TuberculosisPhase 3PREVENT TBNCT00023452
Three Months of Weekly Rifapentine and Isoniazid for M. Tuberculosis Infection
A Phase 3 study testing RPT + INH once weekly for 3 months given by DOT and Isoniazid (INH) daily for 9 months in people with Tuberculosis, run by Centers for Disease Control and Prevention at 26 sites in 4 countries.
Trial summary
Open-label, multi-center, Phase III clinical trial to compare the effectiveness and tolerability of a three-month (12-dose) regimen of weekly rifapentine and isoniazid (3RPT/INH) to the effectiveness of a nine-month (270-dose)regimen of daily isoniazid (9INH) to prevent tuberculosis (TB) among high-risk tuberculin… Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Tuberculosis
- What is being tested?
- RPT + INH once weekly for 3 months given by DOT and Isoniazid (INH) daily for 9 months
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8,053 participants
- Where
- 26 sitesin 4 countries
- Study dates
- Jun 2001to Sep 2013
- 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 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Males or nonpregnant, non-nursing females > 2 years old.
- Tuberculin (PPD) skin test reactors at high risk for developing TB but without evidence of active TB. High-risk reactors are defined as:
- 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.
- 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.
- HIV-seropositive, TST positive (> 5 mm induration) persons.
- 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.
Who cannot join
- Current confirmed culture-positive or clinical TB
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
26 sites in 4 countries.
26 sites in 4 countries
United States21 sites
Emory University, Department of Medicine
Atlanta, Georgia, 30303
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21287-0003
Boston Medical Center
Boston, Massachusetts, 02118
Carolinas Medical Center
Charlotte, North Carolina, 28203
Chicago VA Medical Center (Lakeside)
Chicago, Illinois, 60611
Denver Department of Public Health and Hospitals
Denver, Colorado, 80204
Duke University Medical Center
Durham, North Carolina, 34222
University of North Texas Health Science Center
Fort Worth, Texas, 76107-2699
Hines VA Medical Center
Hines, Illinois, 60141
Michael Debakey Veterans Affairs Medical Center
Houston, Texas, 77009
Central Arkansas Veterans Health System
Little Rock, Arkansas, 72205
LA County/USC Medical Center
Los Angeles, California, 90033
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Columbia University/Presbyterian Medical Center
New York, New York, 10032
Harlem Hospital Center
New York, New York, 10037
New Jersey Medical School
Newark, New Jersey, 07107-3001
Audi L. Murphy VA Hospital
San Antonio, Texas, 78284
UCSD Medical Center
San Diego, California, 92103
University of California, San Francisco
San Francisco, California, 94110
Seattle King County Health Department
Seattle, Washington, 98104
Washington, D.C. VAMC
Washington D.C., District of Columbia, 20422
Canada3 sites
Montreal Chest Institute McGill University
Montreal, Quebec, H2X 2P4Pq Canada
University of British Columbia
Vancouver, British Columbia, Canada V5Z 4R4
University of Manitoba
Winnipeg, Manitoba, CANADA R3A 1R8
Brazil1 site
Universidade Federal do Rio de Janeiro
Rio de Janeiro, cep: 21941.590
About this study
Official title: TBTC Study 26: Effectiveness and Tolerability of Weekly Rifapentine/Isoniazid for 3 Months Versus Daily Isoniazid for 9 Months for the Treatment of Latent Tuberculosis Infection
Open-label, multi-center, Phase III clinical trial to compare the effectiveness and tolerability of a three-month (12-dose) regimen of weekly rifapentine and isoniazid (3RPT/INH) to the effectiveness of a nine-month (270-dose)regimen of daily isoniazid (9INH) to prevent tuberculosis (TB) among high-risk tuberculin skin-test reactors, including children and HIV-infected persons, who require treatment of latent TB infection (LTBI).
Read the detailed description
The PRIMARY objective of this open-label Phase III clinical trial is to compare the effectiveness of a three-month (12-dose) regimen of weekly rifapentine and isoniazid (3RPT/INH) to the effectiveness of a nine-month (270-dose) regimen of daily isoniazid (9INH) to prevent tuberculosis (TB) among high-risk tuberculin skin-test reactors, including children and HIV-infected persons, who require treatment of latent TB infection (LTBI). The 3RPT/INH regimen will be given under direct observation and the 9INH regimen will be self-administered.
