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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Ischaemic Stroke
• Intervention / Treatment: Drug: Recombinant human urokinase; Drug: Aspirin simulation agent; Drug: Aspirin; Drug: rhPro-UK simulation agent

• Study Type: Interventional
• Enrollment (Actual): 149
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Xuanwu Hospital, Capital Medical University
  • Hebei
    • Hengshui, Hebei, China
      • Harrison International Peace Hospital
    • Tangshan, Hebei, China
      • Tangshan Gongren Hospital
  • Inner Mongolia
    • Baotou, Inner Mongolia, China
      • Baotou Central Hospital
    • Baotou, Inner Mongolia, China
      • 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
      • Zhongda Hospital Southeast University
    • 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
    • Meihekou, Jilin, China
      • Meihekou Central Hospital
  • Liaoning
    • Dalian, Liaoning, China
      • Dalian Municipal Central Hospital
    • Shenyang, Liaoning, China
      • The First People's Hospital of Shenyang
    • Shenyang, Liaoning, China
      • Shenyang Military Region General Hospital
  • 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,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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group A; Recombinant human urokinase(rhPro-UK) and Aspirin simulation agent	Drug: Recombinant human urokinase; 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.; Other Names: rhPro-UK; Drug: Aspirin simulation agent; Aspirin simulation agent 300mg is taken orally at the beginning of thrombolysis.
OTHER: Group B; rhPro-UK simulation agent and Aspirn	Drug: Aspirin; Aspirin 300mg is taken orally at the beginning of thrombolysis.; Drug: rhPro-UK simulation agent; 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.

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
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
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.	90 days
Long-term Change from Baseline of NIHSS	NIHSS changes from baseline on 90 days after treatment.	90 days
Long-term Change from Baseline of mRS	mRS 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 at 90 days after treatment.	90 days
Proportion of Long-term Improvement	Proportion of patients achieving a Barthel Index of 75 to 100 at 90 days after treatment.	90 days

Collaborators and Investigators

• Sponsor: Tasly Biopharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 10, 2018
• Primary Completion (ACTUAL): February 28, 2020
• Study Completion (ACTUAL): March 1, 2020

Study Registration Dates

• First Submitted: June 20, 2018
• First Submitted That Met QC Criteria: July 4, 2018
• First Posted (ACTUAL): July 6, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 28, 2020
• Last Update Submitted That Met QC Criteria: April 26, 2020
• Last Verified: April 1, 2020

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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: TASLY-B1440-CTP-Ⅲb

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No