Atrial Fibrillation, Bleeding, Stroke
Conditions
Keywords
Anticoagulation, Antiplatelet Therapy, Post Operative Atrial Fibrillation
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.
Interventions
DRUGAntiplatelet-only strategy
Aspirin 75-325 mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor)
DRUGOral 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)
Sponsors
Icahn School of Medicine at Mount Sinai
National Heart, Lung, and Blood Institute (NHLBI)
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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..
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 TIA 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 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 |
Countries
Brazil, Canada, Germany, United Kingdom, United States
Contacts
CONTACTJonathan Hupf
PRINCIPAL_INVESTIGATORAnnetine C Gelijns, PhD
Icahn School of Medicine at Mount Sinai
STUDY_DIRECTORMarc Gillinov, MD
The Cleveland Clinic
STUDY_DIRECTORJohn Alexander, MD
Duke University
Outcome results
None listed