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

NCT01582711 | Completed Phase 3 Results DMC

• 2 other identifiers: CDC-NCHHSTP 6222TBTC Study 33
• Study Type: interventional
• Target: 1,002
• Locations: 4 countries
• Sites: 12

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.

Conditions

Latent Tuberculosis Infection

Keywords

LTBI; LTB; Latent TB; TB infection

Outcome Measures

Primary Outcomes (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.

  Up to 16 weeks from start of treatment.

Secondary Outcomes (7)

• Treatment Completion Rates Between Participants Randomized to SAT Without Reminders Versus SAT With Weekly SMS Reminders

  Up to 16 weeks from start of treatment.

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

  Up to 16 weeks from start of treatment.

• Availability and Acceptability

  Up to 16 weeks from start of treatment.

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

  Up to 16 weeks from start of treatment.

• Number and Percentage of Participants Reason for Failure to Complete Treatment

  Up to 16 weeks from start of treatment.

Study Arms (3)

3HP Directly Observed Therapy (DOT)

ACTIVE COMPARATOR

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

3HP Self Administered Therapy (SAT)

EXPERIMENTAL

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); Drug: isoniazid and rifapentine

3HP SAT with SMS Reminders

EXPERIMENTAL

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); Behavioral: SMS reminders; Drug: isoniazid and rifapentine

Interventions

Self Administered Therapy (SAT) BEHAVIORAL

Self Administered Therapy (SAT)

Also known as: SAT

3HP SAT with SMS Reminders; 3HP Self Administered Therapy (SAT)

SMS reminders BEHAVIORAL

Short Message Service (SMS) text reminders

Also known as: SMS, phone text reminder

3HP SAT with SMS Reminders

isoniazid and rifapentine DRUG

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

Also known as: PRIFTIN, RPT, P, INH, I

3HP Directly Observed Therapy (DOT); 3HP SAT with SMS Reminders; 3HP Self Administered Therapy (SAT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead

Study Sites (12)

University of California, San Francisco

San Francisco, California, 94110, United States

Location

Denver Public Health Department

Denver, Colorado, 80204, United States

Location

Washington DC Veterans Affairs Medical Center

Washington D.C., District of Columbia, 20422, United States

Location

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

New York, New York, 10032, United States

Location

Duke University

Durham, North Carolina, 27713, United States

Location

Vanderbilt University Medical Center and Nashville Metro Public Health Department

Nashville, Tennessee, 37232-0146, United States

Location

University of North Texas Health Science Center at Fort Worth

Fort Worth, Texas, 76104-4802, United States

Location

Audie L. Murphy VA Hospital

San Antonio, Texas, 78229-4404, United States

Location

South Texas - Department of State Health Services

San Antonio, Texas, 78229-4404, United States

Location

TB and Chest service of Hong Kong

Hong Kong, China

Location

Wits Health Consortium

Soweto, South Africa

Location

Agencia de Salut Publica - Barcelona, Spain and UNTHSC

Barcelona, 08023, Spain

Location

Related Publications (7)

• 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.

  PMID: 22150035 BACKGROUND

• 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.

  PMID: 22157884 BACKGROUND

• 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.

  PMID: 24200264 BACKGROUND

• 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.

  PMID: 25904367 BACKGROUND

• 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.

  PMID: 36815322 DERIVED

• 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.

  PMID: 29393655 DERIVED

• 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.

  PMID: 29114781 DERIVED

Related Links

• Home page of the Tuberculosis Trials Consortium (TBTC) funded by the U.S. Centers for Disease Control and Prevention (CDC)

MeSH Terms

Conditions

Latent Tuberculosis

Interventions

Isoniazid; rifapentine

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Andrey Borisov, MD, MPH, Study Director
• Organization: CDC

pha5@cdc.gov

(404) 639-3311

Study Officials

• Andrey S Borisov, MD, MPH

  U.S. Centers for Disease Control and Prevention (CDC), Atlanta, USA.

  STUDY DIRECTOR

• Robert Belknap, MD

  Division of Infectious Diseases, University of Colorado, Denver, USA.

  STUDY CHAIR

• Robert Belknap, MD

  Division of Infectious Diseases, University of Colorado, Denver, USA.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2012
• First Posted: April 23, 2012
• Study Start: September 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: March 13, 2025
• Results First Posted: March 13, 2025

Record last verified: 2025-02

Locations

US (9); ZA (1); ES (1); CN (1)