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

NCT ID: NCT05429476

Last Updated: 2024-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

234 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-17

Study Completion Date

2024-08-15

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Stroke, Acute Ischemic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Investigators Outcome Assessors

Study Groups

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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)

Group Type EXPERIMENTAL

Tissue Plasminogen Activator (Alteplase)

Intervention Type DRUG

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

Standard therapy

Standard therapy

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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

Intervention Type DRUG

Other Intervention Names

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actilyse activase tPA r-tPA

Eligibility Criteria

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Inclusion Criteria

1. Patients presenting with clinical signs of acute ischemic stroke between 4.5 and 24 hours from stroke onset, or wake-up stroke and unwitnessed stroke (if the midpoint of the last known well time is within 4.5 to 24 hours)
2. Patients aged \> 18 years (or as per local requirements)
3. NIHSS ≥ 1
4. Patients with a posterior circulation ASPECT score (PC-ASPECTS) ≥ 7. If MRI is performed first and the PC-ASPECTS on diffusion-weighted imaging (DWI) is ≥ 7, a non-contrast head CT is not required. If PCASPECTS on DWI is \< 7, the subsequent non-contrast CT must show a PC-ASPECTS ≥ 7 for inclusion
5. Posterior circulation stroke confirmation criteria: If MRI is performed, infarction confirmed by DWI is sufficient. If CT is performed, the non-contrast CT scan must not refute posterior circulation stroke, and clinical signs and symptoms must support the diagnosis, as confirmed by experienced clinicians. If clinical symptoms are atypical, CTA showing symptomatic stenosis or occlusion of large posterior circulation vessels, or CT perfusion showing symptomatic hypoperfusion, can provide additional evidence, though advanced imaging is not mandatory
6. Pre-stroke mRS score \< 2
7. 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 illnesses that prevent 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 mmol/L or \>22.2 mmol/L), with point-of-care glucose testing considered valid
* 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. Infarction of the anterior circulation confirmed by MRI, or vascular examination indicating occlusion of large anterior circulation vessels, or perfusion imaging showing hypoperfusion changes in the anterior circulation area
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 3 months
8. A life expectancy of less than three months
9. The judgment is left to the discretion of the investigator
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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People's Hospital of Anji

Anji, , China

Site Status

Botou City Hospital

Botou, , China

Site Status

Dongyang Affiliated Hospital of Wenzhou Medical University

Dongyang, , China

Site Status

Haiyan People's Hospital

Haiyan, , China

Site Status

Hangzhou First People's Hospital

Hangzhou, , China

Site Status

Second Affiliated Hospital of Zhejiang University, School of Medicine

Hangzhou, , China

Site Status

Huzhou Central Hospital

Huzhou, , China

Site Status

Huzhou First People's Hospital

Huzhou, , China

Site Status

Nanxun District People's Hospital

Huzhou, , China

Site Status

South Taihu Hospital Affiliated to Huzhou College

Huzhou, , China

Site Status

The First People's Hospital Jiashan

Jiashan, , China

Site Status

First Affiliated Hospital of Jiaxing University

Jiaxing, , China

Site Status

Jiaxing Hospital of T.C.M

Jiaxing, , China

Site Status

Second Affiliated Hospital of Jiaxing University

Jiaxing, , China

Site Status

Affiliated Jinhua Hospital, Zhejiang University School of Medicine

Jinhua, , China

Site Status

Longyan First Hospital

Longyan, , China

Site Status

Rui'an People's Hospital

Rui’an, , China

Site Status

China Medical University Shaoxing Hospital

Shaoxing, , China

Site Status

Shengzhou People's Hospital

Shengzhou, , China

Site Status

Taizhou Central Hospital

Taizhou, , China

Site Status

Taizhou Hospital of Zhejiang Province

Taizhou, , China

Site Status

The First People's Hospital of Wenling

Wenling, , China

Site Status

Yongjia People's Hospital

Yongjia, , China

Site Status

Yueqing People's Hospital

Yueqing, , China

Site Status

Zhejiang Hospital

Zhejiang, , China

Site Status

The First People's Hospital Daishan

Zhoushan, , China

Site Status

Zhuji Affiliated Hospital of Wenzhou Medical University

Zhuji, , China

Site Status

Countries

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China

References

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Yan S, Zhou Y, Lansberg MG, Liebeskind DS, Yuan C, Yu H, Chen F, Chen H, Zhang B, Mao L, Zhang X, Wang X, Zhang X, Chen Y, Zhou H, Zhong W, He Y, Chen K, Wang J, Chen H, Huang Y, Campbell BCV, Lou M; EXPECTS Group. Alteplase for Posterior Circulation Ischemic Stroke at 4.5 to 24 Hours. N Engl J Med. 2025 Apr 3;392(13):1288-1296. doi: 10.1056/NEJMoa2413344.

Reference Type DERIVED
PMID: 40174223 (View on PubMed)

Other Identifiers

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EXPECTS

Identifier Type: -

Identifier Source: org_study_id