Prourokinase versus urokinase for recanalization of peripheral occlusions, safety and efficacy: the PURPOSE trial

Abstract

Background: The intraarterial administration of thrombolytic agents is associated with clinical benefits in patients with acute peripheral arterial occlusion, and urokinase has been the agent that has become the standard of care in the United States. Recombinant prourokinase (r-ProUK) offers potential as a novel agent with improved fibrin specificity and, as such, may offer advantages as an attractive alternative to urokinase.

Methods: A randomized, double-blind, parallel, phase II, prospective multicenter trial was undertaken to compare three doses of intra-arterial, catheter-directed r-ProUK (2 mg, 4 mg, or 8 mg/hr for 8 hrs, then 0.5 mg/hr) versus one dose of tissue-culture urokinase (4,000 IU/min for 4 hrs, then 2,000 IU/min) for the treatment of acute lower extremity arterial occlusion of 14 days' duration or less (n = 241). The primary endpoint was complete (>95%) lysis of the occluding thrombus after 8 hours of infusion.

Results: Increased clot lysis at 8 hours, decreased fibrinogen concentration, and an increased rate of hemorrhagic events were observed as the r-ProUK dose was increased from 2 mg/hr to 8 mg/hr. Similarly, a decreased duration of study drug infusion was seen, decreasing from 16.7 +/- 0.90 hours in the 2 mg/hr group to 12.7 +/- 0.97 hours in the 8 mg/hr group. The results for the urokinase group decreased to a level between those observed for the 2 mg and 8 mg r-ProUK group with respect to clot lysis at 8 hours, fibrinogen decrement, and bleeding complications, approximating those observed in the 4 mg/hr r-ProUK group. These results were achieved with a relatively low rate of major bleeding events and no episodes of intracranial hemorrhage.

Conclusions: The 8 mg/hr dose of r-ProUK was associated with an increased rate of thrombolysis relative to the other treatment groups, associated with a slightly increased frequency of bleeding complications and decrements in fibrinogen concentration. Conversely, the 2 mg/hr r-ProUK dose was associated with a slightly slower rate of thrombolysis, but bleeding complications and fibrinogenolysis were diminished. r-ProUK is a novel thrombolytic agent with a dose-related safety and efficacy profile. As such, it offers potential as a useful tool in the treatment of peripheral vascular occlusion.