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.
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.
Brief Title
Anticoagulation for New-Onset Post-Operative Atrial Fibrillation After CABG
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.
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
212-659-9651
Central Contact Email
ellen.moquete@mountsinai.org
Completion Date
Completion Date Type
Estimated
Conditions
Atrial Fibrillation
Stroke
Bleeding
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Keywords
Anticoagulation
Antiplatelet Therapy
Post Operative Atrial Fibrillation
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04045665
Org Class
Other
Org Full Name
Icahn School of Medicine at Mount Sinai
Org Study Id
GCO 08-1078
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Anticoagulation for New-Onset Post-Operative Atrial Fibrillation After CABG
Primary Outcomes
Outcome Description
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.
Outcome Measure
Composite of death, ischemic stroke, TIA, MI, systemic arterial thromboembolism or venous thromboembolism (DVT and/or PE)
Outcome Time Frame
up to 180 days after randomization
Outcome Description
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)
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)
Outcome Measure
Any BARC type 3 or 5
Outcome Time Frame
90 days after randomization
Secondary Ids
Secondary Id
2U01HL088942-12
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
90 days after randomization
Outcome Measure
Net clinical benefit (NCB)
Outcome Time Frame
180 days after randomization
Outcome Measure
Number of participants with Ischemic Stroke event
Outcome Time Frame
180 days after randomization
Outcome Measure
Number of participants with TIA event
Outcome Time Frame
180 days after randomization
Outcome Measure
Number of participants with MI event
Outcome Time Frame
180 days after randomization
Outcome Measure
Number of participants with systematic arterial thromboembolism event
Outcome Time Frame
180 days after randomization
Outcome Measure
Number of participants with venous thromboembolism event
Outcome Time Frame
up to 180 days after randomization
Outcome Measure
Number of cardiovascular mortalities
Outcome Time Frame
up to 180 days after randomization
Outcome Measure
Number of non-cardiovascular mortalities
Outcome Description
BARC Type 2: Any clinically overt sign of hemorrhage that "is actionable" and requires diagnostic studies, hospitalization, or treatment by a health care professional
Outcome Time Frame
90 days after randomization
Outcome Measure
The incidence of BARC 2 bleeding at 90 after randomization
Outcome Description
BARC Type 2: Any clinically overt sign of hemorrhage that "is actionable" and requires diagnostic studies, hospitalization, or treatment by a health care professional
Outcome Time Frame
180 days after randomization
Outcome Measure
The incidence of BARC 2 bleeding at 180 days after randomization
Outcome Description
Number of cardiac arrhythmias including recurrent symptomatic or asymptomatic AF requiring medical attention
Outcome Time Frame
180 days after randomization
Outcome Measure
Number of cardiac arrhythmias
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Daniel Goldstein
Investigator Email
dgoldste@montefiore.org
Investigator Department
Cardiovascular & Thoracic Surgery
Investigator Sponsor Organization
Einstein
Study Department
Cardiovascular and Thoracic Surgery
Study Division
Vascular Surgery
Categories Mesh Debug
Heart/Cardiovascular --- ATRIAL FIBRILLATION
Brain, Spinal Cord & Nervous System --- STROKE
Blood Disorders --- HEMORRHAGE
Heart/Cardiovascular --- ARRHYTHMIAS, CARDIAC
Brain, Spinal Cord & Nervous System --- HEART DISEASES
Heart/Cardiovascular --- HEART DISEASES
Blood Disorders --- CARDIOVASCULAR DISEASES
Blood & Bone Marrow Cancers --- CARDIOVASCULAR DISEASES
Heart/Cardiovascular --- CARDIOVASCULAR DISEASES
Brain, Spinal Cord & Nervous System --- CEREBROVASCULAR DISORDERS
Alzheimer's --- BRAIN DISEASES
Brain, Spinal Cord & Nervous System --- BRAIN DISEASES
Brain, Spine & Nerve Cancers --- BRAIN DISEASES
Alzheimer's --- CENTRAL NERVOUS SYSTEM DISEASES
Brain, Spinal Cord & Nervous System --- CENTRAL NERVOUS SYSTEM DISEASES
Brain, Spine & Nerve Cancers --- CENTRAL NERVOUS SYSTEM DISEASES
Brain, Spinal Cord & Nervous System --- NERVOUS SYSTEM DISEASES
Brain, Spine & Nerve Cancers --- NERVOUS SYSTEM DISEASES
Blood & Bone Marrow Cancers --- VASCULAR DISEASES
Heart/Cardiovascular --- VASCULAR DISEASES
MeSH Terms
ATRIAL FIBRILLATION
STROKE
HEMORRHAGE
ARRHYTHMIAS, CARDIAC
HEART DISEASES
CARDIOVASCULAR DISEASES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
CEREBROVASCULAR DISORDERS
BRAIN DISEASES
CENTRAL NERVOUS SYSTEM DISEASES
NERVOUS SYSTEM DISEASES
VASCULAR DISEASES
ANTICOAGULANTS
HEMATOLOGIC AGENTS
THERAPEUTIC USES
PHARMACOLOGIC ACTIONS
CHEMICAL ACTIONS AND USES