Efficacy and Safety of PCSK9 Inhibitors in Patients With Large-Artery Atherosclerosis (LAA) Ischemic Stroke

NCT07540741 | Recruiting DMC

• 1 other identifier: 2025143
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective multicenter cohort study aims to evaluate the effectiveness and safety of early PCSK9 inhibitor therapy in patients with large-artery atherosclerotic ischemic stroke. The study will compare early neurological improvement, lipid-lowering effect, 90-day functional outcome, recurrent cardio-cerebrovascular events, and safety outcomes between patients treated with evolocumab plus statin and those treated with statin alone.

Conditions

Acute Ischemic Stroke

Keywords

PCSK9 inhibitor; Cohort study; Large-Artery Atherosclerotic; Functional outcome

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with favorable functional outcome at Day 90

  Proportion of participants with modified Rankin Scale (mRS) score 0-2.

  90 ± 7 days after stroke onset

Secondary Outcomes (6)

• Ordinal distribution of mRS at Day 90

  90 ± 7 days after stroke onset

• Incidence of early neurologic deterioration (END) and severe END

  Within 7 days after enrollment

• Change in NIHSS score from baseline

  Up to Day 7 (±2 days)

• Change in LDL-C from baseline

  30 ± 7 days after stroke onset

• Recurrent cardio-cerebrovascular events

  Within 90 days after stroke onset

Other Outcomes (2)

• Adverse events

  From informed consent to Day 90

• Serious adverse events

  From informed consent to Day 90

Study Arms (2)

Exposed

Drug: Evolocumab injection. 140 mg subcutaneously every 2 weeks or 420 mg monthly for 90 days. Other treatment: Daily statin therapy according to routine clinical practice

Non-exposed

Drug: Statin. Daily statin therapy for 90 days according to routine clinical practice.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adult patients aged 18-80 years with acute ischemic stroke of the large-artery atherosclerotic (LAA) subtype, confirmed by clinical and imaging criteria within 72 hours of symptom onset. Eligible participants have baseline LDL-C ≥1.8 mmol/L, NIHSS score 4-20, and a pre-stroke modified Rankin Scale (mRS) score ≤1. Patients are consecutively enrolled from multiple tertiary hospitals in Heilongjiang Province during routine clinical care. All participants are candidates for statin therapy, with or without PCSK9 inhibitor (evolocumab), based on the actual clinical diagnosis and treatment plan. Key exclusions include intracranial hemorrhage, severe cardiac insufficiency, severe hepatic or renal dysfunction, major comorbidities affecting outcomes, and prior PCSK9 inhibitor use.

You may qualify if:

• Age 18-80 years.
• Acute ischemic stroke diagnosed according to the Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke (2023), based on clinical and imaging criteria.
• Large-artery atherosclerotic subtype (TOAST classification) confirmed within 72 hours after stroke onset.
• NIHSS score 4-20 before treatment.
• Pre-stroke modified Rankin Scale (mRS) score ≤1.
• LDL-C ≥1.8 mmol/L before enrollment.
• Able to use evolocumab and statin medications in accordance with the physician's instructions and the prescribing information.
• No prior use of a PCSK9 inhibitor before enrollment.
• Written informed consent provided by the participant or legally authorized representative.

You may not qualify if:

• Hemorrhagic transformation or other intracranial hemorrhage (including hemorrhagic infarction, subarachnoid hemorrhage, subdural hematoma, or epidural hematoma), except cerebral microbleeds detected only by SWI.
• Prior intracranial or extracranial endovascular therapy before enrollment, planned acute endovascular therapy within 90 days, or planned surgery that may affect outcome assessment.
• Severe cardiac insufficiency：NYHA class III or IV.
• Severe hepatic dysfunction (ALT or AST \>3 x upper limit of normal) or severe renal dysfunction (serum creatinine \>2 mg/dL, eGFR \<30 mL/min/1.73 m2, or requiring dialysis).
• Platelet count \<100 x 10\^9/L.
• Pregnancy or breastfeeding.
• Participation in another interventional clinical study within 30 days before enrollment, or concurrent participation in another interventional study that may affect outcome assessment.
• Giant intracranial tumor, giant cerebral aneurysm, or arteriovenous malformation.
• Active gastrointestinal ulcer, active bleeding tendency: corrected international normalized ratio (INR) \> 1.5, bleeding time exceeding the upper limit by more than 1 minute, or increased bleeding risk due to heparin-induced thrombocytopenia; major systemic bleeding occurring within 30 days prior to enrollment.
• Pre-existing neurologic or psychiatric disease likely to affect neurologic or functional outcome assessment; severe neurologic deficit causing loss of independent living; dementia or psychiatric disease preventing completion of follow-up.
• Autoimmune disease (for example systemic sclerosis, systemic lupus erythematosus, Sjogren syndrome, Behcet disease, mixed connective tissue disease, or IgG4-related disease).
• Active seizures, hypotension, hyperthyroidism, asthma, and other allergic respiratory diseases, as well as individuals with a tendency toward allergies.
• Any other condition judged by the investigator to make participation inappropriate or to pose substantial risk.

Sponsors & Collaborators

• First Affiliated Hospital of Harbin Medical University: lead

Study Sites (1)

Harbin, Heilongjiang, China, 150001

Heilongjiang, China

RECRUITING

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

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

Study Officials

• Zhongling Zhang

  First Affiliated Hospital, Harbin Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhongling Zhang

CONTACT

+8613503615988; zhang777hyd@163.com

Shanshan Yang

CONTACT

+8613845104003; yangshanshan81@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: April 13, 2026
• First Posted: April 20, 2026
• Study Start: December 3, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

CN (1)