TBTC Study 24: Intermittent Treatment of TB With Isoniazid Resistance or Intolerance
TBTC Study 24: A Non-Comparative Study of the Efficacy of a Largely-Intermittent, Six-Month Tuberculosis Treatment Regimen Among Patients Who Will Not Receive Isoniazid Due to Initial Isoniazid Resistance or Intolerance
2 other identifiers
interventional
98
2 countries
23
Brief Summary
This study is a prospective, open-label, nonrandomized trial using a largely-intermittent, six-month tuberculosis treatment regimen among patients who will not receive isoniazid due to the presence of initial isoniazid resistance or intolerance. Subjects are enrolled after resistance or intolerance to isoniazid has been documented, and are treated for a total of six months (nine months if baseline chest x-ray shows cavitation and 2-month sputum culture is positive) with twice weekly or thrice weekly rifampin, ethambutol, and pyrazinamide.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Aug 2000
Longer than P75 for not_applicable
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2000
CompletedFirst Submitted
Initial submission to the registry
September 6, 2001
CompletedFirst Posted
Study publicly available on registry
September 10, 2001
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2006
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2010
CompletedAugust 3, 2011
June 1, 2011
6.3 years
September 6, 2001
August 2, 2011
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Combined endpoint of bacteriologic plus clinical failure and relapse within 2 years of completing treatment among patients with isoniazid-resistant tuberculosis and among patients enrolled with intolerance to isoniazid
30 mos
Secondary Outcomes (8)
Occurrence and timing of toxicities and drug intolerances
6 mos
Time to completion and the frequency of successful completion
6 mos
Occurrence of acquired resistance
30 mos
Proportion with documented conversion of 8-week sputum cultures
8 wks
Bacteriologic failure or relapse in patients with resistance to streptomycin
30 mos
- +3 more secondary outcomes
Study Arms (1)
Rifampin+PZA+Ethambutol
EXPERIMENTAL6 mos of intermittent (2 or 3 times weekly) therapy with REZ
Interventions
Eligibility Criteria
You may qualify if:
- Culture-confirmed pulmonary or extrapulmonary tuberculosis due to a strain of M tuberculosis sensitive to rifampin, ethambutol and pyrazinamide based upon specimens (sputum or other pulmonary or extrapulmonary disease site specimens) collected no more than 8 weeks before and no more than 2 weeks after the start of the initial therapy. Susceptibility testing results documenting susceptibility to rifampin and ethambutol must be available at the time of enrollment. Susceptibility results to pyrazinamide may be pending at enrollment as long as pyrazinamide resistance is not known to be present based on prior testing. If pyrazinamide resistance is detected and confirmed (see Study Definitions) the patient will be withdrawn from the study therapy, treatment continued as recommended by the treating physician, and follow-up continued as per the protocol.
- Decision to discontinue or not use isoniazid for one or both of these following conditions within the first 70 days of therapy:
- Isoniazid resistant strain (growth in 0.2 mcg/ml or 0.1 mcg/ml of isoniazid on solid or liquid media, respectively)
- The discontinuation of isoniazid due to intolerance (as judged by the principal investigator - see Study Definitions)
- For patients enrolled after the start of therapy, documentation of adequate initial regimen as recommended in the CDC/ATS Treatment Guidelines (Appendix 1) is required. There are two means by which this requirement can be met:
- The standard 4-drug regimen of isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin or both.
- The same regimen with isoniazid excluded for some or all doses in patients with known isoniazid intolerance or tuberculosis due to an isoniazid-resistant strain (i.e., the 3-drug regimen of rifampin, pyrazinamide and either ethambutol or streptomycin or both)
- A minimum duration of daily treatment as defined by one of two methods:
- daily doses within 17 days (with at least 10 of the 14 doses directly observed)
- directly observed doses within 23 days
- Following the minimum daily phase of therapy, adequate pre-enrollment treatment is defined as directly administered therapy given daily, twice weekly, or thrice weekly using CDC/ATS guidelines. Documenting pre-enrollment therapy is accomplished by hospital medical records and/or clinic entries of DOT.