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
- Tuberculosis
- Being tested
- RPT + INH once weekly for 3 months given by DOT, Isoniazid (INH) daily for 9 months
- Keywords
- Latent TB infection
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RPT + INH once weekly for 3 months given by DOTDrug
Also called INH, isoniazid, I, Rifapentine
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 monthsDrug
Also called Isoniazid, INH, I, 9INH
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.
| Study group | Role | What they receive |
|---|---|---|
| Daily Isoniazid | Active comparator | Isoniazid (INH) daily for 9 months (240 to 270 total doses). Receives: Drug: Isoniazid (INH) daily for 9 months |
| Weekly Isoniazid / Rifapentine | Experimental | Isoniazid / Rifapentine (RPT/INH) weekly for 3 months (11 to 12 total doses) given by Directly Observed Therapy (DOT) Receives: Drug: RPT + INH once weekly for 3 months given by DOT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture-Confirmed or Probable (Clinical) TB Disease in Participants Less Than [<]18 Years of Age at 33 Months After Enrollment
Cumulative TB disease rate defined as number of participants ≥18 years old with culture-confirmed TB disease (defined as positive culture for Mycobacterium tuberculosis [MTB]) and those <18 years old with probable (clinical) TB disease (defined as objective evidence of clinical TB disease [cough, fever, night sweats, weight loss, or hemoptysis] based on history or physical exam plus radiograph, computed tomography [CT] scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for acid-fast bacilli [AFB], or caseating granulomata at autopsy or biopsy) between enrollment and the 990th Day of the Trial (33 months after enrollment, or end of the trial) per 100 participants with (w/)33 months of follow-up calculated using survival analysis methods (Kaplan-Meier approach).
Measured: Baseline up to Month 33
Secondary outcomes (14)
Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture-Confirmed or Probable (Clinical) TB Disease in Participants <18 Years of Age at 24 Months Following Completion of Study Therapy
Cumulative TB disease rate was defined as number of participants ≥18 years old with culture-confirmed TB disease (defined as positive culture for MTB) and those <18 years old with probable (clinical) TB disease (defined as objective evidence of clinical TB disease [cough, fever, night sweats, weight loss, or hemoptysis] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB], or caseating granulomata at autopsy or biopsy) between enrollment and 24 months after completion of study therapy per 100 participants with up to 33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach).
Measured: Baseline up to Month 27 (3RPT/INH) or Month 33 (9INH)
Cumulative Rate of Culture-Confirmed or Probable (Clinical) TB Disease (Regardless of Age) At 33 Months After Enrollment
Cumulative TB disease rate was defined as number of participants (regardless of age) with culture-confirmed TB disease (defined as positive culture for MTB]) or probable (clinical) TB disease (defined as objective evidence of clinical TB disease [cough, fever, night sweats, weight loss, or hemoptysis] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB, or caseating granulomata at autopsy or biopsy) between enrollment and the 990th Day of the Trial (33 months after enrollment, or end of the trial) per 100 participants w/33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach).
Measured: Baseline up to 33 Months
Percentage of Participants With Drug Discontinuation Due to Adverse Drug Reactions Associated With 3RPT/INH or 9INH
Discontinuation of study drug due to an adverse drug reaction associated with either 3RPT/INH or 9INH was defined as discontinuing treatment and/or study due to a treatment-related adverse event (AE) (considered either possibly, probably, or definitely related to the study drug by the investigator).
Measured: Baseline up to 60 days after the last dose of study drug (Month 5 [3RPT/INH] or Month 11 [9INH])
Percentage of Patients With Grade 3 or 4 Drug Toxicities Associated With 3RPT/INH or 9INH
Drug toxicities (or AEs) were graded using Common Toxicity Criteria (CTC version 2.0, Publish Date April 30, 1999, Cancer Therapy Evaluation Program). Grade 3 and 4 drug toxicities associated with 3RPT/INH or 9INH were defined as treatment-related Grade 3 or 4 AEs (considered either possibly, probably, or definitely related to the study drug by the investigator).
Measured: Baseline up to 60 days after the last dose of study drug (Month 5 [3RPT/INH] or Month 11 [9INH])
Percentage of Participants With Death Due to Any Cause
Measured: Baseline up to Month 35
Percentage of Participants With Methadone Withdrawal Associated With 3RPT/INH and 9INH Among Participants Receiving Concomitant Methadone
Among participants concomitantly receiving methadone, the development of methadone withdrawal (defined as having >3 new symptoms for >7 days: nausea and vomiting, abdominal cramps, body aches, restlessness, irritability, dilated pupils, tremors, involuntary twitching, lacrimation, rhinorrhea, sneezing, yawning, excessive perspiration, goose flesh, or diarrhea).
