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Early Aggressive Strategy for Treatment of Lipid-Lowering in Acute Ischemic Stroke Delivered With Endovascular Therapy for Large Artery Occlusion

Phase 3
Not yet recruiting
Conditions
Stroke
Interventions
Drug: guideline-recommended SoC
Drug: Recaticimab (intensive)
Registration Number
NCT07002476
Lead Sponsor
Shanghai East Hospital
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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
652
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Control Groupguideline-recommended SoCGuideline-recommended standard of care
Investigational GroupRecaticimab (intensive)Guideline-recommended standard of care+intensive lipid-lowering therapy
Primary Outcome Measures
NameTimeMethod
favorable functional outcome (defined as an mRS score of 0-2)Day 90

the rate (%) of good functional outcome at 90 days (modified Rankin Scale \[mRS\] score 0-2). Modified Rankin Scale scores of 0 or 1 indicate good function without or with symptoms but not disability, score of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.

Secondary Outcome Measures
NameTimeMethod
Incidence of recurrent ischemic stroke eventsFrom enrollment to the end of treatment at 90 days

Incidence of recurrent ischemic stroke events

Incidence of symptomatic intracranial hemorrhage transformationWithin 24-48 hours

Incidence of symptomatic intracranial hemorrhage transformation within 24-48h;

Incidence of patients with new hemorrhagic strokeFrom enrollment to 90 days

Incidence of patients with new hemorrhagic stroke

Incidence of patients with major adverse cardiovascular eventsFrom enrollment to 90 days

Incidence of major adverse cardiovascular events (MACEs) within 90 days

Number of patients with serious adverse eventsFrom enrollment to 90 days

total number of serious adverse events reported during follow-up, according to standard definitions

Health related quality of lifeDay 90

according to the EQ-5D

NIHSS scoreat 14±3 days or before discharge

0-42, higher scores indicates worse severity

LDL-C goal attainment rateat 14±3 days or before discharge

LDL-C attained equal or lower than 1.8mmol/L or decrease by equal or more than 50%

Mortality rateDay 90

Death within 90 days.

Change in inflammatory markersDay 0, Day 14±3 days or before discharge

Change from baseline in inflammatory markers at 14±3 days or before discharge;

Rate of severe disability(defined as mRS score of 3-5)Day 90

Modified Rankin Scale scores of 0 or 1 indicate good function without or with symptoms but not disability, score of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.

Change from baseline in LDL-CDay 14±3 days or before discharge

Change from baseline in LDL-C at 14±3 days or before discharge

mRS ordinal scoreDay 90

Modified Rankin Scale scores of 0 or 1 indicate good function without or with symptoms but not disability, score of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.

Change from baseline in NIHSS scoreDay 14±3 days or before discharge

0-42, higher scores indicates worse severity

Trial Locations

Locations (1)

Shanghai East Hospital, Tongji University

🇨🇳

Shanghai, China

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