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Trial record 55 of 734 for:    warfarin

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

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ClinicalTrials.gov Identifier: NCT03702582
Recruitment Status : Recruiting
First Posted : October 11, 2018
Last Update Posted : May 29, 2019
Sponsor:
Information provided by (Responsible Party):
Asishana A Osho, Massachusetts General Hospital

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.

Condition or disease Intervention/treatment Phase
Atrial Fibrillation Stroke Bleeding Drug: Rivaroxaban Drug: Warfarin Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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
Masking: None (Open Label)
Masking Description: Statisticians performing comparative analyses of primary outcomes will be blinded as to the allocation designations of patients. Otherwise there will be no masking in the study.
Primary Purpose: Prevention
Official Title: Trial of New Oral Anticoagulants vs. Warfarin for Post Cardiac Surgery Atrial Fibrillation
Actual Study Start Date : April 30, 2019
Estimated Primary Completion Date : April 1, 2022
Estimated Study Completion Date : May 1, 2022


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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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)

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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.


  10. 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.


  11. 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.

  12. 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

  13. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • 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)

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): NCT03702582


Contacts
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Contact: Asishana A Osho, MD, MPH 440-453-2913 asishana.osho@mgh.harvard.edu
Contact: Thoralf M Sundt, MD 617-643-9745 TSUNDT@mgh.harvard.edu

Locations
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United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Asishana A Osho, MD, MPH    440-453-2913    asishana.osho@mgh.harvard.edu   
Contact: Thoralf Sundt, MD    6176439745    tsundt@partners.org   
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
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Principal Investigator: Asishana A Osho, MD, MPH Massachusetts General Hospital
Principal Investigator: Thoralf M Sundt, MD Massachusetts General Hospital

Publications:

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Responsible Party: Asishana A Osho, Clinical Fellow in Surgery, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT03702582     History of Changes
Other Study ID Numbers: 2018P002307
First Posted: October 11, 2018    Key Record Dates
Last Update Posted: May 29, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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.

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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
Keywords provided by Asishana A Osho, Massachusetts General Hospital:
Atrial Fibrillation
Rivaroxaban
Warfarin
Stroke
Anticoagulation
Bleeding
Additional relevant MeSH terms:
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Warfarin
Atrial Fibrillation
Hemorrhage
Cardiovascular Diseases
Arrhythmias, Cardiac
Heart Diseases
Pathologic Processes
Rivaroxaban
Anticoagulants
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action