Measured: Baseline to Month 33
Percentage of Participants With Drug Discontinuation for Any Reason Associated With 3RPT/INH or 9INH
Drug discontinuations for any reason associated with 3RPT/INH or 9INH included all reasons for discontinuation from study treatment, regardless of relationship to treatment.
Measured: Baseline up to Month 3 (3RPT/INH) or Month 9 (9INH)
Percentage of Participants Who Completed the Treatment Regimen
Completion in the 3RPT/INH arm was defined as: received 12 doses of RPT/INH within 16 weeks (12 weeks optimal). However, participants were considered to have completed therapy if at least 11 doses of RPT/INH had been received (~90%) during the 16-week time period. Completion in the 9INH arm was defined as: received 270 doses of INH within 52 weeks (39 weeks optimal). However, participants were considered to have completed therapy if at least 240 doses of INH were received (~90%) during the 52-week period.
Measured: Baseline up to Month 3 (3RPT/INH) or Month 9 (9INH)
Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture Confirmed or Probable (Clinical) TB Disease Among Participants <18 Years of Age Who Completed Study Phase Therapy Within 33 Months of Enrollment
Cumulative TB disease rate was defined as number of participants ≥18 years old with culture-confirmed TB disease (defined as positive culture for MTB) and <18 years old with probable (clinical) TB disease (defined as objective evidence of clinical TB disease [cough, fever, night sweats, weight loss, or hemoptysis] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB], or caseating granulomata at autopsy or biopsy) between enrollment and 33 months after enrollment (for those who completed therapy within 33 months) per 100 participants w/33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach).
Measured: Baseline up to Month 33
Percentage of Participants With Resistance to Study Medications in Isolates of MTB From Participants Who Developed Active TB Disease Within 33 Months of Enrollment
Drug-susceptibility testing (DST) was performed on isolates of MTB obtained from participants who developed signs and symptoms of active TB disease (including sputum specimens or specimens from appropriate body site for extrapulmonary TB disease). DST was performed at site's local laboratory and sent to Sponsor for confirmatory susceptibility testing. DST included all drugs currently used to treat TB disease, including pyrazinamide (PZA) and fluoroquinolones. Susceptibility was tested for other drugs at the Sponsor laboratory at the following concentrations: INH, 0.02, 1.0, and 5.0 micrograms per milliliter (µg/mL) and rifampin (RIF), 1.0 µg/mL. Isolates resistant to RIF were assumed to be resistant to RPT.
Measured: Baseline up to Month 33
Cumulative Rate of Culture-Confirmed or Probable TB Disease in HIV-Infected Participants Within 33 Months After Enrollment
Cumulative TB disease rate was defined as number of HIV-infected participants ≥2 years old with culture-confirmed TB disease (defined as positive culture for MTB) or probable (clinical) TB disease (defined as objective evidence of clinical TB disease [cough, fever, night sweats, weight loss, or hemoptysis] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB], or caseating granulomata at autopsy or biopsy) between enrollment and the 990th day of the trial (33 months after enrollment, or end of the trial) per 100 participants w/33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach).
Measured: Baseline to Month 33
Cumulative Rate of HIV-Infected Participants With Culture-Confirmed or Probable TB Disease at 24 Months After Completion of Study Therapy
Cumulative TB disease rate was defined as number of HIV-infected participants with culture-confirmed TB (defined as positive culture for MTB) or probable (clinical) TB disease (defined as objective evidence of clinical TB disease [cough, fever, night sweats, weight loss, or hemoptysis] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB], or caseating granulomata at autopsy or biopsy) between enrollment and 24 months after completion of study therapy per 100 participants with up to 33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach).
Measured: Baseline up to Month 27 (3RPT/INH) or Month 33 (9INH)
Cumulative Rate of Participants <18 Years Old With Culture-Confirmed or Probable (Clinical) TB Disease Within 33 Months of Enrollment
Cumulative TB disease rate was defined as number of participants <18 years old with culture-confirmed TB disease (defined as positive culture for MTB) or probable (clinical) TB disease (defined as objective evidence of clinical TB disease [cough, fever, night sweats, weight loss, or hemoptysis] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB], or caseating granulomata at autopsy or biopsy) between enrollment and the 990th day of the trial (33 months after enrollment, or end of the trial) per 100 participants w/33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach).
