Is recombinant human prourokinase as effective as alteplase in the treatment of acute ischemic stroke?
In this industry-sponsored, Phase III trial, rhPro-UK was shown to be noninferior to alteplase in the treatment of acute ischemic stroke with a similar rate of symptomatic intracranial bleeding and a significantly decreased risk of systemic bleeding. It is easier to dose (standardized, non–weight-based dosing) and faster to administer (30 minutes vs 1 hour) than alteplase. The authors also note that, in China, this drug is half the price of alteplase (US$787 vs US$1577).
Plan de l'etude:
Randomized controlled trial (nonblinded)
Inpatient (any location) with outpatient follow-up
As a thrombolytic agent, recombinant human prourokinase (rhPro-UK) is easier to administer because of its non–weight-based standard dosing and it is more cost-effective than recombinant tissue plasminogen activator (alteplase). RhPro-UK is currently approved for use in China for the treatment of acute myocardial infarction. In this Phase III randomized controlled multicenter trial from China, investigators randomized 667 patients with acute ischemic stroke who presented within 4.5 hours of stroke onset to receive either rhPro-UK (a 15 mg intravenous bolus, followed by a 20-mg continuous infusion within 30 minutes) or alteplase (0.9 mg/kg with 10% administered as an intravenous bolus, followed by 90% administered as a continuous infusion within 1 hour). Baseline characteristics were similar in the 2 groups, with a mean age of 61 years and a median National Institutes of Health Stroke Scale of 6. In a modified intention-to-treat analysis that excluded patients who withdrew consent, a similar percentage of patients achieved the primary outcome of an excellent functional outcome (0 or 1 on the modified Rankin scale) at 90 days (65.2% in rhPro-UK group vs 64.3% in alteplase group; risk difference 0.89 95.4% CI -6.52 to 8.29), satisfying the prespecified noninferiority margin of a between-group difference of 10%. There were no significant differences detected in all-cause death, recurrent ischemic stroke, or symptomatic intracranial hemorrhage. Both groups had 5 deaths attributed to thrombolysis, mainly due to intracranial hemorrhage. Systemic bleeding at 90 days was more common in the alteplase group (42.4% vs 25.8%; P < .001), driven primarily by gastrointestinal bleeding (26.9% vs 8.8%; P < .001).
Nita Shrikant Kulkarni, MD
Assistant Professor in Hospital Medicine