Trained Immunity by Dual-pathway Inhibition in Coronary Artery Disease

NCT05210725 | Unknown Phase 4

• 1 other identifier: NL2021-13291
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Coronary artery disease (CAD) is a manifestation of systemic atherosclerosis for which single antiplatelet therapy (SAPT) is indicated if patients are stable. Recently dual pathway inhibition (DPI) by combining a low-dose factor Xa inhibitor (rivaroxaban2.5mg twice daily) with a single platelet inhibitor (ASA) has been demonstrated to be beneficial in treating CAD. The exact mechanisms underlying the benefits of DPI, are not completely understood. CAD is characterised by a state of chronic low-grade inflammation, where monocytes from CAD patients have a higher immune responsiveness to ex vivo stimulation with lipopolysaccharide (LPS) compared to healthy matched controls. Surprisingly, the investigators have recently observed an elevation in ex vivo immune responsiveness to LPS stimulation when switching from ASA monotherapy to DPI of ASA combined with rivaroxaban inpatients with peripheral arterial disease (n=11; unpublished). Remarkably this was associated with no changes in systemic inflammation, as determined by Olink proteomics analysis. These findings suggest that factor Xa inhibitors can enhance immune cell responsiveness despite being clinically beneficial to CAD. The exact mechanisms contributing to the observed increased immune responsiveness remain unexplored.

Conditions

Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• Whole blood immune responsiveness

  Change in whole blood immune responsiveness to lipopolysaccharide stimulation when switching from acetylsalicylic acid to dual pathway inhibition (acetylsalicylic acid and low-dose rivaroxaban).

  12 weeks

Secondary Outcomes (3)

• White blood cell count and distribution

  3 months

• Monocyte immune responsiveness

  3 months

• Enrichment of epigenetic marks on genes

  3 months

Study Arms (1)

Stable coronary artery disease

EXPERIMENTAL

Patients with stable coronary artery disease with an indication for single antiplatelet therapy according to international (ESC) guidelines, with a high cardiovascular risk.

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 acetylsalicylic acid (80-00mg once a day, standard care).

Stable coronary artery disease

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:

• In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• stable CAD
• with an indication for single antiplatelet therapy according to international (ESC) guidelines,
• high cardiovascular risk based on a SMART risk score \[9\] of at least 20% and/or the judgement of the cardiologist
• at least 1 year after myocardial infarction or multivessel CAD
• \>16 years old
• Written informed consent

You may not qualify if:

• A potential subject who meets any of the following criteria will be excluded from participation in this study:
• Use of more intensive antithrombotic treatment (dual antiplatelet therapy, DPI, direct oral anticoagulants, vitamin k antagonists)
• Use of immunosuppressant and/or anti-inflammatory therapy, including glucocorticoids, cytostatics, antibodies, immunophilins, interferons, Tumor Necrosis Factor (TNF) binding proteins, mycophenolate and interleukin antagonists
• Contra-indication to rivaroxaban
• Hypersensitivity to rivaroxaban
• at significant risk for major bleeding
• current gastrointestinal ulceration
• presence of malignant neoplasms, with the exception of non-melanoma skin cancer
• recent (\<2 months) brain or spinal injury
• recent (\<3 months) brain or spinal surgery
• recent (\<3 months) intracranial, gastrointestinal or pulmonary hemorrhage
• presence of arteriovenous malformations,
• major intraspinal or intracerebral vascular abnormalities
• congenital or acquired bleeding disorders
• uncontrolled severe arterial hypertension (180 mmHg or more systolic, or 110 mmHg or more diastolic)

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboudumc

Nijmegen, Gelderland, 6525GA, Netherlands

Location

Related Publications (1)

• Groh LA, Willems LH, Fintelman P, Reijnen MMPJ, El Messaoudi S, Warle MC. Dual-Pathway Inhibition with Rivaroxaban and Low-Dose Aspirin Does Not Alter Immune Cell Responsiveness and Distribution in Patients with Coronary Artery Disease. Cardiol Ther. 2024 Mar;13(1):233-242. doi: 10.1007/s40119-023-00342-5. Epub 2023 Dec 6.

  PMID: 38055176 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Rivaroxaban

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Saloua El Messaoudi, MD PhD

  Radboud University Medical Center

  STUDY DIRECTOR

• Michiel C Warlé, MD PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2022
• First Posted: January 27, 2022
• Study Start: March 1, 2022
• Primary Completion: April 15, 2022
• Study Completion: July 1, 2022
• Last Updated: April 20, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)