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Apixaban Versus Warfarin for the Management of Post-operative Atrial Fibrillation

Primary Purpose

Coronary Artery Bypass Grafting, Postoperative Atrial Fibrilation, Stroke

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Apixaban
Warfarin
Sponsored by
Sanford Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Coronary Artery Bypass Grafting focused on measuring apixaban, anticoagulant, CABG, thrombosis, fibrillation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Signed Written Informed Consent
  • Patients diagnosed with new-onset persistent or recurrent atrial fibrillation after isolated CABG surgery. Persistent atrial fibrillation is defined as an episode of >12 hours. Recurrent atrial fibrillation is defined as two or more episodes of atrial fibrillation lasting longer than 30 minutes.
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug. Patients undergoing isolated CABG must have this tested and documented prior to the procedure, and this will be verified prior to randomization.
  • Women must not be breastfeeding.
  • WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s): 30 days of treatment plus 5 half-lives of study drug Apixaban (3 days) or warfarin (8 days) plus 30 days (duration of ovulatory cycle) for a total of 38 days post-treatment completion.
  • Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s): 30 days of treatment plus 5 half-lives of study drug Apixaban (3 days) or warfarin (8 days) plus 90 days (duration of sperm turnover) for a total of 98 days post-treatment completion.

Exclusion Criteria:

  • Atrial fibrillation due to a reversible cause other than recent surgery
  • Patients diagnosed with persistent or paroxysmal atrial fibrillation chronically before undergoing surgery
  • Patients with mechanical heart valves
  • Patients currently experiencing active bleeding precluding initialization of anticoagulation therapy in the opinion of their managing physician, or with increased bleeding risk (as determined by the attending surgeon) believed to be a contraindication to anticoagulation at the time of randomization Planned major surgery requiring stoppage of anticoagulation therapy during trial period
  • Stroke within the previous 7 days
  • Moderate or severe mitral stenosis
  • Conditions other than atrial fibrillation that required anticoagulation (prosthetic mechanical heart valve)
  • Patients taking warfarin, apixaban, rivaroxaban, dabigatran, edoxaban, clopidogrel, ticagrelor, or enoxaparin at home for any indication in the 15 days prior to surgery
  • Patients requiring the use of clopidogrel or ticagrelor during the study period
  • Severe renal insufficiency (serum creatinine level of >2.5 mg/dL or CrCL<25 ml/min) for consecutive measurements
  • Allergies to warfarin or apixaban, or components of warfarin or apixaban

Sites / Locations

  • Sanford Health

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Apixaban

Warfarin

Arm Description

Apixaban is to be dosed at 5 mg by mouth twice daily, except in the case of the criteria listed below in "dose modifications". The duration of therapy will be at least 30 days. The patient's physician may determine that anticoagulation therapy should be continued after the study period, based on their examination of the patient at the 30-day post-operative examination.

While patients are hospitalized, warfarin will be dosed daily, with daily INR monitoring per hospital protocol. Daily doses may vary from 0.5mg to 15mg by mouth, as determined by patient specific factors such as patient size, hepatic function, INR, concomitant medications, diet, or other factors. Based on these factors or others not listed, there may also be days in which the patient is prescribed to not get does not receive a dose of warfarin. After discharge from the hospital, warfarin dosing will be subsequently managed by an anticoagulation clinic, per established protocols. All patients will have a goal INR of 2-3 during the duration of the study. The duration of therapy will be at least 30 days. The patient's physician may determine that anticoagulation therapy should be continued after the study period, based on their examination of the patient at the 30-day post-operative examination.

Outcomes

Primary Outcome Measures

Number of Participants With Strokes
Efficacy will be measured by the freedom from stroke during the study period. Events relating to stroke will be adjudicated using pre-determined definitions by independent committee members that remain blinded to the patient's treatment arm.
Number of Participants With Thromboembolytic Events
Efficacy will be measured by the freedom from thromboembolytic events during the study period. Events relating to thromboembolytic events will be adjudicated using pre-determined definitions by independent committee members that remain blinded to the patient's treatment arm.

