Clinical trial NCT00023439: TBTC NAA Study: Pilot Study of Surrogate Markers for Outcome of TB Treatment
Official title: Study of the Performance of Several Nucleic Acid Amplification Methodologies in the Diagnosis and Management of Active TB
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Tuberculosis
Keywords: tuberculosis
TB
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
Collaborators: name: US Department of Veterans Affairs
First posted: 2001-09-10
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: pulmonary TB suspects

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Central Arkansas Veterans Health System
state: Arkansas
city: Los Angeles
country: United States
facility: LA County/USC Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: Denver Department of Public Health and Hospitals
state: Colorado
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Chicago-Lakeside VAMC
state: Illinois
city: New York
country: United States
facility: Harlem Hospital Center
state: New York
city: Fort Worth
country: United States
facility: University of North Texas Health Science Center
state: Texas
city: San Antonio
country: United States
facility: Audi L. Murphy VA Hospital
state: Texas
city: Seattle
country: United States
facility: Seattle King County Health Department
state: Washington
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Durban
country: South Africa
facility: Nelson R. Mandela School of Medicine
state: KwaZulu Natal
city: Kampala
country: Uganda
facility: Makerere University Medical School
Study officials:
affiliation: Audie L. Murphy VA Hospital
name: Marc Weiner, MD
role: PRINCIPAL_INVESTIGATOR
References: