Evaluation Study of Early Administration of Evolocumab After Thrombolysis in Patients With Atherosclerotic Acute Ischemic Stroke

NCT ID: NCT07301372

Last Updated: 2025-12-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-30
• Study Completion Date: 2026-08-30

Brief Summary

This study is a Phase IIa clinical trial initiated by the researchers, which is prospective, single-center, randomized, open-label, with blinded endpoint evaluation (PROBE design). Patients were screened through the emergency stroke green channel and included if they had an onset within 9 hours, met the criteria for large artery atherosclerosis (LAA) after multimodal imaging screening, received intravenous thrombolysis, and signed informed consent to participate. The study used block randomization (block size of 4), stratified by baseline National Institutes of Health Stroke Scale (NIHSS) score (5-10 vs >10-20) and onset-to-thrombolysis time (<4.5 hours vs 4.5-9 hours).

Intervention group: received subcutaneous injections of Ilyumumab 420 mg (three syringes) within 24 hours after thrombolysis plus standard drug therapy (including statins). Control group: received conventional statin therapy (atorvastatin 20 mg/day) after thrombolysis. All patients received standardized stroke treatment (initiating antiplatelet therapy 24 hours after thrombolysis) and standardized management of blood pressure and blood glucose.

NIHSS scores were assessed every 12 hours within 72 hours post-thrombolysis, and then daily thereafter, to evaluate the effectiveness of combined therapy in reducing early neurological deterioration (END).

Blinding: The study is open-label. An independent Clinical Endpoint Committee (CEC) was established, and all clinical endpoint events (END assessment, 90-day mRS scores) were evaluated in a blinded manner by experts who were completely unaware of group assignments.

Conditions

Acute Stroke

Keywords

PCSK9 inhibitor; Inflammatory factor; Biomarkers of brain injury; Atorvastatin; Early neurological deterioration

Study Design

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

Study Groups

evolocumab

Within 24 hours after thrombolysis, patients received subcutaneous injections of 420 mg evokine and three vials of evokine, along with standard statin therapy (atorvastatin 20 mg/day).

Group Type: EXPERIMENTAL

Ivolumab 420mg (three vials)

Intervention Type: DRUG

Administer 420 mg (three vials) of evolocumab subcutaneously within 24 hours after thrombolysis.

Standard of care

Following thrombolysis, the patient received standard statin therapy (atorvastatin 20 mg/day).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Ivolumab 420mg (three vials)

Administer 420 mg (three vials) of evolocumab subcutaneously within 24 hours after thrombolysis.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age 18-85 years. No gender or sex restrictions, and no gender ratio restrictions.

2. Clinically diagnosed with acute ischemic stroke, with the time from symptom onset to intravenous thrombolysis <9 hours.

1. Within 4.5 hours of symptom onset: This time window is based on the ECASS III criteria (Class IA recommendation) and is currently the standard indication for intravenous thrombolysis in acute ischemic stroke worldwide.

2. 4.5-9 hours: Referring to the EXTEND study criteria, meeting the following multimodal imaging mismatch ratio: ischemic penumbra volume/ischemic core volume >1.2, with an absolute mismatch volume >10 mL and an ischemic core volume <70 mL.

3. The stroke meets the TOAST classification for large artery atherosclerosis (LAA), which includes intracranial arteriosclerosis (ICAS) and extracranial arteriosclerosis (ECAS), and meets one of the following three criteria: large artery stenosis ≥50%, infarct lesion >1.5cm + ipsilateral plaque (no stenosis requirement), or intracranial artery stenosis ≥30% with plaque ulceration.

4. The patient or their legal representative has signed an informed consent form.

Exclusion Criteria

1. CT scan showing signs of intracranial hemorrhage, symptomatic intracranial hemorrhage, or subarachnoid hemorrhage, even if the CT scan results are normal.

2. Patients who must or wish to continue using restrictive medications or any medications that may interfere with the safe conduct of the trial.

3. Acute bleeding tendency, including but not limited to:

1. A known family history of bleeding disorders and a history of a serious bleeding disorder currently present or within the past 6 months.

2. Receiving heparin treatment within the past 48 hours, with an activated partial thromboplastin time (aPTT) exceeding the upper limit of the normal range for laboratory testing.

3. Currently taking an oral vitamin K anticoagulant (e.g., warfarin) with a prolonged prothrombin time (INR > 1.7 or PT > 15 seconds); or currently taking a novel oral anticoagulant (e.g., dabigatran etexilate, rivaroxaban, or apixaban) with an activated partial thromboplastin time (aPTT) and/or prothrombin time (PT) exceeding the upper limit of the local laboratory reference range.

4. Platelet count below 100,000/mm³ at screening.

5. History of central nervous system injury (e.g., tumor, aneurysm, intracranial or spinal surgery).

6. Experiencing traumatic external cardiac compression, obstetric delivery, or non-compressive vascular puncture (e.g., subclavian or jugular vein puncture) within the past 10 days.

7. Known history of suspected intracranial hemorrhage or suspected aneurysm/subarachnoid hemorrhage.

8. Tumors with increased bleeding risk.

9. History of ulcerative gastrointestinal disease, esophageal varices, aneurysm, or arteriovenous malformation within the past 3 months.

10. Associated with bleeding risk. 4. Any known disease significantly associated with this condition.

4. Previous mRS score ≥2, with comorbid dementia or other neurodegenerative diseases.

5. Clinically confirmed non-atherosclerotic intracranial arterial stenosis, such as aortic dissection, vasculitis, moyamoya disease, embolism, immune system disorders, etc.

6. Other comorbid medical histories that may affect endpoint event determination and follow-up, such as history of traumatic brain injury, multiple sclerosis, encephalitis, tumors, poisoning, syphilis, and severe heart, lung, liver, kidney, or endocrine diseases.

7. Pregnant women.

8. Currently participating in other experimental device or drug studies, or having completed other experimental device or drug studies, or having received other experimental treatments for less than 30 days.

9. Having used PCSK9 inhibitors within 4 weeks prior to enrollment.

10. Hypersensitivity to statins or PCSK9 inhibitors.

11. Patients with severe hepatic or renal impairment (eGFR <30 ml/min/1.73 m²).

12. Refusal to sign informed consent.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Affiliated Hospital of Xuzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ren Guo Chen

Role: STUDY_DIRECTOR

the Ethics Committee of the Affiliated Hospital of Xuzhou Medical University

Locations

Department of Neurology

Xuzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yu Feng

Role: CONTACT

Phone: +8615252148124

Email: xyfysjnkfy@126.com

Shi Qin Ju

Role: CONTACT

Phone: +8618335632780

Email: jsq740419@126.com

Facility Contacts

Yan Bo Cheng, MD

Role: primary

Other Identifiers

XYFY2025-KL477-02

Identifier Type: -

Identifier Source: org_study_id