24 Hours Treatment with Alteplase in Patients with Ischemic Stroke

NCT ID: NCT04879615

Last Updated: 2025-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 372 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-21
• Study Completion Date: 2024-09-30

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.

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).

Conditions

Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Alteplase with standard therapy

Group Type: EXPERIMENTAL

Alteplase

Intervention Type: 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)

Standard therapy

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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)

2. Patients aged > 18 years

3. NIHSS range from 4 to 26

5. Pre-stroke mRS score < 2

6. Informed consent has been obtained from the patient, a family member, or a legally responsible person, depending on local ethics requirements

Exclusion Criteria

1. Intended to proceed to endovascular treatment

2. 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

3. Large (more than one-third of the territory of middle cerebral artery) region of clear hypodensity on CT scan

4. Pregnancy, nursing, or unwillingness to use effective contraceptive measures during the trial period

5. Likelihood of non-adherence to the trial protocol or follow-up

6. Any condition that, in the judgment of the investigator, could impose hazards if study therapy is initiated or affect patient participation in the study

7. Participation in other interventional clinical trials within the previous three months

8. Life expectancy of less than three months

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Wuwei People's Hospital

Wuwei, Gansu, China

Chongqing University Jiangjin Hospital

Chongqing, , China

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

Hangzhou, , China

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

Hangzhou, , China

Second Affiliated Hospital of Zhejiang University, School of Medicine

Hangzhou, , China

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

Hangzhou, , China

Huzhou Central Hospital

Huzhou, , China

First Affiliated Hospital of Jiaxing University

Jiaxing, , China

Second Affiliated Hospital of Jiaxing University

Jiaxing, , China

The First People's Hospital of Jiashan

Jiaxing, , China

The Forth Affiliated Hospital of Zhejiang University

Jinhua, , China

Affiliated Hospital of West Anhui Health Vocational College

Liuan, , China

Mianyang Hospital of TCM

Mianyang, , China

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

Mianyang, , China

Nanjing Lishui District Hospital of Traditional Chinese Medicine

Nanjing, , China

Ningbo No. 2 Hospital

Ningbo, , China

Zhongshan Hospital

Shanghai, , China

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

Shaoxing, , China

Suzhou Hospital of Anhui Medical University

Suzhou, , China

The First Affiliated Hospital of Soochow University

Suzhou, , China

Taizhou First People's Hospital

Taizhou, , China

The First People's Hospital of Wenling

Taizhou, , China

First Affiliated Hospital of Wenzhou Medical University

Wenzhou, , China

Zhangzhou Municipal Hospital of Fujian Province

Zhangzhou, , China

The People's Hospital of Danyang

Zhenjiang, , China

Zhongshan City People's Hospital

Zhongshan, , China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 40773205 (View on PubMed)

Other Identifiers

HOPE

Identifier Type: -

Identifier Source: org_study_id