Stabilization of atherosclerosis in carotid artery by Rivaroxaban as evaluated by 3D ultrasound with contrast

Phase 1

• Conditions: Patients with - Stable peripheral artery diseaseand- Asymptomatic, atherosclerotic plaque/stenosis in the carotid artery; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]; asymptomatic regarding cerebral ischaemia including stroke and transient ischaemic attack (TIA) or amaurosis fugax.; MedDRA version: 20.0Level: LLTClassification code 10075495Term: Internal carotid artery atherosclerosisSystem Organ Class: 100000004852

• Registration Number: EUCTR2020-001053-44-DK
• Lead Sponsor: Rigshospitalet, Department of Vascular Surgery

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-04-16
• Last Update Posted: 24 January 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 102

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 < 0.9 and/or significant peripheral arterial stenosis > 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

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).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.