Three Months of Weekly Rifapentine and Isoniazid for M. Tuberculosis Infection
NCT ID: NCT00023452
Last Updated: 2024-08-27
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
8053 participants
INTERVENTIONAL
2001-06-30
2013-09-30
Brief Summary
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Detailed Description
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SECONDARY Objectives:
* Compare the rates of drug discontinuation due to adverse drug reactions associated with 3RPT/INH and 9INH.
* Compare the rates of drug discontinuation for any reason associated with 3RPT/INH and 9INH.
* Compare the rates of any grade 3, 4, or 5 drug toxicity associated with 3RPT/INH and 9INH.
* Compare treatment completion rates of 3RPT/INH and 9INH. Compare the efficacy (i.e., among persons who complete study-phase therapy) of 3RPT/INH and 9INH.
* Compare the effectiveness and tolerability of 3RPT/INH and 9INH in HIV-infected persons.
* Compare the effectiveness and tolerability of 3RPT/INH and 9INH in children \< 18 years old.
* Compare the rates of methadone withdrawal associated with 3RPT/INH and 9INH among persons concomitantly receiving methadone.
* Describe patterns of antibiotic resistance among M. tuberculosis isolates in patients who develop TB despite treatment of latent infection.
Amendment of the study protocol to allow extension of enrollment to children \< 12 years old and HIV-infected persons:
For assessment of the primary outcome, development of TB, a sample size of approximately 4,000 persons per arm will be required. To assess tolerability (one of the secondary outcomes) in sub-groups, children less than 12 years old and HIV-infected persons, a sample size of 644 per strata will be required. A sample size of 8,053 patients for the primary outcome was reached on February 15, 2008 (with expected follow-up completion time in 2010), leaving approximately 454 additional young children and 200 HIV-infected persons to be enrolled to achieve the targets of 644 for each group. The additional data on tolerability in those sub-groups will available for analysis in 2013.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
NONE
Study Groups
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Daily Isoniazid
Isoniazid (INH) daily for 9 months (240 to 270 total doses).
Isoniazid (INH) daily for 9 months
Isoniazid (INH) 5 mg/kg (rounded up to nearest 50 or 100 mg; 300 mg max) daily x 270 doses (9 months) For children age 2 - 11, INH 10-15 mg/kg (round up to nearest 50 or 100 mg; 300 mg max) will be given.
Weekly Isoniazid / Rifapentine
Isoniazid / Rifapentine (RPT/INH) weekly for 3 months (11 to 12 total doses) given by Directly Observed Therapy (DOT)
RPT + INH once weekly for 3 months given by DOT
Rifapentine (RPT) 900 mg once-weekly x 12 doses (3 months) for persons \> 50.0 kg. For persons \< 50.0 kg, the following doses will be given (Weight/Dose): 10.0-14.0 kg / 300 mg; 14.1-25.0 kg / 450 mg; 25.1-32.0 kg / 600 mg; 32.1-50.0 kg / 750 mg.
PLUS
Isoniazid (INH) 15 mg/kg (rounded up to nearest 50 or 100 mg; 900 mg max) once weekly x 12 doses if \> 12 years old. INH 25 mg/kg (round up to nearest 50 or 100 mg; 900 mg max) if 2-11 years old.
Therapy will be given by Directly Observed Therapy (DOT).
Interventions
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RPT + INH once weekly for 3 months given by DOT
Rifapentine (RPT) 900 mg once-weekly x 12 doses (3 months) for persons \> 50.0 kg. For persons \< 50.0 kg, the following doses will be given (Weight/Dose): 10.0-14.0 kg / 300 mg; 14.1-25.0 kg / 450 mg; 25.1-32.0 kg / 600 mg; 32.1-50.0 kg / 750 mg.
PLUS
Isoniazid (INH) 15 mg/kg (rounded up to nearest 50 or 100 mg; 900 mg max) once weekly x 12 doses if \> 12 years old. INH 25 mg/kg (round up to nearest 50 or 100 mg; 900 mg max) if 2-11 years old.
Therapy will be given by Directly Observed Therapy (DOT).
Isoniazid (INH) daily for 9 months
Isoniazid (INH) 5 mg/kg (rounded up to nearest 50 or 100 mg; 300 mg max) daily x 270 doses (9 months) For children age 2 - 11, INH 10-15 mg/kg (round up to nearest 50 or 100 mg; 300 mg max) will be given.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Tuberculin (PPD) skin test reactors at high risk for developing TB but without evidence of active TB. High-risk reactors are defined as:
1. Household and other close contacts of persons with culture-confirmed TB who are TST-positive as part of a contact investigation conducted within two years of the date of enrollment. Close contact is defined as \> 4 hours in a shared airspace during a one-week period. Among close contacts, a positive TST is defined as \> 5 mm induration after 5 TU of PPD placed intradermally using the Mantoux technique.
2. TST converters--converting from a documented negative to positive TST within a two-year period. This is defined as persons with a tuberculin skin test of \> 10 mm within two years of a nonreactive test or persons with an increase of \> 10 mm within a two-year period.
3. HIV-seropositive, TST positive (\> 5 mm induration) persons.
4. Persons with \> 2 cm2 of pulmonary parenchymal fibrosis on chest X-ray, no prior history of TB treatment, \> 5 mm induration on TST, and 3 sputum cultures negative for M. tuberculosis on final report.
* HIV-seropositive close contacts of persons with culture-confirmed TB, regardless of TST status. In addition, HIV-seropositive close contacts of persons with culture-confirmed TB who have a documented history of completing an adequate course of treatment for active TB or latent TB infection, are also eligible.
* Willing to provide signed informed consent, or parental consent and participant assent.
Exclusion Criteria
* Suspected TB (as defined by the site investigator)
* Tuberculosis resistant to isoniazid or rifampin in the source case
* A history of treatment for \> 14 consecutive days with a rifamycin or \> 30 consecutive days with INH during the previous 2 years.
* A documented history of a completing an adequate course of treatment for active TB or latent TB infection in a person who is HIV-seronegative.
* History of sensitivity/intolerance to isoniazid or rifamycins
* Serum aminotransferase aspartate (AST, SGOT) \> 5x upper limit of normal among persons in whom AST is determined
* Pregnant or nursing females
* Persons currently receiving or planning to receive HIV-1 protease inhibitors or nonnucleoside reverse transcriptase inhibitors in the first 90 days after enrollment.
* Weight \< 10.0 kg
2 Years
ALL
No
Sponsors
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US Department of Veterans Affairs
FED
Centers for Disease Control and Prevention
FED
Responsible Party
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Principal Investigators
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Elsa M Villarino, MD, MPH
Role: STUDY_DIRECTOR
Centers for Disease Control and Prevention
Timothy Sterling, MD
Role: STUDY_CHAIR
Vanderbilt University Medical Center
Locations
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Central Arkansas Veterans Health System
Little Rock, Arkansas, United States
LA County/USC Medical Center
Los Angeles, California, United States
UCSD Medical Center
San Diego, California, United States
University of California, San Francisco
San Francisco, California, United States
Denver Department of Public Health and Hospitals
Denver, Colorado, United States
Washington, D.C. VAMC
Washington D.C., District of Columbia, United States
Emory University, Department of Medicine
Atlanta, Georgia, United States
Chicago VA Medical Center (Lakeside)
Chicago, Illinois, United States
Hines VA Medical Center
Hines, Illinois, United States
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States
Boston Medical Center
Boston, Massachusetts, United States
New Jersey Medical School
Newark, New Jersey, United States
Columbia University/Presbyterian Medical Center
New York, New York, United States
Harlem Hospital Center
New York, New York, United States
Carolinas Medical Center
Charlotte, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
University of North Texas Health Science Center
Fort Worth, Texas, United States
Michael Debakey Veterans Affairs Medical Center
Houston, Texas, United States
Audi L. Murphy VA Hospital
San Antonio, Texas, United States
Seattle King County Health Department
Seattle, Washington, United States
Universidade Federal do Rio de Janeiro
Rio de Janeiro, , Brazil
University of British Columbia
Vancouver, British Columbia, Canada
University of Manitoba
Winnipeg, Manitoba, Canada
Montreal Chest Institute McGill University
Montreal, Quebec, Canada
Agencia de Salut Publica
Barcelona, , Spain
Countries
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References
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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.
Moro RN, Mehaffy C, De P, Phillips E, Borisov AS, Sterling TR, Dobos KM. Assessment for Antibodies to Rifapentine and Isoniazid in Persons Developing Flu-Like Reactions During Treatment of Latent Tuberculosis Infection. J Infect Dis. 2024 Nov 15;230(5):1271-1278. doi: 10.1093/infdis/jiae180.
Hedges KNC, Borisov AS, Saukkonen JJ, Scott NA, Hecker EJ, Bozeman L, Dukes Hamilton C, Kerrigan A, Bessler P, Moreno-Martinez A, Arevalo B, Goldberg SV. Nonparticipation reasons in a randomized international trial of a new latent tuberculosis infection regimen. Clin Trials. 2020 Feb;17(1):39-51. doi: 10.1177/1740774519885380. Epub 2019 Nov 6.
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.
Moro RN, Sterling TR, Saukkonen J, Vernon A, Horsburgh CR, Chaisson RE, Hamilton CD, Villarino ME, Goldberg S. Factors associated with non-completion of follow-up: 33-month latent tuberculous infection treatment trial. Int J Tuberc Lung Dis. 2017 Mar 1;21(3):286-296. doi: 10.5588/ijtld.16.0469. Epub 2017 Jan 13.
Sterling TR, Scott NA, Miro JM, Calvet G, La Rosa A, Infante R, Chen MP, Benator DA, Gordin F, Benson CA, Chaisson RE, Villarino ME; Tuberculosis Trials Consortium, the AIDS Clinical Trials Group for the PREVENT TB Trial (TBTC Study 26ACTG 5259) The investigators of the TB Trials Consortium and the AIDS Clinical Trials Group for the PREVENT TB Trial are listed in the Supplement, item 17. Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons. AIDS. 2016 Jun 19;30(10):1607-15. doi: 10.1097/QAD.0000000000001098.
Moro RN, Borisov AS, Saukkonen J, Khan A, Sterling TR, Villarino ME, Scott NA, Shang N, Kerrigan A, Goldberg SV. Factors Associated With Noncompletion of Latent Tuberculosis Infection Treatment: Experience From the PREVENT TB Trial in the United States and Canada. Clin Infect Dis. 2016 Jun 1;62(11):1390-1400. doi: 10.1093/cid/ciw126. Epub 2016 Mar 6.
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.
Villarino ME, Scott NA, Weis SE, Weiner M, Conde MB, Jones B, Nachman S, Oliveira R, Moro RN, Shang N, Goldberg SV, Sterling TR; International Maternal Pediatric and Adolescents AIDS Clinical Trials Group; Tuberculosis Trials Consortium. Treatment for preventing tuberculosis in children and adolescents: a randomized clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and isoniazid. JAMA Pediatr. 2015 Mar;169(3):247-55. doi: 10.1001/jamapediatrics.2014.3158.
Related Links
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(Click here for more information about the Tuberculosis Trials Consortium(TBTC)
Other Identifiers
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CDC TBTC Study 26
Identifier Type: OTHER
Identifier Source: secondary_id
CDC-NCHSTP-3041
Identifier Type: -
Identifier Source: org_study_id
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