Acute Ischemic Stroke
Conditions
Keywords
Extended-Window Intravenous Thrombolysis, Recombinant Human Prourokinase, Noncontrast Computed Tomography, Artificial Intelligence, Tissue-Window Selection, Perfusion Mismatch
Brief summary
This multicenter, prospective, randomized, double-blind, placebo-controlled trial aims to evaluate the efficacy and safety of intravenous recombinant human prourokinase (rhPro-UK) in patients with acute ischemic stroke treated more than 4.5 hours and up to 24 hours after stroke onset, selected using a noncontrast computed tomography-based artificial intelligence (CT-AI) tissue-window algorithm. A total of 826 participants will be randomly assigned in a 1:1 ratio to receive intravenous rhPro-UK or matching placebo, in addition to guideline-recommended standard stroke care. The primary outcome is the proportion of participants achieving a modified Rankin Scale (mRS) score of 0-1 at 90 ± 7 days. Secondary outcomes include functional outcomes, changes in neurological deficits, early neurological improvement at 24 hours and 7 days, and tissue reperfusion at 24-48 hours. Safety outcomes include symptomatic intracranial hemorrhage, parenchymal hematoma, all-cause mortality, and serious systemic bleeding.
Interventions
A total dose of 35 mg will be administered intravenously. The initial 15 mg dissolved in 10 mL solution will be administered by intravenous bolus over 3 minutes, followed by 20 mg dissolved in 90 mL solution administered by intravenous infusion over 30 minutes.
DRUGMatching Placebo for Recombinant Human Prourokinase
Matching placebo will be administered intravenously using the same administration volumes, route, and durations as the active study drug to maintain blinding.
Sponsors
Second Affiliated Hospital, Zhejiang University, School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years. 2. Clinically diagnosed acute ischemic stroke. 3. Time from stroke onset to randomization \>4.5 hours and ≤24 hours. For patients with unknown onset time or wake-up stroke, the estimated onset time will be defined as the midpoint between the last known well time and symptom discovery time. 4. Baseline National Institutes of Health Stroke Scale (NIHSS) score of 4-25. 5. Pre-stroke modified Rankin Scale (mRS) score of 0-1. 6. No planned endovascular treatment at randomization. Patients with large vessel occlusion who are eligible for endovascular treatment must undergo independent evaluation and discussion before study enrollment. Patients who are planned to receive endovascular treatment will not be enrolled. 7. Meeting the CT-AI tissue-window selection criteria: * Predicted ischemic core volume ≤70 mL; * Hypoperfusion-to-core volume ratio \>1.2; * Difference between hypoperfusion and ischemic core volumes ≥10 mL. 8. Written informed consent provided by the participant or their legally authorized representative.
Exclusion criteria
1. Baseline CT showing intracranial hemorrhage, subarachnoid hemorrhage, brain tumor, brain abscess, or other non-ischemic lesions. 2. Baseline CT showing an extensive infarction, severe cerebral edema, or mass effect, or the investigator determines that the risks of intravenous thrombolysis substantially outweigh the potential benefits. 3. Contraindications specified in the prescribing information for recombinant human prourokinase for injection or current intravenous thrombolysis guidelines, other than the extended treatment time window specifically evaluated in this trial, including but not limited to: * Any history of intracranial hemorrhage; * Severe head trauma or stroke, including ischemic stroke, within the previous 3 months; * Recent major surgery or severe trauma; * Active internal bleeding; * Significant coagulation abnormalities; * Platelet count \<100 × 10⁹/L; * Blood pressure that cannot be adequately controlled to meet intravenous thrombolysis requirements despite treatment; * Other conditions associated with substantially increased bleeding risk as determined by the investigator. 4. Pregnancy, breastfeeding, or unwillingness to use effective contraception during the study. 5. Inadequate NCCT image quality for CT-AI analysis or inability of the AI model to generate valid outputs. 6. Participation in another interventional clinical trial within the previous 3 months. 7. Expected survival of less than 3 months. 8. Other conditions considered by the investigator to increase the risk of study treatment or interfere with study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With a Modified Rankin Scale Score of 0-1 at 90 Days | 90 ± 7 days after randomization | The proportion of participants achieving a modified Rankin Scale (mRS) score of 0 or 1. The mRS ranges from 0 (no symptoms) to 6 (death), with lower scores indicating better functional outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ordinal Distribution of Modified Rankin Scale Scores at 90 Days | 90 ± 7 days after randomization | The distribution of modified Rankin Scale (mRS) scores from 0 (no symptoms) to 6 (death), with higher scores indicating worse functional outcomes. |
| Proportion of Participants With a Modified Rankin Scale Score of 0-2 at 90 Days | 90 ± 7 days after randomization | The proportion of participants achieving an mRS score of 0-2. The mRS ranges from 0 (no symptoms) to 6 (death). |
| Proportion of Participants With a Modified Rankin Scale Score of 0-3 at 90 Days | 90 ± 7 days after randomization | The proportion of participants achieving an mRS score of 0-3. The mRS ranges from 0 (no symptoms) to 6 (death). |
| Change in National Institutes of Health Stroke Scale Score From Baseline to 24 Hours | Baseline and 24 hours after randomization | Change in the National Institutes of Health Stroke Scale (NIHSS) score from baseline to 24 hours. The NIHSS ranges from 0 to 42, with higher scores indicating more severe neurological impairment. |
| Change in National Institutes of Health Stroke Scale Score From Baseline to Day 7 | Baseline and 7 days after randomization | Change in NIHSS score from baseline to day 7. The NIHSS ranges from 0 to 42, with higher scores indicating more severe neurological impairment. |
| Proportion of Participants With Early Neurological Improvement at 24 Hours | 24 hours after randomization | The proportion of participants whose NIHSS score decreases by at least 4 points from baseline or reaches 0-1 at 24 hours. |
Countries
China
Contacts
CONTACTMin Lou, PhD, MD
CONTACTWansi Zhong, MD
PRINCIPAL_INVESTIGATORMin Lou, PhD, MD
Second Affiliated Hospital, Zhejiang University, School of Medicine
Outcome results
None listed