Repeated Intravenous Thrombolysis for Ischemic Stroke With Medium to Large Vessel Occlusion Presenting Within 4.5 Hours of Onset With Prourokinase

NCT07550296 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: Y (2026) 15
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

Brief Summary

Ischemic cerebrovascular disease is a common neurological disorder with high incidence, mortality, and disability. Early reperfusion to salvage the ischemic penumbra is the cornerstone of acute ischemic stroke (AIS) treatment. Current reperfusion strategies include intravenous thrombolysis (IVT) and endovascular therapy (EVT). Although alteplase is the first-line thrombolytic agent, its recanalization rate for large vessel occlusion (LVO) is only 10-20%, and for medium vessel occlusion (MeVO), approximately 50% of patients fail to achieve recanalization, leading to poor outcomes. Prourokinase has recently been shown to be non-inferior to alteplase with a better safety profile, and studies suggest that repeated thrombolysis may improve recanalization rates in patients without early clinical improvement after standard IVT. Therefore, this study aims to evaluate the efficacy and safety of an additional intravenous infusion of prourokinase in AIS patients with confirmed medium or large vessel occlusion who show no significant clinical improvement at 1 hour after standard IVT (within 4.5 hours of symptom onset). Patients without early neurological improvement (e.g., \<2-point reduction in NIHSS) and persistent vessel occlusion on imaging will receive a second dose of prourokinase. The primary outcomes include 24-hour recanalization rate (by CTA/MRA), 90-day functional outcome (modified Rankin Scale), and safety endpoints (symptomatic intracranial hemorrhage, mortality). The hypothesis is that additional prourokinase following standard IVT in non-improving patients with medium or large vessel occlusion will significantly increase recanalization rates and improve clinical outcomes without an unacceptable increase in symptomatic intracranial hemorrhage.

Conditions

Acute Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

• rate of vessel recanalization

  24 (-6/+12) hours

Secondary Outcomes (11)

• proportion of excellent functional outcome (modified Rankin Scale (mRS) 0-1)

  90±7 days

• proportion of favorable functional outcome (modified Rankin Scale (mRS) 0-2)

  90±7 days

• ordinal distribution of modified Rankin Scale (mRS)

  90±7 days

• occurrence of early neurological improvement (ENI)

  24 (-6/+12) hours

• change in National Institute of Health stroke scale (NIHSS) score

  24 (-6/+12) hours

Study Arms (2)

PUK group

EXPERIMENTAL

Drug: prourokinase

Control group

NO INTERVENTION

Interventions

prourokinase DRUG

Intravenous administration of prourokinase (20 mg infused over a 30-minute period)

PUK group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 year;
• Acute ischemic stroke presumably caused by large or medium vessel occlusion within 4.5 hours of onset, having received intravenous thrombolysis of prourokinase, and with no planned thrombectomy;
• Measurable neurological deficit before the first intravenous thrombolysis, with NIHSS ≥ 4;
• Baseline pc-ASPECTS/ASPECTS ≥ 6, and for posterior circulation infarction, a Pontine-Midbrain Index ≤ 2 (assessed by CT or DWI);
• No significant clinical improvement (reduction in NIHSS ≤ 2) or neurological deterioration after initial improvement at 1 hour after the first thrombolysis;
• Follow-up imaging (CTA or MRA) at 1 hour after the first thrombolysis rules out intracranial hemorrhage and confirms the presence of large or medium vessel occlusion (internal carotid artery, M1-M3 segments of the middle cerebral artery, A1-A3 segments of the anterior cerebral artery, P1-P3 segments of the posterior cerebral artery, basilar artery or V4 segment of the vertebral artery, PICA, AICA, or SCA);
• The second intravenous thrombolysis can be administered within 6 hours of onset;
• First stroke onset or past stroke without obvious neurological deficit (mRS≤1);
• Signed informed consent.

You may not qualify if:

• Planed for endovascular treatment;
• Significant white matter hyperintensities (Fazekas score 3);
• Any coagulation abnormality before the first thrombolysis, including INR \> 1.5;
• Receipt of dual antiplatelet therapy within 24 hours prior to thrombolysis.；
• Pregnancy；
• Allergy to the investigational drug(s)；
• Comorbidity with other serious diseases;
• Participating in other clinical trials within 3 months;
• Patients not suitable for the study considered by researcher.

Sponsors & Collaborators

• General Hospital of Shenyang Military Region: lead

Study Sites (1)

Hui-Sheng Chen

Shenyang, None Selected, 110016, China

Location

MeSH Terms

Conditions

Ischemic Stroke

Interventions

saruplase

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: April 19, 2026
• First Posted: April 24, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

CN (1)