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

NCT04981041 | Unknown Phase 4 DMC

• 1 other identifier: EPIDAURUS-2020
• Study Type: interventional
• Target: 2,334
• Locations: 1 country
• Sites: 25

Brief Summary

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.

Conditions

Acute Coronary Syndrome; Atrial Fibrillation

Outcome Measures

Primary Outcomes (2)

• Major ischaemic events defined as the composite of all-cause mortality, myocardial infarction, definite or probable stent thrombosis, ischaemic stroke and systemic thromboembolism

  superiority test

  6 weeks

• Bleeding type 2 or higher according to the Bleeding Academic Research Consortium (BARC) criteria

  non-inferiority test

  6 weeks

Secondary Outcomes (11)

• All-cause mortality

  6 weeks

• Myocardial infarction

  6 weeks

• Definite or probable stent thrombosis

  6 weeks

• Ischaemic stroke

  6 weeks

• Systemic thromboembolism

  6 weeks

Study Arms (2)

Potent P2Y12-Inhibition

EXPERIMENTAL

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

Clopidogrel

ACTIVE COMPARATOR

Clopidogrel 75mg q.d. per os

Drug: Clopidogrel

Interventions

Prasugrel or Ticagrelor DRUG

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)

Potent P2Y12-Inhibition

Clopidogrel DRUG

Clopidogrel and NOAC

Clopidogrel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead

Study Sites (25)

Deutsches Herzzentrum München

Munich, Bavaria, 80636, Germany

RECRUITING

Universitätsklinikum Freiburg, Universitäts-Herzzentrum Klinik für Kardiologie & Angiologie, Campus Bad Krozingen

Bad Krozingen, 79189, Germany

RECRUITING

Kerckhoff-Klinik GmbH, Herzzentrum

Bad Nauheim, 61231, Germany

ACTIVE NOT RECRUITING

Campus Benjamin Franklin

Berlin, Germany

RECRUITING

Campus Virchow-Klinikum

Berlin, Germany

RECRUITING

Klinikum Bielefeld gem. GmbH Universitätsklinikum für Kardiologie und Internistische Intensivmedizin

Bielefeld, 33604, Germany

RECRUITING

Herzzentrum Dresden GmbH Universitätsklinik an der Technischen Universität Dresden, Klinik für Innere Medizin und Kardiologie

Dresden, 01307, Germany

RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, Germany

RECRUITING

Klinikum Landkreis Erding

Erding, Germany

RECRUITING

Universitätsklinikum Essen

Essen, Germany

RECRUITING

Universitäres Herzzentrum Universitätsklinikum Frankfurt am Main Goethe-Universität

Frankfurt am Main, 60590, Germany

RECRUITING

Universitätsklinikum Freiburg, Universitäts-Herzzentrum Klinik für Kardiologie & Angiologie, Campus Freiburg

Freiburg im Breisgau, 79106, Germany

RECRUITING

Evangelisches Krankenhaus Hagen-Haspe gGmbH, Klinik für Kardiologie und Rhythmologie

Hagen, 58135, Germany

RECRUITING

Medizinische Hochschule Hannover,Zentrum für Innere Medizin

Hanover, 30625, Germany

RECRUITING

Universitätsklinikum Heidelberg, Klinik für Kardiologie, Angiologie, Pneumologie

Heidelberg, 69120, Germany

RECRUITING

Universitätsklinikum Schleswig-Holstein -Campus Kiel- Klinik für Innere Medizin III mit den Schwerpunkten Kardiologie, Angiologie und internistische Intensivmedizin

Kiel, 25105, Germany

RECRUITING

Herzzentrum Leipzig, Universitätsklinik für Kardiologie

Leipzig, 04289, Germany

RECRUITING

Universitätsmedizin Mainz, Zentrum für Kardiologie - Kardiologie I

Mainz, 55131, Germany

RECRUITING

LMU-Klinikum Campus Grosshadern

Munich, 81377, Germany

RECRUITING

LMU-Klinikum Campus Innenstadt

Munich, Germany

RECRUITING

Klinikum Nürnberg Süd, Klinik für Innere Medizin 8, Schwerpunkt Kardiologie

Nuremberg, 90471, Germany

RECRUITING

Universitätsmedizin Rostock, Zentrum Innere Medizin, Abteilung Kardiologie

Rostock, 18057, Germany

RECRUITING

HBK Hegau-Bodensee Klinikum Singen

Singen, Germany

RECRUITING

Barmherzige Brüder, Klinikum St. Elisabeth Straubing GmbH, II. Medizinische Klinik Innere Medizin, Kardiologie, Intensivmedizin, Pneumologie, Nephrologie und Angiologie

Straubing, 94315, Germany

RECRUITING

Universitätsklinikum Tübingen

Tübingen, Germany

RECRUITING

MeSH Terms

Conditions

Acute Coronary Syndrome; Atrial Fibrillation

Interventions

Prasugrel Hydrochloride; Ticagrelor; Clopidogrel

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arrhythmias, Cardiac; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Ticlopidine; Thienopyridines; Pyridines

Study Officials

• Steffen Massberg, MD

  LMU Klinikum

  PRINCIPAL INVESTIGATOR

• Konstantinos Rizas, MD

  LMU Klinikum

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Konstantinos Rizas, MD

CONTACT

0049; konstantinos.rizas@med.uni-muenchen.de

Steffen Massberg, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. med. Konstantinos Rizas, Assistant Professor of Medicine, Co-Principal Investigator

Study Record Dates

• First Submitted: July 21, 2021
• First Posted: July 28, 2021
• Study Start: December 16, 2021
• Primary Completion: December 16, 2024
• Study Completion: June 16, 2025
• Last Updated: July 14, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (25)