Prourokinase Rivals Alteplase in Acute Stroke Treatment

TOPLINE:

Recombinant human prourokinase is noninferior to alteplase for acute ischemic stroke outcomes and is associated with decreased rates of symptomatic intracranial hemorrhage and major bleeding, a new study shows.

METHODOLOGY:

• PROST-2 was a phase 3, open-label, noninferiority, randomized controlled trial that included 1552 patients (median age, 65 years; 66.5% men) with acute ischemic stroke at 61 hospitals in China.
• Participants were randomly assigned (1:1) to receive either recombinant human prourokinase or alteplase within 4.5 hours of stroke onset.
• Recombinant human prourokinase was administered at a dose of 35 mg, comprising a 15 mg bolus followed by a 20 mg infusion within 30 minutes, whereas alteplase was given at a dose of 0.9 mg/kg (maximum, 90 mg), with 10% of the dose delivered as a bolus within 1 minute and the remainder via IV infusion over 60 minutes.
• The primary efficacy outcome was a modified Rankin Scale (mRS) score of 0-1 at 90 days, and the primary safety outcome was symptomatic intracranial hemorrhage within 36 hours.

TAKEAWAY:

• Recombinant human prourokinase was noninferior to alteplase, with 72% of patients in the prourokinase group and 69% of those in the alteplase group achieving an mRS score of 0 or 1 at 90 days (risk ratio, 1.04; P
• Symptomatic intracranial hemorrhage occurred less frequently in the prourokinase group than in the alteplase group (risk difference, −1.0; P = .021).
• Significantly fewer major bleeding events at 7 days in the prourokinase group vs the alteplase group (risk difference, −1.5; P = .0072).
• All-cause mortality within 7 days did not differ significantly between the groups.

IN PRACTICE:

“These findings support the use of recombinant human prourokinase as a viable alternative to alteplase for patients with ischemic stroke who are eligible for intravenous thrombolysis therapy but ineligible for or who have refused endovascular thrombectomy,” the investigators wrote.

The findings are particularly relevant in countries where endovascular thrombectomy is unavailable or not readily accessible. “In the context of the recent global shortage of thrombolytics, having options is welcome, particularly because the cost of recombinant human prourokinase is approximately half that of alteplase in some countries,” the editorial authors wrote.

SOURCE:

The study was led by Yongjun Wang, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. The accompanying editorial was authored by Guillaume Turc, Department of Neurology, GHU Paris Psychiatrie et Neurosciences, Paris, France, and Thanh N. Nguyen, Boston Medical Center, Boston University Chobanian & Avedisian School of Medicine, Boston. The study and editorial were published online on November 28 in The Lancet Neurology.

LIMITATIONS:

The study included only Chinese patients, potentially limiting the generalizability of the findings to other populations. Women were underrepresented in the study population, and data on stroke mimic rates were not collected. The requirement for written informed consent before enrollment may have delayed the door-to-needle time, and the open-label design may have introduced potential biases despite the blinded evaluation of outcomes.

DISCLOSURES:

This study was funded by Tasly Biopharmaceuticals, the National Key R&D Program of China, the National Natural Science Foundation of China, the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and the Beijing Municipal Science & Technology Commission. The authors of the study declared no conflicts of interest.

One author of the editorial disclosed having lecture and advisory roles in AI-Stroke, while the other disclosed having consulting, speaker, and advisory roles in trials, leading a neurology society, and serving as an associate editor for a medical journal.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.