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

April 19, 2026 updated by: Hui-Sheng Chen, General Hospital of Shenyang Military Region

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

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
122

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
rate of vessel recanalization
Time Frame: 24 (-6/+12) hours
24 (-6/+12) hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
ordinal distribution of modified Rankin Scale (mRS)
Time Frame: 90±7 days
The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome
90±7 days
all-cause mortality
Time Frame: 10±2 days
10±2 days
proportion of excellent functional outcome (modified Rankin Scale (mRS) 0-1)
Time Frame: 90±7 days
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
Time Frame: 24 (-6/+12) hours
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
Time Frame: 10±2 days
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)
Time Frame: 90±7 days
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)
Time Frame: 24 (-6/+12) hours
24 (-6/+12) hours
occurence of any intracranial hemorrhage
Time Frame: 24 (-6/+12) hours
24 (-6/+12) hours
occurence of major systemic bleeding event
Time Frame: 24 (-6/+12) hours
24 (-6/+12) hours
occurence of any bleeding event
Time Frame: 24 (-6/+12) hours
24 (-6/+12) hours
occurrence of early neurological improvement (ENI)
Time Frame: 24 (-6/+12) hours
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
General Hospital of Shenyang Military Region

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 19, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 19, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 24, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 24, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 19, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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