Escalated Single Platelet Inhibition for One Month Plus NOAC in Patients With Atrial Fibrillation and ACS Undergoing PCI (EPIDAURUS)

Escalated Single Platelet Inhibition for One Month Plus Direct Oral Anticoagulation in Patients With Atrial Fibrillation and acUte coRonary Syndrome Undergoing percutaneoUS Coronary Intervention

The selection of the optimal antithrombotic therapy in patients with nonvalvular atrial fibrillation (AF) and acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) is challenging. Until recently, triple antithrombotic therapy (TAT) consisting in Aspirin plus Clopidogrel plus OAC was considered the treatment of choice. While efficiently preventing ischaemic events, TAT is associated with an increase in bleeding complications. Therefore, in the past years several randomized controlled trials challenged TAT by comparing a triple antithrombotic therapy (TAT) regimen based on Vitamin K antagonists (VKA) to a dual antithrombotic regimen (DAT) based on non-vitamin K antagonist oral anticoagulants (NOACs) and P2Y12-inhibitors, mainly Clopidogrel in patients with AF undergoing PCI.

However, approximately 30-40% of patients show low response to Clopidogrel and are not adequately protected against ischaemic events, in particular when presenting with ACS. This is supported by a recent meta-analysis reporting that TAT compared to DAT is associated with lower rates of stent thrombosis within 30 days after PCI. It is therefore reasonable to assume that a more potent platelet inhibition within the first month after PCI might reduce the rate of ischaemic complications observed in AF patients undergoing PCI, when receiving DAT. Moreover, a subsequent de-escalation to a less potent platelet inhibition one month after PCI might prevent an increase in bleeding complications.

In EPIDAURUS the investigators will therefore test the hypothesis that DAT using NOAC plus an escalated antiplatelet therapy with a potent P2Y12-inhibitor for one month followed by Clopidogrel reduces ischaemic events without a relevant increase in bleeding complications in patients with AF and ACS undergoing PCI compared to standard DAT with NOAC plus Clopidogrel.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation; Acute Coronary Syndrome
• Intervention / Treatment: Drug: Prasugrel or Ticagrelor; Drug: Clopidogrel

• Study Type: Interventional
• Enrollment (Actual): 602
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria
    • Medizinische Universität Innsbruck Universitätsklinik für Innere Medizin III - Kardiologie und Angiologie Anichstraße 35 6020 Innsbruck, Austria
• Germany
  • Bad Krozingen, Germany, 79189
    • Universitätsklinikum Freiburg, Universitäts-Herzzentrum Klinik für Kardiologie & Angiologie, Campus Bad Krozingen
  • Bad Nauheim, Germany, 61231
    • Kerckhoff-Klinik GmbH, Herzzentrum
  • Berlin, Germany
    • Campus Benjamin Franklin
  • Berlin, Germany
    • Campus Virchow-Klinikum
  • Berlin, Germany
    • Sana Klinikum Lichtenberg Klinik für Innere Medizin II: Kardiologie Fanningerstraße 32 10365 Berlin
  • Bielefeld, Germany, 33604
    • Klinikum Bielefeld gem. GmbH Universitätsklinikum für Kardiologie und Internistische Intensivmedizin
  • Bonn, Germany
    • Universitätsklinikum Bonn (AöR) Medizinische Klinik und Poliklinik II - Herzzentrum Venusberg-Campus 1 53127 Bonn
  • Coburg, Germany
    • Klinikum Coburg, Kardiologie-Angiologie Ketschendorfer Str. 33 96450 Coburg
  • Dachau, Germany
    • Helios Amper-Klinikum Dachau Kardiologie und Pneumologie Krankenhausstraße 15 85221 Dachau
  • Dresden, Germany, 01307
    • Herzzentrum Dresden GmbH Universitätsklinik an der Technischen Universität Dresden, Klinik für Innere Medizin und Kardiologie
  • Düsseldorf, Germany
    • Universitätsklinikum Düsseldorf
  • Erding, Germany
    • Klinikum Landkreis Erding
  • Essen, Germany
    • Universitätsklinikum Essen
  • Frankfurt am Main, Germany, 60590
    • Universitäres Herzzentrum Universitätsklinikum Frankfurt am Main Goethe-Universität
  • Freiburg im Breisgau, Germany, 79106
    • Universitätsklinikum Freiburg, Universitäts-Herzzentrum Klinik für Kardiologie & Angiologie, Campus Freiburg
  • Friedrichshafen, Germany
    • Klinikum Friedrichshafen, Medizin Campus Bodensee Klinik für Kardiologie, Angiologie, Pneumologie und internistische Intensivmedizin Röntgenstraße 2 88048 Friedrichshafen
  • Hagen, Germany, 58135
    • Evangelisches Krankenhaus Hagen-Haspe gGmbH, Klinik für Kardiologie und Rhythmologie
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover,Zentrum für Innere Medizin
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg, Klinik für Kardiologie, Angiologie, Pneumologie
  • Ingolstadt, Germany
    • Klinikum Ingolstadt Medizinische Klinik I Krumenauerstraße 25 85049 Ingolstadt
  • Kiel, Germany, 25105
    • Universitätsklinikum Schleswig-Holstein -Campus Kiel- Klinik für Innere Medizin III mit den Schwerpunkten Kardiologie, Angiologie und internistische Intensivmedizin
  • Konstanz, Germany
    • Klinikum Konstanz Medizinische Klinik, Studienzentrum Mainaustr. 35 78464 Konstanz
  • Leipzig, Germany, 04289
    • Herzzentrum Leipzig, Universitätsklinik für Kardiologie
  • Lübeck, Germany
    • Universitätsklinikum Schleswig-Holstein (UKSHL) Campus Lübeck Medizinische Klinik II (Kardiologie, Angiologie, Intensivmedizin) Universitäres Herzzentrum Lübeck Ratzeburger Allee 160 23538 Lübeck, Deutschland
  • Mainz, Germany, 55131
    • Universitätsmedizin Mainz, Zentrum für Kardiologie - Kardiologie I
  • Mannheim, Germany
    • Universitätsklinikum Mannheim Medizinische Klinik Kardiologie, Angiologie, Hämostaseologie, Internistische Intensivmedizin Theodor-Kutzer-Ufer 1-3 68167 Mannheim
  • Munich, Germany, 81377
    • LMU-Klinikum Campus Grosshadern
  • Munich, Germany
    • LMU-Klinikum Campus Innenstadt
  • München, Germany
    • München Klinik Bogenhausen, Klinik für Kardiologie und Internistische Intensivmedizin
  • Nuremberg, Germany, 90471
    • Klinikum Nürnberg Süd, Klinik für Innere Medizin 8, Schwerpunkt Kardiologie
  • Paderborn, Germany
    • St. Vincenz Krankenhaus Paderborn Medizinische Klinik II Kardiologie und internistische Intensivmedizin Am Busdorf 2 33098 Paderborn
  • Rostock, Germany, 18057
    • Universitätsmedizin Rostock, Zentrum Innere Medizin, Abteilung Kardiologie
  • Singen, Germany
    • HBK Hegau-Bodensee Klinikum Singen
  • Straubing, Germany, 94315
    • Barmherzige Brüder, Klinikum St. Elisabeth Straubing GmbH, II. Medizinische Klinik Innere Medizin, Kardiologie, Intensivmedizin, Pneumologie, Nephrologie und Angiologie
  • Tübingen, Germany
    • Universitätsklinikum Tübingen
  • Bavaria
    • Munich, Bavaria, Germany, 80636
      • Deutsches Herzzentrum München

