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TuberculosisNCT00023374

TBTC Study 24: Intermittent Treatment of TB With Isoniazid Resistance or Intolerance

A study testing Rifampin, Pyrazinamide and Ethambutol in people with Tuberculosis, run by Centers for Disease Control and Prevention at 23 sites in 2 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

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Tuberculosis
What is being tested?
Rifampin, Pyrazinamide and Ethambutol
Could I receive a placebo?
No, everyone receives an active treatment
How many people
98 participants
Where
23 sitesin 2 countries
Study dates
Aug 2000to Dec 2010
Phase
Interventional
Are there results?
None posted in the registry

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

  • 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 If pyrazinamide resistance is detected and confirmed (see Study Definitions) the patient will be withdrawn from the study therapy, treatment continued as recommended by the treating physician, and follow-up continued as per the protocol.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.
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  • 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:
  • 14 daily doses within 17 days (with at least 10 of the 14 doses directly observed)
  • 14 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;
  • . Total bilirubin level less than 2.5 times upper limit of normal;
  • . Creatinine level less than 2 times upper limit of normal;
  • . Hemoglobin level of at least 7.0 g/dL;
  • . Platelet count of at least 50,000 mm3
  • Karnofsky score of at least 60. See Appendix 6 for Karnofsky scoring system.
  • A negative pregnancy test within the past 14 days for women with child-bearing potential, and a willingness to practice an adequate (preferably barrier) method of birth control. In addition, women with child-bearing potential should be offered information concerning sources of contraceptive counseling and services.
  • Informed consent signed by patient and investigator documenting the willingness to use the 3-drug, intermittent regimen is required, in accordance with state law and local IRB requirements. Patients who are unable to provide informed consent due to an inability to comprehend English may be enrolled by providing informed consent by either of two means:
  • the use of a translator to provide a verbal translation of the IRB-approved English version of the consent form; the translator will sign the English form attesting the translation and the patient will sign the IRB-approved translation of the short form
  • the use of a translated consent document, approved by the IRB, that is in the patient's native language.

Who cannot join

  • 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.

Trial locations and contacts

23 sites in 2 countries.

23 sites in 2 countries

United States20 sites

  • 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

  • Thomas Street Clinic

    Houston, Texas, 77009

  • Central Arkansas Veterans Health System

    Little Rock, Arkansas, 72205

  • LA County/USC Medical Center

    Los Angeles, California, 90033

  • Nashville VA Medical Center

    Nashville, Tennessee, 37212-2637

  • New York University School of Medicine

    New York, New York, 10016

  • 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

  • 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

Other trials in United States

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

Other trials in Canada

About this study

Official title: 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

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.

Read the detailed description

Primary Objective:

To evaluate the efficacy of a directly-observed, largely-intermittent, six-month regimen of rifampin, pyrazinamide, ethambutol among patients with culture confirmed isoniazid-resistant M. tuberculosis.

Secondary Objectives:

To describe the rate, severity and timing of toxicities and drug intolerances associated with this treatment regimen.

To describe the utility of this regimen among patients who are unable to continue the standard 4-drug regimen due to the development of intolerance to isoniazid

Conditions
Tuberculosis
Being tested
Rifampin, Pyrazinamide, Ethambutol, REZ
Keywords
tuberculosis, TB, isoniazid resistance, isoniazid intolerance, treatment, efficacy, toxicity
Medical subject headings
Tuberculosis

What participants receive

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

  • RifampinDrug

    6mos REZ intermittent

  • PyrazinamideDrug

    6mos REZ intermittent

  • EthambutolDrug

    6mos REZ intermittent

  • REZDrug

    Rif+PZA+EMB given 2 or 3 times weekly for 6 months

Study groups in NCT00023374
Study groupRoleWhat they receive
Rifampin+PZA+EthambutolExperimental6 mos of intermittent (2 or 3 times weekly) therapy with REZ
Receives: Drug: Rifampin; Drug: Pyrazinamide; Drug: Ethambutol; Drug: REZ

What is being measured

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

  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

    Measured: 30 mos

Secondary outcomes (8)

  1. Occurrence and timing of toxicities and drug intolerances

    Measured: 6 mos

  2. Time to completion and the frequency of successful completion

    Measured: 6 mos

  3. Occurrence of acquired resistance

    Measured: 30 mos

  4. Proportion with documented conversion of 8-week sputum cultures

    Measured: 8 wks

  5. Bacteriologic failure or relapse in patients with resistance to streptomycin

    Measured: 30 mos

  6. Bacteriologic failure or relapse among patient with history of prior treatment

    Measured: 30 mos

  7. Bacteriologic failure or relapse by duration of isoniazid received

    Measured: 30 mos

  8. Bacteriologic failure or relapse among patients with positive 8-week sputum cultures

    Measured: 30 mos

Timeline

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

  1. First posted10 Sep 2001 (estimated)
  2. Study startAug 2000
  3. Primary completionDec 2006
  4. Study completionDec 2010

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 N/A
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
98 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00023374
Sponsor's protocol ID
CDC-NCHSTP-2340
Other IDs
24
Status last verified
Jun 2011
First submitted
6 Sep 2001
Last updated
3 Aug 2011
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 24903795

  • Funck-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.

    PubMed 23216571

Questions about this trial

What is this clinical trial studying?

A study testing Rifampin, Pyrazinamide and Ethambutol in people with Tuberculosis, run by Centers for Disease Control and Prevention at 23 sites in 2 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 24 inclusion and 5 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 3 Aug 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, Canada. 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.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

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 (time frame: 30 mos). 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 NCT00023374, which also lists 2 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 3 Aug 2011.

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