X-VERT: 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

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01674647
• Collaborator: Janssen Research & Development, LLC (Industry)
• Enrollment: 1,504
• Locations: 178
• Arms: 2
• Duration (Months): 15
• Patients Per Site: 8.4
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Vitamin K antagonist (VKA)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1504 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 [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]

   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.

2. Number of Participants With Major Bleedings as Per Central Adjudication [From randomization up to the date of the last dose of study drug + 2 days]

   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.

Secondary Outcome Measures

1. Number of Participants With Composite of Strokes and Non-central Nervous System Systemic Embolisms [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]

   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.

2. Number of Participants With Composite of Strokes, Transient Ischemic Attacks, Non-central Nervous System Systemic Embolisms, Myocardial Infarctions and All-cause Mortality [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]

   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.

3. Number of Participants With Strokes [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]

   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.

4. Number of Participants With Transient Ischemic Attacks [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]

   All events were adjudicated and confirmed by a CEC blinded to treatment. Number of subjects with TIA were reported.

5. Number of Participants With Non-central Nervous System Systemic Embolisms [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]

   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.

6. Number of Participants With Myocardial Infarctions [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]

   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.

7. Number of Participants With Cardiovascular Deaths [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]

   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.

8. Number of Participants With All-cause Mortality [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]

   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.

