Tuberculosis Trials Consortium: CDC's TB Treatment and Prevention Trials

In brief

• The Tuberculosis Trials Consortium (TBTC) brings together researchers from CDC, public health departments in the U.S. and abroad, academic medical centers, and selected Veterans Affairs (VA) medical centers.
• Its mission is programmatically relevant research on the diagnosis, clinical management and prevention of TB infection and disease.
• The current research cycle runs from January 2021 to December 2030.

What it does

CDC studies whether new or existing drugs and regimens are needed for preventing and treating TB, and how well they work — their dosage, duration, pharmacokinetics and safety. Most of these trials are run by TBTC. Its work:

• expands clinical and epidemiologic knowledge of TB;
• builds research into the care of people with TB infection and disease;
• promotes research within local TB programs, on questions that matter in public health settings;
• offers a forum for international research important to TB control at home and abroad.

CDC's role. CDC oversees and takes part in TBTC's work. Its team — medical officers, epidemiologists, trialists, microbiologists, data staff, students and others — is the consortium's Data and Coordinating Center. It helps write protocols; guides how each trial is run, analyzed and interpreted; monitors all trials centrally; manages data and drug supplies; sets site laboratory standards; handles pharmacovigilance; presents and publishes results; and coordinates administrative, regulatory and financial support.

Governance. Committees run the consortium, with CDC staff on each:

Partners. New TB treatments depend on academic, private and government researchers, health departments, drug makers, regulators and non-governmental groups. CDC works closely with the Food and Drug Administration, the National Institutes of Health and its National Institute of Allergy and Infectious Diseases, and the Global Alliance for TB Drug Development.

Current studies

The pipeline of new and repurposed TB drug candidates is the most promising in 40 years.

• CRUSH-TB / Study 38 (Combination Regimens for Shortening Tuberculosis Treatment), a phase 2C trial, compares new 4-month regimens based on bedaquiline, moxifloxacin and pyrazinamide with the standard 6-month regimen for drug-sensitive TB disease (NCT05766267).
• ASTERoiD / Study 37 (Assessment of the Safety, Tolerability, and Effectiveness of Rifapentine Given Daily for Latent TB Infection), a phase 3 randomized non-inferiority trial, compares 6 weeks of daily rifapentine with the standard 12–16 weeks of rifamycin-based treatment for latent TB infection (NCT03474029).
• Study 35, a phase 1/2 study, is finding the right dose of a new water-dispersible, child-friendly rifapentine given with isoniazid to children aged 0–12, and its safety in children with and without HIV. If it succeeds, a pediatric formulation for latent TB in young children could become available worldwide (NCT03730181).
• Study 31, run with the National Institute of Allergy and Infectious Diseases' AIDS Clinical Trials Group as ACTG A5349, tested 4-month rifapentine-based regimens for drug-sensitive TB; one of the two was non-inferior. It has ended, and analyses continue (NCT02410772).

History

• 1993–94: CDC invited competitive applications to fund TB researchers and sites able to run clinical trials, for 5 years. It chose sites with access to many TB patients, trial experience, qualified teams, and strong plans for recruiting and following patients.
• U.S. Public Health Service Study 22, the group's first trial, compared a once-weekly rifapentine continuation phase with the then-standard twice-weekly rifampin "Denver" regimen, each for the last 4 months of 6-month treatment. It began in 1995, enrolled 1,075 patients in the U.S. and Canada, and reported in 2002.
• 1997–98: CDC and the Study 22 investigators formed TBTC as a structured consortium, adopting bylaws in 1998 (updated 2012 and 2021).
• 1999: a second competition chose 23 centers in the U.S. and Canada for 1999–2009; sites in Brazil, Spain and Sub-Saharan Africa joined in 2003.
• 2009: a third competition. In 2010–2020, sites outside North America grew to include Peru, Spain, South Africa (two), Uganda, Kenya, Vietnam and Hong Kong, with U.S. sites in New York, Washington, DC, Texas (four), Colorado and Tennessee.
• 2021: CDC named the sites for the cycle through December 2030.

What its trials changed

• Study 22 strongly influenced the ATS/CDC/IDSA guidelines for treating TB disease.
• Study 23 led CDC to change its recommendations for treating TB and HIV.
• Studies 26 and 33 led to updated National Tuberculosis Controllers Association/CDC guidelines for treating latent TB infection.
• Study 31/ACTG A5349 was the first trial to succeed with a 4-month regimen for active TB: daily high-dose rifapentine with moxifloxacin for four months was non-inferior to the standard six-month daily regimen for drug-susceptible TB. It led to CDC's interim guidance and updated WHO guidelines.
• Study 34 informed the 2017 ATS/CDC/IDSA guidelines for TB diagnosis.

TBTC trials have enrolled more than 16,000 patients and volunteers over 20 years.

Sites and funding, 2021–2030

Sites are funded either by individual contracts with CDC or as part of a sub-network coordinated at the Washington, DC, VA Medical Center. Both are re-competed every 10 years.

TBTC sites, 2021–2030. CDC. (PDF)

Sources

Based on "Tuberculosis Trials Consortium," Centers for Disease Control and Prevention; a work of the United States government in the public domain. The names of each site's principal investigators, and the consortium's logo, are left out. Typing errors in the source ("ASTERoidD", "Misson") are corrected.