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

Repeated Intravenous Thrombolysis for Ischemic Stroke With Medium to Large Vessel Occlusion Presenting Within 4.5 Hours of Onset With Prourokinase (RITIS-PUK): a Prospective, Randomized, Open Label, Blinded Assessment of Outcome, and Multi-center Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: prourokinase

• Study Type: Interventional
• Enrollment (Estimated): 122
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • None Selected
    • Shenyang, None Selected, China, 110016
      • Hui-Sheng Chen
      • Contact: Yu Cui; Email: cuiyu.spu@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group
Experimental: PUK group	Drug: prourokinase; Intravenous administration of prourokinase (20 mg infused over a 30-minute period)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
rate of vessel recanalization	24 (-6/+12) hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ordinal distribution of modified Rankin Scale (mRS)	The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome	90±7 days
all-cause mortality		10±2 days
proportion of excellent functional outcome (modified Rankin Scale (mRS) 0-1)	The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome	90±7 days
change in National Institute of Health stroke scale (NIHSS) score	the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome	24 (-6/+12) hours
change in National Institute of Health stroke scale (NIHSS) score	the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome	10±2 days
proportion of favorable functional outcome (modified Rankin Scale (mRS) 0-2)	The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome	90±7 days
occurence of symptomatic intracranial hemorrhage (sICH)		24 (-6/+12) hours
occurence of any intracranial hemorrhage		24 (-6/+12) hours
occurence of major systemic bleeding event		24 (-6/+12) hours
occurence of any bleeding event		24 (-6/+12) hours
occurrence of early neurological improvement (ENI)	NI is defined as more than 4-point decrease in National Institute of Health stroke scale score; the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome	24 (-6/+12) hours

Collaborators and Investigators

• Sponsor: General Hospital of Shenyang Military Region

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: April 19, 2026
• First Submitted That Met QC Criteria: April 19, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 19, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; saruplase
• Other Study ID Numbers: Y (2026) 15

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No