Prevention of Cerebral Ischaemia in Stent Treatment for Carotid Artery Stenosis - A Randomised Multi-centre Phase II Trial Comparing Ticagrelor Versus Clopidogrel With Outcome Assessment on MRI (PRECISE-MRI)
Overview
- Phase
- Phase 2
- Intervention
- Ticagrelor
- Conditions
- Carotid Artery Stenosis
- Sponsor
- University Hospital, Basel, Switzerland
- Enrollment
- 210
- Locations
- 15
- Primary Endpoint
- At least one new ischaemic brain lesion after CAS
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
Patients with symptomatic or asymptomatic carotid stenosis in whom carotid artery stenting is planned are randomised between antiplatelet therapy with ticagrelor plus aspirin or clopidogrel plus aspirin and examined with brain MRI before and after stent treatment. The proportion of patients with new ischaemic lesions on MRI after treatment is compared between the two groups.
Detailed Description
Carotid artery stenting (CAS) is an emerging treatment for atherosclerotic carotid stenosis. The main adverse event is embolic stroke during the procedure. Current medical management to prevent peri-procedural embolisation consists of dual antiplatelet therapy with clopidogrel and aspirin. Ticagrelor, a novel reversible inhibitor of the platelet adenosine diphosphate receptor P2Y12, was superior to clopidogrel, as add-on therapy to aspirin, in preventing stent thrombosis, cardiovascular outcome events, and death in patients undergoing coronary artery stenting, without causing an increase in major bleeding events. This study aims to test the hypothesis that ticagrelor is superior to clopidogrel as add-on to aspirin in preventing cerebral embolism during the CAS procedure.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent as documented by signature from the patient;
- •Men or women ≥40 years of age;
- •Moderate (50-69% narrowing of the artery according to the measuring method used in the NASCET trial64) or severe (70-99%) stenosis of the extracranial internal carotid artery caused by atherosclerosis;
- •Symptomatic carotid stenosis (any transient or permanent symptoms caused by focal ischaemia in the vascular territory supplied by the carotid artery in the past 180 days, including ischaemic stroke, transient ischemic attack (TIA), amaurosis fugax or ischaemic retinal infarct), as long as the patient is clinically stable and able to walk unassisted (mRS ≤3) at the time of randomisation; or asymptomatic carotid stenosis (no ischaemic symptoms in the past 180 days);
- •Stenosis amenable for treatment by CAS according to routine clinical work-up (degree of stenosis and suitability of vascular anatomy for CAS must be documented on vascular imaging within 90 days before the screening visit);
- •CAS scheduled to take place within 1-3 days of randomisation.
Exclusion Criteria
- •Inability or unwillingness of the patient to understand and/or comply with study procedures and/or follow-up, e.g. due to language problems, psychological disorders, dementia, etc.;
- •Women who are pregnant or breast feeding, or who intend to become pregnant during the course of the study. Women of childbearing age must take a blood pregnancy test to be eligible for the study within 14 days before randomisation;
- •Lack of safe contraception, defined as: Female Participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the Investigator in individual cases. Female Participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential;
- •Acute ischaemic stroke with symptom onset in the previous 24 hours before randomisation;
- •atrial fibrillation;
- •Fresh thrombus in the relevant carotid artery;
- •Patient clinically unstable at the time of randomisation (includes worsening in NIH Stroke Scale of \>2 points over the previous 24 hours);
- •Patient unable to walk unassisted at the time of randomisation (mRS \>3);
- •Patients with known bleeding diathesis or coagulation disorder (e.g., thrombotic-thrombocytopenic purpura);
- •Any active pathological bleed;
Arms & Interventions
Ticagrelor & Aspirin
Participants will receive a loading dose of 180 mg ticagrelor 1-3 days before stenting followed by a maintenance dose of 90 mg twice daily until 28-32 days after stenting. All participants will receive 75-100 mg aspirin per day throughout the study period.
Intervention: Ticagrelor
Ticagrelor & Aspirin
Participants will receive a loading dose of 180 mg ticagrelor 1-3 days before stenting followed by a maintenance dose of 90 mg twice daily until 28-32 days after stenting. All participants will receive 75-100 mg aspirin per day throughout the study period.
Intervention: Aspirin
Clopidogrel & Aspirin
Participants will receive a loading dose of 300 mg clopidogrel 1-3 days before stenting followed by a maintenance dose of 75 mg once daily until 28-32 days after stenting. All participants will receive 75-100 mg aspirin per day throughout the study period.
Intervention: Clopidogrel
Clopidogrel & Aspirin
Participants will receive a loading dose of 300 mg clopidogrel 1-3 days before stenting followed by a maintenance dose of 75 mg once daily until 28-32 days after stenting. All participants will receive 75-100 mg aspirin per day throughout the study period.
Intervention: Aspirin
Outcomes
Primary Outcomes
At least one new ischaemic brain lesion after CAS
Time Frame: Up to 32 days after CAS
The primary efficacy outcome is the presence of at least one new ischaemic brain lesion on the second MRI scan done 1-3 days after CAS or on the third MRI scan done 28-32 days after CAS, which had not been present on the first MRI scan done 1-3 days before CAS.
Secondary Outcomes
- Composite of any stroke, myocardial infarction, major bleeding, or cardiovascular death(Through study completion, an average of 1 month after randomisation)
- Number of new ischaemic brain lesions after CAS(Up to 32 days after CAS)
- Volume of new ischaemic brain lesions after CAS(Up to 32 days after CAS)
- At least one new haemorrhagic brain lesion after CAS(Up to 32 days after CAS)