rhPro-UK in Acute Ischaemic Stroke Within 4.5 Hours of Stroke Onset Trial 2(PROST-2)
Study Details
Study Description
Brief Summary
Intravenous thrombolysis is the first-line therapy in patients with acute ischemic stroke within 4·5 hours of symptom onset, and recombinant tissue plasminogen activator (alteplase) is the preferred thrombolytic agent for this purpose.
RhPro-UK is a specific plasminogen activator. rhPro-UK only acts on occlusive thrombus and has little effect on hemostatic thrombus. In addition, rhPro-UK does not form covalent complexes with protease inhibitors in plasma, so the concentrations of rhpro-UK and protease inhibitors in the blood do not decrease compared with alteplase. Therefore, rhPro-UK therapies have a potential advantage of less systemic bleeding in treated subjects. Data from several previous studies suggest that rhPro-UK is efficacious when used to treat patients with acute myocardial infarction. On April 2, 2011, rhPro-UK injection was approved by the National Medical Products Administration to treat acute myocardial infarction. Since then, rhPro-UK has been widely used to treat myocardial infarction in China.
Since 2016, we carried a phase 2 clinical trial to explore the dosing of rhPro-UK in patients with acute ischemic stroke, followed by another study with a sample size of 680 patients to initially validate the efficacy and safety of the proposed dose of 35mg. The results of these studies suggested that rhPro-UK was effective, and there were no safety concerns. To further prove the efficacy and safety of rhPro-UK in patients with acute ischemic stroke, we conducted this phase 3 study (PROST-2).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: rhPro-UK Recombinant Human Pro-urokinase (rhPro-UK) |
Drug: rhPro-UK
35 mg, administered intravenously with a bolus of 15 mg within 3 minutes and the remainder by continuous infusion within 30 minutes
|
| Active Comparator: rt-PA Alteplase(rt-PA) |
Drug: rt-PA
0.9 mg/kg (maximum 90 mg), with 10% administered intravenously as a bolus, followed by 90% infusion within 1 hour
|
Outcome Measures
Primary Outcome Measures
- The proportion of patients with excellent functional outcome at 90 days [90±7 days]
The proportion of patients with modified Rankin score (mRS) of 0-1 at 90 days
Secondary Outcome Measures
- The proportion of patients with independent functional outcome at 90 days [90±7 days]
The proportion of patients with modified Rankin score (mRS) of 0-2 at 90 days
- Functional handicap [90±7 days]
The distribution of mRS at 90 days
- The proportion of patients with neurological improvement at 24 hours [22-36 hours]
A reduction in NIHSS score of ≥4 or a score of 0-1 at 24 hours
- The proportion of patients with neurological improvement at 7 days [7 ±2 days]
A reduction in NIHSS score of ≥4 or a score of 0-1 at 7 days
- The change of neurological function at 24 hours [22-36 hours]
The change of NIHSS score between 24 hours and baseline
- The change of neurological function at 7 days [7 ±2 days]
The change of NIHSS score between 7 days and baseline
- Self-care ability in daily life [90±7 days]
The Barthel Index of 95-100 at 90 days
- All-cause death within 7 days [7 days]
- All-cause death within 90 days [90 days]
- Symptomatic intracranial hemorrhage defined as SITS-MOST [22-36 hours]
- Symptomatic intracranial hemorrhage defined as ECASSIII [7 days]
- Any intracranial hemorrhage [7 days]
- Any systematic bleeding event（defined as ISTH） [7 days]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Clinically diagnosed as acute ischemic stroke (according to the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018).
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18 years or older, male or female.
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NIH Stroke Scale（NIHSS）scores of 4 to 25.
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Treatment within 4.5 hours after stroke onset.
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The symptoms of stroke last at least 30 minutes without significant improvement before treatment.
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Informed consent by patient or by patient's guardians.
Exclusion Criteria:
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Prestroke modified rankin scale of ≥2.
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Large areas of hypodense ischaemic changes on baseline CT（Infarction area> 1/3 of the middle cerebral artery feeding area）.
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Intracranial hemorrhage.
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Previous history of intracranial hemorrhage.
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Severe cerebral trauma or stroke history within 3 months.
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Intracranial tumor or giant intracranial aneurysm.
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Intracranial or intraspinal surgery within the past 3 months.
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Gastrointestinal or urinary bleeding within the past 3 weeks.
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History of major surgical procedures or severe trauma within the last 2 weeks (investigator evaluation).
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Puncture in 1 week which can not be oppressed.
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Active visceral hemorrhage.
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Aortic arch dissection.
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Bacterial endocarditis or pericarditis.
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Planned for thrombectomy.
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Patients with systolic blood pressure ≥ 185 mmHg or diastolic blood pressure ≥ 110 mmHg after anti-hypertension treatment.
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High risk of acute hemorrhage include platelet count<10^9/L.
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Received low molecular weight heparin or heparin within 24 hours.
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Using of thrombin inhibitors or factor Xa inhibitor within the past 48 hours.
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Using of oral anticoagulant drugs and PT >15s or INR >1.7.
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Patients with epilepsy or other mental disorders that could not be adhered to at the beginning of stroke.
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Blood glucose < 2.8 mmol/L or > 22.2 mmol/L.
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Allergies to rhPro-UK or rt-PA active ingredients or other components.
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Pregnant women or beastfeeding women.
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Participants in other clinical trials within the past month.
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The investigator believes that the patient is not suitable for the study.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Tasly Biopharmaceuticals Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TASLY-B1440-CTP-Ⅲc