New trial weighs INH against RIF/PZA regimen

Study eyes INH effects on the over-35 crowd

Finding new ways to expand preventive therapy for TB-infected people — either with a new short-course regimen or by expanding the uses of a tried-and-true agent — is the aim of a new study now enrolling patients in San Francisco.

First, the study will look at safety, completion rates, and efficacy of rifampin/pyrazinamide (RIF/PZA), the new short-course prophylactic regimen recently approved for HIV-positive patients latently infected with TB. The RIF/PZA regimen will be tried against isoniazid (INH) — the standard approved therapy — among patients who are HIV-negative.

Just as interesting, the study also is designed to see whether INH works as well among people over age 35 as among younger subjects who meet the current guidelines for receiving prophylaxis with the drug.

"One interesting issue here is whether INH toxicity will turn out to be as high as was previously supposed," says Robert Jasmer, MD, study coordinator and an assistant professor of medicine at the University of California in San Francisco and San Francisco General Hospital. "We could find out that age 35 isn’t an appropriate cut-off after all. There’s also a need to figure out whether RIF/PZA will work as well as INH among HIV-negative people."

Use of INH may be increased

On the basis of data that are still coming in, many experts are beginning to conclude INH can be used more liberally than was originally supposed. A recently published study by Charles Nolan, MD, TB controller of Seattle-King County, suggests that may be the case. Nolan’s study found that out of a total of 11,141 patients placed on INH prophylaxis over a six-year period, only 11 experienced hepatotoxic reactions.1

Though Nolan and colleagues did not routinely offer INH to older patients, Jasmer’s study will do so. The study is designed so that the first arm consists of patients who do meet current criteria for receiving INH, and the second arm does not. Patients in both arms will be randomly assigned to receive either RIF/PZA or INH, Jasmer adds. "We’re going to give INH freely to people over age 35, but we’ll be doing lots of enhanced, very intensive monitoring," he says.

Eventually, Jasmer hopes to enroll 600 patients. Of the 50 who already are enrolled, most are under age 35; and although one subject has dropped out so far, complaining of headache and dizziness, no one in either arm has experienced any major toxicity, he notes.

Reference

    1. Nolan CM, Goldberg SV, Buskin SE. Hepatotoxicity associated with isoniazid preventive therapy. JAMA 1999; 281:1,014-1,018.