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

Overview

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.

Interventions

• Drug guideline-recommended SoC
  Guideline-recommended SoC, including but not limited to oral lipid-lowering drugs, antiplatelet aggregation drugs, anticoagulant drugs, antihypertensive drugs, etc. It is to be determined by the investigator based on the subject's treatment needs.
• Drug Recaticimab (intensive)
  Recaticimab is added to the guideline-recommended SoC. After randomization and before endovascular interventional treatment, patients will receive a subcutaneous injection of Recaticimab. The specific method is: Recaticimab 450 mg (3 vials) as a single subcutaneous injection, until the end of the follow-up for this study.

Primary outcome measures

• favorable functional outcome (defined as an mRS score of 0-2) [Time frame: Day 90]

Secondary outcome measures (12)

• mRS ordinal score [Time frame: Day 90]
• Change from baseline in NIHSS score [Time frame: Day 14±3 days or before discharge]
• Change from baseline in LDL-C [Time frame: Day 14±3 days or before discharge]
• Change in inflammatory markers [Time frame: Day 0, Day 14±3 days or before discharge]
• Rate of severe disability(defined as mRS score of 3-5) [Time frame: Day 90]
• Incidence of recurrent ischemic stroke events [Time frame: From enrollment to the end of treatment at 90 days]
• Incidence of symptomatic intracranial hemorrhage transformation [Time frame: Within 24-48 hours]
• Incidence of patients with new hemorrhagic stroke [Time frame: From enrollment to 90 days]
• Incidence of patients with major adverse cardiovascular events [Time frame: From enrollment to 90 days]
• Number of patients with serious adverse events [Time frame: From enrollment to 90 days]
• Health related quality of life [Time frame: Day 90]
• NIHSS score [Time frame: at 14±3 days or before discharge]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai East Hospital, Tongji University — Shanghai

Identifiers

NCT: NCT07002476 · MA-CVD-II-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