24 Hours Treatment With Alteplase in Patients With Ischemic Stroke

Treatment With Intravenous Alteplase in Ischemic Stroke Patients With Onset Time Between 4.5 and 24 Hours

The development of intravenous thrombolysis has greatly improved the rate of recanalization and reperfusion in patients with acute ischemic stroke, increasing the proportion of patients with good outcome and reduced mortality. The guideline recommends that patients with ischemic stroke should be treated with intravenous thrombolysis within 4.5 hours. The latest meta-analysis found that ischemic stroke with onset time of 4.5-9 hours with infarction core volume <70ml, ischemic penumbra volume >10ml, and hypoperfusion volume / infarction core volume >1.2 could be benefit from intravenous thrombolysis. The DAWN clinical trial has shown that patients with ischemic stroke with large vessel occlusion with onset time of 6-24 hours could be benefit from endovascular treatment after screening by multi-mode imaging. Therefore, we hypothesize that patients with ischemic stroke with onset time of 4.5-24 hours with a definite penumbra may also benefit from intravenous thrombolysis. The purpose of this study is to explore whether the patients with ischemic stroke with onset time of 4.5-24 hours can benefit from intravenous thrombolysis if they meet the standard of CT perfusion screening.

Study Overview

• Status: Recruiting
• Conditions: Stroke
• Intervention / Treatment: Drug: Alteplase

Detailed Description

In recent years, the development of intravenous thrombolysis has greatly improved the rate of recanalization and reperfusion in patients with acute ischemic stroke, increasing the proportion of patients with good outcome and reduced mortality. The guideline recommends that patients with ischemic stroke should be treated with intravenous thrombolysis within 4.5 hours. The latest meta-analysis found that ischemic stroke with onset time of 4.5-9 hours with infarction core volume <70ml, ischemic penumbra volume >10ml, and hypoperfusion volume / infarction core volume >1.2 could be benefit from intravenous thrombolysis (the ratio of mRS 0-1 in 3 months, thrombolysis vs non thrombolysis: 35.4% vs 29.5%). Thus, the time window is not an absolute constant indicator. In theory, compared with time window, the physiological window based on the concept of ischemic penumbra is more reasonable.

In 2015, the AHA/ASA guidelines recommended that patients with ischemic stroke with large vessel occlusion should receive endovascular treatment within 6 hours. The DAWN clinical trial has shown that patients with ischemic stroke with large vessel occlusion with onset time of 6-24 hours could be benefit from endovascular treatment after screening by multi-mode imaging (CT perfusion or MR perfusion). As a result, the 2018 AHA/ASA guidelines extended the endovascular treatment window to 24 hours for patients with large vessel occlusion stroke that meet the standard of perfusion. Therefore, we hypothesize that patients with ischemic stroke with onset time of 4.5-24 hours with a definite penumbra may also benefit from intravenous thrombolysis.

Thus, the purpose of this study is to explore whether the patients with ischemic stroke with onset time of 4.5-24 hours can benefit from intravenous thrombolysis if they meet the standard of CT perfusion screening (infarction core volume <70ml, ischemic penumbra volume >10ml, and hypoperfusion volume / infarction core volume >1.2).

• Study Type: Interventional
• Enrollment (Anticipated): 372
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Hangzhou, China
    • Recruiting
    • Second Affiliated Hospital of Zhejiang University, School of Medicine
    • Contact: Min Lou, PhD, MD; Phone Number: 8615925622176; Email: lm99@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 within 24 hours from the midpoint of sleep).
• Patient's age is >18 years.
• NIHSS 4 to 26.
• Imaging inclusion criteria: infarct core volume ≤ 70 mL and penumbra ≥ 10 mL with at least 20% mismatch (as evaluated by CTP).
• Patient, family member or legally responsible person depending on local ethics requirements has given informed consent.

Exclusion Criteria:

• CT shows intracranial hemorrhage or lesions larger than one third of the territory of the middle cerebral artery.
• Pre-stroke mRS score of more than 1 (indicating previous disability);
• Contraindication for alteplase.
• Plan to receive endovascular treatment.
• A life expectancy of less than three months.
• Any condition that could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study (this applies to patients with severe microangiopathy such as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura). 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	Drug: Alteplase; 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)
NO_INTERVENTION: Standard therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
excellent recovery assessed by the ratio of modefied Rankin Scale (mRS) score of 0-1 (%)	mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome	at 90 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
independent recovery assessed by ratio of modefied Rankin Scale (mRS) score of 0-2 (%)	mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome	at 90 day
the frequency of parenchymal hemorrhage (PH) (%)	the presence of PH is defined according the standard from ECASS-2 study	at day 1
the change on the National Institute of Health stroke scale (NIHSS) score from baseline to 1 day	NIHSS: minimum value = 0, maximum value = 42, and higher scores mean severer symptoms	from baseline to 1 day
the change on the National Institute of Health stroke scale (NIHSS) score from baseline to 7 day	NIHSS: minimum value = 0, maximum value = 42, and higher scores mean severer symptoms	from baseline to 7 day
general recovery assessed by the ratio of modefied Rankin Scale (mRS) score of 0-3 (%)	mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome	at day 90
recovery assessed by modefied Rankin Scale (mRS) score	mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome	at day 90

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Shaoxing People's Hospital; Huizhou Municipal Central Hospital; The Second Affiliated Hospital of Jiaxing University; Lishui Country People's Hospital; First Affiliated Hospital of Jiaxing University; Zhoushan People's Hospital; Fourth Affiliated Hospital of Zhejiang University, School of Medicine

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 21, 2021
• Primary Completion (ANTICIPATED): May 31, 2025
• Study Completion (ANTICIPATED): December 31, 2025

Study Registration Dates

• First Submitted: May 6, 2021
• First Submitted That Met QC Criteria: May 6, 2021
• First Posted (ACTUAL): May 10, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 6, 2023
• Last Update Submitted That Met QC Criteria: February 2, 2023
• Last Verified: January 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
• Other Study ID Numbers: HOPE

Drug and device information, study documents

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