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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Ischaemic Stroke
• Intervention / Treatment: Drug: Recombinant human urokinase; Drug: Alteplase

• Study Type: Interventional
• Enrollment (Actual): 674
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing Luhe Hospital,Capital Medical University
    • Beijing, Beijing, China
      • Xuanwu Hospital, Capital Medical University
  • Guangxi
    • Liuzhou, Guangxi, China
      • Liuzhou Worker's Hospital
  • Hebei
    • Cangzhou, Hebei, China
      • Cangzhou Central Hospital
    • Handan, Hebei, China
      • The First Hospital of Handan
    • Hengshui, Hebei, China
      • Harrison International Peace Hospital
    • Shijiazhuang, Hebei, China
      • The First Hospital of Hebei Medical University
    • Shijiazhuang, Hebei, China
      • The Second Hospital of Hebei Medical University
    • Tangshan, Hebei, China
      • Tangshan Gongren Hospital
  • Heilongjiang
    • Daqing, Heilongjiang, China
      • Daqing Oilfield General Hospital
    • Harbin, Heilongjiang, China
      • The Fourth Affiliated Hospital of Harbin Medical University
    • Harbin, Heilongjiang, China
      • The First Affiliated Hospital of Harbin Medical University
  • Hunan
    • Changsha, Hunan, China
      • The First Hospital of Changsha
  • Inner Mongolia
    • Baotou, Inner Mongolia, China
      • Baotou Central Hospital
    • Baotou, Inner Mongolia, China, 100053
      • First Affiliated Hospital of Baotou Medical College
    • Hohhot, Inner Mongolia, China
      • Inner Mongolia People's Hospital
    • Hohhot, Inner Mongolia, China
      • Affiliated Hospital of Inner Mongolia Medical University
  • Jiangsu
    • Huai'an, Jiangsu, China
      • Huai'an first people's hospital
    • Huai'an, Jiangsu, China
      • The Second People'Hospital of Huai'an
    • Nanjing, Jiangsu, China
      • Nanjing Drum Tower Hospital
    • Xuzhou, Jiangsu, China
      • The Affiliated Hospital of Xuzhou Medical University
    • Xuzhou, Jiangsu, China
      • Xuzhou Central Hospital
  • Jiangxi
    • Pingxiang, Jiangxi, China
      • Jiangxi Pingxiang People's Hospital
  • Jilin
    • Changchun, Jilin, China
      • First Hospital of Jilin University
    • Siping, Jilin, China
      • The Neuropsychiatric Hospital of Jilin Province
  • Liaoning
    • Dalian, Liaoning, China
      • Dalian Municipal Central Hospital
    • Shenyang, Liaoning, China
      • Shenyang Military Region General Hospital
    • Shenyang, Liaoning, China
      • The 163th Hospital of the Chinese People's Liberation Army
  • Shandong
    • Liaocheng, Shandong, China
      • Liaocheng People's Hospital
  • Shanxi
    • Xi'an, Shanxi, China
      • The First Affiliated Hospital of Xi'an Jiaotong University
  • Sichuan
    • Chengdu, Sichuan, China
      • The People's Hospital of Sichuan Province
    • Deyang, Sichuan, China
      • Deyang People's Hospital
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Huanhu Hospital
  • Zhejiang
    • Taizhou, Zhejiang, China
      • Taizhou Hospital of Zhejiang Province
  • Zhengzhou
    • Luoyang, Zhengzhou, China
      • Luoyang Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ischemic stroke with symptoms of neurological deficits.
2. Aged 18 to 80 years（including the critical value）.
3. NIH Stroke Scale（NIHSS）scores of 4 to 25（including the critical value）.
4. Treatment within 4.5 hours after stroke onset.
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. Informed Consent Form signed by the patients or family (legal representatives) must be provided.

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 after stroke.
5. Intracranial tumor, arteriovenous malformation and aneurysm.
6. Iatrogenic Stroke.
7. Planned for thrombectomy.
8. Cardioembolism and atrial fibrillation.
9. Myocardial infarction history within 3 months.
10. Severe cerebral trauma or stroke history within 3 months.
11. Patients with systolic blood pressure ≥ 180mmHg or diastolic blood pressure ≥ 100mmHg after anti-hypertension treatment.
12. Intracranial hemorrhage or subarachnoid hemorrhage on baseline.
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 48h and increased APTT is above ULN.
20. Using of oral anticoagulant drugs and PT >15s or INR >1.7.
21. High risk of acute hemorrhage include platelet count<10^9/L.
22. Using of thrombin inhibitors or factor Xa inhibitor with abnormal results of sensitive laboratory examination.
23. Blood glucose < 2.7 mmol/L or > 22.2 mmol/L.
24. Pregnancy, lactating or menstrual women.
25. The investigator believes that the patient is not suitable for the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Recombinant human urokinase (rhPro-UK)	Drug: Recombinant human urokinase; 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.; Other Names: rhPro-UK
Active Comparator: Group B; Alteplase(rt-PA)	Drug: Alteplase; 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.; Other Names: rt-PA

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tasly Biopharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2018
• Primary Completion (Actual): April 14, 2020
• Study Completion (Actual): May 24, 2020

Study Registration Dates

• First Submitted: March 13, 2018
• First Submitted That Met QC Criteria: May 17, 2018
• First Posted (Actual): May 30, 2018

Study Record Updates

• Last Update Posted (Actual): June 22, 2020
• Last Update Submitted That Met QC Criteria: June 18, 2020
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator
• Other Study ID Numbers: TASLY-B1440-CTP-Ⅲa

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No