Thrombolysis of Urokinase for Minor Stroke (TRUST)

November 12, 2023 updated by: Bo Song, The First Affiliated Hospital of Zhengzhou University

A Phase ⅢB, Prospective, Randomized, Open Label, Blinded-endpoint, Multicenter Trial of the Efficacy and Safety of Urokinase Thrombolysis Comparing With Antiplatelet Agents for Patients With Minor Stroke.

This trial will enroll patients that have been diagnosed with minor stroke, which has occurred within the past 6 hours. TRUST is a prospective multicenter, randomized, blinded-endpoint study to evaluate the efficacy and safety of Urokinase Thrombolysis for patients with minor stroke.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

China is currently faced with the heaviest stroke burden due to the tremendous population and susceptibility to cerebrovascular disease. As has been assessed, deaths caused by cerebrovascular disease are three times of cardiovascular disease. Within whole population with cerebrovascular disease, minor stoke have taken a significant part of the disease burden. Thus the population with minor stoke is one of the most important parts in efficient prevention of cerebrovascular disease. According to phase I and II data from national stoke registration in China, 35.25% to 42.23% cases were minor ischemic strokes. However, in clinical practice, the minor ischemic stroke patients are likely to be ignored and some might have poor prognosis. As has been demonstrated by a number of studies, up to one third of the acute non-disabling ischemic stroke without in-time thrombolysis may suffer from disabling or death at 90-day follow-up.

Several studies have demonstrated the potential benefits of thrombolysis compared usually with placebo, including the Third International Stroke Trail ( IST-3, rt-PA to placebo, patients within 3 hours after attack, with blood pressure lower than 185/110mmHg and NIHSS≤5)，National Institute of Neurological Disorders and Stroke rt-PA Stroke Study（ NINDS, rt-PA to placebo, patients with mild ischemic stroke recognized by 5 different definitions）.

Urokinase is a kind of non-selective plasminogen activator, urokinase acted as effective catalyzer in the transferring of both free and protein-binding plasminogen to plasmin, thus inducing thrombolysis. As one of the widely used medication for intravenous thrombolysis in China, urokinase has been suggested the the efficacy and safety for ischemic stroke. With easier availability and lower price, urokinase has provided a promising alternation to patients who need thrombolysis in China, especially in less developed areas. The Chinese guideline for diagnosis and treatment of acute ischemic stroke 2018 has recommended urokinase as an alternation in the treatment of acute ischemic stroke within 6-hour time window as well, if rt-PA is not available or affordable. However, randomized and multicenter clinical trial of urokinase thrombolysis for minor stroke is still vacant, which couldn't provide more persuasive evidence.

TRUST is a prospective multicenter, randomized, single-blind evaluation study to evaluate the efficacy and safety of Urokinase Thrombolysis for patients with minor stroke. The trail will enroll a total of 1002 minor stroke patients within a 6 hour time window with a NIHSS score ≤5 at the time of randomization. Randomization will be 1:1 to Urokinase Thrombolysis (experimental) or Antiplatelet agents (control). Patients will receive 1 million units urokinase dissolved by 100ml saline through intravenous infusion within 30min or oral antiplatelet agents. All patients will undergo CT or MRI before treatment and will undergo the second CT within 36 hours after treatment. Patients will be followed up at 36h, 7d and 90 days. The primary outcome measures including the proportion of patients with a modified Rankin Scale(mRS) of 0 or 1 at 90-day follow-up and the patients with symptomatic intracranial hemorrhage within 36 hours. Secondary outcome measures cover new vascular events, the Progress of MRS score, Neurological impairment, Daily function evaluations, Quality of life assessments, Overall mortality and Adverse events and severe adverse events within 90 days.

Study Type

Interventional

Enrollment (Actual)

1005

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Yongli Tao, MD;PhD
  • Phone Number: +86-371-66278068
  • Email: tyl2112@126.com

Study Contact Backup

Study Locations

  • China
    • Henan
      • Zhengzhou, Henan, China, 0371
        • The First Affiliated Hospital of Zhengzhou University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adult patients: 18-80 years old
  2. The time from last seen well to treatment < 6 hours
  3. Minor stroke defined as a baseline NIHSS ≤5 at the time of randomization..
  4. First onset or pre-stroke mRS≤1
  5. Informed consent signed

Exclusion Criteria:

1.Hyperdensity on CT suggesting intracranial hemorrhage

2.Large acute stroke >1/3 middle cerebral artery (MCA) territory visible on CT or MRI

3.Other contraindications of intravenous thrombolysis, including but not limited to:

  1. Intracranial tumor, arteriovenous malformation
  2. Coma or confirmed as severe stroke by clinical assessment (e.g. NIHSS ≥25) or proper imaging methods
  3. With seizure
  4. Stroke attack within past three months
  5. Heparin administration within 48h before onset, with APTT longer than upper limit
  6. Stroke history with diabetes
  7. Platelet count ≤100×10^9/L
  8. Difficult to control hypertension, defined by systolic pressure ≥185mmHg or diastolic pressure ≥110 mmHg in 3 tests with at least ten minutes interval, under well guided medications.
  9. Blood glucose <50mg/dl（2.7mmol/l）or >400mg/dl（22.2mmol/l）
  10. Obvious hemorrhage within past 6 months
  11. Oral anti-coagulation drug administration (e.g. warfarin) with INR>1.5
  12. Intracranial hemorrhage or suspected intracranial hemorrhage (including subarachnoid hemorrhage)
  13. Pregnancy or lactation.
  14. History of severe CNS damage (e.g. tumor, arterial aneurysm or CNS surgery)
  15. Hemorrhagic retinopathy, e.g. diabetes (hemorrhages suggested by optic impairment) or other hemorrhagic ocular lesions.
  16. Bacterial endocarditis or pericarditis.
  17. Prolonged or traumatic CPR (>2min), puncture in nonstress vessels within past 10 days, such as subclavian vein puncture.
  18. Acute pancreatitis.
  19. Confirmed ulcerative gastric or intestinal problems within 3 months.
  20. Arterial aneurysm or arteriovenous malformation.
  21. Any tumor that increase risk of hemorrhage.
  22. Severe hepatic diseases, like hepatic failure, liver cirrhosis, portal hypertension, esophageal varices or active hepatitis.
  23. Major surgery, severe trauma or craniocerebral trauma within past 10 days.
  24. Allergy to any components of urokinase.

4.Severe, fatal diseases with less than 3 month expected survival.

5.Intended to receive standard rt-PA thrombolysis or intravascular therapy.

6.Already participating in other studies that conflict to this study.

7.Unable to accomplish the follow-up.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Urokinase thrombolysis
The patients of intervention group will receive 1 millions units urokinase dissolved by 100 saline through intravenous infusion within 30 minutes.
Drug: Urokinase thrombolysis
The patients of intervention group will receive 1 millions units urokinase dissolved by 100 saline through intravenous infusion within 30 minutes.
Other Names:
  • Urokinase
Other: Antiplatelet treatment
The control group will receive antiplatelet agents as decided by the physicians according to Chinese guideline for diagnosis and treatment of acute ischemic stroke 2018
Drug: Aspirin;Clopidogrel
The control group will receive antiplatelet agents as decided by the physicians according to Chinese guideline for diagnosis and treatment of acute ischemic stroke 2018.
Other Names:
  • Antiplatelet treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with a modified Rankin Scale(mRS) of 0 or 1 at 90-day follow-up
Time Frame: 90 Days
mRS has 0-6 points, the higher the worse outcome.
90 Days
Proportion of patients with symptomatic intracranial hemorrhage within 36 hours
Time Frame: 36 hours
Symptomatic intracranial haemorrhage within 36 hours
36 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with new vascular events
Time Frame: 90 days
Proportion of patients with new vascular events within 90 days(Ischemic stroke / hemorrhagic stroke / TIA / myocardial infarction / vascular death)
90 days
MRS score
Time Frame: 90 days
To evaluate the progress of MRS score
90 days
The ratio of patients with MRS 0-1 during the last visit in two groups
Time Frame: 90 days
mRS has 0-6 points, the higher the worse outcome.
90 days
Changes in National Institutes of Health Stroke Scale(NIHSS) score
Time Frame: 90 days
Neurological impairment in two groups (changes in NIHSS score at 90-day follow-up). NIHSS has 0-42 points, the higher the worse outcome.
90 days
Barthel index (BI) score
Time Frame: 90 days
Daily function evaluations(BI score at 90 days). BI has 0-100 points,the higher the bettter outcome.
90 days
Quality of life assessments
Time Frame: 90 days
EuroQol five dimensional questionnaire (EQ-5D scale).
90 days
Overall mortality
Time Frame: 90 days
Overall mortality within 90 days
90 days
Adverse events and severe adverse events
Time Frame: 90 days
Adverse events and severe adverse events in two groups during 90 days
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital of Zhengzhou University

Collaborators

General Hospital of Shenyang Military Region
Beijing Tiantan Hospital
Shanghai 10th People's Hospital

Investigators

  • Principal Investigator: Bo Song, MD;PhD, The First Affiliated Hospital of Zhengzhou University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 4, 2020

Primary Completion (Actual)

February 18, 2023

Study Completion (Actual)

February 18, 2023

Study Registration Dates

First Submitted

June 4, 2020

First Submitted That Met QC Criteria

June 5, 2020

First Posted (Actual)

June 9, 2020

Study Record Updates

Last Update Posted (Estimated)

November 14, 2023

Last Update Submitted That Met QC Criteria

November 12, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017YFC1308202

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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