Clinical trial NCT03702582: Rivaroxaban vs. Warfarin for Post Cardiac Surgery Atrial Fibrillation
Official title: Trial of New Oral Anticoagulants vs. Warfarin for Post Cardiac Surgery Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atrial Fibrillation
Stroke
Bleeding
Keywords: Atrial Fibrillation
Rivaroxaban
Warfarin
Stroke
Anticoagulation
Bleeding
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2018-10-11
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Cardiac surgery patients who meet study criteria and develop recurrent or persistent atrial fibrillation post-operatively will be randomized 1:1 to receive Warfarin or Rivaroxaban for prophylaxis against stroke or other systemic arterial embolism
Primary purpose: PREVENTION

Brief summary: This prospective, randomized, active-controlled, parallel arm study compares the safety and financial benefits of arterial thromboembolism prophylaxis with Warfarin vs. Rivaroxaban (A novel oral anticoagulant) in patients with new onset atrial fibrillation after sternotomy for cardiac operations.

Detailed description: New onset atrial fibrillation (NOAF) is a common occurrence following cardiac surgery, occurring in 20-30% of patients post-operatively. Historically, Vitamin K antagonist therapy with Warfarin has been the treatment of choice for prophylaxis against stroke and systemic arterial thromboembolism in NOAF. Warfarin inhibits the Vitamin K dependent factors involved in both the intrinsic and extrinsic coagulation cascades, thus decreasing systemic clotting. However, Warfarin therapy comes with many challenges including prolonged titration, tedious monitoring requirements and in some cases, increased bleeding risk.

The limitations associated with Warfarin may be mitigated by using new oral anticoagulants (NOACs) like Rivaroxaban which have no routine monitoring requirements. Rivaroxaban is a direct inhibitor of Factor Xa, a central reactant in both the intrinsic and extrinsic coagulation cascades. Studies in non-operative patients with atrial fibrillation have shown that Rivaroxaban is non-inferior to Warfarin for stroke prophylaxis with similar risk profiles. This study aims to compare the efficacy, safety and financial cost of these two drugs when used for the management of new onset atrial fibrillation that occurs after cardiac operations.

Eligibility criteria: Inclusion Criteria:

* Male or Female ≥ 18 years
* At least one of the following procedures: coronary artery bypass grafting, aortic valve repair, mitral valve repair, non-mechanical aortic valve replacement, any combination of these procedures
* Two or more episodes of New Onset Atrial Fibrillation (each lasting \> 20 minutes) or persistent atrial fibrillation lasting \> 24 hours (Or for \>18 hours over a 24-hour interval)
* If female of child-bearing age, use of adequate contraception

Exclusion Criteria:

* Pre-existing paroxysmal atrial fibrillation before cardiac surgery
* Pre-existing indications for therapeutic anticoagulation (Including but not limited to PE, DVT, mechanical valve)
* Moderate-to-severe mitral valve stenosis not surgically corrected
* Pre-existing allergy to study medications
* Recent (\< 1 year) or ongoing pregnancy (Urine pregnancy test will be obtained for women of child bearing age at the time of enrollment into the study)
* Stroke within 1 month prior to surgery or postoperatively prior to initiation of study drugs
* Postoperative bleeding episode prior to initiation of study drug
* Severe dysfunction of another organ system including GFR \< 30 ml/min, baseline INR \> 1.7, ileus or other gastrointestinal pathology hindering ability to absorb oral medications, and known coagulation pathway deficiencies
* Postoperative need for non-aspirin anti-platelet therapy that cannot be discontinued when therapeutic anticoagulation is initiated
* Patient taking medications with known major interactions with study drugs with no therapeutic alternatives)

Primary outcomes:
measure: Postoperative Length of Stay
timeFrame: Up to 6 months following the cardiac operation
Secondary outcomes:
measure: Episode of Major Bleeding (Defined as the occurrence of any of several events listed in the description. No specific scale, questionnaire or instrument will be used)
timeFrame: Up to 30 days after discharge from the initial postoperative hospitalization
measure: Cerebrovascular accident (CVA)
timeFrame: Up to 30 days after discharge from the initial postoperative hospitalization
measure: Other systemic embolism
timeFrame: Up to 30 days after discharge from the initial postoperative hospitalization
measure: Deep venous thrombosis (DVT) and/or Pulmonary Embolism (PE)
timeFrame: Up to 30 days after discharge from the initial postoperative hospitalization
measure: Minor Bleeding
timeFrame: Up to 30 days after discharge from the initial postoperative hospitalization
measure: Number of Transfusions
timeFrame: Up to 30 days after discharge from the initial postoperative hospitalization
measure: Hospital Readmission
timeFrame: Up to 30 days after discharge from the initial postoperative hospitalization
measure: Therapy related costs of anticoagulation
timeFrame: Up to 30 days after discharge from the initial postoperative hospitalization
measure: Performance on the EUROQOL (EQ-5D) Quality of Life Instrument
timeFrame: Up to 30 days after discharge from the initial postoperative hospitalization
measure: Average score on the Perception of Anticoagulant Treatment Questionnaire (PACT-Q2)
timeFrame: Up to 30 days after discharge from the initial postoperative hospitalization
measure: Rate of ongoing atrial fibrillation
timeFrame: Up to 30 days after discharge from the initial postoperative hospitalization
measure: Rate of Mortality
timeFrame: Up to 30 days after discharge from the initial postoperative hospitalization
measure: Rates of adverse clinical outcomes
timeFrame: Up to 30 days after discharge from the initial postoperative hospitalization
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Asishana A Osho, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Thoralf M Sundt, MD
role: PRINCIPAL_INVESTIGATOR
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