Secondary Outcome Measures

Units of Blood Given After Initiation of Anticoagulation Medication
Units of blood or blood products given after the first dose of anticoagulation.
Total Post-operative Length of Stay
This will be measured from the date/time of the end of the subject's surgery until the date/time of the patient's discharge from the hospital. This will be measured in hours, to the nearest tenth of an hour.
Time in Therapeutic Range of INR, if on Warfarin
Time in therapeutic range of INR, if on warfarin, (eg. 2-3), measured as a percentage and defined for each patient using the Rosendaal equation

Full Information

First Posted
August 30, 2016
Last Updated
December 28, 2020
Sponsor
Sanford Health
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT02889562
Brief Title
Apixaban Versus Warfarin for the Management of Post-operative Atrial Fibrillation
Official Title
Apixaban Versus Warfarin for the Management of Post-operative Atrial Fibrillation: a Prospective, Controlled, Randomized Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
September 2016 (undefined)
Primary Completion Date
May 11, 2019 (Actual)
Study Completion Date
May 11, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanford Health
Collaborators
Bristol-Myers Squibb

4. Oversight

5. Study Description

Brief Summary
In this open-label, prospective, randomized pilot study, patients who develop atrial fibrillation after isolated coronary artery bypass grafting surgery will be identified. Patients with persistent atrial fibrillation (>12 hours) or recurrent sustained atrial fibrillation (>2 episodes of atrial fibrillation lasting longer than 30 minutes) will be candidates for inclusion. Upon meeting study inclusion and exclusion criteria, and after informed consent, patients will be randomized to either the standard of care (warfarin per protocol) or apixaban arms of the trial. Routine postoperative care after CABG will occur in both groups. Upon discharge, anticoagulation in both groups will be managed by the anticoagulation clinic. Patients will be followed for 30 days after surgery.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Bypass Grafting, Postoperative Atrial Fibrilation, Stroke, Systemic Embolism, Deep Venous Thrombosis
Keywords
apixaban, anticoagulant, CABG, thrombosis, fibrillation

