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Anticoagulation for New-Onset Post-Operative Atrial Fibrillation After CABG (PACES)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04045665
Recruitment Status : Recruiting
First Posted : August 5, 2019
Last Update Posted : July 16, 2020
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Vanderbilt University Medical Center
Information provided by (Responsible Party):
Annetine Gelijns, Icahn School of Medicine at Mount Sinai

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.


Condition or disease Intervention/treatment Phase
Atrial Fibrillation Stroke Bleeding Drug: Antiplatelet-only strategy Drug: Oral Anticoagulant plus background antiplatelet therapy Phase 3

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, 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): 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 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.

Patients will be offered the option of having biospecimens collected for future research.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3200 participants
Allocation: Randomized
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)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Antiplatelet Therapy
Antiplatelet-only strategy
Drug: Antiplatelet-only strategy
Aspirin 75-325 mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor)

Active Comparator: Oral Anticoagulant
OAC-based strategy
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 75-325mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor)




Primary Outcome Measures :
  1. 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.

  2. 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)



Secondary Outcome Measures :
  1. 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.

  2. Number of participants with Stroke event [ Time Frame: 180 days after randomization ]
  3. Number of participants with TIA event [ Time Frame: 180 days after randomization ]
  4. Number of participants with MI event [ Time Frame: 180 days after randomization ]
  5. Number of participants with systematic arterial thromboembolism event [ Time Frame: 180 days after randomization ]
  6. Number of participants with venous thromboembolism event [ Time Frame: 180 days after randomization ]
  7. Number of cardiovascular mortalities [ Time Frame: up to 180 days after randomization ]
  8. Number of non-cardiovascular mortalities [ Time Frame: up to 180 days after randomization ]
  9. 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

  10. Number of cardiac arrhythmias [ Time Frame: 180 days after randomization ]
    Number of cardiac arrhythmias including recurrent symptomatic AF requiring medical attention



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 (including aortic, mitral, tricuspid or pulmonary)
  • Concomitant or prior surgery for AF during CABG
  • Closure of an atrial septal defect or of a patent foramen ovale during CABG
  • Stage IV or V chronic kidney disease (estimated glomerular filtration rate [eGFR]<30 mL/min/1.73m2)
  • 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

Information from the National Library of Medicine

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


Contacts
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Contact: Ellen Moquete, RN 212-659-9651 ellen.moquete@mountsinai.org

Locations
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Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
National Heart, Lung, and Blood Institute (NHLBI)
Vanderbilt University Medical Center
Investigators
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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
Additional Information:
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Responsible Party: Annetine Gelijns, Chair, Department of Population Health Science & Policy Edmond A. Guggenheim Professor of Health Policy Co-Director, InCHOIR, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT04045665    
Other Study ID Numbers: GCO 08-1078
2U01HL088942-12 ( U.S. NIH Grant/Contract )
First Posted: August 5, 2019    Key Record Dates
Last Update Posted: July 16, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Analytic Code
Time Frame: OtherDe-identified study data sets must be submitted to the designated NHLBI Program Official no later than 3 years after the end of the clinical activity (final patient follow-up, etc.) or 2 years after the main paper of the trial has been published, whichever comes first. Data are prepared by the study coordinating center and sent to the designated PO for review prior to release.
Access Criteria: Anyone who wishes to access the data.Any purpose.Data are available indefinitely at (Link to be included).
URL: https://biolincc.nhlbi.nih.gov/studies/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Annetine Gelijns, Icahn School of Medicine at Mount Sinai:
Anticoagulation
Antiplatelet Therapy
Post Operative Atrial Fibrillation
Additional relevant MeSH terms:
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Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Anticoagulants