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TB Notes 1, 2000
Introduction
Where We've Been and Where We're Going: Perspectives from CDC's Partners in TB Control
Changes I've Seen
TB Control in New York City: A Recent History
Not by DOT Alone
Baltimore at the New Millennium
From Crickets to Condoms and Beyond
The Denver TB Program: Opportunity, Creativity, Persistence, and Luck
National Jewish: The 100-Year War Against TB
Earthquakes, Population Growth, and TB in Los Angeles County
TB in Alaska
CDC and the American Lung Association/ American Thoracic Society: an Enduring Public/Private Partnership
The Unusual Suspects
The Model TB Prevention and Control Centers: History and Purpose
My Perspective on TB Control over the Past Two to Three Decades
History of the IUATLD
Thoughts about the Future of TB Control in the United States
Where We've Been and Where We're Going: Perspectives from CDC
Early History of the CDC TB Division, 1944-1985
CDC Funding for TB Prevention and Control
Managed Care and TB Control - A New Era
Early Research Activities of the TB Control Division
The First TB Drug Clinical Trials
Current TB Drug Trials: The Tuberculosis Trials Consortium (TBTC)
TB Communications and Education
TB Control in the Information Age
Field Services Activities
TB's Public Health Heroes
Infection Control Issues
A Decade of Notable TB Outbreaks: A Selected Review
International Activities
The Role of CDC's Division of Quarantine in the Fight Against TB in the U.S.
The STOP TB Initiative, A Global Partnership
Seize the Moment - Personal Reflections
 
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This is an archived document. The links are no longer being updated.

TB Notes 1, 2000

Current TB Drug Trials: The Tuberculosis Trials Consortium (TBTC)

by Andrew Vernon, MD, MHS
Research and Evaluation Branch, DTBE

Image 1: Logo of the TB Trials Consortium

The USPHS and the Veterans Administration (VA) have a distinguished history of conducting clinical trials to evaluate new drug regimens for both the treatment and prevention of TB. In 1960, CDC assumed a major role in these studies when the USPHS Tuberculosis Division was transferred to CDC. Subsequently, CDC coordinated a series of multicenter clinical trials that helped to establish rifampin-based, short-course therapy as the standard for TB treatment. It also conducted studies to provide the scientific basis for preventive chemotherapy, which remains a major component of our TB elimination strategy.

Support for the infrastructure required for these studies gradually diminished, so that the last completed trial, USPHS Study 21, was nearly terminated several times during its course for lack of adequate funding. With the infusion of federal support for TB control and elimination in the early 1990s, CDC established a consortium of clinical investigators for the specific purpose of conducting USPHS Study 22, a trial of once-weekly isoniazid and rifapentine in the continuation phase of therapy for pulmonary TB. This consortium, whose sites include public health departments, academic medical centers, and VA medical centers (VAMC), required both time and substantial financial resources to establish and support, but is now functioning efficiently.

Did you know that...

Aspirin was developed as a cure for tuberculosis? Researchers in Switzerland looking for a cure for TB were excited to discover that one particular compound was able to relieve the fever and pain of TB patients. They subsequently found that it only provided temporary relief, not a cure, and they put the drug aside. The compound was later rediscovered and named aspirin (from A. Karlen, Man and Microbes, Putnam & Sons, NY, 1995).

Currently new drugs and regimens for both TB treatment and prevention, new diagnostic tests, and new vaccine candidates are becoming available for clinical investigation. Concurrently, the challenges posed by the goal of TB elimination are increasing, as global rates of drug resistance increase and as the costs associated with assuring high rates of adherence rise.

The consortium now provides a unique and important resource for further clinical studies, and has demonstrated its ability to play an important role in TB treatment and prevention.

The original group of clinical sites included 12 academic centers and health departments (7 contracts issued in 1993, and 5 more in 1994), and 15 VAMCs (funded through a Memorandum of Agreement with the Washington, DC, VAMC). Enrollment into USPHS Study 22 began in April 1995, and continued to completion in November 1998. In 1997 CDC began working with the USPHS Study 22 investigators to develop a structure that would engage more fully the capacities of the study investigators in the work of the group. The TBTC was thus organized, with formal by-laws adopted in 1998. Several working committees were established; these are composed of selected Consortium investigators and coordinators, in collaboration with CDC staff. One committee (Core Science) oversees the scientific program of research, a second (Implementation and Quality) supervises the conduct and quality of ongoing studies, and a third (Executive Affairs) serves as the executive arm of the steering committee. This structure is modeled on the Community Programs for Clinical Research on AIDS (CPCRA), which is supported by the National Institute of Allergy and Infectious Diseases (NIAID).

In 1999 the TBTC underwent a formal external re-competition. New 10-year contracts were awarded to 13 offerors (7 prior TBTC members and 6 new sites). The VA side of the consortium underwent a similar process, and funded 10 VA Medical Centers to continue as members of the TBTC.

The current studies of the TBTC are as follows:

Study 22: Randomized open-label trial to evaluate the efficacy of once-weekly isoniazid and rifapentine in the continuation phase of therapy for pulmonary TB. Enrollment closed in November 1998 with 1,004 HIV-negative participants. Follow-up will continue through mid-2001.

Study 22 PK Substudy: Substudy to evaluate isoniazid, rifampin, and rifapentine pharmacokinetics in 150 patients enrolled in Study 22. Currently in analysis.

Serum Bank Study: Collection of documented serum specimens from patients with suspected or proven TB, from baseline through the course of therapy. Nearing completion.

Study 23: Single-arm clinical trial to evaluate the safety and efficacy of rifabutin-containing short-course therapy for HIV-infected TB patients receiving HIV protease inhibitors. Aims to enroll 200 patients over 2 years, with 2-year follow-up. Enrollment began in March 1999.

Study 23a: Substudy to evaluate isoniazid and rifabutin pharmacokinetics in Study 23 TB patients with HIV receiving antiretroviral therapy. Enrollment began July 1999.

Study 23b: Substudy to evaluate rifabutin and nelfinavir pharmacokinetics in TB patients with HIV receiving nelfinavir as part of antiretroviral therapy. CDC IRB approval granted in November 1999.

Study 23c: Substudy to evaluate rifabutin and efavirenz pharmacokinetics in TB patients with HIV receiving efavirenz as part of antiretroviral therapy. Enrollment began December 1999.

Study 24: Single-arm study of largely intermittent, short-course therapy for patients with INH-resistant TB or INH intolerance. Aims to enroll 200 patients over 2 years with 2 years of follow-up. Enrollment began September 1999.

NAA Substudy: Study of the performance of several nucleic acid amplification methodologies in the diagnosis and management of active TB. CDC IRB approval granted in October 1999.

Study 25: Phase I-II dose escalation study of rifapentine using same design as Study 22, with patients completing 2-month standard induction randomized to 600, 900, and 1200 mg of once-weekly rifapentine/isoniazid. Expected to demonstrate safety and tolerability of higher doses of rifapentine, which may improve efficacy, prevent acquired rifampin resistance in HIV-infected patients, and permit use of once-weekly treatment in initial phase. Enrollment began July 1999.

Study 26: Trial of short-course treatment of latent TB infection among contacts of active cases, using a 3-month once-weekly regimen of isoniazid and rifapentine, compared to the recently recommended 2-month daily regimen of rifampin and pyrazinamide. Protocol in design.

For further information about the Consortium, please visit the TBTC web site at http://www.cdc.gov/nchstp/tb/tbtc

 


Released October 2008
Centers for Disease Control and Prevention
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