Patients with - Stable peripheral artery disease and - Asymptomatic, atherosclerotic plaque/stenosis in the carotid artery
Conditions
Sponsors
Rigshospitalet, Department of Vascular Surgery
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Oral and written informed consent. - Adults > 18 years of age. - Acetylsalic acid (aspirin) therapy > 6 months. - Statin therapy > 6 months. - Asymptomatic carotid stenosis. - Hypoechoic carotid plaque with a thickness of 2.5 mm at least. - Stable peripheral artery disease (PAD) defined as at least one of the following: * Previous revascularization with aorta-femoral bypass, infrainguinal bypass, thrombendarterectomy, thrombectomy, endovascular procedures or farmeceutical with heparine and/or thrombolysis. * Previous amputation of food or leg due to arteriel insufficiency. * Current of previous intermittent claudication with one or more of the following: ankle/brachial (ABI) index 50% verificed by angiography or duplex ultrasound. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: General exclusion criteria: - Subjects who are pregnant, breastfeeding, or are of childbearing potential and sexually active and not practicing an effective method of contraception. - Severe cardiac insufficiency with ejection fraction < 30% or New York Heart Association (NYHA) Class III or IV symptoms. - Current acute condition/disease. CEUS exclusion criteria: - Previous allergic reaction towards the contrast SonoVue® - Electronic implantation e.g. pacemaker, ICD, due to use of magnetic field ultrasound. - Patients who cannot cooperate to the ultrasound examination. Rivaroxaban exclusion criteria: - Concomitant participation in another study with investigational drug. - History of hypersensitivity or known contraindication for rivaroxaban, aspirin (acetylsalicyl acid), pantoprazole, or excipients. - Need for other anticoagulant therapy e.g. warferin or other direct oral anticoagulants than rivaroxaban. - Already in treatment with rivaroxaban. - Need for dual antiplatelets therapy or other non-aspirin antiplatelet therapy. - High risk of bleeding e.g.: active significant bleeding, previous or current lesions or conditions with significant risk of major bleedings, recent cerebral, spinal or ocular surgery, recent intracranial bleeding, esophageal varices, arteriovenous malformations, vascular aneurysms or majour intraspinal og intracerebral vascular abnormalities. - Stroke within 1 year or previous haemorrhagic or lacunar stroke. - Any known hepatic disease associated with coagulopathy. - Estimated glomerular filtration rate < 30 mL/min/m2 - Other severe, non-cardiovascular condition/disease associated with poor prognosis (e.g. metastatic cancer) and limits life expectancy. - Systemic treatment with strong inhibitors of CYP3A4 as well as p-glycoprotein (e.g., systemic azole antimycotics, such as ketoconazole, and HIV-protease inhibitors, such as ritonavir). - Strong inducers of CYP3A4 (i.e., rifampicin, rifabutin, phenobarbital, phenytoin, and carbamazepine).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To observe the effect of rivaroxaban on atherosclerotic plaque morphology in carotid artery over time, registered by 3D contrast enhanced ultrasound.;Secondary Objective: Optimizing the risk stratification of future major cardiovascular events by using carotid plaque morphology as a surrogate measure determined by contrast enhanced ultrasound.;Primary end point(s): More hyperechoic carotid plaques in the intervention group, with 1 year rivaroxaban treatment, compared to placebo over time determined by increase in plaque echogenicity with at least 20 % in grey-median-scale (GSM) registered by ultrasound, as an expression of plaque stabilizaton by rivaroxaban.;Timepoint(s) of evaluation of this end point: Primarily after 12 months but also after 3 and 6 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Secondary ultrasound endpoints: Reduction of carotis plaque volumen, thrombus volumen and intraplaque contrastfilling over time in the intervention-rivaroxaban group compared to placebo. 2) Secondary major events endpoints including but not necessary limited to: - Death (all cause mortality). - MACE (Major Adverse Cardiovascular Events): myocardial infarction, stroke, cardiovascular death. - MALE (Major Adverse Limb Events) e.g. acute og chronic critical limb ischaemia and including amputation above the ankle. - Transient ischaemic attack (TIA) - Major bleedings. - Need for cardiovascular revascularization procedure: * Cardiac: percutanous coronary intervention (PCI), coronary artery bypass grafting (CABG). * Carotid: carotid endarterectomy (CEA), endovascular carotid stent (CAS), thrombectomy. * Limb: aorta-femoral bypass, infrainguinal bypass, thrombendarterectomy, thrombectomy, endovascular procedures or farmeceutical with heparine and/or thrombolysis.;Timepoint(s) of evaluation of this end point: 1) Primarily after 12 months but also after 3 and 6 months. 2) 1-5 years. | — |
Countries
Denmark
Contacts
Public ContactCarotis-Rivaroxaban Trial
Rigshospitalet, Department of Vascular Surgery
Outcome results
None listed