EXtending the Time Window for Thrombolysis in Posterior Circulation Stroke Without Early CT Signs

The primary hypothesis being tested in this trial is that ischemic stroke patients in posterior circulation at 4.5 - 24 hours post onset of stroke will have improved clinical outcomes when given intravenous tissue plasminogen activator (tPA) compared to standard care.

Study Overview

• Status: Recruiting
• Conditions: Stroke, Acute Ischemic
• Intervention / Treatment: Drug: Tissue Plasminogen Activator (Alteplase)

Detailed Description

Posterior circulation stroke accounts for 20-25% of all ischemic strokes, with an annual adjusted incidence of 18 per 100,000 person-years. Compared with anterior circulation stroke, posterior circulation stroke is less studied and has poor neurological outcomes, which requires attention. Intravenous thrombolytic therapy has greatly improved the rate of recanalization and reperfusion in patients with acute ischemic stroke, increased the proportion of patients with good prognosis, and reduced mortality. Guidelines recommend intravenous thrombolysis within 4.5 hours of onset or awakening in patients with ischemic stroke. However, the proportion of posterior circulation stroke is low or unreported in most randomized controlled trials, such as 5% of patients in the NINDS study, so it may be inappropriate to apply the results of these trials directly to patients with posterior circulation ischemic stroke.

Multiple studies have also shown a lower risk of post-circulation bleeding complications compared to pre-circulation stroke. A meta-analysis of patients with posterior circulation ischemic stroke (11.9% of posterior circulation stroke) showed that posterior circulation stroke had a lower risk of intracranial hemorrhage due to intravenous thrombolysis, half the risk of anterior circulation stroke, and a higher 3-month good functional outcome. The lower risk of hemorrhagic transformation in posterior circulation stroke is due to the greater tolerance of the posterior circulation area to ischemic injury, possibly due to a greater proportion of white matter and arterial collaterals, especially in the brainstem. In addition, the smaller infarct size of posterior circulation stroke compared with anterior circulation stroke also reduced the risk of bleeding in these patients.

Therefore, the purpose of this study was to investigate whether patients with posterior circulation stroke with onset or discovery time of 4.5-24 hours could benefit from intravenous thrombolysis in the Chinese population.

• Study Type: Interventional
• Enrollment (Anticipated): 233
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Jiashan, Zhejiang, China
      • Recruiting
      • The First People's Hospital of Jiashan
      • Contact: Tinghuan Wang; Phone Number: 18867650389; Email: tinghuanwang@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients presented with clinical signs of acute ischemic stroke between 4.5 and 24 hours of stroke onset or awakening with stroke (if between 4.5 and 24 hours from the midpoint of sleep).
• Patient's age is > 18 years (or as per local requirements).
• NIHSS ≥ 1.
• Patients with post circulation ASPECT score ≥ 7.
• Patients meet at least one of the below criteria: post circulation stroke considered by experienced clinicians, or infarction of posterior circulation confirmed by MRI, or the vascular examination indicates that there are symptomatic stenosis or occlusion of large posterior circulation vessels, or the perfusion image indicates that there are symptomatic hypoperfusion changes in the posterior circulation area.
• Pre-stroke mRS score < 2.
• Patients do not receive endovascular treatment at patients' and treating clinician's discretion
• Patient, family member or legally responsible person depending on local ethics requirements has given informed consent.

Exclusion Criteria:

• Contraindication for alteplase.
• A life expectancy of less than three months.
• The judgment is left to the discretion of the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Alteplase with standard therapy; Patients will receive standard dose intravenous alteplase (0.9 mg per kilogram, the first 10% administered as an initial bolus and the remainder over a 1-hour period, with a maximum dose of 90 mg)	Drug: Tissue Plasminogen Activator (Alteplase); Tissue Plasminogen Activator (Alteplase) 0.9 mg/kg up to a maximum of 90mg, intravenous, 10% as bolus and the remainder over 1 hour Other Names: Actilyse Activase tPA r-tPA; Other Names: tPA; r-tPA; actilyse; activase
NO_INTERVENTION: Standard therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
independent recovery assessed by ratio of modefied Rankin Scale (mRS) score of 0-2 (%) at 90 days	mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
recovery assessed by modefied Rankin Scale (mRS) score at 90 days	mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome	90 days
excellent recovery assessed by the ratio of modefied Rankin Scale (mRS) score of 0-1 (%) at 90 days	mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome	90 days
Change in ≥ 8 National Institutes of Health Stroke Scale (NIHSS) points or reaching ≤ 1 on this scale at 24 hours	NIHSS: minimum value = 0, maximum value = 42, and higher scores mean severer symptoms	24 hours
Change in ≥ 8 National Institutes of Health Stroke Scale (NIHSS) points or reaching ≤ 1 on this scale at 7 days	NIHSS: minimum value = 0, maximum value = 42, and higher scores mean severer symptoms	7 days
independent recovery assessed by ratio of modefied Rankin Scale (mRS) score of 0-2 (%) at 1 year	mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome	1 year
Symptomatic Intracerebral Hemorrhage (sICH) at 24 hours	Symptomatic hemorrhage defined by SITS-MOST criteria: type 2 parenchymal hematoma associated with ≥4 point increase in NIHSS	24 hours
Symptomatic Intracerebral Hemorrhage (sICH) at 7 days	Symptomatic hemorrhage defined by SITS-MOST criteria: type 2 parenchymal hematoma associated with ≥4 point increase in NIHSS	7 days

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 17, 2022
• Primary Completion (ANTICIPATED): May 30, 2024
• Study Completion (ANTICIPATED): August 31, 2024

Study Registration Dates

• First Submitted: June 19, 2022
• First Submitted That Met QC Criteria: June 19, 2022
• First Posted (ACTUAL): June 23, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 3, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator; Plasminogen
• Other Study ID Numbers: EXPECTS

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