Study of rhPro-UK in Patients With Acute Ischaemic Stroke in 4.5 Hours After Stroke Onset(PROST)

Study Overview
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Brief Summary
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This is a randomized, rt-PA controlled, open-label phase 3 clinical study to evaluate the efficacy and safety of recombinant human urokinase(rhPro-UK) versus rt-PA thrombolysis for patients with acute ischaemic stroke in 4.5 hours after stroke onset.

Official Title
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A Phase III Trial to Assess the Efficacy and Safety of Recombinant Human Prourokinase in the Treatment of Acute Acute Ischaemic Stroke in 4.5 Hours After Stroke Onset

Conditions
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Acute Ischaemic Stroke

Intervention / Treatment
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* Drug: Recombinant human urokinase
* Drug: Alteplase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ischemic stroke with symptoms of neurological deficits. Aged 18 to 80 years（including the critical value）. NIH Stroke Scale（NIHSS）scores of 4 to 25（including the critical value）. Treatment within 4.5 hours after stroke onset. The symptoms of stroke last at least 30 minutes without significant improvement before treatment. CT showed negative or signs of early infarction. Informed Consent Form signed by the patients or family (legal representatives) must be provided. Exclusion Criteria: Patients with premorbid modified Rankin Scale (mRS) score ≥2 CT showed multiple infarctions（low density> 1/3 cerebral hemisphere）. Transient ischemic attack. Epileptic seizure after stroke. Intracranial tumor, arteriovenous malformation and aneurysm. Iatrogenic Stroke. Planned for thrombectomy. Cardioembolism and atrial fibrillation. Myocardial infarction history within 3 months. Severe cerebral trauma or stroke history within 3 months. Patients with systolic blood pressure ≥ 180mmHg or diastolic blood pressure ≥ 100mmHg after anti-hypertension treatment. Intracranial hemorrhage or subarachnoid hemorrhage on baseline. Active visceral hemorrhage. Patients with intracerebral hemorrhage history. Patients with diabetic retinopathy history. Puncture in 1 week which can not be oppressed. Major surgery or severe trauma within 2 weeks. Intracranial surgery, intraspinal surgery or solid organ biopsy within 30 days. Heparin treatment within 48h and increased APTT is above ULN. Using of oral anticoagulant drugs and PT >15s or INR >1.7. High risk of acute hemorrhage include platelet count<10^9/L. Using of thrombin inhibitors or factor Xa inhibitor with abnormal results of sensitive laboratory examination. Blood glucose < 2.7 mmol/L or > 22.2 mmol/L. Pregnancy, lactating or menstrual women. The investigator believes that the patient is not suitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Recombinant human urokinase (rhPro-UK) | Drug: Recombinant human urokinase<br>* Patients receive rhPro-UK 35mg,15mg of which is given as a bolus within 3 minutes followed by dlivery of the remaining 20 mg as a constant infusion over a period of 30 minutes.<br>* Other names: rhPro-UK;|
| Active Comparator: Group B<br>Alteplase(rt-PA) | Drug: Alteplase<br>* Patients receive rt-PA in a dose of 0.9mg per kilogram of body weight(maximum,90 mg),10 percent of which was given as a blous followed by delivery of the remaining 90 percent as a constant infusion over a period of 60 minutes.<br>* Other names: rt-PA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional handicap | Proportion of patients achieving a Modified Rankin Scale(mRS,which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) of 0 to 1 at 90 days after treatment. | 90days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Neurological Improvement | Proportion of patients achieving a NIHSS(national institutes of health stroke scale) ≦1 or reduction of ≥4 NIHSS points at 24 hours after treatment. | 90 days | 
| Scores of Neurological Improvement | NIHSS changes from baseline at 24 hours after treatment | 24 hours | 
| Long-term Change from Baseline | NIHSS, mRS and Barthel Index(which assesses the ability to perform activities of daily living, on a scale that ranges from 0 to 100) changes from baseline on 90 days after treatment. | 90 days | 
| Proportion of Long-term Improvement | Proportion of patients achieving a mRS of 0 to 2 and a Barthel Index of 75 to 100 at 90 days after treatment. | 90 days | 
| Systemic hemorrhage | Severe systemic hemorrhage | 90days | 
| Symptomatic intracerebral hemorrhage | Symptomatic intracerebral hemorrhage (sICH) | 90days | 
| Death | Death | 7 days and 90 days | 
| Recurrence | Recurrence of stroke | 7 days | 
| Liver function | The incidence of ALT≥3ULN in liver biochemical examination | 7 days | 
| Renal function | The incidence of Scr rising to 3 times or ≥ 4mg/dl more than the base value | 7 days |