Reveal Transition - A Mechanistic Study in Transition / Stabilized Phase of CAD (RevealTrans)

Reveal Transition: Rivaroxaban-Evaluation of Variables Enhancing Antithrombotic Efficacy and Longterm-Outcome in Stabilized Patients With Cardiovascular Disease. A Mechanistic Study in Transition / Stabilized Phase of CAD

Longterm oral anticoagulation with very low dose rivaroxaban (2.5mg bid) in combination with aspirin has been shown superior over standard aspirin monotherapy in patients with stable coronary artery disease (CAD) in the COMPASS trial. To date, there are no data comparing these - antithrombotic strategies and to provide insights about mechanistic effects of very low dose rivaroxaban on top of aspirin for longterm treatment.

Thus, the goal of the planned pilot study will be to identify effects of rivaroxaban on platelet function, platelet-mediated vascular inflammation and particularly, platelet-mediated thrombin generation as well as the underlying mechanisms and to reveal differences in mechanistic effects during longterm treatment with combined novel antiplatelet/anticoagulant strategies. This study is planned as descriptive study.

Study Overview

• Status: Withdrawn
• Conditions: Cardiovascular Diseases
• Intervention / Treatment: Diagnostic test: Rivaroxaban

• Study Type: Observational

Contacts and Locations

Study Locations

• Germany
  • Tuebingen, Germany, 72076
    • University Hospital Tuebingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients post troponin-positive acute coronary syndromes (STEMI n=17 + NSTEMI n=17) or stable CAD + peripheral artery disease (PAD) (n=17) with additional risk factors (see inclusion cirteria) who underwent PCI.

Description

Inclusion Criteria:

1. patients≥ 18 years.
2. troponin-positive acute coronary syndrome (NSTEMI/STEMI) with planned dual antiplatelet therapy (DAPT, ASA + ticagrelor) for 12 months or stable CAD with previous PCI and drug eluting-stent (DES) + pre-existing PAD under treatment with DAPT (ASA + clopidogrel).
3. Patients with coronary artery disease who are younger than 65 years of age are required to have documentation of atherosclerosis involving at least two vascular beds or to have at least two additional risk factors (current smoking, diabetes mellitus, an estimated glomerular filtration rate [GFR] <60 ml per minute, heart failure, or nonlacunar ischemic stroke ≥1 month earlier).
4. informed written consent.

Exclusion Criteria:

1. any condition that requires longterm or already ongoing full oral anticoagulation (e.g. recent systemic embolism, prosthetic heart valves or chronic atrial fibrillation).
2. patients with increased bleeding risk preventing guideline adherent dual antiplatelet therapy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Stable coronary and peripheral artery disease (CAD/PAD); Stable CAD/PAD patients with previous percutaneous coronary intervention and drug eluting stent-implantation treated with dual antiplatelet therapy (ASA+clopidogrel)	Diagnostic test: Rivaroxaban; In stable CAD/PAD patients with previous PCI and DES-implantation treated with DAPT (ASA+clopidogrel) platelet rich plasma (PRP) and washed platelets as well as serum/plasma/urinary samples will be collected between 2 and 4 weeks before switching from DAPT to ASA + rivaroxaban (2,5 mg b.i.d.), between 2 and 4 weeks under monotherapy with ASA 100mg o.d., and between 2 and 4 weeks under therapy with ASA 100mg o.d. + rivaroxaban (2,5 mg b.i.d.) and treated ex vivo with rivaroxaban to asses platelet activation and function, platelet-triggered thrombin generation and platelet-dependent vascular inflammation.
Acute coronary artery disease (ACS); Patients with troponin-positive ACS (NSTEMI/STEMI) with planned percutaneous coronary intervention and drug eluting stent-implantation treated with P2Y12 inhibitor (ticagrelor) and ASA	Diagnostic test: Rivaroxaban; In stable CAD/PAD patients with previous PCI and DES-implantation treated with DAPT (ASA+clopidogrel) platelet rich plasma (PRP) and washed platelets as well as serum/plasma/urinary samples will be collected between 2 and 4 weeks before switching from DAPT to ASA + rivaroxaban (2,5 mg b.i.d.), between 2 and 4 weeks under monotherapy with ASA 100mg o.d., and between 2 and 4 weeks under therapy with ASA 100mg o.d. + rivaroxaban (2,5 mg b.i.d.) and treated ex vivo with rivaroxaban to asses platelet activation and function, platelet-triggered thrombin generation and platelet-dependent vascular inflammation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammation, Thrombogenicity and Mechanistic Insights During Transition from acute to chronic phase	Define the course of vascular inflammation and thrombogenicity during transition from acute to chronic phase after percutaneous coronary intervention and to provide mechanistic insights of very low dose rivaroxaban (VLDR) on platelet activation and function, platelet-triggered thrombin generation and platelet-dependent vascular inflammation. Platelet function as well as platelet-dependent vascular inflammation will be determined by flow cytometry, thrombinoscopy, spectrofluorimetry, aggregometry, total thromus-formation analysis system (T-TAS) and thrombelastography (TEG) studies	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker Expression	To reveal course of prothrombotic and inflammatory markers after acute coronary syndromes to better understand the transition from acute to stabilized phase.	2 years

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Collaborators: Bayer
• Investigators: Principal Investigator: Tobias Geisler, Professor, University Hospital of Tuebingen; Principal Investigator: Oliver Alexander Borst, Professor, University Hospital of Tuebingen

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2019
• Primary Completion (Anticipated): May 1, 2020
• Study Completion (Actual): May 14, 2020

Study Registration Dates

• First Submitted: July 18, 2019
• First Submitted That Met QC Criteria: July 23, 2019
• First Posted (Actual): July 25, 2019

Study Record Updates

• Last Update Posted (Actual): July 18, 2022
• Last Update Submitted That Met QC Criteria: July 13, 2022
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: Reveal Transition

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No