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

Atrial Fibrillation Clinical Trial

— EPIDAURUS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04981041
• Other study ID #: EPIDAURUS-2020
• Status: Recruiting
• Phase: Phase 4
• Start date: December 16, 2021
• Est. completion date: June 16, 2025

Study information

• Verified date: July 2023
• Source: Ludwig-Maximilians - University of Munich
• Contact: Konstantinos Rizas, MD
• Phone: 0049
• Email: konstantinos.rizas[@]med.uni-muenchen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2334
• Est. completion date: June 16, 2025
• Est. primary completion date: December 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Atrial Fibrillation
• Syndrome

Intervention

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)
• Clopidogrel
Clopidogrel and NOAC

Locations

Country	Name	City	State
Germany	Universitätsklinikum Freiburg, Universitäts-Herzzentrum Klinik für Kardiologie & Angiologie, Campus Bad Krozingen	Bad Krozingen
Germany	Kerckhoff-Klinik GmbH, Herzzentrum	Bad Nauheim
Germany	Campus Benjamin Franklin	Berlin
Germany	Campus Virchow-Klinikum	Berlin
Germany	Klinikum Bielefeld gem. GmbH Universitätsklinikum für Kardiologie und Internistische Intensivmedizin	Bielefeld
Germany	Herzzentrum Dresden GmbH Universitätsklinik an der Technischen Universität Dresden, Klinik für Innere Medizin und Kardiologie	Dresden
Germany	Universitätsklinikum Düsseldorf	Düsseldorf
Germany	Klinikum Landkreis Erding	Erding
Germany	Universitätsklinikum Essen	Essen
Germany	Universitäres Herzzentrum Universitätsklinikum Frankfurt am Main Goethe-Universität	Frankfurt am Main
Germany	Universitätsklinikum Freiburg, Universitäts-Herzzentrum Klinik für Kardiologie & Angiologie, Campus Freiburg	Freiburg
Germany	Evangelisches Krankenhaus Hagen-Haspe gGmbH, Klinik für Kardiologie und Rhythmologie	Hagen
Germany	Medizinische Hochschule Hannover,Zentrum für Innere Medizin	Hannover
Germany	Universitätsklinikum Heidelberg, Klinik für Kardiologie, Angiologie, Pneumologie	Heidelberg
Germany	Universitätsklinikum Schleswig-Holstein -Campus Kiel- Klinik für Innere Medizin III mit den Schwerpunkten Kardiologie, Angiologie und internistische Intensivmedizin	Kiel
Germany	Herzzentrum Leipzig, Universitätsklinik für Kardiologie	Leipzig
Germany	Universitätsmedizin Mainz, Zentrum für Kardiologie - Kardiologie I	Mainz
Germany	Deutsches Herzzentrum München	Munich	Bayern
Germany	LMU-Klinikum Campus Grosshadern	Munich
Germany	LMU-Klinikum Campus Innenstadt	Munich
Germany	Klinikum Nürnberg Süd, Klinik für Innere Medizin 8, Schwerpunkt Kardiologie	Nürnberg
Germany	Universitätsmedizin Rostock, Zentrum Innere Medizin, Abteilung Kardiologie	Rostock
Germany	HBK Hegau-Bodensee Klinikum Singen	Singen
Germany	Barmherzige Brüder, Klinikum St. Elisabeth Straubing GmbH, II. Medizinische Klinik Innere Medizin, Kardiologie, Intensivmedizin, Pneumologie, Nephrologie und Angiologie	Straubing
Germany	Universitätsklinikum Tübingen	Tübingen

Sponsors (1)

Lead Sponsor	Collaborator
Ludwig-Maximilians - University of Munich

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Bleeding type 2 or higher according to the Bleeding Academic Research Consortium (BARC) criteria	non-inferiority test	6 weeks
Secondary	All-cause mortality		6 weeks
Secondary	Myocardial infarction		6 weeks
Secondary	Definite or probable stent thrombosis		6 weeks
Secondary	Ischaemic stroke		6 weeks
Secondary	Systemic thromboembolism		6 weeks
Secondary	Cardiovascular mortality		6 weeks
Secondary	Bleeding type 2 or more according to the Bleeding Academic Research Consortium	superiority testing	6 weeks
Secondary	Urgent revascularization		6 weeks
Secondary	All-cause mortality		6 months
Secondary	Unplanned hospitalization due to acute heart failure or acute coronary syndrome		6 months
Secondary	Ischaemic stroke		6 months