Measured: Baseline up to Month 33
Cumulative Rate of Participants <12 Years Old With Culture-Confirmed or Probable (Clinical) TB Disease Within 33 Months of Enrollment
Cumulative TB disease rate was defined as number of participants <12 years old with culture-confirmed TB disease (defined as positive culture for MTB) or probable (clinical) TB disease (defined as objective evidence of clinical TB disease [cough, fever, night sweats, weight loss, or hemoptysis] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB], or caseating granulomata at autopsy or biopsy) between enrollment and the 990th day of the trial (33 months after enrollment, or end of the trial) per 100 participants w/33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach).
Measured: Baseline up to Month 33
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2001 (estimated)
- Study startJun 2001
- Primary completionOct 2010
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 8,053 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centers for Disease Control and Prevention
- Sponsor type
- US federal agency
- Collaborators
- US Department of Veterans Affairs
- Responsible party
- Sponsor
- Investigators
- Elsa M Villarino, MD, MPH, Study director, Centers for Disease Control and PreventionTimothy Sterling, MD, Study chair, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00023452
- Sponsor's protocol ID
- CDC-NCHSTP-3041
- Other IDs
- CDC TBTC Study 26
- Acronym
- PREVENT TB
- Status last verified
- Jul 2024
- First submitted
- 6 Sep 2001
- Last updated
- 27 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- 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 22150035Moro 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.
PubMed 38640958Hedges 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.
PubMed 31690107Moro 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 29393655Moro 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.
PubMed 28087928Sterling 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.
PubMed 27243774Moro 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.
PubMed 26951571Sterling 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 25904367Villarino 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.
PubMed 25580725
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TBTC Study 26: Effectiveness and Tolerability of Weekly Rifapentine/Isoniazid for 3 Months Versus Daily Isoniazid for 9 Months for the Treatment of Latent Tuberculosis Infection
- ClinicalTrials.gov ID
- NCT00023452
- Acronym / sponsor ID
- PREVENT TB / CDC-NCHSTP-3041
- Conditions
- Tuberculosis
- Keywords
- Latent TB infection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8,053 participants (actual)
- Lead sponsor
- Centers for Disease Control and PreventionUS federal agency
- Collaborators
- US Department of Veterans Affairs
- Study start
- Jun 2001
- Primary completion
- Oct 2010 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 10 Sep 2001 (estimated)
- Results
- Posted 27 Sep 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Open-label, multi-center, Phase III clinical trial to compare the effectiveness and tolerability of a three-month (12-dose) regimen of weekly rifapentine and isoniazid (3RPT/INH) to the effectiveness of a nine-month (270-dose)regimen of daily isoniazid (9INH) to prevent tuberculosis (TB) among high-risk tuberculin skin-test reactors, including children and HIV-infected persons, who require treatment of latent TB infection (LTBI).
Detailed description
The PRIMARY objective of this open-label Phase III clinical trial is to compare the effectiveness of a three-month (12-dose) regimen of weekly rifapentine and isoniazid (3RPT/INH) to the effectiveness of a nine-month (270-dose) regimen of daily isoniazid (9INH) to prevent tuberculosis (TB) among high-risk tuberculin skin-test reactors, including children and HIV-infected persons, who require treatment of latent TB infection (LTBI). The 3RPT/INH regimen will be given under direct observation and the 9INH regimen will be self-administered.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Daily Isoniazid | Active comparator | Drug: Isoniazid (INH) daily for 9 monthsIsoniazid (INH) daily for 9 months (240 to 270 total doses). |
| Weekly Isoniazid / Rifapentine | Experimental | Drug: RPT + INH once weekly for 3 months given by DOTIsoniazid / Rifapentine (RPT/INH) weekly for 3 months (11 to 12 total doses) given by Directly Observed Therapy (DOT) |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Males or nonpregnant, non-nursing females > 2 years old.
- Tuberculin (PPD) skin test reactors at high risk for developing TB but without evidence of active TB. High-risk reactors are defined as:
- 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.
Key exclusion criteria (10 listed)
- Current confirmed culture-positive or clinical TB
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RPT + INH once weekly for 3 months given by DOTAlso: INH, isoniazid, I, RifapentineRifapentine (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). | Drug | Weekly Isoniazid / Rifapentine |
| Isoniazid (INH) daily for 9 monthsAlso: Isoniazid, INH, I, 9INHIsoniazid (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. | Drug | Daily Isoniazid |
Primary outcome
Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture-Confirmed or Probable (Clinical) TB Disease in Participants Less Than [<]18 Years of Age at 33 Months After Enrollment
Time frame: Baseline up to Month 33
Cumulative TB disease rate defined as number of participants ≥18 years old with culture-confirmed TB disease (defined as positive culture for Mycobacterium tuberculosis [MTB]) and those <18 years old with probable (clinical) TB disease (defined as objective evidence of clinical TB disease [cough, fever, night sweats, weight loss, or hemoptysis] based on history or physical exam plus radiograph, computed tomography [CT] scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for acid-fast bacilli [AFB], or caseating granulomata at autopsy or biopsy) between enrollment and the 990th Day of the Trial (33 months after enrollment, or end of the trial) per 100 participants with (w/)33 months of follow-up calculated using survival analysis methods (Kaplan-Meier approach).
14 secondary outcomes
Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture-Confirmed or Probable (Clinical) TB Disease in Participants <18 Years of Age at 24 Months Following Completion of Study Therapy
Time frame: Baseline up to Month 27 (3RPT/INH) or Month 33 (9INH)
Cumulative Rate of Culture-Confirmed or Probable (Clinical) TB Disease (Regardless of Age) At 33 Months After Enrollment
Time frame: Baseline up to 33 Months
Percentage of Participants With Drug Discontinuation Due to Adverse Drug Reactions Associated With 3RPT/INH or 9INH
Time frame: Baseline up to 60 days after the last dose of study drug (Month 5 [3RPT/INH] or Month 11 [9INH])
Percentage of Patients With Grade 3 or 4 Drug Toxicities Associated With 3RPT/INH or 9INH
Time frame: Baseline up to 60 days after the last dose of study drug (Month 5 [3RPT/INH] or Month 11 [9INH])
Percentage of Participants With Death Due to Any Cause
Time frame: Baseline up to Month 35
Percentage of Participants With Methadone Withdrawal Associated With 3RPT/INH and 9INH Among Participants Receiving Concomitant Methadone
Time frame: Baseline to Month 33
Percentage of Participants With Drug Discontinuation for Any Reason Associated With 3RPT/INH or 9INH
Time frame: Baseline up to Month 3 (3RPT/INH) or Month 9 (9INH)
Percentage of Participants Who Completed the Treatment Regimen
Time frame: Baseline up to Month 3 (3RPT/INH) or Month 9 (9INH)
Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture Confirmed or Probable (Clinical) TB Disease Among Participants <18 Years of Age Who Completed Study Phase Therapy Within 33 Months of Enrollment
Time frame: Baseline up to Month 33
Percentage of Participants With Resistance to Study Medications in Isolates of MTB From Participants Who Developed Active TB Disease Within 33 Months of Enrollment
Time frame: Baseline up to Month 33
Cumulative Rate of Culture-Confirmed or Probable TB Disease in HIV-Infected Participants Within 33 Months After Enrollment
Time frame: Baseline to Month 33
Cumulative Rate of HIV-Infected Participants With Culture-Confirmed or Probable TB Disease at 24 Months After Completion of Study Therapy
Time frame: Baseline up to Month 27 (3RPT/INH) or Month 33 (9INH)
Cumulative Rate of Participants <18 Years Old With Culture-Confirmed or Probable (Clinical) TB Disease Within 33 Months of Enrollment
Time frame: Baseline up to Month 33
Cumulative Rate of Participants <12 Years Old With Culture-Confirmed or Probable (Clinical) TB Disease Within 33 Months of Enrollment
Time frame: Baseline up to Month 33
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22150035Sterling 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.
- Derived from this study: PubMed 38640958Moro 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.
- Derived from this study: PubMed 31690107Hedges 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.
- Derived from this study: PubMed 29393655Moro 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.
- Derived from this study: PubMed 28087928Moro 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.
- Derived from this study: PubMed 27243774Sterling 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.
- Derived from this study: PubMed 26951571Moro 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.
- Derived from this study: PubMed 25904367Sterling 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.
- Derived from this study: PubMed 25580725Villarino 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elsa M Villarino, MD, MPH study director
Centers for Disease Control and Prevention
Timothy Sterling, MD study chair
Vanderbilt University Medical Center
26 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing RPT + INH once weekly for 3 months given by DOT and Isoniazid (INH) daily for 9 months in people with Tuberculosis, run by Centers for Disease Control and Prevention at 26 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 8 inclusion and 10 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 27 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, Canada, Brazil, 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 27 Sep 2012). 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?
Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture-Confirmed or Probable (Clinical) TB Disease in Participants Less Than [<]18 Years of Age at 33 Months After Enrollment (time frame: Baseline up to Month 33). 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 NCT00023452, which also lists 9 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 27 Aug 2024.