Trial tests rifapentine as quick prophylaxis
Should be gentler than RIF/PZA
A new short-course regimen for latent TB infection (LTBI), which researchers hope will be kinder and gentler than rifampin/pyrazinamide (RIF/PZA), should begin enrolling patients soon, says Rick O’Brien, MD, chief of research and evaluation at the Division of TB Elimination at the Centers for Disease Control and Prevention in Atlanta and head of the CDC’s TB Trials Consortium (TBTC). (See related story, p. 95.)
The two-armed study, Study 26 of the TBTC, will pit 12 once-weekly doses of rifapentine coupled with isoniazid (INH) against nine months of daily self-administered INH, says O’Brien. It’s expected that the dose level of rifapentine will be set at 900 mg, he adds. The study population will consist of patients who are HIV-negative. The forthcoming trial marks the first time rifapentine, the latest drug to be added to be the TB armamentarium, will be tried as a way to treat LTBI.
Significantly, the new study won’t compare the new short-course combination directly against RIF/PZA, a regimen that already has been approved for treatment of LTBI. At one point, researchers designing the protocol did think about doing so, either by adding a third arm of RIF/PZA or by making RIF/PZA the control arm instead of INH alone, says O’Brien. Logistical difficulties associated with patient enrollment eventually swayed the argument against including RIF/PZA in the comparison.
On the plus side, opting to test the regimen against INH means the study population will be HIV-negative, which should be good news for clinicians, O’Brien adds. After all, he points out, most patients who need treatment for LTBI are either contacts or are foreign-born, and members of both groups are more likely to be seronegative for the AIDS virus than not. "Plus, we want [more] experience with HIV-negative patients."
As for the higher 900 mg dose level, patients in a separate trial currently under way — the TBTC’s Study 25 — seem to be tolerating the higher dose without any problems, says O’Brien. Even though no results from Study 25 have been announced formally, the study was designed in phases so patients can’t be enrolled in a 1,200 mg group until the preceding group taking a 900 mg dose has been judged to be doing well. Because researchers have gotten the go-ahead to move into the 1,200 mg dose phase, it’s safe to infer that the 900 mg level has passed the tests for safety and tolerability, O’Brien notes.
Once enrollment is under way at TBTC sites in the United States, there is a chance that Europeans will join in the trial, O’Brien says. Although Europeans historically haven’t treated patients for LTBI, a professional committee on the continent is formulating standards for prophylaxis, he says.
The new U.S. guide for treatment of LTBI already has begun to circulate among European TB experts, and at least one clinician has told O’Brien he’s interested in collaborating in the new study.
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