Rivaroxaban vs. Warfarin for Post Cardiac Surgery Atrial Fibrillation (NEW-AF)

October 22, 2023 updated by: Asishana A Osho, Massachusetts General Hospital

Trial of New Oral Anticoagulants vs. Warfarin for Post Cardiac Surgery Atrial Fibrillation

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rivaroxaban

Rivaroxaban: Direct inhibitor of Factor Xa, an enzyme that stimulates the formation of thrombin from prothrombin (A critical step in both the intrinsic and extrinsic aspects of the coagulation cascade)

Dosage form: Per Os (Oral)

Dosage and Frequency: 20 mg every evening with the evening meal (No titration requirements). For patients with decreased glomerular filtration rate (GFR between 15 ml/min and 50 ml/min), dosing will be decreased to 15 mg every evening with the evening meal.

Duration: 30 days (Possibility of continuation after post-operative cardiology clinic visit)
Drug: Rivaroxaban
Anticoagulant drug that works via direct inhibition of factor Xa. FDA approved for prophylaxis against stroke in non-valvular atrial fibrillation
Other Names:
  • Xarelto
  • Database of Molecules (PubChem CID): 6433119
Active Comparator: Warfarin

Warfarin: Competitive inhibitor of vitamin K epoxide reductase complex 1, an important enzyme in the activation pathway for vitamin K dependent coagulation factors

Dosage form: Per Os (Oral)

Dosage and Frequency: Initial dose of 2 - 5 mg nightly after the evening meal (QHS) with appropriate titration to goal INR 2.0 - 3.0 (Initial dose based on weight, age, gender, co-morbidities and concurrent medications). INR will be checked daily to weekly depending on stability of dosing and medication regimen.

Duration: 30 days (Possibility of continuation after post-operative Cardiology clinic visit)
Drug: Warfarin
Anticoagulation drug that works via inhibition of vitamin K dependent clotting factors. FDA approved for prophylaxis against stroke in atrial fibrillation
Other Names:
  • Coumadin
  • Database of Molecules (PubChem CID): 54678486

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Postoperative Length of Stay
Time Frame: Up to 6 months following the cardiac operation
Length of inpatient stay in days from time of departure from the operating room
Up to 6 months following the cardiac operation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Time Frame: Up to 30 days after discharge from the initial postoperative hospitalization
Major bleeding defined as re-operation or other therapeutic intervention for bleeding (including but not limited to colonoscopy, upper endoscopy and urologic procedures for hematuria), development of any intracranial bleeding, cessation of study drug for bleeding concerns, reversal of study drug for bleeding concerns and/or new transfusion requirement > 2 units of blood after drug administration
Up to 30 days after discharge from the initial postoperative hospitalization
Cerebrovascular accident (CVA)
Time Frame: Up to 30 days after discharge from the initial postoperative hospitalization
Rates of cerebrovascular accident including stroke and transient ischemic attack (TIA)
Up to 30 days after discharge from the initial postoperative hospitalization
Other systemic embolism
Time Frame: Up to 30 days after discharge from the initial postoperative hospitalization
Rates of non-neurological systemic arterial embolism involving any organ system
Up to 30 days after discharge from the initial postoperative hospitalization
Deep venous thrombosis (DVT) and/or Pulmonary Embolism (PE)
Time Frame: Up to 30 days after discharge from the initial postoperative hospitalization
Occurrence of pathologic venous thrombo-embolism including DVT and PE
Up to 30 days after discharge from the initial postoperative hospitalization
Minor Bleeding
Time Frame: Up to 30 days after discharge from the initial postoperative hospitalization
Minor bleeding defined as blood transfusions <= 2 units or drop in hemoglobin greater 3g/dL following administration of study drugs
Up to 30 days after discharge from the initial postoperative hospitalization
Number of Transfusions
Time Frame: Up to 30 days after discharge from the initial postoperative hospitalization
The number of units of blood transfused for each participant after initiation of study drugs
Up to 30 days after discharge from the initial postoperative hospitalization
Hospital Readmission
Time Frame: Up to 30 days after discharge from the initial postoperative hospitalization
Readmissions will be counted in this calculation if patients are admitted to the hospital. Emergency room visits without admission and outpatient visits will not count toward this calculation of readmission rates.
Up to 30 days after discharge from the initial postoperative hospitalization
Therapy related costs of anticoagulation
Time Frame: Up to 30 days after discharge from the initial postoperative hospitalization
Specific drug related costs will be estimated in dollars for patients in each intervention arm. This will include costs of all administered drug doses as well as costs of associated laboratory studies and mileage based costs of travel to INR testing centers
Up to 30 days after discharge from the initial postoperative hospitalization
Performance on the EUROQOL (EQ-5D) Quality of Life Instrument
Time Frame: Up to 30 days after discharge from the initial postoperative hospitalization

