Clinical trial NCT04981041: Escalated Single Platelet Inhibition for One Month Plus NOAC in Patients With Atrial Fibrillation and ACS Undergoing PCI
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Atrial Fibrillation
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
First posted: 2021-07-28
Enrollment: 2334
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Major ischaemic events defined as the composite of all-cause mortality, myocardial infarction, definite or probable stent thrombosis, ischaemic stroke and systemic thromboembolism
timeFrame: 6 weeks
measure: Bleeding type 2 or higher according to the Bleeding Academic Research Consortium (BARC) criteria
timeFrame: 6 weeks
Secondary outcomes:
measure: All-cause mortality
timeFrame: 6 weeks
measure: Myocardial infarction
timeFrame: 6 weeks
measure: Definite or probable stent thrombosis
timeFrame: 6 weeks
measure: Ischaemic stroke
timeFrame: 6 weeks
measure: Systemic thromboembolism
timeFrame: 6 weeks
measure: Cardiovascular mortality
timeFrame: 6 weeks
measure: Bleeding type 2 or more according to the Bleeding Academic Research Consortium
timeFrame: 6 weeks
measure: Urgent revascularization
timeFrame: 6 weeks
measure: All-cause mortality
timeFrame: 6 months
measure: Unplanned hospitalization due to acute heart failure or acute coronary syndrome
timeFrame: 6 months
measure: Ischaemic stroke
timeFrame: 6 months
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Deutsches Herzzentrum München
state: Bayern
city: Bad Krozingen
country: Germany
facility: Universitätsklinikum Freiburg, Universitäts-Herzzentrum Klinik für Kardiologie & Angiologie, Campus Bad Krozingen
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik GmbH, Herzzentrum
city: Berlin
country: Germany
facility: Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Campus Virchow-Klinikum
city: Bielefeld
country: Germany
facility: Klinikum Bielefeld gem. GmbH Universitätsklinikum für Kardiologie und Internistische Intensivmedizin
city: Dresden
country: Germany
facility: Herzzentrum Dresden GmbH Universitätsklinik an der Technischen Universität Dresden, Klinik für Innere Medizin und Kardiologie
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Erding
country: Germany
facility: Klinikum Landkreis Erding
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt am Main
country: Germany
facility: Universitäres Herzzentrum Universitätsklinikum Frankfurt am Main Goethe-Universität
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Universitäts-Herzzentrum Klinik für Kardiologie & Angiologie, Campus Freiburg
city: Hagen
country: Germany
facility: Evangelisches Krankenhaus Hagen-Haspe gGmbH, Klinik für Kardiologie und Rhythmologie
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover,Zentrum für Innere Medizin
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg, Klinik für Kardiologie, Angiologie, Pneumologie
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein -Campus Kiel- Klinik für Innere Medizin III mit den Schwerpunkten Kardiologie, Angiologie und internistische Intensivmedizin
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig, Universitätsklinik für Kardiologie
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz, Zentrum für Kardiologie - Kardiologie I
city: Munich
country: Germany
facility: LMU-Klinikum Campus Grosshadern
city: Munich
country: Germany
facility: LMU-Klinikum Campus Innenstadt
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg Süd, Klinik für Innere Medizin 8, Schwerpunkt Kardiologie
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock, Zentrum Innere Medizin, Abteilung Kardiologie
city: Singen
country: Germany
facility: HBK Hegau-Bodensee Klinikum Singen
city: Straubing
country: Germany
facility: Barmherzige Brüder, Klinikum St. Elisabeth Straubing GmbH, II. Medizinische Klinik Innere Medizin, Kardiologie, Intensivmedizin, Pneumologie, Nephrologie und Angiologie
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
Study officials:
affiliation: LMU Klinikum
name: Steffen Massberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: LMU Klinikum
name: Konstantinos Rizas, MD
role: PRINCIPAL_INVESTIGATOR
References: