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

• Sponsor: Icahn School of Medicine at Mount Sinai (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04045665
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Vanderbilt University Medical Center (Other)
• Enrollment: 3,200
• Locations: 73
• Arms: 2
• Anticipated Duration (Months): 71.6
• Patients Per Site: 43.8
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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 4

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): 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 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.

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.

Study Design

• Study Type: Interventional
• Anticipated 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, the United Kingdom and Brazil..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..
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Anticoagulation for New-Onset Post-Operative Atrial Fibrillation After CABG
• Actual Study Start Date: Dec 13, 2019
• Anticipated Primary Completion Date: Dec 1, 2024
• Anticipated Study Completion Date: Dec 1, 2025

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

1. Composite of death, stroke, TIA, MI, systemic arterial thromboembolism or venous thromboembolism (DVT and/or PE) [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 [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) [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 [180 days after randomization]

3. Number of participants with TIA event [180 days after randomization]

4. Number of participants with MI event [180 days after randomization]

5. Number of participants with systematic arterial thromboembolism event [180 days after randomization]

6. Number of participants with venous thromboembolism event [180 days after randomization]

7. Number of cardiovascular mortalities [up to 180 days after randomization]

8. Number of non-cardiovascular mortalities [up to 180 days after randomization]

9. The incidence of BARC 2 bleeding at 90 days 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

10. Number of cardiac arrhythmias [180 days after randomization]

    Number of cardiac arrhythmias including recurrent symptomatic AF requiring medical attention

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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)

1. 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

1. 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

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CHI St. Vincent, Arkansas	Little Rock	Arkansas	United States	72205
2	University of Southern California	Los Angeles	California	United States	90033
3	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
4	Stanford University	Stanford	California	United States	94305
5	Medical Center of Aurora	Aurora	Colorado	United States	80012
6	Western Connecticut Hospital Systems	Danbury	Connecticut	United States	06810
7	Yale New Haven	New Haven	Connecticut	United States	06520-8039
8	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
9	Emory University	Atlanta	Georgia	United States	30308
10	Piedmont Healthcare Inc.	Atlanta	Georgia	United States	30309
11	Lutheran Medical Center	Fort Wayne	Indiana	United States	46825
12	Indiana University	Indianapolis	Indiana	United States	46202
13	Ascension St. Vincent	Indianapolis	Indiana	United States	46260
14	Ochsner Clinic	New Orleans	Louisiana	United States	70121
15	Maine Medical Center	Portland	Maine	United States	04102
16	University of Maryland	Baltimore	Maryland	United States	21201
17	Suburban Hospital	Bethesda	Maryland	United States	20814
18	Massachusetts Genera Hospital	Boston	Massachusetts	United States	02114
19	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
20	Boston Medical Center	Boston	Massachusetts	United States	02118
21	Baystate Health	Springfield	Massachusetts	United States	01199
22	University of Michigan	Ann Arbor	Michigan	United States	48109
23	Mayo Clinic	Rochester	Minnesota	United States	55905
24	Mid America Health Institute	Kansas City	Missouri	United States	64111
25	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03766
26	Montefiore Medical Center	Bronx	New York	United States	10467
27	Northwell Health System	Great Neck	New York	United States	11023
28	The Mount Sinai Hospital	New York	New York	United States	10029
29	Columbia University Medical Center	New York	New York	United States	10032
30	Duke University	Durham	North Carolina	United States	27710
31	East Carolina University	Greenville	North Carolina	United States	27858
32	WakeMed	Raleigh	North Carolina	United States	27610
33	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
34	Ohio State University Medical Center	Columbus	Ohio	United States	43210
35	Ascension St. John	Tulsa	Oklahoma	United States	74103
36	University of Pittsburgh Medical Center	Hermitage	Pennsylvania	United States	16148
37	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
38	Allegheny Health Network	Pittsburgh	Pennsylvania	United States	15212
39	Baylor College of Medicine	Houston	Texas	United States	77030
40	Baylor Research Institute	Plano	Texas	United States	75093
41	Intermountain CV Research	Murray	Utah	United States	84107
42	University of Utah	Salt Lake City	Utah	United States	84112
43	University of Vermont	Burlington	Vermont	United States	05401
44	University of Virginia Health System	Charlottesville	Virginia	United States	22908
45	Inova Health	Falls Church	Virginia	United States	22042
46	West Virginia University	Morgantown	West Virginia	United States	26506
47	University of Wisconsin	Madison	Wisconsin	United States	53792
48	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G2B7
49	London Health Sciences Centre	London	Ontario	Canada	N6A 5A5
50	University of Ottawa Heart Institute	Ottawa	Ontario	Canada	K1Y 4W7
51	Sunnybrook Hospital	Toronto	Ontario	Canada	M4N 3M5
52	Toronto General Hospital	Toronto	Ontario	Canada	M5B 1W8
53	Montreal Heart Institute	Montreal	Quebec	Canada	H1T 1C8
54	Centre Hospitalier de l'Université de Montréal	Montreal	Quebec	Canada	H2W 1T8
55	Hôpital du Sacré-Cœur de Montréal	Montreal	Quebec	Canada	H4J 1C5
56	Hôpital Laval	Quebec		Canada	G1V 4G5
57	University Heart Center Hamburg	Berlin	Brandenburg	Germany	11353
58	Heart Center Leipzig	Berlin	Brandenburg	Germany	13347
59	University Medical Center Göttingen	Göttingen	Lower Saxony	Germany
60	University Medical Center Jena	Jena	Thuringia	Germany
61	Clinic Bad Neustadt - Medical Center for Heart and Vascular Diseases	Bad Neustadt An Der Saale		Germany
62	HDZ-NRW Bad Oeynhausen	Bad Oeynhausen		Germany
63	Charité Berlin - Benjamin Franklin Campus	Berlin		Germany
64	Charité Berlin - Rudolf Virchow Campus	Berlin		Germany
65	German Heart Center Berlin	Berlin		Germany
66	Medical Center Braunschweig	Braunschweig		Germany
67	University Medical Center Frankfurt	Frankfurt		Germany
68	Heart Center, University of Freiburg	Freiburg		Germany
69	University Medical Center Heidelberg	Heidelberg		Germany
70	University Medical Center Schleswig-Holstein Kiel	Kiel		Germany
71	University Medical Center Schleswig-Holstein Lübeck	Lübeck		Germany
72	German Heart Center Munich	Munich		Germany
73	Medical Center of the Ludwig-Maximilians-University Munich	Munich		Germany

Sponsors and Collaborators

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

Investigators

• 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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The Cardiothoracic Surgical Trials Network

Publications

None provided.

• 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
• First Posted: Aug 5, 2019
• Last Update Posted: Aug 23, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by 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: Anticoagulation; Antiplatelet Therapy; Post Operative Atrial Fibrillation
• Additional relevant MeSH terms: Atrial Fibrillation; Anticoagulants

Study Results

No Results Posted as of Aug 23, 2022