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Apixaban
Arm Type
Active Comparator
Arm Description
Apixaban is to be dosed at 5 mg by mouth twice daily, except in the case of the criteria listed below in "dose modifications". The duration of therapy will be at least 30 days. The patient's physician may determine that anticoagulation therapy should be continued after the study period, based on their examination of the patient at the 30-day post-operative examination.
Arm Title
Warfarin
Arm Type
Active Comparator
Arm Description
While patients are hospitalized, warfarin will be dosed daily, with daily INR monitoring per hospital protocol. Daily doses may vary from 0.5mg to 15mg by mouth, as determined by patient specific factors such as patient size, hepatic function, INR, concomitant medications, diet, or other factors. Based on these factors or others not listed, there may also be days in which the patient is prescribed to not get does not receive a dose of warfarin. After discharge from the hospital, warfarin dosing will be subsequently managed by an anticoagulation clinic, per established protocols. All patients will have a goal INR of 2-3 during the duration of the study. The duration of therapy will be at least 30 days. The patient's physician may determine that anticoagulation therapy should be continued after the study period, based on their examination of the patient at the 30-day post-operative examination.
Intervention Type
Drug
Intervention Name(s)
Apixaban
Other Intervention Name(s)
Eliquis
Intervention Description
Study arm that patient can be randomized to. Apixaban is a novel, orally active, potent, direct selective inhibitor of coagulation FXa that directly and reversibly binds to the active site of FXa and exerts anticoagulant and antithrombotic effects by diminishing the conversion of prothrombin to thrombin.
Intervention Type
Drug
Intervention Name(s)
Warfarin
Other Intervention Name(s)
Coumadin
Intervention Description
Study arm that patient can be randomized to. Warfarin therapy has been the mainstay of therapy for patients with POAF. While the duration of therapy is usually short (3-4 weeks), complications of anticoagulation do occur. Additionally, warfarin therapy for POAF is associated with increased length of stay, need for monitoring, and bleeding complications.
Primary Outcome Measure Information:
Title
Number of Participants With Strokes
Description
Efficacy will be measured by the freedom from stroke during the study period. Events relating to stroke will be adjudicated using pre-determined definitions by independent committee members that remain blinded to the patient's treatment arm.
Time Frame
30 days
Title
Number of Participants With Thromboembolytic Events
Description
Efficacy will be measured by the freedom from thromboembolytic events during the study period. Events relating to thromboembolytic events will be adjudicated using pre-determined definitions by independent committee members that remain blinded to the patient's treatment arm.
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Units of Blood Given After Initiation of Anticoagulation Medication
Description
Units of blood or blood products given after the first dose of anticoagulation.
Time Frame
30 days
Title
Total Post-operative Length of Stay
Description
This will be measured from the date/time of the end of the subject's surgery until the date/time of the patient's discharge from the hospital. This will be measured in hours, to the nearest tenth of an hour.
Time Frame
30 days
Title
Time in Therapeutic Range of INR, if on Warfarin
Description
Time in therapeutic range of INR, if on warfarin, (eg. 2-3), measured as a percentage and defined for each patient using the Rosendaal equation
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed Written Informed Consent Patients diagnosed with new-onset persistent or recurrent atrial fibrillation after isolated CABG surgery. Persistent atrial fibrillation is defined as an episode of >12 hours. Recurrent atrial fibrillation is defined as two or more episodes of atrial fibrillation lasting longer than 30 minutes. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug. Patients undergoing isolated CABG must have this tested and documented prior to the procedure, and this will be verified prior to randomization. Women must not be breastfeeding. WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s): 30 days of treatment plus 5 half-lives of study drug Apixaban (3 days) or warfarin (8 days) plus 30 days (duration of ovulatory cycle) for a total of 38 days post-treatment completion. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s): 30 days of treatment plus 5 half-lives of study drug Apixaban (3 days) or warfarin (8 days) plus 90 days (duration of sperm turnover) for a total of 98 days post-treatment completion. Exclusion Criteria: Atrial fibrillation due to a reversible cause other than recent surgery Patients diagnosed with persistent or paroxysmal atrial fibrillation chronically before undergoing surgery Patients with mechanical heart valves Patients currently experiencing active bleeding precluding initialization of anticoagulation therapy in the opinion of their managing physician, or with increased bleeding risk (as determined by the attending surgeon) believed to be a contraindication to anticoagulation at the time of randomization Planned major surgery requiring stoppage of anticoagulation therapy during trial period Stroke within the previous 7 days Moderate or severe mitral stenosis Conditions other than atrial fibrillation that required anticoagulation (prosthetic mechanical heart valve) Patients taking warfarin, apixaban, rivaroxaban, dabigatran, edoxaban, clopidogrel, ticagrelor, or enoxaparin at home for any indication in the 15 days prior to surgery Patients requiring the use of clopidogrel or ticagrelor during the study period Severe renal insufficiency (serum creatinine level of >2.5 mg/dL or CrCL<25 ml/min) for consecutive measurements Allergies to warfarin or apixaban, or components of warfarin or apixaban