9. Number of Participants With Composite of Major and Non-major Bleeding Events [From randomization up to the date of the last dose of study drug + 2 days]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1		Mobile	Alabama	United States	36608
2		Scottsdale	Arizona	United States	85258
3		East Palo Alto	California	United States	94303
4		El Cajon	California	United States	92020
5		National City	California	United States	91950
6		Sacramento	California	United States	95819
7		Santa Rosa	California	United States	95494
8		Torrance	California	United States	90502-2004
9		New Haven	Connecticut	United States	06520
10		Stamford	Connecticut	United States	06905
11		Wilmington	Delaware	United States	19803
12		Clearwater	Florida	United States	33756
13		Daytona Beach	Florida	United States	32117
14		Deltona	Florida	United States	32725
15		Ft. Lauderdale	Florida	United States	33308
16		Ft. Lauderdale	Florida	United States	33316
17		Hollywood	Florida	United States	33021
18		Jacksonville	Florida	United States	32216
19		Lakeland	Florida	United States	33805
20		Melbourne	Florida	United States	32901
21		Miami	Florida	United States	33135
22		Orlando	Florida	United States	32806
23		St. Augustine	Florida	United States	32216
24		Tallahassee	Florida	United States	32308
25		Savannah	Georgia	United States	31419
26		Aurora	Illinois	United States	60504
27		Chicago	Illinois	United States	60612
28		Chicago	Illinois	United States	60637
29		Elk Grove Village	Illinois	United States	60007
30		Joliet	Illinois	United States	60435
31		Rockford	Illinois	United States	61107
32		Annapolis	Maryland	United States	21401
33		Columbia	Maryland	United States	21044
34		Rockville	Maryland	United States	20853
35		Lincoln	Nebraska	United States	68516
36		North Las Vegas	Nevada	United States	89086
37		Bridgewater	New Jersey	United States	08807
38		Manalapan	New Jersey	United States	07716
39		Albuquerque	New Mexico	United States	87102
40		Buffalo	New York	United States	14215
41		New York	New York	United States	10013
42		New York	New York	United States	10032
43		Troy	New York	United States	12180
44		Asheville	North Carolina	United States	28805
45		Cantan	Ohio	United States	44708
46		Cleveland	Ohio	United States	44195
47		Mansfield	Ohio	United States	44906
48		Toledo	Ohio	United States	43623
49		Beaver	Pennsylvania	United States	15009
50		Butler	Pennsylvania	United States	16001
51		Doylestown	Pennsylvania	United States	18901
52		Hershey	Pennsylvania	United States	17033
53		Philadelphia	Pennsylvania	United States	19102
54		Philadelphia	Pennsylvania	United States	19141
55		Rapid City	South Dakota	United States	57701
56		Johnson City	Tennessee	United States	37604
57		Nashville	Tennessee	United States	37203
58		Nashville	Tennessee	United States	37232
59		Austin	Texas	United States	78745
60		Dallas	Texas	United States	75231
61		Fort Sam Houston	Texas	United States	78234-6200
62		Tyler	Texas	United States	75701
63		Layton	Utah	United States	84041
64		Bellingham	Washington	United States	98225
65		Burien	Washington	United States	98166
66		Wausau	Wisconsin	United States	54401
67		Leuven	Vlaams Brabant	Belgium	3000
68		Bruxelles - Brussel		Belgium	1070
69		Gilly		Belgium	6060
70		Hasselt		Belgium	3500
71		Liege		Belgium	4000
72		MOL		Belgium	2400
73		Curitiba	Parana	Brazil	80730-150
74		Porto Alegre	Rio Grande do Sul	Brazil	90610-000
75		Campinas	Sao Paulo	Brazil	13010-001
76		Campinas	Sao Paulo	Brazil	13060904
77		Sao Paulo		Brazil	05403-900
78		Edmonton	Alberta	Canada	T5H 3V9
79		Victoria	British Columbia	Canada	V8R 4R2
80		Saint John	New Brunswick	Canada	E2L 4L2
81		St. John's	Newfoundland and Labrador	Canada	A1B 3V6
82		Hamilton	Ontario	Canada	L8L 2X2
83		Toronto	Ontario	Canada	M5B 1W8
84		Montreal	Quebec	Canada	H1T 1C8
85		Montreal	Quebec	Canada	H2W 1T8
86		Quebec		Canada	G1V 4G5
87		Guangzhou	Guangdong	China	510080
88		Wuhan	Hubei	China
89		Changsha	Hunan	China	410011
90		Nanchang	Jiangxi	China	330006
91		Changchun	Jilin	China
92		Xi'an	Shaanxi	China	710061
93		Urumqi	Xinjiang	China
94		Beijing		China	100029
95		Shanghai		China	200080
96		Shenyang		China
97		Hellerup		Denmark	2900
98		Herning		Denmark	7400
99		København NV		Denmark	2400
100		Viborg		Denmark	8800
101		Helsinki		Finland	FIN-00260
102		Jyväskylä		Finland	40620
103		Lappeenranta		Finland
104		Oulu		Finland
105		Pori		Finland	28500
106		Rovaniemi		Finland	96101
107		Tampere		Finland	FIN-33520
108		Turku		Finland	20521
109		Vaasa		Finland	65130
110		Arras		France	62000
111		Lille Cedex		France	59037
112		Paris cedex 13		France	75013
113		Paris		France	75012
114		Paris		France	75018
115		Pessac		France	33604
116		TOULOUSE cedex		France	31059
117		Tours		France	37044
118		Vandoeuvre-les-nancy		France	54500
119		Freiburg	Baden-Württemberg	Germany	79106
120		Nürnberg	Bayern	Germany	90471
121		Frankfurt	Hessen	Germany	60596
122		Bad Oeynhausen	Nordrhein-Westfalen	Germany	32545
123		Essen	Nordrhein-Westfalen	Germany	45147
124		Mönchengladbach	Nordrhein-Westfalen	Germany	41063
125		Mainz	Rheinland-Pfalz	Germany	55131
126		Dresden	Sachsen	Germany	01067
127		Leipzig	Sachsen	Germany	04289
128		Berlin		Germany	13353
129		Hamburg		Germany	20246
130		Alexandroupolis		Greece	68100
131		Attica / Athens		Greece	11526
132		Heraklion		Greece	711 10
133		Thessaloniki		Greece	54642
134		Acquaviva delle Fonti	Bari	Italy	70021
135		San Fermo della Battaglia	Como	Italy	22020
136		San Donato Milanese	Milano	Italy	20097
137		Mestre	Venezia	Italy	30174
138		Ancona		Italy	60126
139		Catania		Italy	95126
140		Roma		Italy	00169
141		Torino		Italy	10126
142		Arnhem		Netherlands	6815 AD
143		Haarlem		Netherlands	2035 RC
144		Heerlen		Netherlands	6419 PC
145		Leeuwarden		Netherlands	8934 AD
146		Maastricht		Netherlands	6229 HX
147		Martinho do Bispo	Coimbra	Portugal	3041-801
148		Carnaxide	Lisboa	Portugal	2795-53
149		Almada		Portugal	2801-951
150		Faro		Portugal	8000-386
151		Lisboa		Portugal	1169-024
152		Vila Nova de Gaia		Portugal	4434-502
153		Singapore		Singapore	119228
154		Singapore		Singapore	168752
155		Singapore		Singapore	308433
156		Singapore		Singapore	768828
157		Alberton	Gauteng	South Africa	1449
158		Soweto	Gauteng	South Africa	2013
159		Cape Town	Western Cape	South Africa	7450
160		Cape Town	Western Cape	South Africa	7505
161		Kuils River	Western Cape	South Africa	7580
162		Somerset West	Western Cape	South Africa	7130
163		Worcester	Western Cape	South Africa	6850
164		Bloemfontein		South Africa	9301
165		Sabadell	Barcelona	Spain	08208
166		Majadahonda	Madrid	Spain	28222
167		Barcelona		Spain	08036
168		Granada		Spain	18012
169		Madrid		Spain	28007
170		Pamplona		Spain	31008
171		Chesterfield	Derbyshire	United Kingdom	S44 5BL
172		Bournemouth	Dorset	United Kingdom	BH7 7DW
173		Welwyn Garden City	Hertfordshire	United Kingdom	AL7 4HQ
174		Leicester	Leicestershire	United Kingdom	LE3 9QP
175		Nottingham	Nottinghamshire	United Kingdom	NG5 1PB
176		Cliftonville		United Kingdom	NN1 5BD
177		London		United Kingdom	SW17 0RE
178		Portsmouth		United Kingdom	PO6 3LY

