DUAL Pathway Inhibition to Improve Endothelial Function in Peripheral Artery Disease

NCT04218656 | Completed Phase 4

• 1 other identifier: NL2019-6036
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Peripheral Artery Disease

Outcome Measures

Primary Outcomes (1)

• Carotid artery reactivity

  The change in proportion of patients with carotid artery reactivity constriction from baseline (Aspirin alone) to 3 months after adding low dose rivaroxaban

  3 months

Secondary Outcomes (1)

• Plasma endothelin-1 levels

  3 months

Study Arms (2)

Group A

EXPERIMENTAL

111 patients with intermittent claudication

Drug: Rivaroxaban 2.5 Mg Oral Tablet

Group B

EXPERIMENTAL

48 patients with critical limb ischemia with pain at rest and/or foot ulcers

Drug: Rivaroxaban 2.5 Mg Oral Tablet

Interventions

Rivaroxaban 2.5 Mg Oral Tablet DRUG

2.5 mg rivaroxaban twice a day in addition to Aspirin 100mg once a day (standard care).

Also known as: Xarelto

Group A; Group B

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (2)

Rijnstate hospital

Arnhem, 6815 AD, Netherlands

Location

Radboudumc

Nijmegen, 6525 GA, Netherlands

Location

Related Publications (22)

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MeSH Terms

Conditions

Peripheral Arterial Disease

Interventions

Rivaroxaban

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michiel C Warlé, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Michel MPJ Reijnen, Professor

  Rijnstate

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two single clinical cohorts will be studied.

Study Record Dates

• First Submitted: December 23, 2019
• First Posted: January 6, 2020
• Study Start: June 8, 2020
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: January 14, 2022

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2)