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cornelius Dyke, MD
Organizational Affiliation
Sanford Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sanford Health
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58122
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26482512
Citation
Anderson E, Johnke K, Leedahl D, Glogoza M, Newman R, Dyke C. Novel oral anticoagulants vs warfarin for the management of postoperative atrial fibrillation: clinical outcomes and cost analysis. Am J Surg. 2015 Dec;210(6):1095-102; discussion 1102-3. doi: 10.1016/j.amjsurg.2015.07.005. Epub 2015 Sep 18.
Results Reference
background
PubMed Identifier
19878532
Citation
Schulman S, Angeras U, Bergqvist D, Eriksson B, Lassen MR, Fisher W; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost. 2010 Jan;8(1):202-4. doi: 10.1111/j.1538-7836.2009.03678.x. Epub 2009 Oct 30.
Results Reference
background
PubMed Identifier
23850476
Citation
Piccini JP, Zhao Y, Steinberg BA, He X, Mathew JP, Fullerton DA, Hegland DD, Hernandez AF, Mills RM, Klaskala W, Peterson ED. Comparative effectiveness of pharmacotherapies for prevention of atrial fibrillation following coronary artery bypass surgery. Am J Cardiol. 2013 Oct 1;112(7):954-60. doi: 10.1016/j.amjcard.2013.05.029. Epub 2013 Jul 11.
Results Reference
background
PubMed Identifier
21257002
Citation
Lahiri MK, Fang K, Lamerato L, Khan AM, Schuger CD. Effect of race on the frequency of postoperative atrial fibrillation following coronary artery bypass grafting. Am J Cardiol. 2011 Feb 1;107(3):383-6. doi: 10.1016/j.amjcard.2010.09.032.
Results Reference
background
PubMed Identifier
20570180
Citation
Rostagno C, La Meir M, Gelsomino S, Ghilli L, Rossi A, Carone E, Braconi L, Rosso G, Puggelli F, Mattesini A, Stefano PL, Padeletti L, Maessen J, Gensini GF. Atrial fibrillation after cardiac surgery: incidence, risk factors, and economic burden. J Cardiothorac Vasc Anesth. 2010 Dec;24(6):952-8. doi: 10.1053/j.jvca.2010.03.009. Epub 2010 May 31.
Results Reference
background
PubMed Identifier
26009291
Citation
Raiten JM, Ghadimi K, Augoustides JG, Ramakrishna H, Patel PA, Weiss SJ, Gutsche JT. Atrial fibrillation after cardiac surgery: clinical update on mechanisms and prophylactic strategies. J Cardiothorac Vasc Anesth. 2015;29(3):806-16. doi: 10.1053/j.jvca.2015.01.001. No abstract available.
Results Reference
background
PubMed Identifier
11673357
Citation
Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, Halperin JL, Kay GN, Klein WW, Levy S, McNamara RL, Prystowsky EN, Wann LS, Wyse DG, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Russell RO, Smith SC Jr, Klein WW, Alonso-Garcia A, Blomstrom-Lundqvist C, de Backer G, Flather M, Hradec J, Oto A, Parkhomenko A, Silber S, Torbicki A; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation); North American Society of Pacing and Electrophysiology. ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology. Circulation. 2001 Oct 23;104(17):2118-50. No abstract available.
Results Reference
background
PubMed Identifier
21870978
Citation
Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. doi: 10.1056/NEJMoa1107039. Epub 2011 Aug 27.
Results Reference
background
PubMed Identifier
19717844
Citation
Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. doi: 10.1056/NEJMoa0905561. Epub 2009 Aug 30. Erratum In: N Engl J Med. 2010 Nov 4;363(19):1877.
Results Reference
background
PubMed Identifier
21830957
Citation
Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep 8;365(10):883-91. doi: 10.1056/NEJMoa1009638. Epub 2011 Aug 10.
Results Reference
background
PubMed Identifier
32476465
Citation
Chapin TW, Leedahl DD, Brown AB, Pasek AM, Sand MG, Loy ML, Dyke CM. Comparison of Anticoagulants for Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting: A Pilot Study. J Cardiovasc Pharmacol Ther. 2020 Nov;25(6):523-530. doi: 10.1177/1074248420929483. Epub 2020 Jun 1.
Results Reference
derived
Links:
URL
http://www.micromedexsolutions.com
Description
Apixaban. DrugPoints Summary. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village, CO.
URL
http://www.micromedexsolutions.com
Description
Rivaroxaban. DrugPoints Summary. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village, CO.
URL
http://www.micromedexsolutions.com
Description
Dabigatran Etexilate Mesylate. DrugPoints Summary. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village, CO.

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Apixaban Versus Warfarin for the Management of Post-operative Atrial Fibrillation

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