Anticoagulation for New-Onset Post-Operative Atrial Fibrillation After CABG

Stroke Clinical Trial

— PACES  

Official title:

Anticoagulation for New-Onset Post-Operative Atrial Fibrillation After CABG

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04045665
• Other study ID #: GCO 08-1078
• Secondary ID: 2U01HL088942-12
• Status: Recruiting
• Phase: Phase 3
• Start date: December 13, 2019
• Est. completion date: June 30, 2025

Study information

• Verified date: November 2023
• Source: Icahn School of Medicine at Mount Sinai
• Contact: Ellen Moquete, RN
• Phone: 212-659-9651
• Email: ellen.moquete[@]mountsinai.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 3200
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Bleeding
• Stroke

Intervention

Drug:
• Antiplatelet-only strategy
Aspirin 75-325 mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor)
• Oral Anticoagulant plus background antiplatelet therapy
OAC with vitamin K antagonist (VKA) with international normalized ratio (INR) target 2-3 or any approved direct oral anticoagulant OR apixaban, rivaroxaban, edoxaban or dabigatran) in addition to background antiplatelet therapy with aspirin 75-325mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor)

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	Centre Hospitalier de l'Université de Montréal	Montreal	Quebec
Canada	Hôpital du Sacré-Cœur de Montréal	Montreal	Quebec
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	University of Ottawa Heart Institute	Ottawa
Canada	Hôpital Laval	Quebec
Canada	Sunnybrook Hospital	Toronto	Ontario
Canada	Toronto General Hospital	Toronto
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	Charité Berlin - Rudolf Virchow Campus	Berlin
Germany	German Heart Center Berlin	Berlin
Germany	Heart Center Leipzig	Berlin	Brandenburg
Germany	University Heart Center Hamburg	Berlin	Brandenburg
Germany	University Hospital Bonn	Bonn
Germany	Medical Center Braunschweig	Braunschweig
Germany	University Medical Center Frankfurt	Frankfurt
Germany	Heart Center, University of Freiburg	Freiburg
Germany	University Medical Center Göttingen	Göttingen	Lower Saxony
Germany	University Medical Center Heidelberg	Heidelberg
Germany	University Medical Center Jena	Jena	Thuringia
Germany	University Medical Center Schleswig-Holstein Kiel	Kiel
Germany	University Medical Center Schleswig-Holstein Lübeck	Lübeck
Germany	University Hospital Magdeburg	Magdeburg
Germany	German Heart Center Munich	Munich
Germany	Medical Center of the Ludwig-Maximilians-University Munich	Munich
United Kingdom	University Hospitals Bristol NHS Foundation Trust	Bristol
United Kingdom	Hull University Teaching Hospitals NHS Trust	Cottingham
United Kingdom	Liverpool Heart and Chest Hospital NHS Foundation Trust	Liverpool	England
United Kingdom	Barts Health NHS Trust	London	England
United Kingdom	Imperial College Healthcare NHS Trust	London	England
United Kingdom	South Tees Hospitals NHS Foundation Trust	Middlesbrough
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Oxford
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton
United Kingdom	Royal Wolverhampton NHS Trust	Wolverhampton	England
United Kingdom	University Hospitals Sussex NHS Foundation Trust	Worthing
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Piedmont Healthcare Inc.	Atlanta	Georgia
United States	Medical Center of Aurora	Aurora	Colorado
United States	Johns Hopkins	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Suburban Hospital	Bethesda	Maryland
United States	Boston Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	University of Vermont	Burlington	Vermont
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Western Connecticut Hospital Systems	Danbury	Connecticut
United States	Duke University	Durham	North Carolina
United States	Inova Health	Falls Church	Virginia
United States	Lutheran Medical Center	Fort Wayne	Indiana
United States	Northwell Health System	Great Neck	New York
United States	East Carolina University	Greenville	North Carolina
United States	University of Pittsburgh Medical Center	Hermitage	Pennsylvania
United States	Baylor College of Medicine	Houston	Texas
United States	Ascension St. Vincent	Indianapolis	Indiana
United States	Indiana University	Indianapolis	Indiana
United States	Mid America Health Institute	Kansas City	Missouri
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	CHI St. Vincent, Arkansas	Little Rock	Arkansas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	West Virginia University	Morgantown	West Virginia
United States	Intermountain CV Research	Murray	Utah
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Yale Medicine	New Haven	Connecticut
United States	Ochsner Clinic	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	The Mount Sinai Hospital	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Allegheny Health Network	Pittsburgh	Pennsylvania
United States	Baylor Research Institute	Plano	Texas
United States	Maine Medical Center	Portland	Maine
United States	WakeMed	Raleigh	North Carolina
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	Baystate Health	Springfield	Massachusetts
United States	Stanford University	Stanford	California
United States	Ascension St. John	Tulsa	Oklahoma
United States	MedStar Washington Hospital Center	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	National Heart, Lung, and Blood Institute (NHLBI), Vanderbilt University Medical Center

Countries where clinical trial is conducted

United States,  Canada,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of death, ischemic stroke, TIA, MI, systemic arterial thromboembolism or venous thromboembolism (DVT and/or PE)	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.	up to 180 days after randomization
Primary	Any BARC type 3 or 5	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)	90 days after randomization
Secondary	Net clinical benefit (NCB)	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.	90 days after randomization
Secondary	Number of participants with Ischemic Stroke event		180 days after randomization
Secondary	Number of participants with TIA event		180 days after randomization
Secondary	Number of participants with MI event		180 days after randomization
Secondary	Number of participants with systematic arterial thromboembolism event		180 days after randomization
Secondary	Number of participants with venous thromboembolism event		180 days after randomization
Secondary	Number of cardiovascular mortalities		up to 180 days after randomization
Secondary	Number of non-cardiovascular mortalities		up to 180 days after randomization
Secondary	The incidence of BARC 2 bleeding at 90 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	90 days after randomization
Secondary	The incidence of BARC 2 bleeding at 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	180 days after randomization
Secondary	Number of cardiac arrhythmias	Number of cardiac arrhythmias including recurrent symptomatic or asymptomatic AF requiring medical attention	180 days after randomization

External Links

•   The Cardiothoracic Surgical Trials Network