Sponsors and Collaborators

• Bayer
• Janssen Research & Development, LLC

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

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.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT01674647
• Other Study ID Numbers: 15693; 2011-002234-39
• First Posted: Aug 29, 2012
• Last Update Posted: Apr 30, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by Bayer: rivaroxaban; oral anticoagulant; nonvalvular atrial fibrillation; cardioversion; stroke; transient ischemic attack; thromboembolism; cardiovascular event
• Additional relevant MeSH terms: Atrial Fibrillation; Vitamin K; Rivaroxaban

Study Results

Participant Flow

Recruitment Details	The study was conducted at 141 centers (involving 144 investigators) in Europe, South Africa, North America, and Asia Pacific.
Pre-assignment Detail	Overall, 1584 subjects were screened and 80 subjects did not complete or pass screening. 1504 subjects were randomized; 1002 were assigned to rivaroxaban and 502 to vitamin K antagonist (VKA).

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Vitamin K Antagonist (VKA)
Arm/Group Description	Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.	Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Period Title: Treatment Period
STARTED	1002	502
Subjects Received Treatment	988	499
COMPLETED	846	400
NOT COMPLETED	156	102
Period Title: Treatment Period
STARTED	982	487
COMPLETED	924	446
NOT COMPLETED	58	41

Baseline Characteristics

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Vitamin K Antagonist (VKA)	Total
Arm/Group Description	Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.	Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.	Total of all reporting groups
Overall Participants	1002	502	1504
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.9 (10.6)	64.7 (10.5)	64.9 (10.5)
Sex: Female, Male (Count of Participants)
Female	275 27.4%	135 26.9%	410 27.3%
Male	727 72.6%	367 73.1%	1094 72.7%
CHADS 2 score (units on scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on scale]	1.3 (1.1)	1.4 (1.1)	1.4 (1.1)
CHA 2 DS 2 VASc score (units on scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on scale]	2.3 (1.6)	2.3 (1.6)	2.3 (1.6)

