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Thrombolysis With rhPro-UK in 4.5-6 Hours After Acute Ischemic Stroke in a Double-blinded,Controlled Trial (PROUD)

Primary Purpose

Acute Ischaemic Stroke

Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Recombinant human urokinase
Aspirin
rhPro-UK simulation agent
Aspirin simulation agent
Sponsored by
Tasly Biopharmaceuticals Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Ischaemic Stroke

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Ischemic stroke with symptoms of neurological deficits.
  2. Aged 18 to 80 years,male or famale.
  3. NIH Stroke Scale（NIHSS）scores of 4 to 25.
  4. Treatment 4.5 to 6 hours after stroke onset.(Stroke onset time is defined as the last time a patient with no clinical neurological deficit,for patients who wake up with stroke symptoms, consider that stroke occurs when the patient begins to fall asleep).
  5. The symptoms of stroke last at least 30 minutes without significant improvement before treatment.
  6. CT showed negative or signs of early infarction.
  7. Patients and/or their families are willing to participate in this study and agree to sign informed consent.

Exclusion Criteria:

  1. Patients with premorbid modified Rankin Scale(mRS) score ≥2
  2. CT showed multiple infarctions（low density> 1/3 cerebral hemisphere）.
  3. Transient ischemic attack.
  4. Epileptic seizure when stroke onset.
  5. Intracranial tumor, arteriovenous malformation and aneurysm.
  6. Iatrogenic Stroke.
  7. Thrombectomy is planned.
  8. Cardioembolism and atrial fibrillation.
  9. Myocardial infarction history within 3 months.
  10. Severe cerebral trauma or stroke history within 3 months.
  11. Blood pressure is still out of control after aggressive antihypertensive treatment.Uncontrolled blood pressure is defined as systolic blood pressure≥ 180mmHg or diastolic blood pressure≥100mmHg.
  12. High density lesions (bleeding) and subarachnoid hemorrhage is revealed by emergency CT examination.
  13. Active visceral hemorrhage.
  14. Patients with intracerebral hemorrhage history.
  15. Patients with diabetic retinopathy history.
  16. Puncture in 1 week which can not be oppressed.
  17. Major surgery or severe trauma within 2 weeks.
  18. Intracranial surgery, intraspinal surgery or solid organ biopsy within 30 days.
  19. Heparin treatment within 48 hours (APTT above normal upper limit).
  20. Taking anticoagulant drugs orally, and PT >15s or INR >1.7.
  21. High risk of acute hemorrhage include platelet count<10^9/L.
  22. Taking thrombin inhibitors or factor Xa inhibitor with abnormal results of sensitive laboratory examination(e.g. APTT, INR, PLT, FIB、TT or appropriate Ⅹ a factor activity test, etc.).
  23. Blood glucose < 2.7 mmol/L or > 22.2 mmol/L.
  24. Pregnancy, lactating or menstrual women.
  25. Patients who have difficulty swallowing and are unable to take medications orally.
  26. Clinician thinks patient doesn't fit to participate in the test of other diseases or conditions.

Sites / Locations

  • XuanWu Hospital, Capital Medical University
  • Harrison International Peace Hospital
  • Tangshan Gongren Hospital
  • Baotou Central Hospital
  • First Affiliated Hospital of Baotou Medical College
  • Affiliated Hospital of Inner Mongolia Medical University
  • Inner Mongolia People's Hospital
  • Huai'an First People's Hospital
  • The Second People'Hospital of Huai'an
  • Zhongda Hospital Southeast University
  • The Affiliated Hospital of Xuzhou Medical University
  • Xuzhou Central Hospital
  • Jiangxi Pingxiang People's Hospital
  • First Hospital of Jilin University
  • Meihekou Central Hospital
  • Dalian Municipal Central Hospital
  • Shenyang Military Region General Hospital
  • The First People's Hospital of Shenyang
  • Luoyang Central Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Group A

Group B

Arm Description

Recombinant human urokinase(rhPro-UK) and Aspirin simulation agent

rhPro-UK simulation agent and Aspirn

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Scores of Neurological Improvement
NIHSS changes from baseline at 24 hours after treatment
Index Long-term Change from Baseline of Barthel Index
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.
Long-term Change from Baseline of NIHSS
NIHSS changes from baseline on 90 days after treatment.
Long-term Change from Baseline of mRS
mRS changes from baseline on 90 days after treatment.
Proportion of Long-term Improvement
Proportion of patients achieving a mRS of 0 to 2 at 90 days after treatment.
Proportion of Long-term Improvement
Proportion of patients achieving a Barthel Index of 75 to 100 at 90 days after treatment.
Systemic hemorrhage
Severe systemic hemorrhage
Symptomatic intracerebral hemorrhage
Symptomatic intracerebral hemorrhage (sICH)
Death
Death
Recurrence
Recurrence of stroke

Full Information

First Posted
June 20, 2018
Last Updated
April 26, 2020
Sponsor
Tasly Biopharmaceuticals Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT03578822
Brief Title
Thrombolysis With rhPro-UK in 4.5-6 Hours After Acute Ischemic Stroke in a Double-blinded,Controlled Trial
Acronym
PROUD
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 4.5-6 Hours After Stroke Onset
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
August 10, 2018 (Actual)
Primary Completion Date
February 28, 2020 (Actual)
Study Completion Date
March 1, 2020 (Actual)

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
This is a randomized,controlled, double-blinded, phase 3 clinical study to evaluate the efficacy and safety of recombinant human urokinase(rhPro-UK) versus basic treatment for patients with acute ischaemic stroke in 4.5-6 hours after stroke onset.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Ischaemic Stroke

