Explore the Efficacy and Safety of Once-daily Oral Rivaroxaban for the Prevention of Cardiovascular Events in Subjects With Nonvalvular Atrial Fibrillation Scheduled for Cardioversion

This study is currently recruiting participants.
Verified April 2013 by Bayer
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by:
Bayer
ClinicalTrials.gov Identifier:
NCT01674647
First received: August 27, 2012
Last updated: April 25, 2013
Last verified: April 2013
  Purpose

A study for patients with abnormal heart rhythm (atrial fibrillation) who need to undergo cardioversion (procedure to restore normal heart rhythm). The study will compare patients assigned randomly (like flipping a coin) to either Rivaroxaban or vitamin K antagonist (VKA). The study will measure common medical outcomes for this type of patient such as bleeding and stroke.


Condition Intervention Phase
Atrial Fibrillation
Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Vitamin K antagonist (VKA)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Prospective, Randomized, Open-label, Parallel-group, Active-controlled, Multicenter Study Exploring the Efficacy and Safety of Once-daily Oral Rivaroxaban (BAY59-7939) Compared With That of Dose-adjusted Oral Vitamin K Antagonists (VKA) for the Prevention of Cardiovascular Events in Subjects With Nonvalvular Atrial Fibrillation Scheduled for Cardioversion

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Composite number of the following events, adjudicated centrally: stroke, transient ischemic attack, non-central nervous system systemic embolism, myocardial infarction and cardiovascular death [ Time Frame: Up to 100 days ] [ Designated as safety issue: No ]
  • Number of major bleedings as per central adjudication [ Time Frame: Up to 100 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Composite number of strokes and non-central nervous system systemic embolisms [ Time Frame: Up to 100 days ] [ Designated as safety issue: No ]
  • Composite number of strokes, transient ischemic attacks, non-central nervous system systemic embolisms, myocardial infarctions and all-cause mortality [ Time Frame: Up to 100 days ] [ Designated as safety issue: No ]
  • Number of strokes [ Time Frame: Up to 100 days ] [ Designated as safety issue: No ]
  • Number of transient ischemic attacks [ Time Frame: Up to 100 days ] [ Designated as safety issue: No ]
  • Number of non-central nervous system systemic embolisms [ Time Frame: Up to 100 days ] [ Designated as safety issue: No ]
  • Number of myocardial infarctions [ Time Frame: Up to 100 days ] [ Designated as safety issue: No ]
  • Number of cardiovascular deaths [ Time Frame: Up to 100 days ] [ Designated as safety issue: No ]
  • All-cause mortality [ Time Frame: Up to 100 days ] [ Designated as safety issue: No ]
  • Composite number of major and non-major bleeding events [ Time Frame: Up to 100 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 1500
Study Start Date: October 2012
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rivaroxaban (Xarelto, BAY59-7939)
A Direct Cardioversion Strategy can be performed only if sufficient anticoagulation is proven during the last 21 days prior to randomization and/or a transesophageal echocardiogram (TEE) is planned before cardioversion. Rivaroxaban will be given for 1-5 days before planned direct cardioversion. The run-in of 1-5 days is needed due to potential pretreatment with VKA. Treatment with rivaroxaban will be continued for 42 days after the cardioversion. A Delayed Cardioversion Strategy will be chosen if sufficient anticoagulation is not proven during the last 21 days prior to randomization and no TEE is planned. Rivaroxaban will be given for at least 21 (+4) days before the planned cardioversion, to a maximum of 56 (+4) days prior to planned cardioversion.
Drug: Rivaroxaban (Xarelto, BAY59-7939)
Rivaroxaban 20 mg orally once daily; subjects with moderate renal impairment (ie, CrCl of 30 to 49 mL/min, inclusive) will receive the adjusted dose of 15 mg orally once daily in the study
Active Comparator: Vitamin K antagonist (VKA)
A Direct Cardioversion Strategy can be performed only if sufficient anticoagulation is proven during the last 21 days prior to randomization and/or a transesophageal echocardiogram (TEE) is planned before cardioversion. VKA will be given for 1-5 days before planned direct cardioversion. The run-in of 1-5 days is needed due to potential pretreatment with VKA. Treatment with VKA will be continued for 42 days after the cardioversion. A Delayed Cardioversion Strategy will be chosen if sufficient anticoagulation is not proven during the last 21 days prior to randomization and no TEE is planned. VKA will be given for at least 21 (+4) days before the planned cardioversion, to a maximum of 56 (+4) days prior to planned cardioversion.
Drug: Vitamin K antagonist (VKA)
VKA orally once daily titrated to a target international normalized ratio (INR) of 2.5 (range 2.0-3.0, inclusive); the VKA type (eg, warfarin, acenocoumarol, phenprocoumon, fluindione, etc) will be assigned by the investigator according to local treatment standards

