TB Notes Newsletter
No. 2, 2013
CLINICAL RESEARCH BRANCH UPDATES
The Tuberculosis Trials Consortium (TBTC) held its 33rd semi-annual meeting on May 14–16 in Decatur, GA. Exciting scientific advances and developments for TB control were presented. The consortium continues to develop its longstanding collegiality, collaboration, and high-value productivity, in support of its mission “to conduct programmatically relevant clinical, laboratory, and epidemiologic research concerning the diagnosis, clinical management, treatment, and prevention of tuberculosis infection and disease.”
Dr. Robert Belknap of Denver Public Health, protocol chair, presented progress in TBTC Study 33, “iAdhere,” a phase 4, open label randomized clinical trial of delivery modes for the 12-dose, 3-month regimen of INH and rifapentine (3HP) for treatment of latent TB infection (LTBI). TBTC Study 26 (Sterling, NEJM 2011; 365:2155) demonstrated that 3HP, by directly observed therapy (DOT), “was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate.” CDC (MMWR 2011 60:1650) also recommended 3HP by DOT “as an equal alternative to 9 months of daily self-supervised INH for treating LTBI in otherwise healthy patients aged >12 years...” The first question TB program directors often ask is whether 3HP can be given safely and effectively by self-administered therapy (SAT). Study 33 will help answer this question with the TBTC’s meticulous evaluation of 1000 participants with LTBI, randomized equally into treatment by 1) DOT, 2) standard SAT, or 3) SAT enhanced with weekly text message reminders. As of May 15 for the NTCA report, a total of 439 participants had been enrolled at 11 TBTC sites (487 by July 9, 2013); complete enrollment is expected in the first quarter of 2014.
Dr. Susan Dorman of Johns Hopkins University and Dr. Rada Savic of the University of California at San Francisco presented very encouraging, almost uniformly positive findings from TBTC Study 29x, a phase 2, double-blind evaluation of the safety, tolerability, and efficacy of increasing doses of daily rifapentine, administered in place of rifampin, in otherwise standard induction phase treatment of pulmonary TB. Preliminary findings were presented at the May 2013 international conference of the American Thoracic Society (ATS). Study 29x enrolled and treated 334 participants at 18 TBTC sites. In a pharmacokinetic analysis, the researchers found that a single high absolute dose of rifapentine, at either 900 mg or 1200 mg daily, rather than more complicated weight-based dosing, best provides substantial rifapentine exposure without safety or tolerability concerns. Rifapentine arms had earlier times to stable culture conversion than rifampin on solid and in liquid media. Interestingly, among patients with cavitary disease, the rifapentine arms had substantially improved time to conversion in liquid media when compared to rifampin.
Many of those in attendance at the meeting are hopeful that the next TBTC study will transform TB treatment globally by demonstrating the safety, tolerability, and effectiveness of a 3- or 4-month treatment regimen. Current standard treatment of drug-susceptible TB requires at least 6 months; finding shorter treatment regimens is one of the greatest immediate needs of programmatic TB control and elimination. Based on Study 29x findings, the consortium is writing the protocol for TBTC Study 31, Rifapentine-containing treatment-shortening regimens for pulmonary tuberculosis: A randomized, open-label, controlled phase 3 clinical trial. In preparation for this important treatment-shortening trial, the consortium is 1) conducting data management enhancements using FDA-preferred standards (CDISC), 2) standardizing and incorporating new methods in laboratory practices, 3) optimizing retention practices for study participants during phase-3 follow-up, and 4) enhancing and practicing assessments for disease relapse.
Collaborating attendees at the meeting included representatives from NIAID (Dr. Richard Haffner, Dr. Barbara Laughon), from the TB Alliance (Dr. Stephen Murray), from ACTG (Dr. Sue Swindells, Dr. Janet Anderson), from the Otsuka Novel Products TB team (Dr. Jeff Hafkin), from Sanofi (Isabelle Cieren-Puiseux, Dr. Marilyn Maroni, and Dr. Cathy Canteloube), and from Treatment Action Group (TAG) (Erica Lessem and Mike Frick), in addition to investigators and coordinators from TBTC clinical sites. Community Research Advisory Group (CRAG) members also participated actively.
The TBTC’s contributions to improved treatment of TB infection and disease in the United States and globally are made possible by the tremendous dedication and hard work of staff at participating clinical and support sites and at the Data and Coordinating Center at the Division of TB Elimination in Atlanta.
—Reported by members of the TBTC Data and Coordinating Center
In 1993, the CDC established the Tuberculosis Trials Consortium (TBTC) for the purpose of conducting clinical trials of new drugs and regimens for the treatment and prevention of tuberculosis. The Tuberculosis Trials Consortium is comprised of investigators from 19 clinical research sites including US academic institutions, County Health Departments, and VA Medical Centers both domestic and internationally. The TBTC has been globally recognized as one of the leading TB clinical research groups in the world whose consortium conducts trials that are programmatically relevant.
The Community Research Advisory Group (CRAG) has been a vital and growing component of the Tuberculosis Trials Consortium (TBTC) for several years, partly supported and mentored by the Treatment Action Group (TAG). CRAG has contributed to evaluation of the TBTC’s informed consent process and other activities. At the recent TBTC meeting in Atlanta, Dorothy Namutamba (CRAG co-chair) described how she organized and operationalized the first meeting of the Kampala, Uganda, Community Advisory Board (CAB), which was attended by TBTC site coordinators and other non-TBTC research coordinators in Kampala. This initial meeting provided an opportunity to introduce the concepts of community advisory boards and community engagement to study coordinators. The session generated a rich discussion, as well as the opportunity to hear research priorities from the community perspective.
The Kampala CAB’s next steps will include building the capacity of the CAB; participants decided that future CAB meetings should include educative sessions where TBTC members can give presentations on TB and TB research. To raise awareness about the TB research that is taking place in Uganda, Dorothy wrote an article published in New Vision, Uganda’s leading daily newspaper, on the need for TB research and how this can aid some of the programmatic shortfalls and gaps (access here: http://www.newvision.co.ug/news/ 642730-tb-a-neglected-disease-in-uganda.html).
—Reported by Beverly DeVoe-Payton and
Stefan Goldberg, MD,
Div of TB Elimination, and