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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT01582711
First received: February 10, 2012
Last updated: September 26, 2014
Last verified: September 2014
  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
Endpoint Classification: Safety/Efficacy Study
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 ]

Enrollment: 1002
Study Start Date: September 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (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

  Hide Detailed Description

Detailed Description:

The World Health Organization (WHO) estimates that approximately 2.3 billion people are infected with Mycobacterium tuberculosis. Approximately 1.7 million people die of TB each year, the second most common infectious cause of death in the world. In order to improve TB control worldwide, an affordable, effective, short course treatment for latent TB infection (LTBI) is a global priority.

Candidates for LTBI treatment are those persons with a positive TST or IGRA, particularly if they also have risk factors for progressing to active TB, including individuals likely to be recently infected. The Prevent TB Study (TBTC Study 26) was an open-label, randomized, phase III controlled clinical trial with over 8,000 high risk TST reactors enrolled. The study compared rifapentine and INH (3RPT/INH) given once-weekly by directly observed treatment (DOT) for 3 months (12 doses) compared with 9 months of daily, self-administered INH. The results demonstrated the safety and efficacy of the shorter regimen. Moreover, the once weekly therapy had significantly higher treatment completion rates than the standard 9 INH regimen.

One of the most effective strategies for assuring adherence with therapy is to have each dose of medication directly administered by a health care worker who observes and records the ingestion of the drugs. DOT for active TB has been successfully used in many settings to improve treatment completion, however cost and logistical constraints of DOT remain. The estimated cost of giving 12 weekly DOT doses to all LTBI patients is likely prohibitive for TB control programs worldwide. This may lead to a decreased uptake of the new regimen or implementation using SAT where adherence has not been studied. Therefore, to apply the Prevent TB study results more broadly, a new study evaluating treatment completion of 3 RPT/INH given as SAT is conducted.

Medication adherence is defined by whether patients take a treatment as prescribed. The effectiveness of any treatment is determined largely by adherence. In clinical practice and research, indirect measures of adherence are commonly used. Indirect measures of adherence include patient self-report, evaluation of pharmacy dispensation records, pill counts, and the use of electronic prescription bottle monitors. Patient self-reported adherence is accurate when non-adherence is reported but tends to overestimate true adherence. Self-report is not discerning enough to be utilized as a sole measure of adherence in research settings where adherence is the primary outcome. Pill counts have been utilized successfully in research and clinical settings for real-time assessment but also tend to overestimate adherence. Electronic drug monitors such as the Medication Event Monitoring System (MEMS) are the best available tools to assess the timing and patterns of adherence. This study uses a combination of indirect measures including MEMS, pill counts, and self-report to provide the most accurate assessment of adherence to once weekly, self-administered RPT/INH.

The number of cellular phone users globally has increased dramatically in the last decade. Cell phones and SMS reminders have been used successfully in randomized controlled clinical trials to improve adherence to vaccines, HIV medications, and asthma treatment. SMS appear to be cost-effective ways to reach patients in remote locations. This study examines effect of SMS on medication adherence.

The goal of this open label clinical trial is to compare the adherence to 3RPT/INH given by DOT versus SAT or SAT with a weekly SMS reminder. The primary assessment of adherence will be treatment completion which is defined as taking at least 90% of the doses (11/12 doses of each drug) within 16 weeks of initiation. Secondary objectives include evaluating the patterns of adherence in participants who fail to complete, determining the feasibility and impact of using SMS reminders on treatment completion with SAT, evaluating the tolerability and any adverse events associated with each treatment arm, monitoring for the development of active TB, determining the drug susceptibility for participants who develop active TB, and measuring important patient-related expenditures associated with each study arm. The trial will be conducted in patients diagnosed with LTBI and recommended for treatment.

  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

Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94110
United States, Colorado
Denver Public Health Department
Denver, Colorado, United States, 80204
United States, District of Columbia
Washington DC Veterans Affairs Medical Center
Washington, District of Columbia, United States, 20422
United States, New York
Columbia University College of Physicians and Surgeons and New York City Department of
New York, New York, United States, 10032
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27713
United States, Tennessee
Vanderbilt University Medical Center and Nashville Metro Public Health Department
Nashville, Tennessee, United States, 37232-0146
United States, Texas
University of North Texas Health Science Center at Fort Worth
Fort Worth, Texas, United States, 76104-4802
South Texas - Department of State Health Services
San Antonio, Texas, United States, 78229-4404
Audie L. Murphy VA Hospital
San Antonio, Texas, United States, 78229-4404
China
TB and Chest service of Hong Kong
Hong Kong, China
South Africa
Wits Health Consortium
Soweto, South Africa
Spain
Agencia de Salut Publica - Barcelona, Spain and UNTHSC
Barcelona, Spain, 08023
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: September 26, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration
Spain: Ministry of Health
Spain: Spanish Agency of Medicines
Hong Kong: Department of Health
Hong Kong: Ethics Committee
South Africa: Human Research Ethics Committee
South Africa: Medicines Control Council

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

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

ClinicalTrials.gov processed this record on November 25, 2014