search
Back to results

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

Primary Purpose

Latent Tuberculosis Infection

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Self Administered Therapy (SAT)
SMS reminders
isoniazid and rifapentine
Sponsored by
Centers for Disease Control and Prevention
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Latent Tuberculosis Infection focused on measuring LTBI, LTB, Latent TB, TB infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • University of California, San Francisco
  • Denver Public Health Department
  • Washington DC Veterans Affairs Medical Center
  • Columbia University College of Physicians and Surgeons and New York City Department of Health
  • Duke University
  • Vanderbilt University Medical Center and Nashville Metro Public Health Department
  • University of North Texas Health Science Center at Fort Worth
  • Audie L. Murphy VA Hospital
  • South Texas - Department of State Health Services
  • TB and Chest service of Hong Kong
  • Wits Health Consortium
  • Agencia de Salut Publica - Barcelona, Spain and UNTHSC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

3HP Directly Observed Therapy (DOT)

3HP Self Administered Therapy (SAT)

3HP SAT with SMS Reminders

Arm Description

900mg of isoniazid plus 900mg of rifapentine given weekly for 3 months (12 weeks, 12 doses) under Directly Observed Therapy (DOT)

900mg of isoniazid plus 900mg of rifapentine given weekly for 3 months (12 weeks, 12 doses) as patient 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). In addition, patient receives phone Short Message Service (SMS) reminders weekly.

Outcomes

Primary Outcome Measures

Treatment completion rate.
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
Treatment completion rates between the DOT arm and the SAT arm without SMS reminders.
Treatment completion rates between the SAT arm with SMS reminders and the SAT arm without SMS reminders.
Rates of treatment discontinuation by category.
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.
Rates of any drug-related grade 3, 4, or 5 adverse events between the DOT arm and the SAT arms (both combined and individually)
Rates and timing of treatment discontinuations between the DOT arm and the SAT arms (both combined and individually).
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).
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).

Full Information

First Posted
February 10, 2012
Last Updated
July 30, 2015
Sponsor
Centers for Disease Control and Prevention
search

1. Study Identification

Unique Protocol Identification Number
NCT01582711
Brief Title
Study 33: Adherence to Latent Tuberculosis Infection Treatment 3HP SAT Versus 3HP DOT
Acronym
iAdhere
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.
Study Type
Interventional

2. Study Status

Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centers for Disease Control and Prevention

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Latent Tuberculosis Infection
Keywords
LTBI, LTB, Latent TB, TB infection

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1002 (Actual)

