CDC poised for trials of short-course regimen
Adding RFP to regimen will yield 12 doses
A study of a new, short-course regimen proposed for the treatment of latent TB infection likely will begin enrolling patients by next summer, says Rick O’Brien, MD, MPH, chief of the Research and Evaluation Branch at the Division for Tuberculosis Elimination (DTBE) at the Centers for Disease Control and Prevention (CDC) in Atlanta. "This will be a major, major study," says O’Brien. "I’m very excited about this."
The forthcoming trial, which will be conducted by the CDC’s Tuberculosis Trials Consortium, or TBTC, will team rifapentine (RFP) — a long-acting antibiotic only recently approved for use against TB — with isoniazid (INH) in a once-weekly dosing schedule with a three-month duration. That translates to just 12 doses in all.
Though protocol for the work, formally titled "Study 26 of the TBTC," is still being refined, O’Brien says the study is expected to consist of three arms. Along with the once-weekly INH/RFP combination, other parts probably will include a nine-month course of INH and a two-month course of rifampin (RIF) and pyrazinamide (PZA). Both HIV-infected and HIV-noninfected patients are expected to be enrolled, O’Brien says.
"Everything’s very preliminary because it’s only been discussed by the protocol team," he adds. Even so, the DTBE already has given an enthusiastic nod to the study, and O’Brien says he expects that trial sites will start enrolling patients within the next year — if all goes well, as soon as next summer.
The promise held out by INH/RFP is twofold. First, if the combination regimen proves safe and effective, it will offer the convenience of a short-course, prophylactic regimen with doses that need to be given just once a week. Though forthcoming recommendations from the DTBE are expected to urge providers to give RIF/PZA for just two months, the regimen is supposed to be administered daily. With extremely recalcitrant patients, providers have been known to fudge the daily dosing requirement, backing it down to just twice a week, but how efficacious that will prove is not known.
Researchers also hope fewer side effects will beset the new regimen than is the case with RIF/PZA, which so far has spawned a number of complaints of gastrointestinal upsets.
Enthusiasm over Study 26 is matched by the high energy level at the TBTC. This year, two more sites have been added, bringing the number of contractors, whose names were just announced last month, to a total of 23. This year, contract terms have been extended from five to 10 years, with the CDC retaining its option to renew on an annual basis.
The extended contract length and the addition of more sites reflect the CDC’s attitude toward the TBTC, says O’Brien. "It suggests we’re projecting this consortium will have a substantial life," he says. "It also reflects the high priority the CDC gives to research and, specifically, to drug studies."
TBTC continues with more TB studies
The TBTC was born in 1997 when sites were recruited for what became Study 22, a trial that gauged the efficacy of rifapentine — coupled with INH and in place of RIF — in the continuation phase therapy for TB disease. Once sites for that study were recruited and the various headaches of putting together the trial infrastructure were finally resolved, the decision was made to keep the hard-won trial apparatus in place and to continue with more studies, O’Brien says.
This year’s contract awards total about $5 million, parceled out among 13 sites funded directly by the CDC’s DTBE and another 10 funded through a memorandum of understanding with the federal Department of Veterans Affairs Hospitals.
In accordance with its mandate from the DTBE, the trials consortium is focusing its work primarily on finding new treatments for latent TB infections, says O’Brien. "The consortium is especially well-positioned to enroll patients into latent TB studies. A lot of this year’s new sites have exceptionally strong programs for the provision of preventive therapy and [for] doing operational research on preventive therapy. My hunch is they will recruit well."
This new year, the TBTC’s new sites include Boston Medical Center (John Bernardo, MD, principal investigator, or PI), Columbia University in New York City (Neil Schluger, MD, PI), Montreal Chest Institute and McGill University (Richard Menzies, MD, PI), University of British Columbia in Vancouver (Mark Fitzgerald, MD, PI), the University of Southern California in San Francisco (Charles Daley, MD, PI), and Seattle/King County Department of Health (Charles Nolan, MD, PI).
Sites where TBTC contracts have been renewed include New York University (William Rahm, PI), the National TB Center at the New Jersey Medical School (Bonita Mangura, MD, MPH, PI), Univer sity of North Texas Health Sciences Center in Fort Worth (Stephen Weis, DO, PI), University of Southern California/Los Angeles County (Brenda Jones MD, PI), University of Manitoba (Earl Hirshfield, MD, PI), Denver Health and Hospital Authority (Randall Reves, MD, PI), and Johns Hopkins University (Richard Chaisson, MD, PI.)
Of those, O’Brien singles out for kudos the University of North Texas site: "They’ve been our primary enroller. They have an outstanding investigator, and they have excellent staff. Plus, they’ve got one more key element, which is lots of patients."
The Veterans Affairs sites named as this year’s contractors include facilities in Washington, DC; Little Rock, AR; Durham, NC; two Chicago VA hospitals, Hines and Lakeside; Houston; San Antonio; Nashville; and Charlotte.
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