Prourokinase Shows No Advantage Over Standard Care for Mild Ischemic Stroke: PUMICE Trial Findings

Trials to date have not established the superiority of alteplase or tenecteplase over standard care in patients with mild ischemic stroke, while also raising concerns about their safety profiles. In this context, prourokinase emerges as a potential alternative fibrinolytic agent that may offer a more favorable safety profile. However, the benefit-risk profile of prourokinase in the treatment of mild stroke remains unclear. To address this gap, Yunyun Xiong, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, and colleagues aimed to evaluate the efficacy and safety of prourokinase in patients with mild ischemic stroke when administered within 4.5 hours of symptom onset.

For this purpose, the researchers conducted a multicenter, prospective, open-label, blinded-end point randomized clinical trial across 89 hospitals in China from November 2022 to December 2023, with a three-month follow-up. The study included patients with a baseline National Institutes of Health Stroke Scale score of 5 or less, treated within 4.5 hours of symptom onset, excluding those intended for endovascular therapy. Participants were randomized 1:1 to receive either prourokinase (35 mg) or standard care, which included antiplatelet or anticoagulant therapy.

The primary outcome was a modified Rankin Scale score of 0 or 1 at day 90, with safety outcomes including symptomatic intracranial hemorrhage and death.

The following were the key findings of the study:

• Of 3836 patients screened, 1446 were enrolled in the trial. The median age of participants was 65.9 years, and 948 were male.
• Seven-hundred twenty-three patients were assigned to the prourokinase group and 723 to the standard care group.
• The primary outcome was achieved in 88.5% of patients in the prourokinase group and 91.0% in the standard care group (relative risk: 0.97).
• Symptomatic intracranial hemorrhage occurred in 0.7% with prourokinase and 0% with standard care.
• Mortality at 90 days was 2.3% in the prourokinase group and 1.4% in the standard care group.

“The findings of the PUMICE randomized clinical trial indicate that thrombolysis with prourokinase did not demonstrate superiority over standard care in improving functional outcomes for patients with mild ischemic stroke treated within 4.5 hours of symptom onset and exhibited a comparable safety profile,” the researchers concluded.

Reference:

Xiong Y, Meng X, Jin A, et al. Prourokinase vs Standard Care for Patients With Mild Ischemic Stroke: The PUMICE Randomized Clinical Trial. JAMA Neurol. Published online January 21, 2025. doi:10.1001/jamaneurol.2024.4688