8. Arms, Groups, and Interventions

Arm Title
3HP Directly Observed Therapy (DOT)
Arm Type
Active Comparator
Arm Description
900mg of isoniazid plus 900mg of rifapentine given weekly for 3 months (12 weeks, 12 doses) under Directly Observed Therapy (DOT)
Arm Title
3HP Self Administered Therapy (SAT)
Arm Type
Experimental
Arm Description
900mg of isoniazid plus 900mg of rifapentine given weekly for 3 months (12 weeks, 12 doses) as patient Self Administered Therapy (SAT)
Arm Title
3HP SAT with SMS Reminders
Arm Type
Experimental
Arm Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Self Administered Therapy (SAT)
Other Intervention Name(s)
SAT
Intervention Description
Self Administered Therapy (SAT)
Intervention Type
Behavioral
Intervention Name(s)
SMS reminders
Other Intervention Name(s)
SMS, phone text reminder
Intervention Description
Short Message Service (SMS) text reminders
Intervention Type
Drug
Intervention Name(s)
isoniazid and rifapentine
Other Intervention Name(s)
PRIFTIN, RPT, P, INH, I
Intervention Description
rifapentine (PRIFTIN, RPT) 900 mg and isoniazid (INH) 900mg, once-weekly, for 12 weeks (12 doses)
Primary Outcome Measure Information:
Title
Treatment completion rate.
Description
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.
Time Frame
Up to 16 weeks from start of treatment.
Secondary Outcome Measure Information:
Title
Treatment completion rates between the DOT arm and the SAT arm with SMS reminders
Time Frame
Up to 16 weeks from start of treatment.
Title
Treatment completion rates between the DOT arm and the SAT arm without SMS reminders.
Time Frame
Up to 16 weeks from start of treatment.
Title
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.
Title
Rates of treatment discontinuation by category.
Description
Categories of treatment discontinuation include: due to adverse events due to patient choice due to inability to locate patient other
Time Frame
Up to 16 weeks from start of treatment.
Title
Rates of SMS reminders utilization.
Time Frame
Up to 16 weeks from start of treatment.
Title
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.
Title
Rates and timing of treatment discontinuations between the DOT arm and the SAT arms (both combined and individually).
Description
This includes discontinuations due to: non-adherence any adverse event (AE) a diagnosis of active TB other reasons
Time Frame
Up to 16 weeks from start of treatment.
Title
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.
Title
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrey S Borisov, MD, MPH
Organizational Affiliation
U.S. Centers for Disease Control and Prevention (CDC), Atlanta, USA.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Robert Belknap, MD
Organizational Affiliation
Division of Infectious Diseases, University of Colorado, Denver, USA.
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Robert Belknap, MD
Organizational Affiliation
Division of Infectious Diseases, University of Colorado, Denver, USA.
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
Denver Public Health Department
City
Denver
State/Province
Colorado
ZIP/Postal Code
80204
Country
United States
Facility Name
Washington DC Veterans Affairs Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20422
Country
United States
Facility Name
Columbia University College of Physicians and Surgeons and New York City Department of Health
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27713
Country
United States
Facility Name
Vanderbilt University Medical Center and Nashville Metro Public Health Department
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-0146
Country
United States
Facility Name
University of North Texas Health Science Center at Fort Worth
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104-4802
Country
United States
Facility Name
Audie L. Murphy VA Hospital
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229-4404
Country
United States
Facility Name
South Texas - Department of State Health Services
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229-4404
Country
United States
Facility Name
TB and Chest service of Hong Kong
City
Hong Kong
Country
China
Facility Name
Wits Health Consortium
City
Soweto
Country
South Africa
Facility Name
Agencia de Salut Publica - Barcelona, Spain and UNTHSC
City
Barcelona
ZIP/Postal Code
08023
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
22150035
Citation
Sterling TR, Villarino ME, Borisov AS, Shang N, Gordin F, Bliven-Sizemore E, Hackman J, Hamilton CD, Menzies D, Kerrigan A, Weis SE, Weiner M, Wing D, Conde MB, Bozeman L, Horsburgh CR Jr, Chaisson RE; TB Trials Consortium PREVENT TB Study Team. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011 Dec 8;365(23):2155-66. doi: 10.1056/NEJMoa1104875.
Results Reference
background
PubMed Identifier
22157884
Citation
Centers for Disease Control and Prevention (CDC). Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent Mycobacterium tuberculosis infection. MMWR Morb Mortal Wkly Rep. 2011 Dec 9;60(48):1650-3. Erratum In: MMWR Morb Mortal Wkly Rep. 2012 Feb 3;61:80.
Results Reference
background
PubMed Identifier
24200264
Citation
Shepardson D, Marks SM, Chesson H, Kerrigan A, Holland DP, Scott N, Tian X, Borisov AS, Shang N, Heilig CM, Sterling TR, Villarino ME, Mac Kenzie WR. Cost-effectiveness of a 12-dose regimen for treating latent tuberculous infection in the United States. Int J Tuberc Lung Dis. 2013 Dec;17(12):1531-7. doi: 10.5588/ijtld.13.0423.
Results Reference
background
PubMed Identifier
25904367
Citation
Sterling TR, Moro RN, Borisov AS, Phillips E, Shepherd G, Adkinson NF, Weis S, Ho C, Villarino ME; Tuberculosis Trials Consortium. Flu-like and Other Systemic Drug Reactions Among Persons Receiving Weekly Rifapentine Plus Isoniazid or Daily Isoniazid for Treatment of Latent Tuberculosis Infection in the PREVENT Tuberculosis Study. Clin Infect Dis. 2015 Aug 15;61(4):527-35. doi: 10.1093/cid/civ323. Epub 2015 Apr 22.
Results Reference
background
PubMed Identifier
29393655
Citation
Moro RN, Scott NA, Vernon A, Tepper NK, Goldberg SV, Schwartzman K, Leung CC, Schluger NW, Belknap RW, Chaisson RE, Narita M, Machado ES, Lopez M, Sanchez J, Villarino ME, Sterling TR. Exposure to Latent Tuberculosis Treatment during Pregnancy. The PREVENT TB and the iAdhere Trials. Ann Am Thorac Soc. 2018 May;15(5):570-580. doi: 10.1513/AnnalsATS.201704-326OC.
Results Reference
derived
PubMed Identifier
29114781
Citation
Belknap R, Holland D, Feng PJ, Millet JP, Cayla JA, Martinson NA, Wright A, Chen MP, Moro RN, Scott NA, Arevalo B, Miro JM, Villarino ME, Weiner M, Borisov AS; TB Trials Consortium iAdhere Study Team. Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection: A Randomized Trial. Ann Intern Med. 2017 Nov 21;167(10):689-697. doi: 10.7326/M17-1150. Epub 2017 Nov 7.
Results Reference
derived
Links:
URL
http://www.cdc.gov/tb/topic/research/tbtc/introduction.htm
Description
Home page of the Tuberculosis Trials Consortium (TBTC) funded by the U.S. Centers for Disease Control and Prevention (CDC)

Learn more about this trial

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

We'll reach out to this number within 24 hrs