Clinical trial NCT07002476: Early Aggressive Strategy for Treatment of Lipid-Lowering in Acute Ischemic Stroke Delivered With Endovascular Therapy for Large Artery Occlusion
Official title: A Prospective, Multicenter, Open-Label, Randomized Controlled Study of Early Intensive Lipid-Lowering in Endovascular Treatment for Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Stroke
Keywords: acute ischemic stroke
LDL-Cholersterol lowering
Endovascular Therapy
PCSK9
clinical trials
Lead sponsor: Shanghai East Hospital
Sponsor class: OTHER
First posted: 2025-06-03
Enrollment: 652
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A prospective, multicenter, open-label, randomized controlled study to assess the effects of early intensive lipid-lowering initiated before endovascular treatment setting on (i) functional outcome in patients with acute ischemic stroke between preoperative intensive lipid-lowering therapy with PCSK9 inhibitor (PCSK9i) and guideline-recommended standard of care (SoC)(ii) safety in these patients.

Detailed description: As a prospective, multicenter, open-label, randomized controlled clinical study, EAST-LDL will enroll 652 patients with acute ischemic stroke with anterior circulation large vessel occlusion undergoing endovascular treatment from approximately 10 clinical sites in China. This study aims to evaluate the effects of functional outcome according to an ordinal analysis of the full range of scores on the mRS, safety of lipid-lowering therapy, LDL-C goal attainment rate, change in inflammatory markers, incidence of recurrent ischemic stroke events , incidence of symptomatic intracranial hemorrhage transformation within 48 hours, incidence of new-onset hemorrhagic stroke, and incidence of MACEs in patients between early intensive lipid-lowering therapy with PCSK9 inhibitor and guideline-recommended standard of care treatment.

Eligibility criteria: Inclusion Criteria:

* Adults (age 18 years and older);
* Imaging diagnosis of acute ischemic stroke with anterior circulation large vessel occlusion (including: internal carotid artery, middle cerebral artery M1 and M2, anterior cerebral artery A1 and A2);
* Planned to undergo endovascular intervention within 24 hours of symptom onset (or last known well time) according to local guidelines;
* Provision of informed consent by the patient or his/her legally authorized representative (or by an appropriate agent according to local requirements).

Exclusion Criteria:

* ASPECTS score ≤5 on cranial CT imaging;
* Pre-existing functional impairment, with mRS score \>2;
* Patients who are allergic to PCSK9 inhibitors;
* Patients who have received PCSK9 monoclonal antibody within 1 month prior to enrollment or PCSK9 siRNA therapy within 6 months prior to enrollment;
* Severe renal insufficiency, defined as estimated glomerular filtration rate (eGFR) \< 15 mL/min/1.73m2 at final screening;
* Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 times the upper limit of normal;
* Severe, concomitant non-cardiovascular disease expected to reduce life expectancy to less than 3 months;
* Pregnant or lactating women;
* Patients who are participating in other clinical trials;
* Other conditions deemed unsuitable for inclusion in the clinical study by the investigator.

Primary outcomes:
measure: favorable functional outcome (defined as an mRS score of 0-2)
timeFrame: Day 90
Secondary outcomes:
measure: mRS ordinal score
timeFrame: Day 90
measure: Change from baseline in NIHSS score
timeFrame: Day 14±3 days or before discharge
measure: Change from baseline in LDL-C
timeFrame: Day 14±3 days or before discharge
measure: Change in inflammatory markers
timeFrame: Day 0, Day 14±3 days or before discharge
measure: Rate of severe disability(defined as mRS score of 3-5)
timeFrame: Day 90
measure: Incidence of recurrent ischemic stroke events
timeFrame: From enrollment to the end of treatment at 90 days
measure: Incidence of symptomatic intracranial hemorrhage transformation
timeFrame: Within 24-48 hours
measure: Incidence of patients with new hemorrhagic stroke
timeFrame: From enrollment to 90 days
measure: Incidence of patients with major adverse cardiovascular events
timeFrame: From enrollment to 90 days
measure: Number of patients with serious adverse events
timeFrame: From enrollment to 90 days
measure: Health related quality of life
timeFrame: Day 90
measure: NIHSS score
timeFrame: at 14±3 days or before discharge
measure: LDL-C goal attainment rate
timeFrame: at 14±3 days or before discharge
measure: Mortality rate
timeFrame: Day 90
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital, Tongji University
Study officials:
affiliation: Tongji University
name: Shanghai East Hospital
role: STUDY_CHAIR
References: