TBTC NAA Study: Pilot Study of Surrogate Markers for Outcome of TB Treatment

Tuberculosis Clinical Trial

Official title:

Study of the Performance of Several Nucleic Acid Amplification Methodologies in the Diagnosis and Management of Active TB

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00023439
• Other study ID #: CDC-NCHSTP-2530
• Secondary ID: NAA TBTC
• Status: Completed
• Phase: N/A
• First received: September 6, 2001
• Last updated: August 2, 2011
• Start date: May 2000

Study information

• Verified date: June 2011
• Source: Centers for Disease Control and Prevention
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

This is a pilot study to evaluate the performance of several nucleic acid amplification methodologies in the diagnosis and management of active tuberculosis

Description:

This study evaluates potential surrogate markers of treatment failure and relapse as a substudy of ongoing Tuberculosis Trials Consortium (TBTC) disease treatment studies. After enrollment is complete, specimens from cases of treatment failure and relapse will be evaluated in comparison to control samples to measure the prognostic value of the following tests: 1) quantitative rRNA in 2-month sputum to predict relapse, 2) MTB 85B mRNA to detect reactivation, 3) 1- to 4-month NAA and broth culture tests to predict relapse, 4) mRNA, rRNA and DNA at and after end of therapy to predict relapse, 5)sputum rRNA and blood DNA to detect recurrence during prodrome, 6) sputum rRNA compared to cultures to diagnose "paradoxical reactions," 7) compare blood DNA to cultures at end of induction and end of treatment, 8) compare accuracies of different NAA assays and standard cultures, 9) determine MTD rRNA assay positive to negative conversion time, 10) characterize quality and quantity of sputum over time in relation to culture and clinical outcome, 11) assess ability of clinical, radiographic, and microbiologic risk factors to predict treatment failure and relapse.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. (1) Enrollment in another TBTC treatment study, or (2) Suspected or culture-confirmed pulmonary TB (designated "NAA2"). Acceptable as indicators of suspected tuberculosis -- culture -- will be a positive AFB smear or a positive M. tuberculosis NAA test for MTB.

2. (For NAA2 cases only): Collection of a sputum specimen for NAA processing, obtained in the interval from 14 days before, to 17 days after the start of anti-tuberculosis treatment.

3. Physician recommendation and patient willingness to receive tuberculosis therapy as described in another TBTC treatment trial or in accordance with CDC/ATS recommendations as outlined below:

Induction phase therapy will be initiated with 4-drugs (isoniazid, PZA, rifamycin and either ethambutol or streptomycin) by directly observed therapy (DOT).

• The induction regimen:

1. Induction regimens must have at least 40 DOT doses (if daily) or at least 56 DOT daily dose equivalents (if twice weekly). No more than 2 of every 7 total doses may be self-administered. Total induction doses (both DOT and self-administered) should not exceed 70. Induction should be completed within 12 weeks

2. The ethambutol or streptomycin may be discontinued if the patient continues on adequate induction therapy with INH, rifampin and PZA, and if the M. tuberculosis isolate is susceptible to INH and rifampin.

• If this induction regimen is not tolerated by the patient, a rifampin-containing regimen compatible with CDC/ATS recommendations is an acceptable alternative.

4. Age 18 years or older

5. Willingness to practice effective contraception (if female and of child-bearing potential)

6. Provision of written informed consent. Signed by both the patient and investigator, in accordance with Institutional Review Board requirements

Exclusion Criteria:

• Treatment with a drug(s) with high anti-mycobacterial activity for more than 15 days in the two months PRIOR to the start of anti-tuberculosis treatment, unless co-enrolled in TBTC Study 23, TBTC Study 24 or another TBTC treatment study.

• Patients with only extrapulmonary tuberculosis, unless co-enrolled in TBTC Studies 23, TBTC Study 24, or another TBTC treatment study.

• Skeletal tuberculosis

• Silicotuberculosis

• Patient intolerance of rifamycins, or MTB resistance to rifamycins

• Pregnancy or breast feeding

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Other:
• Nucleic Acid Amplification Methods for diagnosis
no intervention

Locations

Country	Name	City	State
Canada	University of British Columbia	Vancouver	British Columbia
Canada	University of Manitoba	Winnipeg	Manitoba
South Africa	Nelson R. Mandela School of Medicine	Durban	KwaZulu Natal
Uganda	Makerere University Medical School	Kampala
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Chicago-Lakeside VAMC	Chicago	Illinois
United States	Denver Department of Public Health and Hospitals	Denver	Colorado
United States	University of North Texas Health Science Center	Fort Worth	Texas
United States	Central Arkansas Veterans Health System	Little Rock	Arkansas
United States	LA County/USC Medical Center	Los Angeles	California
United States	Harlem Hospital Center	New York	New York
United States	Audi L. Murphy VA Hospital	San Antonio	Texas
United States	University of California, San Francisco	San Francisco	California
United States	Seattle King County Health Department	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Centers for Disease Control and Prevention	VA Office of Research and Development

Countries where clinical trial is conducted

United States,  Canada,  South Africa,  Uganda, 

External Links

•   (Click here for more information about the Tuberculosis Trials Consortium(TBTC)