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
149 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group A
Arm Type
Experimental
Arm Description
Recombinant human urokinase(rhPro-UK) and Aspirin simulation agent
Arm Title
Group B
Arm Type
Other
Arm Description
rhPro-UK simulation agent and Aspirn
Intervention Type
Drug
Intervention Name(s)
Recombinant human urokinase
Other Intervention Name(s)
rhPro-UK
Intervention Description
Patients receive rhPro-UK 35mg,15mg of which is given as a bolus within 3min followed by dlivery of the remaining 20 mg as a constant infusion over a period of 30 min.
Intervention Type
Drug
Intervention Name(s)
Aspirin
Intervention Description
Aspirin 300mg is taken orally at the beginning of thrombolysis.
Intervention Type
Drug
Intervention Name(s)
rhPro-UK simulation agent
Intervention Description
Patients receive rhPro-UK simulation agent 35mg,15mg of which is given as a bolus within 3min followed by dlivery of the remaining 20 mg as a constant infusion over a period of 30 min.
Intervention Type
Drug
Intervention Name(s)
Aspirin simulation agent
Intervention Description
Aspirin simulation agent 300mg is taken orally at the beginning of thrombolysis.
Primary Outcome Measure Information:
Title
Functional handicap
Description
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.
Time Frame
90days
Secondary Outcome Measure Information:
Title
Proportion of Neurological Improvement
Description
Proportion of patients achieving a NIHSS(national institutes of health stroke scale) ≦1 or reduction of ≥4 NIHSS points at 24 hours after treatment.
Time Frame
90 days
Title
Scores of Neurological Improvement
Description
NIHSS changes from baseline at 24 hours after treatment
Time Frame
24 hours
Title
Index Long-term Change from Baseline of Barthel Index
Description
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.
Time Frame
90 days
Title
Long-term Change from Baseline of NIHSS
Description
NIHSS changes from baseline on 90 days after treatment.
Time Frame
90 days
Title
Long-term Change from Baseline of mRS
Description
mRS changes from baseline on 90 days after treatment.
Time Frame
90 days
Title
Proportion of Long-term Improvement
Description
Proportion of patients achieving a mRS of 0 to 2 at 90 days after treatment.
Time Frame
90 days
Title
Proportion of Long-term Improvement
Description
Proportion of patients achieving a Barthel Index of 75 to 100 at 90 days after treatment.
Time Frame
90 days
Title
Systemic hemorrhage
Description
Severe systemic hemorrhage
Time Frame
90days
Title
Symptomatic intracerebral hemorrhage
Description
Symptomatic intracerebral hemorrhage (sICH)
Time Frame
90days
Title
Death
Description
Death
Time Frame
7 days and 90 days
Title
Recurrence
Description
Recurrence of stroke
Time Frame
7 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ischemic stroke with symptoms of neurological deficits. Aged 18 to 80 years,male or famale. NIH Stroke Scale（NIHSS）scores of 4 to 25. Treatment 4.5 to 6 hours after stroke onset.(Stroke onset time is defined as the last time a patient with no clinical neurological deficit,for patients who wake up with stroke symptoms, consider that stroke occurs when the patient begins to fall asleep). The symptoms of stroke last at least 30 minutes without significant improvement before treatment. CT showed negative or signs of early infarction. Patients and/or their families are willing to participate in this study and agree to sign informed consent. 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 when stroke onset. Intracranial tumor, arteriovenous malformation and aneurysm. Iatrogenic Stroke. Thrombectomy is planned. Cardioembolism and atrial fibrillation. Myocardial infarction history within 3 months. Severe cerebral trauma or stroke history within 3 months. Blood pressure is still out of control after aggressive antihypertensive treatment.Uncontrolled blood pressure is defined as systolic blood pressure≥ 180mmHg or diastolic blood pressure≥100mmHg. High density lesions (bleeding) and subarachnoid hemorrhage is revealed by emergency CT examination. 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 48 hours (APTT above normal upper limit). Taking anticoagulant drugs orally, and PT >15s or INR >1.7. High risk of acute hemorrhage include platelet count<10^9/L. Taking thrombin inhibitors or factor Xa inhibitor with abnormal results of sensitive laboratory examination(e.g. APTT, INR, PLT, FIB、TT or appropriate Ⅹ a factor activity test, etc.). Blood glucose < 2.7 mmol/L or > 22.2 mmol/L. Pregnancy, lactating or menstrual women. Patients who have difficulty swallowing and are unable to take medications orally. Clinician thinks patient doesn't fit to participate in the test of other diseases or conditions.
Facility Information:
Facility Name
XuanWu Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Harrison International Peace Hospital
City
Hengshui
State/Province
Hebei
Country
China
Facility Name
Tangshan Gongren Hospital
City
Tangshan
State/Province
Hebei
Country
China
Facility Name
Baotou Central Hospital
City
Baotou
State/Province
Inner Mongolia
Country
China
Facility Name
First Affiliated Hospital of Baotou Medical College
City
Baotou
State/Province
Inner Mongolia
Country
China
Facility Name
Affiliated Hospital of Inner Mongolia Medical University
City
Hohhot
State/Province
Inner Mongolia
Country
China
Facility Name
Inner Mongolia People's Hospital
City
Hohhot
State/Province
Inner Mongolia
Country
China
Facility Name
Huai'an First People's Hospital
City
Huai'an
State/Province
Jiangsu
Country
China
Facility Name
The Second People'Hospital of Huai'an
City
Huai'an
State/Province
Jiangsu
Country
China
Facility Name
Zhongda Hospital Southeast University
City
Nanjing
State/Province
Jiangsu
Country
China
Facility Name
The Affiliated Hospital of Xuzhou Medical University
City
Xuzhou
State/Province
Jiangsu
Country
China
Facility Name
Xuzhou Central Hospital
City
Xuzhou
State/Province
Jiangsu
Country
China
Facility Name
Jiangxi Pingxiang People's Hospital
City
Pingxiang
State/Province
Jiangxi
Country
China
Facility Name
First Hospital of Jilin University
City
Changchun
State/Province
Jilin
Country
China
Facility Name
Meihekou Central Hospital
City
Meihekou
State/Province
Jilin
Country
China
Facility Name
Dalian Municipal Central Hospital
City
Dalian
State/Province
Liaoning
Country
China
Facility Name
Shenyang Military Region General Hospital
City
Shenyang
State/Province
Liaoning
Country
China
Facility Name
The First People's Hospital of Shenyang
City
Shenyang
State/Province
Liaoning
Country
China
Facility Name
Luoyang Central Hospital
City
Luoyang
State/Province
Zhengzhou
Country
China

12. IPD Sharing Statement

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Thrombolysis With rhPro-UK in 4.5-6 Hours After Acute Ischemic Stroke in a Double-blinded,Controlled Trial

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