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

NCT ID: NCT02889562

Last Updated: 2021-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2019-05-11

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Apixaban

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Warfarin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Eliquis; Coumadin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Sanford Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cornelius Dyke, MD

Role: PRINCIPAL_INVESTIGATOR

Sanford Health

Locations

Sanford Health

Fargo, North Dakota, United States

Countries

United States

References

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Reference Type: DERIVED

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.micromedexsolutions.com

Apixaban. DrugPoints Summary. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village, CO.

http://www.micromedexsolutions.com

Rivaroxaban. DrugPoints Summary. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village, CO.

http://www.micromedexsolutions.com

Dabigatran Etexilate Mesylate. DrugPoints Summary. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village, CO.

Other Identifiers

CV185-505

Identifier Type: -

Identifier Source: org_study_id