Anticoagulation for New-Onset Post-Operative Atrial Fibrillation After CABG
- Conditions
- Atrial FibrillationStrokeBleeding
- Interventions
- Drug: Antiplatelet-only strategyDrug: Oral Anticoagulant plus background antiplatelet therapy
- Registration Number
- NCT04045665
- Lead Sponsor
- Icahn School of Medicine at Mount Sinai
- Brief Summary
The primary objective of this study is to evaluate the effectiveness (prevention of thromboembolic events) and safety (major bleeding) of adding oral anticoagulation (OAC) to background antiplatelet therapy in patients who develop new-onset post-operative atrial fibrillation (POAF) after isolated coronary artery bypass graft (CABG) surgery.
All patients with a qualifying POAF event, who decline randomization, will be offered the option of enrollment in a parallel registry that captures their baseline risk profile and their treatment strategy in terms of anticoagulants or antiplatelets received. These patients will also be asked to fill out a brief decliner survey.
- Detailed Description
This is a prospective, multicenter, open-label, randomized trial comparing OAC with no OAC (1:1 ratio) in patients who develop new-onset POAF after CABG. The primary effectiveness endpoint is the composite of death, ischemic stroke, transient ischemic attack (TIA), myocardial infarction (MI), systemic arterial thromboembolism or venous thromboembolism (VTE) at 90 days after randomization. The primary safety endpoint is BARC (Bleeding Academic Research Consortium) grade 3 or 5 bleeding at 90 days after randomization. The overall intent is to evaluate the trade-off in prevention of thromboembolic events versus an increase in bleeding.
Patients will be randomly assigned to the following treatment strategies:
* OAC-based strategy (experimental arm): OAC with vitamin K antagonist (VKA) with international normalized ratio (INR) target 2-3 or any approved direct oral anticoagulant (apixaban, rivaroxaban, edoxaban or dabigatran) in addition to background antiplatelet therapy with aspirin 75-325mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor)
* Antiplatelet-only strategy (control arm): single antiplatelet therapy with aspirin 75-325mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor)
The protocol-specified duration of anticoagulation is 90 days. Patients, who are randomized to the control arm and develop recurrent AF after 30 days, may be crossed-over to an OAC. Accrual is expected to take 60 months. Study follow-up visits will be performed at 90 days and phone follow-up at days 30, 60, and 180 days.
Data for patients enrolled in the registry will be ascertained from the local clinical site via a review of medical records. The baseline risk profile of registry patients (i.e., patients eligible but unwilling to be randomized) will be analyzed and compared to that of patients randomized in the trial. The usage of anticoagulant and antiplatelet therapies in the registry population overall and baseline CHA2DS2-VASC ischemic stroke risk score will also be determined.
Up to 500 patients will also be offered the option to participate in a digital health substudy which includes a wearable heart rhythm monitor device for 30 days post discharge.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 3200
- Patients of age ≥18 years who undergo isolated CABG for coronary artery disease
- POAF that persists for >60 minutes or is recurrent (more than one episode) within 7 days after the index CABG surgery
-
Clinical history of either permanent, persistent or paroxysmal atrial fibrillation
-
Any pre-existing clinical indication for long-term OAC
-
Any absolute contraindication to OAC
-
Planned use of post-operative dual antiplatelet therapy (DAPT)
a. This includes, but is not limited to, patients with recent PCI with drug-eluting or bare-metal stent.
-
Cardiogenic shock
-
Major perioperative complication* occurring between CABG and randomization
a. including, but not limited to, stroke, TIA, MI, major bleeding (BARC type 4 bleeding), severe sepsis, renal failure requiring dialysis, or need for reoperation due to bleeding (e.g. pericardial tamponade).
-
Concomitant left atrial appendage closure during CABG
-
Concomitant valve surgery during CABG or prior valve surgery (including aortic, mitral, tricuspid or pulmonary)
-
Concomitant mitral valve annuloplasty during CABG
-
Concomitant carotid artery endarterectomy during CABG
-
Concomitant aortic root replacement during CABG
-
Concomitant surgery for AF during CABG
-
Liver cirrhosis or Child-Pugh Class C chronic liver disease
-
Pharmacologic therapy with an investigational drug or device within 30-days prior to randomization or plan to enroll patient in an investigational drug or device trial during participation in this trial
-
Pregnancy at the time of randomization
-
Unable or unwilling to provide inform consent
-
Unable or unwilling to comply with the study treatment and follow-up
-
Existence of underlying disease that limits life expectancy to less than one year
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Antiplatelet Therapy Antiplatelet-only strategy Antiplatelet-only strategy Oral Anticoagulant Oral Anticoagulant plus background antiplatelet therapy OAC-based strategy
- Primary Outcome Measures
Name Time Method Composite of death, ischemic stroke, TIA, MI, systemic arterial thromboembolism or venous thromboembolism (DVT and/or PE) up to 180 days after randomization Composite score of death, ischemic stroke, transient ischemic attack (TIA), myocardial infarction (MI), systemic arterial thromboembolism or venous thromboembolism (deep venous thrombosis and/or pulmonary embolism). Composite score calculated by number of events.
Any BARC type 3 or 5 90 days after randomization The Bleeding Academic Research Consortium (BARC) - any type 3 or 5 bleeding thrombosis and/or pulmonary.
Type 3: a. Overt bleeding plus hemoglobin drop of 3 to \< 5 g/dL (provided hemoglobin drop is related to bleed); transfusion with overt bleeding
b. Overt bleeding plus hemoglobin drop \< 5 g/dL (provided hemoglobin drop is related to bleed); cardiac tamponade; bleeding requiring surgical intervention for control; bleeding requiring IV vasoactive agents
c. Intracranial hemorrhage confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision.
type 5: a. Probable fatal bleeding
b. Definite fatal bleeding (overt or autopsy or imaging confirmation)
- Secondary Outcome Measures
Name Time Method Net clinical benefit (NCB) 90 days after randomization Defined as the integration of the trial's primary effectiveness and safety endpoint to capture overall risk and benefit of anticoagulation. NCB will be assessed as a two-dimensional outcome with the observed NCB plotted versus effectiveness and safety, and a curve drawn. the confidence intervals will be compared to this curve.
Number of participants with Ischemic Stroke event 180 days after randomization Number of participants with MI event 180 days after randomization Number of participants with systematic arterial thromboembolism event 180 days after randomization Number of participants with TIA event 180 days after randomization Number of participants with venous thromboembolism event 180 days after randomization Number of cardiovascular mortalities up to 180 days after randomization Number of non-cardiovascular mortalities up to 180 days after randomization The incidence of BARC 2 bleeding at 90 after randomization 90 days after randomization BARC Type 2: Any clinically overt sign of hemorrhage that "is actionable" and requires diagnostic studies, hospitalization, or treatment by a health care professional
The incidence of BARC 2 bleeding at 180 days after randomization 180 days after randomization BARC Type 2: Any clinically overt sign of hemorrhage that "is actionable" and requires diagnostic studies, hospitalization, or treatment by a health care professional
Number of cardiac arrhythmias 180 days after randomization Number of cardiac arrhythmias including recurrent symptomatic or asymptomatic AF requiring medical attention
Trial Locations
- Locations (96)
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Ascension St. Vincent
🇺🇸Indianapolis, Indiana, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Duke University
🇺🇸Durham, North Carolina, United States
Royal Wolverhampton NHS Trust
🇬🇧Wolverhampton, England, United Kingdom
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Jersey Shore University Medical Center
🇺🇸Neptune, New Jersey, United States
University Medical Center Jena
🇩🇪Jena, Thuringia, Germany
Liverpool Heart and Chest Hospital NHS Foundation Trust
🇬🇧Liverpool, England, United Kingdom
Barts Health NHS Trust
🇬🇧London, England, United Kingdom
The Mount Sinai Hospital
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Northwell Health System
🇺🇸Great Neck, New York, United States
WakeMed
🇺🇸Raleigh, North Carolina, United States
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
University of Pittsburgh Medical Center
🇺🇸Hermitage, Pennsylvania, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny Health Network
🇺🇸Pittsburgh, Pennsylvania, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Baylor Research Institute
🇺🇸Plano, Texas, United States
Intermountain CV Research
🇺🇸Murray, Utah, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
University of Vermont
🇺🇸Burlington, Vermont, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Montreal Heart Institute
🇨🇦Montreal, Quebec, Canada
Sunnybrook Hospital
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier de l'Université de Montréal
🇨🇦Montreal, Quebec, Canada
Hôpital du Sacré-Cœur de Montréal
🇨🇦Montreal, Quebec, Canada
University Heart Center Hamburg
🇩🇪Berlin, Brandenburg, Germany
Toronto General Hospital
🇨🇦Toronto, Canada
Hôpital Laval
🇨🇦Quebec, Canada
Heart Center Leipzig
🇩🇪Berlin, Brandenburg, Germany
University Medical Center Göttingen
🇩🇪Göttingen, Lower Saxony, Germany
Clinic Bad Neustadt - Medical Center for Heart and Vascular Diseases
🇩🇪Bad Neustadt An Der Saale, Germany
HDZ-NRW Bad Oeynhausen
🇩🇪Bad Oeynhausen, Germany
Charité Berlin - Benjamin Franklin Campus
🇩🇪Berlin, Germany
University Hospital Bonn
🇩🇪Bonn, Germany
German Heart Center Berlin
🇩🇪Berlin, Germany
Charité Berlin - Rudolf Virchow Campus
🇩🇪Berlin, Germany
Frankfurt University Hospital
🇩🇪Frankfurt, Germany
Medical Center Braunschweig
🇩🇪Braunschweig, Germany
University Medical Center Heidelberg
🇩🇪Heidelberg, Germany
Heinrich Heine University Düsseldorf
🇩🇪Düsseldorf, Germany
University Medical Center Frankfurt
🇩🇪Frankfurt, Germany
University Medical Center Schleswig-Holstein Kiel
🇩🇪Kiel, Germany
University Medical Center Schleswig-Holstein Lübeck
🇩🇪Lübeck, Germany
Medical Center of the Ludwig-Maximilians-University Munich
🇩🇪Munich, Germany
University Hospital Magdeburg
🇩🇪Magdeburg, Germany
German Heart Center Munich
🇩🇪Munich, Germany
Imperial College Healthcare NHS Trust
🇬🇧London, England, United Kingdom
Royal Papworth Hospital NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
University Hospitals Bristol NHS Foundation Trust
🇬🇧Bristol, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
South Tees Hospitals NHS Foundation Trust
🇬🇧Middlesbrough, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
🇬🇧Sheffield, United Kingdom
University Hospital Southampton NHS Foundation Trust
🇬🇧Southampton, United Kingdom
University Hospitals Sussex NHS Foundation Trust
🇬🇧Worthing, United Kingdom
CHI St. Vincent, Arkansas
🇺🇸Little Rock, Arkansas, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Medical Center of Aurora
🇺🇸Aurora, Colorado, United States
Stanford University
🇺🇸Stanford, California, United States
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Lutheran Medical Center
🇺🇸Fort Wayne, Indiana, United States
Piedmont Healthcare Inc.
🇺🇸Atlanta, Georgia, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Maine Medical Center
🇺🇸Portland, Maine, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Suburban Hospital
🇺🇸Bethesda, Maryland, United States
Baystate Health
🇺🇸Springfield, Massachusetts, United States
Inova Health
🇺🇸Falls Church, Virginia, United States
University of Ottawa Heart Institute
🇨🇦Ottawa, Canada
Heart Center, University of Freiburg
🇩🇪Freiburg, Germany
Oxford University Hospitals NHS Foundation Trust
🇬🇧Oxford, United Kingdom
University Hospitals Plymouth NHS Trust
🇬🇧Plymouth, United Kingdom
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Western Connecticut Hospital Systems
🇺🇸Danbury, Connecticut, United States
Ascension St. John
🇺🇸Tulsa, Oklahoma, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University Hospitals of Leicester NHS Trust
🇬🇧Leicester, United Kingdom
Yale Medicine
🇺🇸New Haven, Connecticut, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
Mid America Health Institute
🇺🇸Kansas City, Missouri, United States
Ochsner Clinic
🇺🇸New Orleans, Louisiana, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Hull University Teaching Hospitals NHS Trust
🇬🇧Cottingham, United Kingdom
Blackpool Teaching Hospitals NHS Foundation Trust
🇬🇧Blackpool, United Kingdom