Back to resultsrhPro-UK in Acute Ischaemic Stroke Within 4.5 Hours of Stroke Onset Trial 2(PROST-2) (PROST-2)
Primary Purpose
Acute Ischemic Stroke
Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
rhPro-UK
rt-PA
Sponsored by
About this trial
This is an interventional treatment trial for Acute Ischemic Stroke
Eligibility Criteria
Inclusion Criteria: Clinically diagnosed as acute ischemic stroke (according to the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018). 18 years or older, male or female. NIH Stroke Scale（NIHSS）scores of 4 to 25. Treatment within 4.5 hours after stroke onset. The symptoms of stroke last at least 30 minutes without significant improvement before treatment. Informed consent by patient or by patient's guardians. Exclusion Criteria: Prestroke modified rankin scale of ≥2. Large areas of hypodense ischaemic changes on baseline CT（Infarction area> 1/3 of the middle cerebral artery feeding area）. Intracranial hemorrhage. Previous history of intracranial hemorrhage. Severe cerebral trauma or stroke history within 3 months. Intracranial tumor or giant intracranial aneurysm. Intracranial or intraspinal surgery within the past 3 months. Gastrointestinal or urinary bleeding within the past 3 weeks. History of major surgical procedures or severe trauma within the last 2 weeks (investigator evaluation). Puncture in 1 week which can not be oppressed. Active visceral hemorrhage. Aortic arch dissection. Bacterial endocarditis or pericarditis. Planned for thrombectomy. Patients with systolic blood pressure ≥ 185 mmHg or diastolic blood pressure ≥ 110 mmHg after anti-hypertension treatment. High risk of acute hemorrhage include platelet count<10^9/L. Received low molecular weight heparin or heparin within 24 hours. Using of thrombin inhibitors or factor Xa inhibitor within the past 48 hours. Using of oral anticoagulant drugs and PT >15s or INR >1.7. Patients with epilepsy or other mental disorders that could not be adhered to at the beginning of stroke. Blood glucose < 2.8 mmol/L or > 22.2 mmol/L. Allergies to rhPro-UK or rt-PA active ingredients or other components. Pregnant women or beastfeeding women. Participants in other clinical trials within the past month. The investigator believes that the patient is not suitable for the study.
Sites / Locations
- Beijing Tiantan Hospital, Capital Medical University
- Nanyang Second General HospitalRecruiting
- Keahiketeng Banner Traditional Chinese Medicine Mongolian Medicine Hospital
- Beipiao Central Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
rhPro-UK
rt-PA
Arm Description
Recombinant Human Pro-urokinase (rhPro-UK)
Alteplase(rt-PA)
Outcomes
Primary Outcome Measures
The proportion of patients with excellent functional outcome at 90 days
A score of 0 or 1 on the modified Rankin scale(which ranges from 0 [no symptoms] to 6 [death]) at 90 days indicated an excellent functional outcome.
Secondary Outcome Measures
The proportion of patients with independent functional outcome at 90 days
A score of 0-2 on the modified Rankin scale(which ranges from 0 [no symptoms] to 6 [death]) at 90 days indicated an independent functional outcome.
Functional handicap
The distribution of the modified Rankin scale(which ranges from 0 [no symptoms] to 6 [death]) at 90 days
The proportion of patients with neurological improvement at 24 hours
A reduction in NIHSS score of ≥4 or a score of 0-1 indicated neurological improvement. Total scores on the NIHSS range from 0 to 42, with higher values reflecting more severe cerebral infarcts.
The proportion of patients with neurological improvement at 7 days
A reduction in NIHSS score of ≥4 or a score of 0-1 indicated neurological improvement. Total scores on the NIHSS range from 0 to 42, with higher values reflecting more severe cerebral infarcts.
The change of neurological function at 24 hours
NIHSS score was used to assess neurological function. Total scores on the NIHSS range from 0 to 42, with higher values reflecting more severe cerebral infarcts.
The change of neurological function at 7 days
NIHSS score was used to assess neurological function. Total scores on the NIHSS range from 0 to 42, with higher values reflecting more severe cerebral infarcts.
Self-care ability in daily life
The Barthel Index(which ranges from 0[complete dependence on help with activities of daily living] to 100[independence]) of 95-100 at 90 days
All-cause death within 7 days
All-cause death within 90 days
Symptomatic intracranial hemorrhage defined as SITS-MOST
Symptomatic intracranial hemorrhage defined as ECASSIII
Any intracranial hemorrhage
Any systematic bleeding event（defined as ISTH）
Full Information
NCT ID
NCT05700591
First Posted
January 17, 2023
Last Updated
February 7, 2023
Sponsor
Tasly Biopharmaceuticals Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05700591
Brief Title
rhPro-UK in Acute Ischaemic Stroke Within 4.5 Hours of Stroke Onset Trial 2(PROST-2)
Acronym
PROST-2
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 29, 2023 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tasly Biopharmaceuticals Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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, a phase 2 clinical trial was carried 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, investigators conducted this phase 3 study (PROST-2).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Ischemic Stroke
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
1552 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
rhPro-UK
Arm Type
Experimental
Arm Description
Recombinant Human Pro-urokinase (rhPro-UK)
Arm Title
rt-PA
Arm Type
Active Comparator
Arm Description
Alteplase(rt-PA)
Intervention Type
Drug
Intervention Name(s)
rhPro-UK
Intervention Description
35 mg, administered intravenously with a bolus of 15 mg within 3 minutes and the remainder by continuous infusion within 30 minutes
Intervention Type
Drug
Intervention Name(s)
rt-PA
Intervention Description
0.9 mg/kg (maximum 90 mg), with 10% administered intravenously as a bolus, followed by 90% infusion within 1 hour
Primary Outcome Measure Information:
Title
The proportion of patients with excellent functional outcome at 90 days
Description
A score of 0 or 1 on the modified Rankin scale(which ranges from 0 [no symptoms] to 6 [death]) at 90 days indicated an excellent functional outcome.
Time Frame
90±7 days
Secondary Outcome Measure Information:
Title
The proportion of patients with independent functional outcome at 90 days
Description
A score of 0-2 on the modified Rankin scale(which ranges from 0 [no symptoms] to 6 [death]) at 90 days indicated an independent functional outcome.
Time Frame
90±7 days
Title
Functional handicap
Description
The distribution of the modified Rankin scale(which ranges from 0 [no symptoms] to 6 [death]) at 90 days
Time Frame
90±7 days
Title
The proportion of patients with neurological improvement at 24 hours
Description
A reduction in NIHSS score of ≥4 or a score of 0-1 indicated neurological improvement. Total scores on the NIHSS range from 0 to 42, with higher values reflecting more severe cerebral infarcts.
Time Frame
22-36 hours
Title
The proportion of patients with neurological improvement at 7 days
Description
A reduction in NIHSS score of ≥4 or a score of 0-1 indicated neurological improvement. Total scores on the NIHSS range from 0 to 42, with higher values reflecting more severe cerebral infarcts.
Time Frame
7 ±2 days
Title
The change of neurological function at 24 hours
Description
NIHSS score was used to assess neurological function. Total scores on the NIHSS range from 0 to 42, with higher values reflecting more severe cerebral infarcts.
Time Frame
22-36 hours
Title
The change of neurological function at 7 days
Description
NIHSS score was used to assess neurological function. Total scores on the NIHSS range from 0 to 42, with higher values reflecting more severe cerebral infarcts.
Time Frame
7 ±2 days
Title
Self-care ability in daily life
Description
The Barthel Index(which ranges from 0[complete dependence on help with activities of daily living] to 100[independence]) of 95-100 at 90 days
Time Frame
90±7 days
Title
All-cause death within 7 days
Time Frame
7 days
Title
All-cause death within 90 days
Time Frame
90 days
Title
Symptomatic intracranial hemorrhage defined as SITS-MOST
Time Frame
22-36 hours
Title
Symptomatic intracranial hemorrhage defined as ECASSIII
Time Frame
7 days
Title
Any intracranial hemorrhage
Time Frame
7 days
Title
Any systematic bleeding event（defined as ISTH）
Time Frame
7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Clinically diagnosed as acute ischemic stroke (according to the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018).
18 years or older, male or female.
NIH Stroke Scale（NIHSS）scores of 4 to 25.
Treatment within 4.5 hours after stroke onset.
The symptoms of stroke last at least 30 minutes without significant improvement before treatment.
Informed consent by patient or by patient's guardians.
Exclusion Criteria:
Prestroke modified rankin scale of ≥2.
Large areas of hypodense ischaemic changes on baseline CT（Infarction area> 1/3 of the middle cerebral artery feeding area）.
Intracranial hemorrhage.
Previous history of intracranial hemorrhage.
Severe cerebral trauma or stroke history within 3 months.
Intracranial tumor or giant intracranial aneurysm.
Intracranial or intraspinal surgery within the past 3 months.
Gastrointestinal or urinary bleeding within the past 3 weeks.
History of major surgical procedures or severe trauma within the last 2 weeks (investigator evaluation).
Puncture in 1 week which can not be oppressed.
Active visceral hemorrhage.
Aortic arch dissection.
Bacterial endocarditis or pericarditis.
Planned for thrombectomy.
Patients with systolic blood pressure ≥ 185 mmHg or diastolic blood pressure ≥ 110 mmHg after anti-hypertension treatment.
High risk of acute hemorrhage include platelet count<10^9/L.
Received low molecular weight heparin or heparin within 24 hours.
Using of thrombin inhibitors or factor Xa inhibitor within the past 48 hours.
Using of oral anticoagulant drugs and PT >15s or INR >1.7.
Patients with epilepsy or other mental disorders that could not be adhered to at the beginning of stroke.
Blood glucose < 2.8 mmol/L or > 22.2 mmol/L.
Allergies to rhPro-UK or rt-PA active ingredients or other components.
Pregnant women or beastfeeding women.
Participants in other clinical trials within the past month.
The investigator believes that the patient is not suitable for the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yongjun Wang, M.D.
Phone
13911172565
Email
Yongjunwang111@aliyun.com
First Name & Middle Initial & Last Name or Official Title & Degree
Shuya Li
Email
shuyali85@163.com
Facility Information:
Facility Name
Beijing Tiantan Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yongjun Wang
Phone
13911172565
Email
Yongjunwang111@aliyun.com
Facility Name
Nanyang Second General Hospital
City
Nanyang
State/Province
Henan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yan Song
Facility Name
Keahiketeng Banner Traditional Chinese Medicine Mongolian Medicine Hospital
City
Chifeng
State/Province
Inner Mongolia
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guozhi Lu
Facility Name
Beipiao Central Hospital
City
Chaoyang
State/Province
Liaoning
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yutong Ma
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
rhPro-UK in Acute Ischaemic Stroke Within 4.5 Hours of Stroke Onset Trial 2(PROST-2)
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