DUAL Pathway Inhibition to Improve Endothelial Function in Peripheral Artery Disease

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis, causing patients to be at high risk of major adverse cardiovascular and limb events. Therefore, single antiplatelet therapy is recommended when patients are symptomatic or have undergone revascularization. Rivaroxaban (2.5 mg twice a day) in addition to Aspirin (100 mg once a day) has shown to be effective in reducing morbidity and mortality from major cardiovascular and limb events in patients with stable peripheral or carotid artery disease compared to Aspirin alone. Although a higher rate of major bleeding was detected, the incidence of fatal or critical organ bleedings was not increased.

Endothelial dysfunction is one of the first signs of atherosclerosis and is related to major cardiovascular events. The level of vascular endothelial dysfunction can be measured using the carotid artery reactivity (CAR) test. The investigators hypothesized that a combination of low-dose rivaroxaban and antiplatelet therapy would improve endothelial function in PAD patients.

The investigators aim to study the effectiveness of this combination therapy in improving vascular endothelial function in patients with stable or symptomatic PAD.

Therefore the investigators will study two clinical cohorts of lower extremity PAD patients (n=159) with intermittent claudication (group A: Fontaine stages 1-2) or critical limb ischemia with pain at rest and/or foot ulcers (group B: Fontaine stages 3-4) who have an indication for single antiplatelet therapy.

Aspirin 100mg once a day + 2.5 mg rivaroxaban twice a day will be given during 3 months, preceded by a run-in period of Aspirin alone (100 mg once a day) as reference.

The change in proportion of patients with CAR-constriction from baseline (Aspirin alone) to 3 months after adding low dose rivaroxaban will be compared for both study groups (A and B).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Radboud University
• Treatments: Aspirin; Rivaroxaban

Criteria

Inclusion Criteria:

• Symptomatic or stable lower extremity PAD patients (Fontaine stages 2-4) with an indication for single antiplatelet therapy according to international (ESC) guidelines

• >16 years old

• Written informed consent

Exclusion Criteria:

• Patients having or at risk of major bleeding:

• Gastrointestinal ulceration

• Current malignant neoplasms

• Brain or spinal injury

• Brain, spinal or ophthalmic surgery

• Intracranial hemorrhage

• Known or suspected esophageal varices

• Arteriovenous malformations

• Major intraspinal or intracerebral vascular abnormalities

• Hepatic disease associated with coagulopathy and clinically relevant bleeding risk, including cirrhotic patients with Child Pugh B and C

• Use of selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors

• Patients with prosthetic valves

• Patients with a history of asthma attacks caused by salicylates

• Severe renal impairment (creatinine clearance <30 ml/min)

• Systemic treatment with strong CYP3A4 and/or P-glycoprotein inhibitors (i.e. azole-antimyotics, HIV protease inhibitors)

• Concomitant treatment with other anticoagulants

• Concomitant treatment with methotrexate at a weekly dosage of >15 mg

• Pregnant or lactating

• Known hypersensitivity to Aspirin or rivaroxaban