Outcome Measures

1. Primary Outcome

Title	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
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The primary population for the efficacy analysis was the modified intention-to-treat (mITT) population. mITT population included all the randomized subjects in whom a left atrial/left atrial appendage (LA/LAA) thrombus was not diagnosed during a transesophageal echocardiogram (TEE) performed before the first planned cardioversion in the study.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Vitamin K Antagonist (VKA)
Arm/Group Description	Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.	Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Measure Participants	978	492
Number [Participants]	5 0.5%	5 1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban (Xarelto, BAY59-7939), Vitamin K Antagonist (VKA)
	Comments	Descriptive comparison of crude estimates of the cumulative incidence and estimation of risk ratio, all with 95% confidence intervals
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; 0.15 to 1.73
	Parameter Dispersion	Type: Value:
	Estimation Comments	Crude estimate of the cumulative incidence for rivaroxaban (Xarelto, BAY59-7939): 0.51% (0.20% - 1.17%). Crude estimate of the cumulative incidence for Vitamin K antagonist (VKA): 1.02% (0.40% - 2.34%).

2. Primary Outcome

Title	Number of Participants With Major Bleedings as Per Central Adjudication
Description	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.
Time Frame	From randomization up to the date of the last dose of study drug + 2 days

Outcome Measure Data

Analysis Population Description

The safety profile was analyzed using the safety analysis set (SAF) population. SAF population included all randomized subjects who received at least 1 dose of study medication.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Vitamin K Antagonist (VKA)
Arm/Group Description	Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.	Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Measure Participants	988	499
Number [Participants]	6 0.6%	4 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban (Xarelto, BAY59-7939), Vitamin K Antagonist (VKA)
	Comments	Descriptive comparison of crude estimates of the cumulative incidence and estimation of risk ratio, all with 95% confidence intervals
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 95%; 0.21 to 2.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	Crude estimate of the cumulative incidence for rivaroxaban (Xarelto, BAY59-7939): 0.61% (0.26% - 1.27%). Crude estimate of the cumulative incidence for Vitamin K antagonist (VKA): 0.80% (0.27% - 2.00%).

3. Secondary Outcome

Title	Number of Participants With Composite of Strokes and Non-central Nervous System Systemic Embolisms
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The primary population for the efficacy analysis was the mITT population. mITT population included all the randomized subjects in whom a LA/LAA thrombus was not diagnosed during a TEE performed before the first planned cardioversion in the study.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Vitamin K Antagonist (VKA)
Arm/Group Description	Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.	Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Measure Participants	978	492
Number [Participants]	2 0.2%	3 0.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban (Xarelto, BAY59-7939), Vitamin K Antagonist (VKA)
	Comments	Descriptive comparison of crude estimates of the cumulative incidence and estimation of risk ratio, all with 95% confidence intervals
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95%; 0.06 to 2.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	Crude estimate of the cumulative incidence for rivaroxaban (Xarelto, BAY59-7939): 0.20% (0.04% - 0.71%). Crude estimate of the cumulative incidence for Vitamin K antagonist (VKA): 0.61% (0.17% - 1.72%).

4. Secondary Outcome

Title	Number of Participants With Composite of Strokes, Transient Ischemic Attacks, Non-central Nervous System Systemic Embolisms, Myocardial Infarctions and All-cause Mortality
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The primary population for the efficacy analysis was the mITT population. mITT population included all the randomized subjects in whom a LA/LAA thrombus was not diagnosed during a TEE performed before the first planned cardioversion in the study.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Vitamin K Antagonist (VKA)
Arm/Group Description	Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.	Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Measure Participants	978	492
Number [Participants]	6 0.6%	6 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban (Xarelto, BAY59-7939), Vitamin K Antagonist (VKA)
	Comments	Descriptive comparison of crude estimates of the cumulative incidence and estimation of risk ratio, all with 95% confidence intervals
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; 0.16 to 1.55
	Parameter Dispersion	Type: Value:
	Estimation Comments	Crude estimate of the cumulative incidence for rivaroxaban (Xarelto, BAY59-7939): 0.61% (0.27% - 1.29%). Crude estimate of the cumulative incidence for Vitamin K antagonist (VKA): 1.22% (0.53% - 2.51%).

5. Secondary Outcome

Title	Number of Participants With Strokes
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The primary population for the efficacy analysis was the mITT population. mITT population included all the randomized subjects in whom a LA/LAA thrombus was not diagnosed during a TEE performed before the first planned cardioversion in the study.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Vitamin K Antagonist (VKA)
Arm/Group Description	Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.	Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Measure Participants	978	492
Number [Participants]	2 0.2%	2 0.4%

6. Secondary Outcome

Title	Number of Participants With Transient Ischemic Attacks
Description	All events were adjudicated and confirmed by a CEC blinded to treatment. Number of subjects with TIA were reported.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The primary population for the efficacy analysis was the mITT population. mITT population included all the randomized subjects in whom a LA/LAA thrombus was not diagnosed during a TEE performed before the first planned cardioversion in the study.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Vitamin K Antagonist (VKA)
Arm/Group Description	Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.	Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Measure Participants	978	492
Number [Participants]	0 0%	0 0%

7. Secondary Outcome

Title	Number of Participants With Non-central Nervous System Systemic Embolisms
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The primary population for the efficacy analysis was the mITT population. mITT population included all the randomized subjects in whom a LA/LAA thrombus was not diagnosed during a TEE performed before the first planned cardioversion in the study.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Vitamin K Antagonist (VKA)
Arm/Group Description	Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.	Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Measure Participants	978	492
Number [Participants]	0 0%	1 0.2%

8. Secondary Outcome

Title	Number of Participants With Myocardial Infarctions
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The primary population for the efficacy analysis was the mITT population. mITT population included all the randomized subjects in whom a LA/LAA thrombus was not diagnosed during a TEE performed before the first planned cardioversion in the study.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Vitamin K Antagonist (VKA)
Arm/Group Description	Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.	Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Measure Participants	978	492
Number [Participants]	1 0.1%	1 0.2%

9. Secondary Outcome

Title	Number of Participants With Cardiovascular Deaths
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The primary population for the efficacy analysis was the mITT population. mITT population included all the randomized subjects in whom a LA/LAA thrombus was not diagnosed during a TEE performed before the first planned cardioversion in the study.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Vitamin K Antagonist (VKA)
Arm/Group Description	Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.	Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Measure Participants	978	492
Number [Participants]	4 0.4%	2 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban (Xarelto, BAY59-7939), Vitamin K Antagonist (VKA)
	Comments	Descriptive comparison of crude estimates of the cumulative incidence and estimation of risk ratio, all with 95% confidence intervals
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.18 to 5.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	Crude estimate of the cumulative incidence for rivaroxaban (Xarelto, BAY59-7939): 0.41% (0.14% - 1.02%). Crude estimate of the cumulative incidence for Vitamin K antagonist (VKA): 0.41% (0.07% - 1.41%).

10. Secondary Outcome

Title	Number of Participants With All-cause Mortality
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The primary population for the efficacy analysis was the mITT population. mITT population included all the randomized subjects in whom a LA/LAA thrombus was not diagnosed during a TEE performed before the first planned cardioversion in the study.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Vitamin K Antagonist (VKA)
Arm/Group Description	Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.	Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Measure Participants	978	492
Number [Participants]	5 0.5%	3 0.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban (Xarelto, BAY59-7939), Vitamin K Antagonist (VKA)
	Comments	Descriptive comparison of crude estimates of the cumulative incidence and estimation of risk ratio, all with 95% confidence intervals
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.20 to 3.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	Crude estimate of the cumulative incidence for rivaroxaban (Xarelto, BAY59-7939): 0.51% (0.20% - 1.17%). Crude estimate of the cumulative incidence for Vitamin K antagonist (VKA): 0.61% (0.17% - 1.72%).

11. Secondary Outcome

Title	Number of Participants With Composite of Major and Non-major Bleeding Events
Description	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.
Time Frame	From randomization up to the date of the last dose of study drug + 2 days

Outcome Measure Data

Analysis Population Description

The safety profile was analyzed using the SAF population. SAF population included all randomized subjects who received at least 1 dose of study medication.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Vitamin K Antagonist (VKA)
Arm/Group Description	Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.	Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
Measure Participants	988	499
Number [Participants]	33 3.3%	14 2.8%

Adverse Events

Time Frame	From first administration of study drug to date of last study drug + 2 days
Arm/Group Title	Rivaroxaban (Xarelto; BAY59-7939)		Vitamin K Antagonist
Arm/Group Description	Subjects randomized to treatment with rivaroxaban received rivaroxaban 20 milligram (mg) orally once daily. Subjects with moderate renal impairment [i.e., Creatinine clearance (CrCl) of 30 to 49 milliliter per minute (mL/min), inclusive] at screening received the adjusted dose of 15 mg once daily. The duration of the treatment period for a given subject depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, the cardioversion procedure was performed within 1-5 days after randomization. Rivaroxaban was given for 1-5 days before planned direct cardioversion and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received rivaroxaban for 21 (+4) to 56 (+4) days prior to cardioversion and for 42 days thereafter. The investigator assessed whether or not long-term anticoagulation was warranted and treated the subject according to standard of care. Then subjects entered 30-day follow-up period.		Subjects assigned to treatment with VKA received VKA orally once daily titrated to a target INR of 2.5 (range 2.0-3.0, inclusive). The specific VKA was given by the investigator based on local standard of practice. For all subjects randomized to receive VKA, the investigator assessed if a parenteral anticoagulant drug, particularly before cardioversion, was needed as bridging therapy with VKA as standard of care (until target INR was achieved). The duration depended on the cardioversion strategy. For subjects in the Direct Cardioversion Strategy, cardioversion was performed within 1-5 days after randomization. VKA was given for 1-5 days before it and for 42 days thereafter. Subjects in the Delayed Cardioversion Strategy received VKA for 21 (+4) to 56 (+4) days before cardioversion and for 42 days thereafter. The investigator assessed if long-term anticoagulation was warranted and treated the subject according to standard of care or not. Then subjects entered 30-day follow-up period.
All Cause Mortality
	Rivaroxaban (Xarelto; BAY59-7939)		Vitamin K Antagonist
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rivaroxaban (Xarelto; BAY59-7939)		Vitamin K Antagonist
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	93/988 (9.4%)		38/499 (7.6%)
Blood and lymphatic system disorders
Anaemia	1/988 (0.1%)		0/499 (0%)
Cardiac disorders
Acute myocardial infarction	1/988 (0.1%)		0/499 (0%)
Angina pectoris	2/988 (0.2%)		0/499 (0%)
Arrhythmia supraventricular	1/988 (0.1%)		0/499 (0%)
Atrial fibrillation	8/988 (0.8%)		4/499 (0.8%)
Atrial flutter	4/988 (0.4%)		1/499 (0.2%)
Atrial tachycardia	1/988 (0.1%)		0/499 (0%)
Atrial thrombosis	4/988 (0.4%)		3/499 (0.6%)