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men or women aged >= 18 years
  • Hemodynamically stable nonvalvular atrial fibrillation longer than 48 hours or of unknown duration
  • Scheduled for cardioversion (electrical or pharmacological) of nonvalvular atrial fibrillation
  • Women of childbearing potential and men must agree to use adequate contraception when sexually active

Exclusion Criteria:

  • Severe, disabling stroke (modified Rankin score of 4- 5, inclusive) within 3 months or any stroke within 14 days prior to randomization
  • Transient ischemic attack within 3 days prior to randomization
  • Acute thromboembolic events or thrombosis (venous/arterial) within the last 14 days prior to randomization
  • Acute Myocardial infarction (MI) within the last 14 days prior to randomization
  • Cardiac-related criteria: known presence of cardiac thombus or myxoma or valvular atrial fibrillation
  • Active bleeding or high risk for bleeding contraindicating anticoagulant therapy
  • Concomitant medications: indication for anticoagulant therapy other than atrial fibrillation, chronic aspirin therapy > 100 mg daily or dual antiplatelet therapy, strong inhibitors of both cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp) if used systemically
  • Concomitant conditions: childbearing potential without proper contraceptive measures, pregnancy, or breast feeding; hypersensitivity to investigational treatment or comparator treatment; calculated creatinine clearance (CrCl) < 30 mL/minute; hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk; any severe condition that would limit life expectancy to less than 6 months; planned invasive procedure with potential for uncontrolled bleeding; inability to take oral medication; ongoing drug addiction or alcohol abuse
  • Any other contraindication listed in the local labeling for the comparator treatment or experimental treatment
  • Participation in a study with an investigational drug or medical device within 30 days prior to randomization
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01674647

Contacts
Contact: Bayer Clinical Trials Contact clinical-trials-contact@bayerhealthcare.com
Contact: For trial location information: (Phone Menu Options '3' or '4') (+)1-888-84 22397

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Pamplona, Spain, 31008
United Kingdom
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Chesterfield, Derbyshire, United Kingdom, S44 5BL
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Bournemouth, Dorset, United Kingdom, BH7 7DW
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Welwyn Garden City, Hertfordshire, United Kingdom, AL7 4HQ
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Leicester, Leicestershire, United Kingdom, LE3 9QP
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Northampton, Northamptonshire, United Kingdom, NN1 5BD
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London, United Kingdom, SW17 0RE
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Portsmouth, United Kingdom, PO6 3LY
Sponsors and Collaborators
Bayer
Janssen Research & Development, LLC
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Medical Affairs Therapeutic Area Head, Bayer Healthcare AG
ClinicalTrials.gov Identifier: NCT01674647     History of Changes
Other Study ID Numbers: 15693, 2011-002234-39
Study First Received: August 27, 2012
Last Updated: April 25, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Canada: Health Canada
China: Food and Drug Administration
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: Ministry of Health and Welfare
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Portugal: National Pharmacy and Medicines Institute
Singapore: Health Sciences Authority
South Africa: Department of Health
Spain: Ministry of Health, Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Bayer:
rivaroxaban
oral anticoagulant
nonvalvular atrial fibrillation
cardioversion
stroke
transient ischemic attack
thromboembolism
cardiovascular event

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Vitamin K
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 16, 2013