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

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ClinicalTrials.gov Identifier: NCT02889562
Recruitment Status : Recruiting
First Posted : September 5, 2016
Last Update Posted : June 29, 2017
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Sanford Health

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.

Condition or disease Intervention/treatment Phase
Coronary Artery Bypass Grafting Postoperative Atrial Fibrilation Stroke Systemic Embolism Deep Venous Thrombosis Drug: Apixaban Drug: Warfarin Phase 2 Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Apixaban Versus Warfarin for the Management of Post-operative Atrial Fibrillation: a Prospective, Controlled, Randomized Pilot Study
Study Start Date : September 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Apixaban
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.
Drug: Apixaban
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.
Other Name: Eliquis

Active Comparator: Warfarin

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.

Drug: Warfarin
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.
Other Name: Coumadin




Primary Outcome Measures :
  1. Freedom from stroke or thromboembolic event [ Time Frame: 30 days ]

    Efficacy will be measured by the freedom from systemic thromboembolism or stroke during the study period. Events relating to thromboembolism or stroke will be adjudicated using pre-determined definitions by independent committee members that remain blinded to the patient's treatment arm.

    Safety, including major and minor bleeding will be quantified and defined by the Society on Thrombosis and Haemostasis, as described in section 6.4.2, subsection (2).



Secondary Outcome Measures :
  1. Units of blood given after initiation of anticoagulation medication [ Time Frame: 30 days ]
    Units of blood or blood products given after the first dose of anticoagulation.

  2. Total post-operative length of stay [ Time Frame: 30 days ]
    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.

  3. Duration from diagnosis of post-operative atrial fibrillation (POAF) to discharge from the hospital [ Time Frame: 30 days ]
    This will be measured from the time of the EKG that is obtained after AFib is noted on telemetry (confirming the diagnosis of AFib), until hospital discharge. This will be measured in hours, to the nearest tenth of an hour.

  4. Time in therapeutic range of INR, if on warfarin [ Time Frame: 30 days ]
    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

  5. Patient compliance percentage to apixaban [ Time Frame: 30 days ]
    compliance percentage to apixaban: measured by asking the patient to bring any unused medication to their 30-day post-operative appointment, where remaining tablets will be counted. This will be calculated as a percentage using the following equation: (# doses prescribed - # of doses not taken and returned to investigator at follow up appointment) / # days prescribed.



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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:

  • 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

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): NCT02889562


Contacts
Contact: Lora Black 6053126436 lora.black@sanfordhealth.org

Locations
United States, North Dakota
Sanford Health Recruiting
Fargo, North Dakota, United States, 58122
Contact: Lora Black    605-312-6436    lora.black@sanfordhealth.org   
Principal Investigator: Cornelius Dyke, MD         
Sub-Investigator: Todd Chapin, PharmD         
Sponsors and Collaborators
Sanford Health
Bristol-Myers Squibb
Investigators
Principal Investigator: Cornelius Dyke, MD Sanford Health

Additional Information:
Publications:
Fuster V, Rydén LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, Halperin JL, Kay GN, Klein WW, Lévy 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, Blomström-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.

Responsible Party: Sanford Health
ClinicalTrials.gov Identifier: NCT02889562     History of Changes
Other Study ID Numbers: CV185-505
First Posted: September 5, 2016    Key Record Dates
Last Update Posted: June 29, 2017
Last Verified: June 2017

Keywords provided by Sanford Health:
apixaban
anticoagulant
CABG
thrombosis
fibrillation

Additional relevant MeSH terms:
Atrial Fibrillation
Thrombosis
Embolism
Venous Thrombosis
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Apixaban
Warfarin
Anticoagulants
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action