Ticagrelor Versus Clopidogrel in Carotid Artery Stenting

NCT02677545 | Completed Phase 2 DMC

• 1 other identifier: D5130C00171; me10Bonati
• Study Type: interventional
• Target: 210
• Locations: 6 countries
• Sites: 15

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.

Conditions

Carotid Artery Stenosis

Outcome Measures

Primary Outcomes (1)

• At least one new ischaemic brain lesion 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.

  Up to 32 days after CAS

Secondary Outcomes (4)

• 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

Study Arms (2)

Ticagrelor & Aspirin

EXPERIMENTAL

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.

Drug: Ticagrelor; Drug: Aspirin

Clopidogrel & Aspirin

ACTIVE COMPARATOR

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.

Drug: Clopidogrel; Drug: Aspirin

Interventions

Ticagrelor DRUG

Also known as: Brilique

Ticagrelor & Aspirin

Clopidogrel DRUG

Also known as: Plavix

Clopidogrel & Aspirin

Aspirin DRUG

Clopidogrel & Aspirin; Ticagrelor & Aspirin

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• Severe thrombocytopenia (platelet count \<50'000/uL); platelet count must be documented within 30 days before randomisation
• History of previous symptomatic intracranial haemorrhage at any time (asymptomatic microbleeds do not qualify)
• History of gastrointestinal bleed within the past 6 months;
• Any contraindication to non-contrast MRI, including but not limited to: cardiac pacemaker incompatible with MRI; metal implants incompatible with MRI; claustrophobia);
• Contraindications to ticagrelor, clopidogrel, or acetylsalicylic acid (ASA), or to any of their excipients, including known hypersensitivity or allergy;

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (15)

Ghent University Hospital - Dept thoracic and vascular surgery

Ghent, 9000, Belgium

Location

AZ Groeninge VZW

Kortrijk, 8500, Belgium

Location

University Hospital Aachen, Klinik für Diagnostische und Interventionelle Neuroradiologie

Aachen, 52074, Germany

Location

Asklepios Kliniken Hamburg GmbH

Hamburg, 20099, Germany

Location

Universitätsklinikum Heidelberg, Neurologische Klinik

Heidelberg, 69120, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, 24105, Germany

Location

Ospedale Civile di Mirano, Department of Cardiology

Mirano, 30035, Italy

Location

UOC Neuroradiologia, Ospedale dell'Angelo

Venezia, 30174, Italy

Location

AMC Medical Research BV on behalf of Academisch Medisch Centrum

Amsterdam, 1105, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584, Netherlands

Location

Kantonsspital Aarau Klinik für Neurologie

Aarau, 5001, Switzerland

Location

University Hospital Basel

Basel, 4031, Switzerland

Location

Insel Gruppe AG, Department of Neurology

Bern, 3010, Switzerland

Location

Stadtspital Triemli Zürich/Department of Cardiology

Zurich, 8063, Switzerland

Location

Sheffield Clinical Research Facility, Northern General Hospital

Sheffield, S57AU, United Kingdom

Location

MeSH Terms

Conditions

Carotid Stenosis

Interventions

Ticagrelor; Clopidogrel; Aspirin

Condition Hierarchy (Ancestors)

Carotid Artery Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Leo H Bonati, MD

  Department of Neurology and Stroke Center, University Hospital Basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2016
• First Posted: February 9, 2016
• Study Start: December 1, 2016
• Primary Completion: April 28, 2022
• Study Completion: April 28, 2022
• Last Updated: June 28, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share

Locations

GB (1); BE (2); DE (4); NL (2); CH (4); IT (2)