Anticoagulation for New-Onset Post-Operative Atrial Fibrillation After CABG (PACES)
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|ClinicalTrials.gov Identifier: NCT04045665|
Recruitment Status : Recruiting
First Posted : August 5, 2019
Last Update Posted : February 20, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Atrial Fibrillation Stroke Bleeding||Drug: Antiplatelet-only strategy Drug: Oral Anticoagulant plus background antiplatelet therapy||Phase 3|
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, 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 75-100 mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor)
- Antiplatelet-only strategy (control arm): with aspirin 75-100 mg 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 36 months. Study follow-up visits will be performed at 90 days and phone follow-up at 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 stroke risk score will also be determined.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||3200 participants|
|Intervention Model:||Parallel Assignment|
|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.|
|Masking:||None (Open Label)|
|Official Title:||Anticoagulation for New-Onset Post-Operative Atrial Fibrillation After CABG|
|Actual Study Start Date :||December 13, 2019|
|Estimated Primary Completion Date :||December 2022|
|Estimated Study Completion Date :||December 1, 2023|
Active Comparator: Antiplatelet Therapy
Drug: Antiplatelet-only strategy
Aspirin 75-100 mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor)
Active Comparator: Oral Anticoagulant
Drug: 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 75-100 mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor)
- Composite of death, stroke, TIA, MI, systemic arterial thromboembolism or venous thromboembolism (DVT and/or PE) [ Time Frame: up to 180 days after randomization ]Composite score of death, 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 [ Time Frame: 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)
- Net clinical benefit (NCB) [ Time Frame: 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 Stroke event [ Time Frame: 180 days after randomization ]
- Number of participants with TIA event [ Time Frame: 180 days after randomization ]
- Number of participants with MI event [ Time Frame: 180 days after randomization ]
- Number of participants with systematic arterial thromboembolism event [ Time Frame: 180 days after randomization ]
- Number of participants with venous thromboembolism event [ Time Frame: 180 days after randomization ]
- Number of cardiovascular mortalities [ Time Frame: up to 180 days after randomization ]
- Number of non-cardiovascular mortalities [ Time Frame: up to 180 days after randomization ]
- The incidence of BARC 2 bleeding at 90 days after randomization [ Time Frame: 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
- Number of cardiac arrhythmias [ Time Frame: 180 days after randomization ]Number of cardiac arrhythmias including recurrent symptomatic AF requiring medical attention
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04045665
|Contact: Ellen Moquete, RNfirstname.lastname@example.org|
|Principal Investigator:||Annetine C Gelijns, PhD||Icahn School of Medicine at Mount Sinai|
|Study Director:||Marc Gillinov, MD||The Cleveland Clinic|
|Study Director:||John Alexander, MD||Duke University|