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
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- General Hospital of Shenyang Military Region
- Enrollment
- 122
- Locations
- 1
- Primary Endpoint
- rate of vessel recanalization
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
PUK group
Intervention: prourokinase (Drug)
Control group
Outcomes
Primary Outcomes
rate of vessel recanalization
Time Frame: 24 (-6/+12) hours
Secondary Outcomes
- occurence of any bleeding event(24 (-6/+12) hours)
- 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)
- occurence of major systemic bleeding event(24 (-6/+12) hours)
- occurrence of early neurological improvement (ENI)(24 (-6/+12) hours)
- change in National Institute of Health stroke scale (NIHSS) score(24 (-6/+12) hours)
- change in National Institute of Health stroke scale (NIHSS) score(10±2 days)
- all-cause mortality(10±2 days)
- occurence of symptomatic intracranial hemorrhage (sICH)(24 (-6/+12) hours)
- occurence of any intracranial hemorrhage(24 (-6/+12) hours)
Investigators
Hui-Sheng Chen
Director
General Hospital of Shenyang Military Region