PCSK9 Inhibitor for Intracranial Atherosclerotic Symptomatic Stenosis

Official title

PCSK9 Inhibitor for Intracranial Atherosclerotic Symptomatic Stenosis (PICASSO): A Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Trial

Overview

An investigator-initiated, prospective, multicenter, randomized, double-blind, placebo-controlled trial comparing the 1-year incidence of stroke in patients with AIS or TIA within 7 days who are treated with either placebo or Recaticimab.

Detailed description

This is an investigator-initiated, prospective, multicenter, randomized, double-blind, placebo-controlled trial to determine the efficacy of Recaticimab (PCSK9 inhibitor) administered within 7 days of symptom onset in patients with symptomatic intracranial atherosclerotic stenosis (sICAS) in reducing incident stroke within 1 year.

Study intervention: (1) Participants in the intervention group will receive Recaticimab 300mg subcutaneous Q8W for 1 year. (2) Participants in the control group will receive matched placebo subcutaneous Q8W for 1 year. All participants will receive best medical management (BMM), including intensive statins treatment and dual antiplatelet therapy.

A total of 5276 participants are anticipated to be recruited for this study. Eligible participants will be 1:1 randomly assigned to receive Recaticimab or placebo.

Interventions

• Drug Recaticimab
  Recaticimab 300mg subcutaneous Q8W for 1 year.
• Drug Placebo
  Matched placebo subcutaneous Q8W for 1 year.

Primary outcome measures

• Any new stroke [Time frame: 1 year (±2) weeks]

Secondary outcome measures (12)

• Composite cardiovascular events [Time frame: 1 year (±2) weeks]
• Ischemic stroke [Time frame: 1 year (±2) weeks]
• Hemorrhagic stroke [Time frame: 1 year (±2) weeks]
• Non-fatal stroke [Time frame: 1 year (±2) weeks]
• Myocardial infarction [Time frame: 1 year (±2) weeks]
• Death from cardiovascular causes [Time frame: 1 year (±2) weeks]
• Quality of life (EQ-5D-5L) [Time frame: 1 year (±2) weeks]
• NIHSS scores [Time frame: 7(±1) days or discharge]
• Modified Rankin Scale score at 90 days [Time frame: 90 (±14) days]
• Modified Rankin Scale score at 1 year [Time frame: 1 year (±2) weeks]
• Safety outcome: intracranial hemorrhage [Time frame: 1 year (±2) weeks]
• Safety outcome: Death [Time frame: 1 year (±2) weeks]

Eligibility criteria

Inclusion criteria

1\. Aged ≥30 years and ≤80 years.

Patients aged between 30 to 49 are required to meet at least one of the following criteria:

• Insulin dependent diabetes for at least 15 years.
• At least 2 of the following atherosclerotic risk factors: hypertension (BP > 140/90 or on antihypertensive therapy); dyslipidemia (LDL > 130 mg /dL or HDL < 40 mg/dL or fasting triglycerides > 150 mg/dL or on lipid lowering therapy); smoking; non-insulin dependent diabetes or insulin dependent diabetes of less than 15 years duration; family history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, stroke, carotid endarterectomy or stenting, peripheral vascular surgery in parent or sibling who was < 55 years of age for men or < 65 for women at the time of the event.
• History of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, carotid endarterectomy or stenting, or peripheral vascular surgery for atherosclerotic disease.
• Any stenosis of an extracranial carotid or vertebral artery, another intracranial artery, subclavian artery, coronary artery, iliac or femoral artery, other lower or upper extremity artery, mesenteric artery, or renal artery that was documented by non-invasive vascular imaging or catheter angiography and is considered atherosclerotic.
• Aortic arch atheroma documented by non-invasive vascular imaging or catheter angiography vi. any aortic aneurysm documented by non-invasive vascular imaging or catheter angiography that is considered atherosclerotic.

2\. Diagnosed with acute ischemic stroke or moderate-to-high risk transient ischemic attack (ABCD2 score ≥4).

3\. CTA or DSA confirmed intracranial atherosclerotic stenosis >50%, which was responsible for the incident.

4\. The time from symptom onset to initiation of study treatment is within 7 days.

5\. Signed informed consent.

Exclusion criteria

• Baseline NIHSS ≥26.
• Suspected cardiogenic ischemic cerebrovascular diseases (e.g., combined with atrial fibrillation, heart valve prosthesis, atrial myxoma, endocarditis, etc.).
• Source of symptoms is possible related to ipsilateral carotid disease.
• Other ischemic cerebrovascular diseases with specific causes (e.g., aortic dissection, vasculitis, vascular malformation, etc.).
• Non-cerebral vascular disease (e.g., intracranial tumors, multiple sclerosis).
• Hemorrhagic stroke or hemorrhagic transformation of cerebral infarction before randomization.
• Pre-existing contraindications of using PCSK9 inhibitors.
• Use of any PCSK9 inhibitors within the past 3 months.
• Pregnant or childbearing-age women who have no effective contraceptives or positive pregnancy test records.
• Patients who are participating in other trials.
• Hepatic or renal dysfunction, defined as AST and/or ALT >3ULN，eGFR<30mL/min, or Crea >220μmol/L (2.5mg/dL).
• Uncontrolled hypertension defined as systolic blood pressure (BP) >220mmHg or diastolic BP >120mmHg.
• Life expectancy is less than 1 year due to severe non-cardiovascular disease.
• Angioplasty or stenting procedure is planned before randomization.
• Unable to finish the follow-up visit due to geographical factor or other reasons (e.g., dementia, alcoholism, substance abuse, severe mental disease, etc.)

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

Quadruple blind

Primary purpose

Prevention

Study locations

China · 1 center

• Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University — Guangzhou

Identifiers

NCT: NCT07119918 · PICASSO

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