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 (X-VERT)

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

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Vitamin K antagonist (VKA)

• Study Type: Interventional
• Enrollment (Actual): 1504
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles - Brussel, Belgium, 1070
  • Gilly, Belgium, 6060
  • Hasselt, Belgium, 3500
  • Liege, Belgium, 4000
  • MOL, Belgium, 2400
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
• Brazil
  • Sao Paulo, Brazil, 05403-900
  • Parana
    • Curitiba, Parana, Brazil, 80730-150
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil, 13010-001
    • Campinas, Sao Paulo, Brazil, 13060904
• Canada
  • Quebec, Canada, G1V 4G5
  • Alberta
    • Edmonton, Alberta, Canada, T5H 3V9
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 4R2
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
    • Toronto, Ontario, Canada, M5B 1W8
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
    • Montreal, Quebec, Canada, H2W 1T8
• China
  • Beijing, China, 100029
  • Shanghai, China, 200080
  • Shenyang, China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
  • Hubei
    • Wuhan, Hubei, China
  • Hunan
    • Changsha, Hunan, China, 410011
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
  • Jilin
    • Changchun, Jilin, China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
  • Xinjiang
    • Urumqi, Xinjiang, China
• Denmark
  • Hellerup, Denmark, 2900
  • Herning, Denmark, 7400
  • København NV, Denmark, 2400
  • Viborg, Denmark, 8800
• Finland
  • Helsinki, Finland, FIN-00260
  • Jyväskylä, Finland, 40620
  • Lappeenranta, Finland
  • Oulu, Finland
  • Pori, Finland, 28500
  • Rovaniemi, Finland, 96101
  • Tampere, Finland, FIN-33520
  • Turku, Finland, 20521
  • Vaasa, Finland, 65130
• France
  • Arras, France, 62000
  • Lille Cedex, France, 59037
  • Paris, France, 75018
  • Paris, France, 75012
  • Paris cedex 13, France, 75013
  • Pessac, France, 33604
  • TOULOUSE cedex, France, 31059
  • Tours, France, 37044
  • Vandoeuvre-les-nancy, France, 54500
• Germany
  • Berlin, Germany, 13353
  • Hamburg, Germany, 20246
  • Baden-Württemberg
    • Freiburg, Baden-Württemberg, Germany, 79106
  • Bayern
    • Nürnberg, Bayern, Germany, 90471
  • Hessen
    • Frankfurt, Hessen, Germany, 60596
  • Nordrhein-Westfalen
    • Bad Oeynhausen, Nordrhein-Westfalen, Germany, 32545
    • Essen, Nordrhein-Westfalen, Germany, 45147
    • Mönchengladbach, Nordrhein-Westfalen, Germany, 41063
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
  • Sachsen
    • Dresden, Sachsen, Germany, 01067
    • Leipzig, Sachsen, Germany, 04289
• Greece
  • Alexandroupolis, Greece, 68100
  • Attica / Athens, Greece, 11526
  • Heraklion, Greece, 711 10
  • Thessaloniki, Greece, 54642
• Italy
  • Ancona, Italy, 60126
  • Catania, Italy, 95126
  • Roma, Italy, 00169
  • Torino, Italy, 10126
  • Bari
    • Acquaviva delle Fonti, Bari, Italy, 70021
  • Como
    • San Fermo della Battaglia, Como, Italy, 22020
  • Milano
    • San Donato Milanese, Milano, Italy, 20097
  • Venezia
    • Mestre, Venezia, Italy, 30174
• Netherlands
  • Arnhem, Netherlands, 6815 AD
  • Haarlem, Netherlands, 2035 RC
  • Heerlen, Netherlands, 6419 PC
  • Leeuwarden, Netherlands, 8934 AD
  • Maastricht, Netherlands, 6229 HX
• Portugal
  • Almada, Portugal, 2801-951
  • Faro, Portugal, 8000-386
  • Lisboa, Portugal, 1169-024
  • Vila Nova de Gaia, Portugal, 4434-502
  • Coimbra
    • Martinho do Bispo, Coimbra, Portugal, 3041-801
  • Lisboa
    • Carnaxide, Lisboa, Portugal, 2795-53
• Singapore
  • Singapore, Singapore, 119228
  • Singapore, Singapore, 168752
  • Singapore, Singapore, 308433
  • Singapore, Singapore, 768828
• South Africa
  • Bloemfontein, South Africa, 9301
  • Gauteng
    • Alberton, Gauteng, South Africa, 1449
    • Soweto, Gauteng, South Africa, 2013
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7505
    • Cape Town, Western Cape, South Africa, 7450
    • Kuils River, Western Cape, South Africa, 7580
    • Somerset West, Western Cape, South Africa, 7130
    • Worcester, Western Cape, South Africa, 6850
• Spain
  • Barcelona, Spain, 08036
  • Granada, Spain, 18012
  • Madrid, Spain, 28007
  • Pamplona, Spain, 31008
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
• United Kingdom
  • Cliftonville, United Kingdom, NN1 5BD
  • London, United Kingdom, SW17 0RE
  • Portsmouth, United Kingdom, PO6 3LY
  • Derbyshire
    • Chesterfield, Derbyshire, United Kingdom, S44 5BL
  • Dorset
    • Bournemouth, Dorset, United Kingdom, BH7 7DW
  • Hertfordshire
    • Welwyn Garden City, Hertfordshire, United Kingdom, AL7 4HQ
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE3 9QP
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
  • Arizona
    • Scottsdale, Arizona, United States, 85258
  • California
    • East Palo Alto, California, United States, 94303
    • El Cajon, California, United States, 92020
    • National City, California, United States, 91950
    • Sacramento, California, United States, 95819
    • Santa Rosa, California, United States, 95494
    • Torrance, California, United States, 90502-2004
  • Connecticut
    • New Haven, Connecticut, United States, 06520
    • Stamford, Connecticut, United States, 06905
  • Delaware
    • Wilmington, Delaware, United States, 19803
  • Florida
    • Clearwater, Florida, United States, 33756
    • Daytona Beach, Florida, United States, 32117
    • Deltona, Florida, United States, 32725
    • Ft. Lauderdale, Florida, United States, 33316
    • Ft. Lauderdale, Florida, United States, 33308
    • Hollywood, Florida, United States, 33021
    • Jacksonville, Florida, United States, 32216
    • Lakeland, Florida, United States, 33805
    • Melbourne, Florida, United States, 32901
    • Miami, Florida, United States, 33135
    • Orlando, Florida, United States, 32806
    • St. Augustine, Florida, United States, 32216
    • Tallahassee, Florida, United States, 32308
  • Georgia
    • Savannah, Georgia, United States, 31419
  • Illinois
    • Aurora, Illinois, United States, 60504
    • Chicago, Illinois, United States, 60637
    • Chicago, Illinois, United States, 60612
    • Elk Grove Village, Illinois, United States, 60007
    • Joliet, Illinois, United States, 60435
    • Rockford, Illinois, United States, 61107
  • Maryland
    • Annapolis, Maryland, United States, 21401
    • Columbia, Maryland, United States, 21044
    • Rockville, Maryland, United States, 20853
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
  • Nevada
    • North Las Vegas, Nevada, United States, 89086
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
    • Manalapan, New Jersey, United States, 07716
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
  • New York
    • Buffalo, New York, United States, 14215
    • New York, New York, United States, 10032
    • New York, New York, United States, 10013
    • Troy, New York, United States, 12180
  • North Carolina
    • Asheville, North Carolina, United States, 28805
  • Ohio
    • Cantan, Ohio, United States, 44708
    • Cleveland, Ohio, United States, 44195
    • Mansfield, Ohio, United States, 44906
    • Toledo, Ohio, United States, 43623
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
    • Butler, Pennsylvania, United States, 16001
    • Doylestown, Pennsylvania, United States, 18901
    • Hershey, Pennsylvania, United States, 17033
    • Philadelphia, Pennsylvania, United States, 19141
    • Philadelphia, Pennsylvania, United States, 19102
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
  • Tennessee
    • Johnson City, Tennessee, United States, 37604
    • Nashville, Tennessee, United States, 37232
    • Nashville, Tennessee, United States, 37203
  • Texas
    • Austin, Texas, United States, 78745
    • Dallas, Texas, United States, 75231
    • Fort Sam Houston, Texas, United States, 78234-6200
    • Tyler, Texas, United States, 75701
  • Utah
    • Layton, Utah, United States, 84041
  • Washington
    • Bellingham, Washington, United States, 98225
    • Burien, Washington, United States, 98166
  • Wisconsin
    • Wausau, Wisconsin, United States, 54401

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Composite of the Following Events, Adjudicated Centrally: Stroke, Transient Ischemic Attack, Non-central Nervous System Systemic Embolism, Myocardial Infarction and Cardiovascular Death	Stroke, TIA, Non-CNS Embolism, MI and cardiovascular death were adjudicated and confirmed by Clinical Endpoints Committee (CEC). Stroke included hemorrhagic and ischemic infarction. TIA including information if with or without matching lesion. Non CNS systemic embolism included emboli in peripheral arterial of the upper and lower extremities, ocular and retinal (pulmonary embolism and MI were excluded from the category). MI was assessed based on either cardiac biomarkers, new abnormal Q waves appeared on electrocardiogram for >= 2 leads, or autopsy confirmation. Cardiovascular death included death in subjects with non-valvular atrial fibrillation (AF). Number of subjects with composite events were reported.	From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment
Number of Participants With Major Bleedings as Per Central Adjudication	Bleeding events were adjudicated and confirmed by CEC blinded to treatment. The CEC categorized the bleeding events as major or non-major. The bleeding events were defined per the International Society on Thrombosis and Hemostasis (ISTH) criteria. Major bleeding was clinically overt bleeding associated with a fall in hemoglobin of 2 gram per deciliter (g/dL) or higher, leading to a transfusion of 2 or more units of packed red blood cells or whole blood, occurring in a critical site or contributing to death. Number of subjects with confirmed adjudicated bleeding events occurring in greater than (>)1 total subjects were reported.	From randomization up to the date of the last dose of study drug + 2 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Composite of Strokes and Non-central Nervous System Systemic Embolisms	Stroke and Non-CNS Embolism were adjudicated and confirmed by CEC. Stroke included hemorrhagic and ischemic infarction. Non CNS systemic embolism included emboli in peripheral arterial of the upper and lower extremities, ocular and retinal (pulmonary embolism and MI were excluded from the category). Number of subjects with composite events were reported.	From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment
Number of Participants With Composite of Strokes, Transient Ischemic Attacks, Non-central Nervous System Systemic Embolisms, Myocardial Infarctions and All-cause Mortality	Stroke, TIA, Non- CNS systemic embolism, MI and all-cause mortality were adjudicated and confirmed by CEC. Stroke included hemorrhagic and ischemic infarction. TIA including information if with or without matching lesion. Non CNS systemic embolism included emboli in peripheral arterial of the upper and lower extremities, ocular and retinal (pulmonary embolism and MI were excluded from the category). MI was assessed based on either cardiac biomarkers, new abnormal Q waves appeared on electrocardiogram for >= 2 leads, or autopsy confirmation. All-cause mortality included vascular death and non-vascular death. Number of subjects with composite events were reported.	From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment
Number of Participants With Strokes	All events were adjudicated and confirmed by a CEC blinded to treatment. Stroke included hemorrhagic (Stroke with local collections of intraparenchymal blood. Subarachnoid hemorrhage, subdural hemorrhage, and epidural hemorrhage were excluded), ischemic infarction (Stroke without focal collection of intracranial blood) and unknown (No imaging data and anatomic findings were available). Number of subjects with strokes were reported.	From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment
Number of Participants With Transient Ischemic Attacks	All events were adjudicated and confirmed by a CEC blinded to treatment. Number of subjects with TIA were reported.	From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment
Number of Participants With Non-central Nervous System Systemic Embolisms	All events were adjudicated and confirmed by a CEC blinded to treatment. Non CNS systemic embolism included emboli in peripheral arterial of the upper and lower extremities, ocular and retinal (pulmonary embolism and MI were excluded from the category). Number of subjects with non-CNS embolism were reported.	From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment
Number of Participants With Myocardial Infarctions	All events were adjudicated and confirmed by a CEC blinded to treatment. MI was assessed based onmeither cardiac biomarkers, new abnormal Q waves appeared on electrocardiogram for >= 2 leads, or autopsy confirmation. Number of subjects with MI were reported.	From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment
Number of Participants With Cardiovascular Deaths	All events were adjudicated and confirmed by a CEC blinded to treatment. Any death that was not clearly non-vascular (e.g., deaths due to spontaneous bleeding, myocardial infarction, stroke, cardiac failure, and arrhythmia). Number of subjects with cardiovascular deaths were reported.	From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment
Number of Participants With All-cause Mortality	All events were adjudicated and confirmed by a CEC blinded to treatment. All-cause mortality included vascular death and non-vascular death. Number of subjects with all-cause mortality were reported.	From randomization to the date of last dose of study drug +2 days for subjects who completed planned treatment or the earlier date [last planned dose, follow-up visit at the end of 30-day follow-up period] for subjects who prematurely stopped treatment
Number of Participants With Composite of Major and Non-major Bleeding Events	All events were adjudicated and confirmed by a CEC blinded to treatment. The CEC categorized the bleeding events as major or non-major. The bleeding events were defined per the ISTH criteria. Clinically relevant bleeding included major bleeding (overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of 2 or more units of packed red blood cells or whole blood, occurring in a critical site or contributing to death) and non-major bleeding associated with medical intervention, unscheduled physician contact, (temporary) cessation of study treatment, discomfort for the participants such as pain, or impairment of activities of daily life. Number of subjects with clinically relevant major and non-major bleeding events were reported.	From randomization up to the date of the last dose of study drug + 2 days

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Cappato R, Ezekowitz MD, Klein AL, Camm AJ, Ma CS, Le Heuzey JY, Talajic M, Scanavacca M, Vardas PE, Kirchhof P, Hemmrich M, Lanius V, Meng IL, Wildgoose P, van Eickels M, Hohnloser SH; X-VeRT Investigators. Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation. Eur Heart J. 2014 Dec 14;35(47):3346-55. doi: 10.1093/eurheartj/ehu367. Epub 2014 Sep 2.
• Hai Z, Guangrui S. Cardiac paraganglioma. Eur Heart J. 2018 Jun 14;39(23):2219. doi: 10.1093/eurheartj/ehu241. No abstract available.

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: August 27, 2012
• First Submitted That Met QC Criteria: August 27, 2012
• First Posted (Estimate): August 29, 2012

Study Record Updates

• Last Update Posted (Estimate): April 30, 2015
• Last Update Submitted That Met QC Criteria: April 10, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: stroke; thromboembolism; transient ischemic attack; rivaroxaban; cardioversion; cardiovascular event; oral anticoagulant; nonvalvular atrial fibrillation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrin Modulating Agents; Protease Inhibitors; Micronutrients; Vitamins; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Antifibrinolytic Agents; Hemostatics; Coagulants; Vitamin K; Rivaroxaban
• Other Study ID Numbers: 15693; 2011-002234-39 (EudraCT Number)