Trained Immunity by Dual-pathway Inhibition in Coronary Artery Disease

NCT ID: NCT05210725

Last Updated: 2022-04-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-01
• Study Completion Date: 2022-07-01

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from ASA monotherapy to DPI of ASA combined with rivaroxaban inpatients with peripheral arterial disease (n=11; unpublished).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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stable coronary artery disease

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

Group Type: EXPERIMENTAL

Rivaroxaban 2.5 Mg Oral Tablet

Intervention Type: DRUG

2.5 mg rivaroxaban twice a day in addition to acetylsalicylic acid (80-00mg once a day, standard care).

Interventions

Rivaroxaban 2.5 Mg Oral Tablet

2.5 mg rivaroxaban twice a day in addition to acetylsalicylic acid (80-00mg once a day, standard care).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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)
• Severe hepatic disease: Child Pugh B or C [10]
• Severe kidney failure: estimated glomerular filtration rate<15 ml/min or requiring dialysis
• severe heart failure with known ejection fraction < 30% or New York Heart Association class III or IV symptoms [12]
• concomitant treatment with medication with a strong pharmacokinetic interaction with rivaroxaban, leading to contra-indication according to the "regionale_NOAC_richtlijn" [12]
• Pregnant or breastfeeding women
• Unable to give informed consent

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Saloua El Messaoudi, MD PhD

Role: STUDY_DIRECTOR

Radboud University Medical Center

Michiel C Warlé, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

Radboudumc

Nijmegen, Gelderland, Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 38055176 (View on PubMed)

Other Identifiers

NL2021-13291

Identifier Type: -

Identifier Source: org_study_id