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Trained Immunity by Dual-pathway Inhibition in Coronary Artery Disease (DUALCAD)

Primary Purpose

Coronary Artery Disease

Status
Active
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Rivaroxaban 2.5 Mg Oral Tablet
Sponsored by
Radboud University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronary Artery Disease

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Radboudumc

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Stable coronary artery disease

Arm Description

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

White blood cell count and distribution
changes in white blood cell count and distribution when switching from acetylsalicylic acid to dual pathway inhibition (acetylsalicylic acid and low-dose rivaroxaban).
Monocyte immune responsiveness
Change in monocyte immune responsiveness to LPS stimulation when switching from acetylsalicylic acid to dual pathway inhibition (acetylsalicylic acid and low-dose rivaroxaban).
Enrichment of epigenetic marks on genes
Enrichment of epigenetic marks on genes when switching from acetylsalicylic acid to dual pathway inhibition (acetylsalicylic acid and low-dose rivaroxaban).

Full Information

First Posted
January 13, 2022
Last Updated
April 19, 2022
Sponsor
Radboud University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT05210725
Brief Title
Trained Immunity by Dual-pathway Inhibition in Coronary Artery Disease
Acronym
DUALCAD
Official Title
Trained Immunity by Dual-pathway Inhibition (Low-dose Rivaroxaban and Acetylsalicylic Acid) in Coronary Artery Disease'
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 1, 2022 (Actual)
Primary Completion Date
April 15, 2022 (Actual)
Study Completion Date
July 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Stable coronary artery disease
Arm Type
Experimental
Arm Description
Patients with stable coronary artery disease with an indication for single antiplatelet therapy according to international (ESC) guidelines, with a high cardiovascular risk.
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban 2.5 Mg Oral Tablet
Intervention Description
2.5 mg rivaroxaban twice a day in addition to acetylsalicylic acid (80-00mg once a day, standard care).
Primary Outcome Measure Information:
Title
Whole blood immune responsiveness
Description
Change in whole blood immune responsiveness to lipopolysaccharide stimulation when switching from acetylsalicylic acid to dual pathway inhibition (acetylsalicylic acid and low-dose rivaroxaban).
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
White blood cell count and distribution
Description
changes in white blood cell count and distribution when switching from acetylsalicylic acid to dual pathway inhibition (acetylsalicylic acid and low-dose rivaroxaban).
Time Frame
3 months
Title
Monocyte immune responsiveness
Description
Change in monocyte immune responsiveness to LPS stimulation when switching from acetylsalicylic acid to dual pathway inhibition (acetylsalicylic acid and low-dose rivaroxaban).
Time Frame
3 months
Title
Enrichment of epigenetic marks on genes
Description
Enrichment of epigenetic marks on genes when switching from acetylsalicylic acid to dual pathway inhibition (acetylsalicylic acid and low-dose rivaroxaban).
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Saloua El Messaoudi, MD PhD
Organizational Affiliation
Radboud University Medical Center
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Michiel C Warlé, MD PhD
Organizational Affiliation
Radboud University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Radboudumc
City
Nijmegen
State/Province
Gelderland
ZIP/Postal Code
6525GA
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
No

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Trained Immunity by Dual-pathway Inhibition in Coronary Artery Disease

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