Survival Without Disability Not Improved With Intra-Arterial Urokinase in Stroke

Intra-arterial thrombolysis by urokinase following near-complete to complete reperfusion by endovascular thrombectomy fails to significantly increase the likelihood of survival without disability at 3 months among patients with ischemic stroke due to large vessel occlusion, according to study findings published in JAMA.

Investigators evaluated the efficacy and adverse events of intra-arterial urokinase after near-complete to complete reperfusion by thrombectomy for acute ischemic stroke due to large vessel occlusion. The percentage of patients achieving survival without disability (modified Rankin Scale score of 0 or 1) at 3 months was the primary efficacy outcome. Mortality at 3 months and symptomatic intracranial hemorrhage incidence within 48 hours were the primary safety outcomes.

This randomized, open-label, investigator-initiated blinded-endpoint clinical trial was conducted at 35 comprehensive stroke centers in China and recruited 535 patients (median age, 69 years; 41.8% women) from mid-November 2022 through March 2024, with final follow-up early in July 2024. Included patients had proximal intracranial large vessel occlusion presenting within 24 hours of symptom onset, and achieved near-complete or complete reperfusion by endovascular thrombectomy. Prior to the procedure, patients did not receive intravenous thrombolysis.

Participants were randomly assigned 1:1 to receive a single dose of 100,000 IU intra-arterial urokinase injected into the initial target territory (intra-arterial urokinase group; n=267) or assigned to the control group without intra-arterial thrombolysis (n=267).

Eligible patients were aged at least 18 years and able to complete usual activities of daily living without support before the stroke. At baseline, more than 60% of patients in each group had hypertension, more than one-third had atrial fibrillation, and about one-quarter were smokers within the last 5 years. The median baseline National Institutes of Health Stroke Scale score was 15 in both groups, the median baseline Alberta Stroke Program Early CT Score was 8 in both groups, and the median time from symptom onset to randomization had only a 1-minute difference between groups.

Almost all patients (99.6%) completed the trial. In the intra-arterial urokinase group, 45.1% of patients survived without disability at 3 months, as did 40.2% of patients in the control group (adjusted risk ratio [aRR], 1.13; 95% CI, 0.94-1.36; P =.19).

No significant between-group differences in the intra-arterial urokinase group vs the control group were found for mortality at 3 months (18.4% vs 17.3%; adjusted hazard ratio, 1.06; 95% CI, 0.71-1.59; P =.77) or for the incidence of symptomatic intracranial hemorrhage (4.1% vs 4.1%; aRR, 1.05; 95% CI, 0.45-2.44; P =.91).

Study limitations include the open-label design; no correction for multiple testing of safety outcomes, secondary outcomes, or subgroup analysis; and limited generalizability due to the exclusion of patients who received intravenous thrombolysis before endovascular thrombectomy.

“Among patients with acute ischemic stroke due to large vessel occlusion, adjunct intra-arterial urokinase after near-complete to complete reperfusion by endovascular thrombectomy did not significantly increase the likelihood of survival without disability at 90 days,” the investigators concluded. “The incidence of symptomatic intracranial hemorrhage, mortality, any intracranial hemorrhage, and systemic bleeding did not differ significantly between the 2 groups.”

Disclosure: This research was supported by Wuhan Humanwell Pharmaceutical Co.

Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on The Cardiology Advisor