Clinical trial NCT04045665: Anticoagulation for New-Onset Post-Operative Atrial Fibrillation After CABG
Official title: Anticoagulation for New-Onset Post-Operative Atrial Fibrillation After CABG
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Atrial Fibrillation
Stroke
Bleeding
Keywords: Anticoagulation
Antiplatelet Therapy
Post Operative Atrial Fibrillation
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Vanderbilt University Medical Center
First posted: 2019-08-05
Enrollment: 3200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multicenter randomized clinical trial comparing OAC to no-OAC in addition to concomitant antiplatelet therapy in 3,200 eligible patients who develop POAF after isolated CABG. The trial will be conducted by the Cardiothoracic Surgical Trials Network (CTSN), the German Society for Thoracic and Cardiovascular Surgery (DGTHG) and other European sites, the United Kingdom and Brazil..
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Composite of death, ischemic stroke, TIA, MI, systemic arterial thromboembolism or venous thromboembolism (DVT and/or PE)
timeFrame: up to 180 days after randomization
measure: Any BARC type 3 or 5
timeFrame: 90 days after randomization
Secondary outcomes:
measure: Net clinical benefit (NCB)
timeFrame: 90 days after randomization
measure: Number of participants with Ischemic Stroke event
timeFrame: 180 days after randomization
measure: Number of participants with TIA event
timeFrame: 180 days after randomization
measure: Number of participants with MI event
timeFrame: 180 days after randomization
measure: Number of participants with systematic arterial thromboembolism event
timeFrame: 180 days after randomization
measure: Number of participants with venous thromboembolism event
timeFrame: 180 days after randomization
measure: Number of cardiovascular mortalities
timeFrame: up to 180 days after randomization
measure: Number of non-cardiovascular mortalities
timeFrame: up to 180 days after randomization
measure: The incidence of BARC 2 bleeding at 90 after randomization
timeFrame: 90 days after randomization
measure: The incidence of BARC 2 bleeding at 180 days after randomization
timeFrame: 180 days after randomization
measure: Number of cardiac arrhythmias
timeFrame: 180 days after randomization
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: CHI St. Vincent, Arkansas
state: Arkansas
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Medical Center of Aurora
state: Colorado
city: Danbury
country: United States
facility: Western Connecticut Hospital Systems
state: Connecticut
city: New Haven
country: United States
facility: Yale Medicine
state: Connecticut
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Healthcare Inc.
state: Georgia
city: Fort Wayne
country: United States
facility: Lutheran Medical Center
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Indianapolis
country: United States
facility: Ascension St. Vincent
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Clinic
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Bethesda
country: United States
facility: Suburban Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Health
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Mid America Health Institute
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Great Neck
country: United States
facility: Northwell Health System
state: New York
city: New York
country: United States
facility: The Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Raleigh
country: United States
facility: WakeMed
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Tulsa
country: United States
facility: Ascension St. John
state: Oklahoma
city: Hermitage
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Plano
country: United States
facility: Baylor Research Institute
state: Texas
city: Murray
country: United States
facility: Intermountain CV Research
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Falls Church
country: United States
facility: Inova Health
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
city: Montreal
country: Canada
facility: Hôpital du Sacré-Cœur de Montréal
state: Quebec
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
city: Quebec
country: Canada
facility: Hôpital Laval
city: Toronto
country: Canada
facility: Toronto General Hospital
city: Berlin
country: Germany
facility: University Heart Center Hamburg
state: Brandenburg
city: Berlin
country: Germany
facility: Heart Center Leipzig
state: Brandenburg
city: Göttingen
country: Germany
facility: University Medical Center Göttingen
state: Lower Saxony
city: Jena
country: Germany
facility: University Medical Center Jena
state: Thuringia
city: Bad Neustadt An Der Saale
country: Germany
facility: Clinic Bad Neustadt - Medical Center for Heart and Vascular Diseases
city: Bad Oeynhausen
country: Germany
facility: HDZ-NRW Bad Oeynhausen
city: Berlin
country: Germany
facility: Charité Berlin - Benjamin Franklin Campus
city: Berlin
country: Germany
facility: Charité Berlin - Rudolf Virchow Campus
city: Berlin
country: Germany
facility: German Heart Center Berlin
city: Bonn
country: Germany
facility: University Hospital Bonn
city: Braunschweig
country: Germany
facility: Medical Center Braunschweig
city: Düsseldorf
country: Germany
facility: Heinrich Heine University Düsseldorf
city: Frankfurt
country: Germany
facility: Frankfurt University Hospital
city: Frankfurt
country: Germany
facility: University Medical Center Frankfurt
city: Freiburg
country: Germany
facility: Heart Center, University of Freiburg
city: Heidelberg
country: Germany
facility: University Medical Center Heidelberg
city: Kiel
country: Germany
facility: University Medical Center Schleswig-Holstein Kiel
city: Lübeck
country: Germany
facility: University Medical Center Schleswig-Holstein Lübeck
city: Magdeburg
country: Germany
facility: University Hospital Magdeburg
city: Munich
country: Germany
facility: German Heart Center Munich
city: Munich
country: Germany
facility: Medical Center of the Ludwig-Maximilians-University Munich
city: Liverpool
country: United Kingdom
facility: Liverpool Heart and Chest Hospital NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: Barts Health NHS Trust
state: England
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
state: England
city: Wolverhampton
country: United Kingdom
facility: Royal Wolverhampton NHS Trust
state: England
city: Blackpool
country: United Kingdom
facility: Blackpool Teaching Hospitals NHS Foundation Trust
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital NHS Foundation Trust
city: Cottingham
country: United Kingdom
facility: Hull University Teaching Hospitals NHS Trust
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
city: Middlesbrough
country: United Kingdom
facility: South Tees Hospitals NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
city: Worthing
country: United Kingdom
facility: University Hospitals Sussex NHS Foundation Trust
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Annetine C Gelijns, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Marc Gillinov, MD
role: STUDY_DIRECTOR
affiliation: Duke University
name: John Alexander, MD
role: STUDY_DIRECTOR
References:
citation: Taha A, Nielsen SJ, Bergfeldt L, Ahlsson A, Friberg L, Bjorck S, Franzen S, Jeppsson A. New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting and Long-Term Outcome: A Population-Based Nationwide Study From the SWEDEHEART Registry. J Am Heart Assoc. 2021 Jan 5;10(1):e017966. doi: 10.1161/JAHA.120.017966. Epub 2020 Nov 30.