- Age: 18 years or older
- Documentation of negative test for human immunodeficiency virus (HIV) infection. Documentation means written copies of HIV laboratory test results. A negative HIV test result within the 6 months prior to enrollment is acceptable.
- Documentation of study baseline laboratory parameters. Baseline laboratory parameters obtained no more than 2 weeks prior to enrollment and must be within the following limits:
- Amino aspartate transferase (AST) activity less than 3 times upper limit of normal;
- +9 more criteria
You may not qualify if:
- Patients with known treatment-limiting reaction to rifamycins, pyrazinamide, or ethambutol.
- Diagnosis of silicotuberculosis or tuberculosis of the central nervous system
- Patients who, during initial therapy with CDC/ATS recommended therapy with isoniazid, rifampin and pyrazinamide plus either ethambutol or streptomycin or both, have received greater than 21 days of treatment with additional drugs with known antituberculosis activity - see Concomitant Medications During Study Phase Therapy.
- Patients with isoniazid intolerance or isoniazid-resistant tuberculosis who during pre-enrollment therapy have missed a total of two weeks of directly observed therapy doses due to non-compliance.
- Patients enrolled due to isoniazid intolerance who during pre-enrollment therapy have missed a total of over 4 weeks of directly observed therapy doses for management of drug intolerance.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (23)
Central Arkansas Veterans Health System
Little Rock, Arkansas, 72205, United States
LA County/USC Medical Center
Los Angeles, California, 90033, United States
University of California, San Francisco
San Francisco, California, 94110, United States
Denver Department of Public Health and Hospitals
Denver, Colorado, 80204, United States
Washington, D.C. VAMC
Washington D.C., District of Columbia, 20422, United States
Chicago VA Medical Center (Lakeside)
Chicago, Illinois, 60611, United States
Hines VA Medical Center
Hines, Illinois, 60141, United States
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21287-0003, United States
Boston Medical Center
Boston, Massachusetts, 02118, United States
New Jersey Medical School
Newark, New Jersey, 07107-3001, United States
New York University School of Medicine
New York, New York, 10016, United States
Columbia University/Presbyterian Medical Center
New York, New York, 10032, United States
Harlem Hospital Center
New York, New York, 10037, United States
Carolinas Medical Center
Charlotte, North Carolina, 28203, United States
Duke University Medical Center
Durham, North Carolina, 34222, United States
Nashville VA Medical Center
Nashville, Tennessee, 37212-2637, United States
University of North Texas Health Science Center
Fort Worth, Texas, 76107-2699, United States
Thomas Street Clinic
Houston, Texas, 77009, United States
Audi L. Murphy VA Hospital
San Antonio, Texas, 78284, United States
Seattle King County Health Department
Seattle, Washington, 98104, United States
University of British Columbia
Vancouver, British Columbia, Canada V5Z 4R4, Canada
University of Manitoba
Winnipeg, Manitoba, CANADA R3A 1R8, Canada
Montreal Chest Institute McGill University
Montreal, Quebec, H2X 2P4Pq Canada, Canada
Related Publications (2)
Reves R, Heilig CM, Tapy JM, Bozeman L, Kyle RP, Hamilton CD, Bock N, Narita M, Wing D, Hershfield E, Goldberg SV; Tuberculosis Trials Consortium. Intermittent tuberculosis treatment for patients with isoniazid intolerance or drug resistance. Int J Tuberc Lung Dis. 2014 May;18(5):571-80. doi: 10.5588/ijtld.13.0304.
PMID: 24903795DERIVEDFunck-Jensen KL, Dalsgaard J, Grove EL, Hvas AM, Kristensen SD. Increased platelet aggregation and turnover in the acute phase of ST-elevation myocardial infarction. Platelets. 2013;24(7):528-37. doi: 10.3109/09537104.2012.738838. Epub 2012 Dec 5.
PMID: 23216571DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Randall Reves, MD
Denver Health and Hospitals, Denver CO
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- FED
Study Record Dates
First Submitted
September 6, 2001
First Posted
September 10, 2001
Study Start
August 1, 2000
Primary Completion
December 1, 2006
Study Completion
December 1, 2010
Last Updated
August 3, 2011
Record last verified: 2011-06