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NCT Number: NCT07550296

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

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.

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Key information

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Hui-Sheng Chen

Shenyang, None Selected, 110016, China

Location status: Recruiting

Location contact

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Prourokinase

Drug

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

Primary outcomes

  1. rate of vessel recanalization

    Time frame: 24 (-6/+12) hours

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. all-cause mortality

    Time frame: 10±2 days

  8. occurence of symptomatic intracranial hemorrhage (sICH)

    Time frame: 24 (-6/+12) hours

  9. occurence of any intracranial hemorrhage

    Time frame: 24 (-6/+12) hours

  10. occurence of major systemic bleeding event

    Time frame: 24 (-6/+12) hours

  11. occurence of any bleeding event

    Time frame: 24 (-6/+12) hours

Sponsors and collaborators

Lead sponsor

General Hospital of Shenyang Military Region

Other

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Apr 24, 2026
Registry last updated
Jun 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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