Participants will be administered the EUROQOL-5D-3L (5 dimensions, 3 levels) questionnaire to derive an estimate of the health state. This is comprised of a 5 questions survey and a single visual analog scale highlighting perceived health levels

For the 5 questions survey, each question related to mobility, selfcare, mood, pain and/or functionality is answered on a three point scale with higher number representing worse outcomes. The entire dataset is used to generate a health state based on the unique pattern of answers. These health states are then compared against standardized country-based value sets which provide an assessment of quality of life based on societal preferences.

The visual analog scale is single answer between 0 and 100 representing the patient's perception of their health state. 0 represents the worst health imaginable and 100 represents the best.
Up to 30 days after discharge from the initial postoperative hospitalization
Average score on the Perception of Anticoagulant Treatment Questionnaire (PACT-Q2)
Time Frame: Up to 30 days after discharge from the initial postoperative hospitalization

Participants will be administered the PACT-Q2 questionnaire which is comprised of a convenience subscale and a satisfaction subscale.

For the convenience subscale, each of 13 questions is answered on a 1-5 rating scale with higher numbers representing worse outcomes. A sub-scale score is generated by inverting the score from each element and calculating the sum. Range on the inverted scale is 13 - 65. Higher scores represent better outcomes.

For the satisfaction subscale, each of 7 questions is answered on a 1-5 rating scale with higher numbers representing better outcomes. The total score on this subscale is generated by adding up scores from all elements. Range on this subscale is 7-35. Higher scores represent better outcomes.

A composite score is generated by adding up scores from both subscales and recalibrating on a 0-100 scale by adding the scores together and applying the formula: COMPOSITE SCORE=100×(Sum-20)/80. Higher scores represent more favorable outcomes.
Up to 30 days after discharge from the initial postoperative hospitalization
Rate of ongoing atrial fibrillation
Time Frame: Up to 30 days after discharge from the initial postoperative hospitalization
EKGs will be obtained at various time points during the study to determine whether participants remain in atrial fibrillation during the follow up period. From each EKG, existence of p-waves, regularity of the overall wave form and heart rate will be evaluated to determine if patients remain in atrial fibrillation or if they have spontaneously converted to a normal sinus rhythm.
Up to 30 days after discharge from the initial postoperative hospitalization
Rate of Mortality
Time Frame: Up to 30 days after discharge from the initial postoperative hospitalization
Mortality during study follow up will be documented and rates will compared across intervention groups. Cause of death will be documented
Up to 30 days after discharge from the initial postoperative hospitalization
Rates of adverse clinical outcomes
Time Frame: Up to 30 days after discharge from the initial postoperative hospitalization
Other adverse clinical outcomes will be documented and rates compared between intervention arms including: Acute Kidney Injury, Infection, Heart Failure, Pericardial Effusion, Myocardial infarction, Pleural Effusion and Hepatic dysfunction
Up to 30 days after discharge from the initial postoperative hospitalization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Investigators

  • Principal Investigator: Asishana A Osho, MD, MPH, Massachusetts General Hospital
  • Principal Investigator: Thoralf M Sundt, MD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 30, 2019

Primary Completion (Actual)

October 1, 2023

Study Completion (Actual)

October 1, 2023

Study Registration Dates

First Submitted

October 5, 2018

First Submitted That Met QC Criteria

October 8, 2018

First Posted (Actual)

October 11, 2018

Study Record Updates

Last Update Posted (Actual)

October 24, 2023

Last Update Submitted That Met QC Criteria

October 22, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018P002307

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

At this time there is no plan to make Individual Participant Data available to other researchers. As the study develops, investigators will consider making an individual participant data sharing plan if there is interest from other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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