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Written informed consent
• Age ≥ 18 years
• Atrial fibrillation requiring oral anticoagulation
• STEMI or NSTEMI (biomarker positive acute coronary syndrome) and successful completion of PCI (randomization will take place within 24h after successful PCI)

Exclusion Criteria:

• Chronic renal insufficiency with glomerular filtration rate < 15 ml/min/1.73m2
• History of ischaemic stroke or transient ischaemic attack (both contraindications for Prasugrel) and history of intracranial bleeding (contraindication for Ticagrelor)
• Contraindication for Clopidogrel or Aspirin
• Contraindication for P2Y12-inhibitor
• Severe chronic liver disease (Child-Pugh C)
• Indication for oral anticoagulation with Vitamin K antagonists
• Moderate to severe mitral stenosis or mechanical heart valve
• Any bleeding BARC type ≥ 2 within the last 4 weeks before index procedure
• Pregnancy or lactation
• Inability to cooperate with the protocol requirements
• Life expectancy < 6 months
• Participation in another investigational drug study
• Previous enrolment in this study
• For women of childbearing potential no negative pregnancy test and no agree to use a reliable method of birth control during the study
• Previous treatment with GP IIb/IIIa inhibitors within the last 12 hours
• A known genetic disorder involved in the metabolism of the study medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Potent P2Y12-Inhibition; Prasugrel 10mg (5 mg in patients ≥ 75 years old or weighing < 60 kg) q.d. per os or Ticagrelor 90mg bid per os	Drug: Prasugrel or Ticagrelor; Escalated antiplatelet therapy with a potent P2Y12- inhibitor for one month in patients with atrial fibrillation and indication for treatment non-vitamin K antagonist oral anticoagulants (NOACs)
Active Comparator: Clopidogrel; Clopidogrel 75mg q.d. per os	Drug: Clopidogrel; Clopidogrel and NOAC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major ischaemic events defined as the composite of all-cause mortality, myocardial infarction, definite or probable stent thrombosis, ischaemic stroke systemic thromboembolism and urgent revascularization	superiority test	6 weeks
Death and Bleeding type 2 or higher according to the Bleeding Academic Research Consortium (BARC) criteria	non-inferiority test	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality		6 months
All-cause mortality		6 weeks
Myocardial infarction		6 weeks
Definite or probable stent thrombosis		6 weeks
Ischaemic stroke		6 weeks
Systemic thromboembolism		6 weeks
Cardiovascular mortality		6 weeks
Bleeding type 2 or more according to the Bleeding Academic Research Consortium	superiority testing	6 weeks
Urgent revascularization		6 weeks
Unplanned hospitalization due to acute heart failure or acute coronary syndrome		6 months
Ischaemic stroke		6 months

Collaborators and Investigators

• Sponsor: Ludwig-Maximilians - University of Munich
• Investigators: Principal Investigator: Steffen Massberg, MD, LMU Klinikum; Principal Investigator: Konstantinos Rizas, MD, LMU Klinikum

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2021
• Primary Completion (Actual): May 22, 2026
• Study Completion (Actual): May 30, 2026

Study Registration Dates

• First Submitted: July 21, 2021
• First Submitted That Met QC Criteria: July 21, 2021
• First Posted (Actual): July 28, 2021

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 30, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Myocardial Ischemia; Pathological Conditions, Signs and Symptoms; Atrial Fibrillation; Acute Coronary Syndrome; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Purines; Nucleosides; Ribonucleosides; Thiophenes; Adenosine; Purine Nucleosides; Piperazines; Ticlopidine; Thienopyridines; Ticagrelor; Clopidogrel; Prasugrel Hydrochloride
• Other Study ID Numbers: EPIDAURUS-2020

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