24 Hours Treatment with Alteplase in Patients with Ischemic Stroke

NCT04879615 | Completed Phase 3

• 1 other identifier: HOPE
• Study Type: interventional
• Target: 372
• Locations: 1 country
• Sites: 26

Brief Summary

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.

Conditions

Stroke

Outcome Measures

Primary Outcomes (1)

• 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 days

Secondary Outcomes (8)

• Independent recovery assessed by ratio of modefied Rankin Scale (mRS) score of 0-2 (%)

  at 90 days

• Ratio of modefied Rankin Scale (mRS) score of 0-3 (%)

  at 90 days

• Ordinal distribution of mRS score

  at 90 days

• Major neurologic improvement defined as an improvement of ≥8 points on the NIHSS compared with the initial deficit or a score of ≤1 achieved (%)

  at 24 hours

• Major neurologic improvement defined as an improvement of ≥8 points on the NIHSS compared with the initial deficit or a score of ≤1 achieved (%)

  at 7 days

Study Arms (2)

Alteplase with standard therapy

EXPERIMENTAL

Drug: Alteplase

Standard therapy

NO INTERVENTION

Interventions

Alteplase DRUG

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)

Alteplase with standard therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients presenting with clinical signs of acute ischemic stroke between 4.5 and 24 hours from stroke onset, or awakening and unwitnessed stroke (if the midpoint of the last known well time is within 4.5 to 24 hours)
• Patients aged \> 18 years
• NIHSS range from 4 to 26
• Pre-stroke mRS score \< 2
• Informed consent has been obtained from the patient, a family member, or a legally responsible person, depending on local ethics requirements

You may not qualify if:

• Intended to proceed to endovascular treatment
• Contraindications for alteplase:
• Allergy to alteplase
• Rapidly improving symptoms at the discretion of the investigator
• The presence of epileptic seizures, hemiplegia after seizures (Todd's palsy), or other neurological/mental illness that prevents cooperation or willingness to participate
• Persistent blood pressure elevation (systolic ≥180 mmHg or diastolic ≥100 mmHg) despite treatment
• Blood glucose levels outside the acceptable range (\<2.8 or \>22.2 mmol/L, point-of-care glucose testing accepted)
• High risk of bleeding due to active internal bleeding, major surgery, trauma, gastrointestinal, or urinary tract hemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days
• Known impairments in coagulation due to comorbid disease or anticoagulant use, including an INR \>1.7 or prothrombin time \>15 seconds for those on warfarin, recent use of direct thrombin inhibitors or direct factor Xa inhibitors without reversal capability, or full-dose heparin/heparinoid within the last 24 hours with an aPTT above normal limits
• Known defect in platelet function or a platelet count below 100,000/mm³
• History of ischemic stroke, myocardial infarction, intracranial hemorrhage, severe traumatic brain injury, or intraspinal operation within the previous 3 months, or known intracranial neoplasm, arteriovenous malformation, or giant aneurysm
• Acute or past intracerebral hemorrhage identified by CT or MRI
• Large (more than one-third of the territory of middle cerebral artery) region of clear hypodensity on CT scan
• Pregnancy, nursing, or unwillingness to use effective contraceptive measures during the trial period
• Likelihood of non-adherence to the trial protocol or follow-up

Sponsors & Collaborators

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

Study Sites (26)

Wuwei People's Hospital

Wuwei, Gansu, China

Location

Chongqing University Jiangjin Hospital

Chongqing, China

Location

Binjiang Campus of Second Affiliated Hospital of Zhejiang University, School of Medicine

Hangzhou, China

Location

Bo Ao Campus of Second Affiliated Hospital of Zhejiang University, School of Medicine

Hangzhou, China

Location

Second Affiliated Hospital of Zhejiang University, School of Medicine

Hangzhou, China

Location

Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College)

Hangzhou, China

Location

Huzhou Central Hospital

Huzhou, China

Location

First Affiliated Hospital of Jiaxing University

Jiaxing, China

Location

Second Affiliated Hospital of Jiaxing University

Jiaxing, China

Location

The First People's Hospital of Jiashan

Jiaxing, China

Location

The Forth Affiliated Hospital of Zhejiang University

Jinhua, China

Location

Affiliated Hospital of West Anhui Health Vocational College

Liuan, China

Location

Mianyang Hospital of TCM

Mianyang, China

Location

The First People's Hospital of Mianyang (SiChuan Mianyang 404 Hospital)

Mianyang, China

Location

Nanjing Lishui District Hospital of Traditional Chinese Medicine

Nanjing, China

Location

Ningbo No. 2 Hospital

Ningbo, China

Location

Zhongshan Hospital

Shanghai, China

Location

Shaoxing People's Hospital (Shaoxing Hospital of Zhejiang University)

Shaoxing, China

Location

Suzhou Hospital of Anhui Medical University

Suzhou, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, China

Location

Taizhou First People's Hospital

Taizhou, China

Location

The First People's Hospital of Wenling

Taizhou, China

Location

First Affiliated Hospital of Wenzhou Medical University

Wenzhou, China

Location

Zhangzhou Municipal Hospital of Fujian Province

Zhangzhou, China

Location

The People's Hospital of Danyang

Zhenjiang, China

Location

Zhongshan City People's Hospital

Zhongshan, China

Location

Related Publications (1)

• Zhou Y, He Y, Campbell BCV, Liebeskind DS, Yuan C, Chen H, Zhang Y, Yi T, Luo Z, Zhang Z, Meng C, Cheng J, Ouyang H, Hu J, Wang F, Zhang S, Fang Q, Hu H, Zhang X, Chen Y, Zhong W, Lansberg MG, Yan S, Lou M; HOPE investigators. Alteplase for Acute Ischemic Stroke at 4.5 to 24 Hours: The HOPE Randomized Clinical Trial. JAMA. 2025 Sep 2;334(9):788-797. doi: 10.1001/jama.2025.12063.

  PMID: 40773205 DERIVED

MeSH Terms

Conditions

Stroke

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2021
• First Posted: May 10, 2021
• Study Start: June 21, 2021
• Primary Completion: June 30, 2024
• Study Completion: September 30, 2024
• Last Updated: March 5, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (26)