The multicenter Retrospective Evaluation of Thrombolytic Reperfusion of Occlusions (RETRO) trial found a 4.3% incidence of major bleeds with urokinase, compared with an 8.3% rate with the clot-busting tPA, according to principal investigator Dr. Kenneth Ouriel, chair of vascular surgery at the Cleveland Clinic. Results were announced Tuesday at the International Symposium on Endovascular Therapy in Miami.

The initial study was based on experience at 19 sites between January 1999 and July 2000. Of 472 cases, 345 were treated with tPA, and 58 with recombinant tPA (r-tPA) or other antithrombolytic agents, but only 69 were lysed with Abbokinase (urokinase). Sales of the popular agent were discontinued in 1999 when the FDA accused its producer, Abbott Pharmaceuticals, of violating good manufacturing practice standards.

The preliminary study found that the incidence of intracranial bleeding for all of the agents was lower than expected. Only one patient, who had been administered tPA, had a intracranial bleed. The overall 84% clinical success rate of tPA was slightly better than those of urokinase and r-tPA, but the difference was not statistically significant, Ouriel said.

The study's design problems will be addressed in RETRO II, which enlarges its scope to cases treated in 1998 to capture more urokinase cases. Results will be tabulated and submitted for publication by the end of January. Both Abbott and Genentech, the developer of tPA, are interested in the findings.

"If we find again that bleeding is lower with urokinase, we may see many people go back to urokinase when it becomes available around mid-year. If it is no better than tPA, we may see few people go back to this drug," Ouriel said.

Abbott filed a supplemental new drug application with the FDA in December 2001. The company hopes that approval to begin sales will be issued before mid-year, a company spokesperson said.

Although Genentech was criticized for the high cost of tPA when Activase was introduced in the early 1980s, physicians have devised ways to use the agent economically. It is cheaper than urokinase when used in off-label applications for thrombolysis in the peripheral vascular system, especially when doses are split, Ouriel said.

Neuroradiologists became concerned when urokinase was withdrawn, because it had been widely used for stroke interventions.

"Urokinase was everyone's favorite drug when it went off the market. Although tPA and other agents have replaced it with some success, many physicians would like to see urokinase come back," he said.

Clot-dissolving r-tPA is sold by Centocor, a subsidiary of Johnson & Johnson, under the Retevase label.

By James Brice