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Latent Tuberculosis InfectionPhase 3iAdhereNCT01582711

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

A Phase 3 study testing Self Administered Therapy (SAT), SMS reminders and isoniazid and rifapentine in people with Latent Tuberculosis Infection, run by Centers for Disease Control and Prevention at 12 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Latent Tuberculosis Infection
What is being tested?
Self Administered Therapy (SAT), SMS reminders and isoniazid and rifapentine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,002 participants
Where
12 sitesin 4 countries
Study dates
Sep 2012to Oct 2014
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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)

Trial locations and contacts

12 sites in 4 countries.

12 sites in 4 countries

United States9 sites
  • Denver Public Health Department

    Denver, Colorado, 80204

  • Duke University

    Durham, North Carolina, 27713

  • University of North Texas Health Science Center at Fort Worth

    Fort Worth, Texas, 76104-4802

  • Vanderbilt University Medical Center and Nashville Metro Public Health Department

    Nashville, Tennessee, 37232-0146

  • Columbia University College of Physicians and Surgeons and New York City Department of Health

    New York, New York, 10032

  • Audie L. Murphy VA Hospital

    San Antonio, Texas, 78229-4404

  • South Texas - Department of State Health Services

    San Antonio, Texas, 78229-4404

  • University of California, San Francisco

    San Francisco, California, 94110

  • Washington DC Veterans Affairs Medical Center

    Washington D.C., District of Columbia, 20422

Other trials in United States

China1 site
  • TB and Chest service of Hong Kong

    Hong Kong

Other trials in China

South Africa1 site
  • Wits Health Consortium

    Soweto

Other trials in South Africa

Spain1 site
  • Agencia de Salut Publica - Barcelona, Spain and UNTHSC

    Barcelona, 08023

Other trials in Spain

About this study

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.

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.
Read the 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.

Being tested
Self Administered Therapy (SAT), SMS reminders, isoniazid and rifapentine
Keywords
LTBI, LTB, Latent TB, TB infection
Medical subject headings
Latent Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Self Administered Therapy (SAT)Behavioural

    Also called SAT

    Self Administered Therapy (SAT)

  • SMS remindersBehavioural

    Also called SMS, phone text reminder

    Short Message Service (SMS) text reminders

  • isoniazid and rifapentineDrug

    Also called PRIFTIN, RPT, P, INH

    rifapentine (PRIFTIN, RPT) 900 mg and isoniazid (INH) 900mg, once-weekly, for 12 weeks (12 doses)

Study groups in NCT01582711
Study groupRoleWhat they receive
3HP Directly Observed Therapy (DOT)Active comparator900mg of isoniazid plus 900mg of rifapentine given weekly for 3 months (12 weeks, 12 doses) under Directly Observed Therapy (DOT)
Receives: Drug: isoniazid and rifapentine
3HP Self Administered Therapy (SAT)Experimental900mg of isoniazid plus 900mg of rifapentine given weekly for 3 months (12 weeks, 12 doses) as patient Self Administered Therapy (SAT)
Receives: Behavioral: Self Administered Therapy (SAT); Drug: isoniazid and rifapentine
3HP SAT with SMS RemindersExperimental900mg 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.
Receives: Behavioral: Self Administered Therapy (SAT); Behavioral: SMS reminders; Drug: isoniazid and rifapentine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Treatment Completion Rate.

    To compare the 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.

    Measured: Up to 16 weeks from start of treatment.

Secondary outcomes (7)
  1. Treatment Completion Rates Between Participants Randomized to SAT Without Reminders Versus SAT With Weekly SMS Reminders

    To compare the treatment completion rates between participants randomized to SAT without reminders versus SAT with weekly SMS reminders

    Measured: Up to 16 weeks from start of treatment.

  2. The Percentage of Participants Who Completed Treatment Based on SOC vs SOC Plus MEMS

    The number and proportion of participants who adhered (completed treatment) based on pill count and self-report, considered to be standard of care (SOC) vs. the number of participants who completed treatment based on SOC plus MEMS cap.

    Measured: Up to 16 weeks from start of treatment.

  3. Availability and Acceptability

    To determine the availability and acceptability of using SMS reminders among all patients consenting to participate in the study.

    Measured: Up to 16 weeks from start of treatment.

  4. Number and Percentage of Participants With Drug-related Grade 3 or 4 Adverse Events or Death

    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)

    Measured: Up to 16 weeks from start of treatment.

  5. Number and Percentage of Participants Reason for Failure to Complete Treatment

    To compare the frequency, timing, and causes for failure to complete treatment between the DOT arm and the SAT arms (both combined and individually) including discontinuation due to:

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

    Measured: Up to 16 weeks from start of treatment.

  6. Patient-specific Cost

    To collect patient-specific cost data related to the DOT and SAT arms

    Measured: Up to 20 weeks from start of treatment.

  7. Antituberculosis Drug Resistance

    To describe the pattern of antituberculosis drug resistance among Mycobacterium tuberculosis strains cultured from participants who develop active TB.

    Measured: Up to 16 weeks from start of treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Apr 2012 (estimated)
  2. Study startSep 2012
  3. Primary completionOct 2014
  4. Study completionOct 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,002 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01582711
Sponsor's protocol ID
CDC-NCHHSTP 6222
Other IDs
TBTC Study 33
Acronym
iAdhere
Status last verified
Feb 2025
First submitted
10 Feb 2012
Last updated
13 Mar 2025
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 22150035
  • 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.

    PubMed 22157884
  • 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.

    PubMed 24200264
  • 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.

    PubMed 25904367
  • Sadowski C, Belknap R, Holland DP, Moro RN, Chen MP, Wright A, Millet JP, Cayla JA, Scott NA, Borisov A, Gandhi NR. Symptoms and Systemic Drug Reactions in Persons Receiving Weekly Rifapentine Plus Isoniazid (3HP) Treatment for Latent Tuberculosis Infection. Clin Infect Dis. 2023 Jun 16;76(12):2090-2097. doi: 10.1093/cid/ciad083.

    PubMed 36815322
  • 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.

    PubMed 29393655
  • 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.

    PubMed 29114781

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Self Administered Therapy (SAT), SMS reminders and isoniazid and rifapentine in people with Latent Tuberculosis Infection, run by Centers for Disease Control and Prevention at 12 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States, China, South Africa, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment Completion Rate. (time frame: Up to 16 weeks from start of treatment.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01582711, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2025.

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