Acute Ischemic Stroke
Conditions
Keywords
acute ischemic stroke, endovascular therapy, PCSK9 inhibitors, Lipid-Lowering Therapy, Early Artery Reocclusion
Brief summary
This is a prospective, multicenter, randomized controlled clinical study to evaluate the efficacy of PCSK9 inhibitor in addition to standard therapy in patients with acute ischemic stroke undergoing endovascular therapy.
Interventions
DRUGPCSK9 inhibitor
PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) inhibitors are a class of monoclonal antibody drugs that lower low-density lipoprotein cholesterol (LDL-C) by inhibiting the PCSK9 protein, which increases the liver's ability to remove LDL-C from the blood. This intervention involves the use of established PCSK9 inhibitor agents.
Sponsors
Nanfang Hospital, Southern Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years. * Meets the diagnostic criteria for acute ischemic stroke according to the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2023. * Severe stenosis or occlusion of large anterior circulation vessels confirmed by DSA, MRA, or CTA. * Preoperative NIHSS score ≥ 4 and \< 25. * Meets the indications for endovascular therapy per the Chinese Guidelines for Endovascular Therapy of Acute Ischemic Stroke 2023, and successful reperfusion of the target vessel (mTICI ≥ 2b) achieved via emergency endovascular intervention. * LDL-C \> 1.8 mmol/L or non-HDL cholesterol \> 2.6 mmol/L. * Signed informed consent provided by the patient or their legally authorized representative.
Exclusion criteria
* Confirmed non-atherosclerotic causes of vascular stenosis/occlusion (e.g., cardioembolism, vasculitis, vascular malformation, moyamoya disease, iatrogenic causes). * History of intracranial hemorrhage or systemic bleeding within the past 3 months. * Presence of hemorrhagic transformation (PH1/PH2) immediately after the procedure. * Severe hepatic impairment: ALT \> 3 times the upper limit of normal, INR \> 1.2, hepatic encephalopathy, or history of drug-induced liver injury. * Use of PCSK9 inhibitors within 6 months prior to enrollment. * Pre-stroke mRS ≥ 2. * Terminal illness (e.g., malignancy, end-stage renal disease) with an expected survival of \< 3 months. * Pregnancy or lactation. * Other neurological diseases that may interfere with neurological function assessment during follow-up. * Allergy or intolerance to PCSK9 inhibitors or statins. * Participation in another interventional clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional outcome: The proportion of mordified Rankin Scale of 0 to 2 points | 90 days after the stroke onset | The proportion of mordified Rankin Scale of 0 to 2 points at 90 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of target vessel reocclusion or recurrent infarction | 90 days after the stroke onset | Reocclusion of the responsible vessel confirmed by CTA/MRA/DSA, or new cerebral infarction in the same territory confirmed by diffusion-weighted MRI. |
| Reduction amplitude of low-density lipoprotein (LDL-C) | Within 7 days post-treatment | Absolute and relative reduction of LDL-C levels from baseline to Day 7. |
| Mortality rate | 90 days after the stroke onset | All-cause mortality at 90 days. |
| Incidence of symptomatic hemorrhagic transformation | Within 7 days post-treatment | Hemorrhagic transformation associated with neurological deterioration (increase in NIHSS ≥4 points) confirmed by CT or MRI. |
| Incidence of acute liver injury | Within 90 days post-treatment | Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 times the upper limit of normal. |
| Proportion of patients with early neurological improvement | 7 days post-treatment | Defined as a reduction of ≥4 points on the National Institutes of Health Stroke Scale (NIHSS) score or a complete resolution of neurological deficits (NIHSS=0) within 7 days after treatment. |
| Distribution of modified Rankin Scale (mRS) scores | 90 days after the stroke onset | Shift analysis of mRS scores at 90 days (range 0-6). |
| Incidence of malignant brain edema | 48 to 96 hours after onset | Defined as the presence of cerebral edema with mass effect on cranial CT or MRI within 48 to 96 hours after symptom onset, including midline shift ≥ 5 mm and/or compression of ventricles or cisterns. |
| Midline shift distance | 72 to 96 hours after onset | Maximum distance of midline shift (in millimeters) measured on axial CT or MRI. |
| Incidence of adverse events | Within 90 days post-treatment | All adverse events and serious adverse events, recorded and graded according to CTCAE v5.0. |
| Proportion of patients with early neurological deterioration | Within 7 days post-treatment | Defined as an increase of ≥4 points on the NIHSS score within 7 days post-treatment. |
Countries
China
Contacts
Primary ContactKaibin Huang, Ph.D.
Backup ContactSuyue Pan, Ph.D.
Outcome results
None listed