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

Study Overview
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Brief Summary
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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.

Official Title
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Apixaban Versus Warfarin for the Management of Post-operative Atrial Fibrillation: a Prospective, Controlled, Randomized Pilot Study

Conditions
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Coronary Artery Bypass Grafting, Postoperative Atrial Fibrilation, Stroke, Systemic Embolism, Deep Venous Thrombosis

Intervention / Treatment
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* Drug: Apixaban
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Apixaban<br>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<br>* 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.<br>* Other names: Eliquis;|
| Active Comparator: Warfarin<br>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<br>* 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.<br>* Other names: Coumadin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 30 days | 
| 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. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Units of Blood Given After Initiation of Anticoagulation Medication | Units of blood or blood products given after the first dose of anticoagulation. | 30 days | 
| 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. | 30 days | 
| 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 | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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apixaban, anticoagulant, CABG, thrombosis, fibrillation