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

Phase 4

Recruiting

• Conditions: Acute Coronary Syndrome; Atrial Fibrillation
• Interventions: Drug: Prasugrel or Ticagrelor; Drug: Clopidogrel

• Registration Number: NCT04981041
• Lead Sponsor: Ludwig-Maximilians - University of Munich

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-21
• Study First Submitted QC: 2021-07-21
• Study First Posted: 2021-07-28
• Study Start: 2021-12-16
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-13
• Last Update Posted: 2023-07-14
• Primary Completion: 2024-12-16
• Study Completion: 2025-06-16

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 2334

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Potent P2Y12-Inhibition	Prasugrel or Ticagrelor	Prasugrel 10mg (5 mg in patients ≥ 75 years old or weighing \< 60 kg) q.d. per os or Ticagrelor 90mg bid per os
Clopidogrel	Clopidogrel	Clopidogrel 75mg q.d. per os

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (25)

Deutsches Herzzentrum München; 🇩🇪 Munich, Bayern, Germany

Kerckhoff-Klinik GmbH, Herzzentrum; 🇩🇪 Bad Nauheim, Germany

Universitätsklinikum Freiburg, Universitäts-Herzzentrum Klinik für Kardiologie & Angiologie, Campus Bad Krozingen; 🇩🇪 Bad Krozingen, Germany

Campus Benjamin Franklin; 🇩🇪 Berlin, Germany

Campus Virchow-Klinikum; 🇩🇪 Berlin, Germany

Klinikum Bielefeld gem. GmbH Universitätsklinikum für Kardiologie und Internistische Intensivmedizin; 🇩🇪 Bielefeld, Germany

Universitätsklinikum Düsseldorf; 🇩🇪 Düsseldorf, Germany

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

Universitätsmedizin Mainz, Zentrum für Kardiologie - Kardiologie I; 🇩🇪 Mainz, 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

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

Universitätsmedizin Rostock, Zentrum Innere Medizin, Abteilung Kardiologie; 🇩🇪 Rostock, Germany

HBK Hegau-Bodensee Klinikum Singen; 🇩🇪 Singen, Germany

Universitätsklinikum Tübingen; 🇩🇪 Tübingen, 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