral: SMS reminders
Short Message Service (SMS) text reminders
Other Names:
  • SMS
  • phone text reminder
Drug: isoniazid and rifapentine
rifapentine (PRIFTIN, RPT) 900 mg and isoniazid (INH) 900mg, once-weekly, for 12 weeks (12 doses)
Other Names:
  • PRIFTIN
  • RPT
  • P
  • INH
  • I

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and non-pregnant, non-nursing females
  • Age > 18 years
  • Weight > 45kg and considered appropriate to receive RPT 900mg and INH 900mg once weekly by the local site investigator
  • Willingness to provide signed informed consent.
  • Clinical indication for LTBI treatment such as: 1) persons with a positive tuberculin skin test (TST) as defined by CDC criteria or a positive interferon-gamma release assay (IGRA) defined per the manufacturers' guidelines AND one of the following: close contact to someone with culture confirmed TB, HIV infection, or > 2 cm2 of pulmonary parenchymal fibrosis on chest X-ray and no prior history of TB treatment; 2) TST or IGRA converters defined as a documented change from negative to positive within a two-year period; 3) Persons with any other clinical indication for LTBI treatment as locally defined including persons with a negative TST and/or IGRA (e.g. HIV-infected close contacts to an active pulmonary TB cases)

Exclusion Criteria:

  • Confirmed or suspected active TB
  • Contacts to a source case with known resistance to isoniazid or rifampin
  • Persons with a history (by written documentation or self-report) of ever receiving > 1 week of treatment for active or latent TB, regardless of whether the course was completed, because adherence may be different in people who previously took TB treatment
  • Persons who are not considered candidates for SAT by the local investigator
  • History of sensitivity or intolerance to isoniazid or rifamycins
  • Serum alanine aminotransferase (ALT, SGPT) > 5x upper limit of normal among persons in whom an ALT is determined
  • Persons with HIV-infection who 1) have a CD4 < 350 or 2) are currently receiving or planning to receive antiretroviral therapy in the first 120 days after study initiation (e.g., HIV-1 protease inhibitors, nucleoside or non-nucleoside reverse transcriptase inhibitors, CCR5 inhibitors or integrase inhibitors)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01582711

Contacts
Contact: Andrey S Borisov, MD, MPH 404-639-8056 ABorisov@cdc.gov

Locations
United States, California
University of California, San Francisco Not yet recruiting
San Francisco, California, United States, 94110
Contact: Payam Nahid, MD, MPH    415-206-5464    pnahid@ucsf.edu   
United States, Colorado
Denver Public Health Department Recruiting
Denver, Colorado, United States, 80204
Contact: Robert Belknap, MD    303-602-7244    Robert.Belknap@dhha.org   
United States, District of Columbia
Washington DC Veterans Affairs Medical Center Recruiting
Washington, District of Columbia, United States, 20422
Contact: Debra Benator, MD    202-745-8000    debra.benator@va.gov   
Contact: S. Sonia Qasba, MD    240-777-1800    Sonia.Qasba@montgomerycountymd.gov   
United States, New York
Columbia University College of Physicians and Surgeons and New York City Department of Not yet recruiting
New York, New York, United States, 10032
Contact: Neil Schluger, MD    212-305-9817    11@columbia.edu   
Contact: Joseph Burzynski, MD    (212)368-1500    jburzyns@health.nyc.gov   
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27713
Contact: Carol Dukes Hamilton, MD, MHS    919-544-7040    chamilton@fhi360.org   
Contact: Jason Stout, MD, MHS    (919)668-0826    stout002@mc.duke.edu   
United States, Tennessee
Vanderbilt University Medical Center and Nashville Metro Public Health Department Recruiting
Nashville, Tennessee, United States, 37232-0146
Contact: Timothy Sterling, MD    615-343-0193    timothy.sterling@vanderbilt.edu   
United States, Texas
University of North Texas Health Science Center at Fort Worth Recruiting
Fort Worth, Texas, United States, 76104-4802
Contact: Michel Fernandez, MD    817-321-4948    Michel.Fernandez@unthsc.edu   
Contact: Stephen Weis, DO    (817)321-4937    Stephen.Weis@unthsc.edu   
South Texas - Department of State Health Services Recruiting
San Antonio, Texas, United States, 78229-4404
Contact: Marc Weiner, MD    210-617-5300    weiner@uthscsa.edu   
Contact: Richard Wing, MD    (956)423-0130    Richard.Wing@dshs.state.tx.us   
Audie L. Murphy VA Hospital Recruiting
San Antonio, Texas, United States, 78229-4404
Contact: Marc Weiner, MD    210-617-5300    WEINER@UTHSCSA.EDU   
Brazil
Hospital Universitario Clementino Fraga Filho - Rio de Janeiro, Brazil and Johns Hopkins Not yet recruiting
Rio de Janeiro, Brazil, 21941-913
Contact: Marcus Conde    55-21-25622432    marcusconde@hucff.ufrj.br   
Contact: Fernanda Mello    55-21-25622432    fcqmello@hucff.ufrj.br   
China
TB and Chest service of Hong Kong Not yet recruiting
Hong Kong, China
Contact: Chi-Chiu Leung, MBBS    852-97101028    cc_leung@dh.gov.hk   
Contact: Kwok-Chiu Chang, MBBS, MSc    852-25911147    kc_chang@dh.gov.hk   
South Africa
Wits Health Consortium Not yet recruiting
Soweto, South Africa
Contact: Neil Martinson, MD    +27 (11) 989-9729    martinson@phru.co.za   
Spain
Agencia de Salut Publica - Barcelona, Spain and UNTHSC Not yet recruiting
Barcelona, Spain, 08023
Contact: Joan Cayla, MD, MPH    0034 93 -238- 4555    jcayla@aspb.cat   
Contact: Jose Maria Miro, MD, MPH    (0034) 93-227-5586    miro@medicina.ub.es   
Sponsors and Collaborators
Investigators
Study Director: Andrey S Borisov, MD, MPH U.S. Centers for Disease Control and Prevention (CDC), Atlanta, USA.
Study Chair: Robert Belknap, MD Division of Infectious Diseases, University of Colorado, Denver, USA.
Principal Investigator: Robert Belknap, MD Division of Infectious Diseases, University of Colorado, Denver, USA.
  More Information

Additional Information:
Publications:
Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT01582711     History of Changes
Other Study ID Numbers: CDC-NCHHSTP 6222, TBTC Study 33
Study First Received: February 10, 2012
Last Updated: October 10, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Centers for Disease Control and Prevention:
LTBI
LTB
Latent TB
TB infection

Additional relevant MeSH terms:
Tuberculosis
Latent Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Isoniazid
Rifapentine
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Lipid Regulating Agents
Antibiotics, Antitubercular
Leprostatic Agents

ClinicalTrials.gov processed this record on July 26, 2014