Bradyarrhythmia	1/988 (0.1%)		0/499 (0%)
Bradycardia	3/988 (0.3%)		3/499 (0.6%)
Cardiac arrest	3/988 (0.3%)		0/499 (0%)
Cardiac failure	8/988 (0.8%)		2/499 (0.4%)
Cardiac failure acute	1/988 (0.1%)		0/499 (0%)
Cardiac failure chronic	1/988 (0.1%)		0/499 (0%)
Cardiac failure congestive	10/988 (1%)		2/499 (0.4%)
Cardiogenic shock	0/988 (0%)		1/499 (0.2%)
Cardiomyopathy	0/988 (0%)		1/499 (0.2%)
Coronary artery disease	0/988 (0%)		1/499 (0.2%)
Intracardiac thrombus	1/988 (0.1%)		0/499 (0%)
Mitral valve incompetence	3/988 (0.3%)		0/499 (0%)
Pericardial effusion	1/988 (0.1%)		0/499 (0%)
Rhythm idioventricular	1/988 (0.1%)		0/499 (0%)
Sick sinus syndrome	0/988 (0%)		2/499 (0.4%)
Sinus bradycardia	0/988 (0%)		2/499 (0.4%)
Tachycardia induced cardiomyopathy	1/988 (0.1%)		0/499 (0%)
Ventricular arrhythmia	1/988 (0.1%)		0/499 (0%)
Ventricular tachycardia	1/988 (0.1%)		0/499 (0%)
Eye disorders
Blindness transient	0/988 (0%)		1/499 (0.2%)
Gastrointestinal disorders
Abdominal pain	4/988 (0.4%)		0/499 (0%)
Constipation	1/988 (0.1%)		0/499 (0%)
Diarrhoea	1/988 (0.1%)		0/499 (0%)
Gastrointestinal haemorrhage	1/988 (0.1%)		0/499 (0%)
Haematochezia	1/988 (0.1%)		0/499 (0%)
Lower gastrointestinal haemorrhage	1/988 (0.1%)		1/499 (0.2%)
Nausea	2/988 (0.2%)		0/499 (0%)
Oesophagitis	0/988 (0%)		1/499 (0.2%)
Rectal haemorrhage	2/988 (0.2%)		0/499 (0%)
Upper gastrointestinal haemorrhage	1/988 (0.1%)		2/499 (0.4%)
Vomiting	1/988 (0.1%)		0/499 (0%)
General disorders
Chest discomfort	1/988 (0.1%)		1/499 (0.2%)
Chest pain	5/988 (0.5%)		0/499 (0%)
Medical device site reaction	0/988 (0%)		1/499 (0.2%)
Non-cardiac chest pain	1/988 (0.1%)		0/499 (0%)
Infections and infestations
Bronchitis	1/988 (0.1%)		1/499 (0.2%)
Bronchitis viral	1/988 (0.1%)		0/499 (0%)
Cellulitis	2/988 (0.2%)		1/499 (0.2%)
Diverticulitis	0/988 (0%)		1/499 (0.2%)
Gastroenteritis	0/988 (0%)		1/499 (0.2%)
Pharyngitis	1/988 (0.1%)		0/499 (0%)
Pneumonia	2/988 (0.2%)		3/499 (0.6%)
Pseudomembranous colitis	1/988 (0.1%)		0/499 (0%)
Urinary tract infection	0/988 (0%)		1/499 (0.2%)
Injury, poisoning and procedural complications
Subdural haematoma	0/988 (0%)		1/499 (0.2%)
Wound haemorrhage	1/988 (0.1%)		0/499 (0%)
Investigations
Arteriogram coronary	0/988 (0%)		1/499 (0.2%)
Electrocardiogram PR prolongation	1/988 (0.1%)		0/499 (0%)
Electrocardiogram T wave abnormal	1/988 (0.1%)		0/499 (0%)
Liver function test abnormal	1/988 (0.1%)		0/499 (0%)
Metabolism and nutrition disorders
Hyponatraemia	1/988 (0.1%)		0/499 (0%)
Musculoskeletal and connective tissue disorders
Arthritis reactive	0/988 (0%)		1/499 (0.2%)
Back pain	0/988 (0%)		1/499 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder neoplasm	1/988 (0.1%)		0/499 (0%)
Lung neoplasm malignant	1/988 (0.1%)		0/499 (0%)
Malignant pleural effusion	1/988 (0.1%)		0/499 (0%)
Nervous system disorders
Carotid artery stenosis	1/988 (0.1%)		0/499 (0%)
Dizziness	0/988 (0%)		1/499 (0.2%)
Haemorrhage intracranial	1/988 (0.1%)		0/499 (0%)
Presyncope	1/988 (0.1%)		0/499 (0%)
Syncope	2/988 (0.2%)		0/499 (0%)
Thalamus haemorrhage	1/988 (0.1%)		0/499 (0%)
Psychiatric disorders
Delirium	1/988 (0.1%)		0/499 (0%)
Renal and urinary disorders
Haematuria	1/988 (0.1%)		0/499 (0%)
Renal failure acute	0/988 (0%)		2/499 (0.4%)
Urogenital haemorrhage	0/988 (0%)		1/499 (0.2%)
Reproductive system and breast disorders
Vaginal haemorrhage	1/988 (0.1%)		0/499 (0%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	0/988 (0%)		1/499 (0.2%)
Asthma	1/988 (0.1%)		0/499 (0%)
Dyspnoea	4/988 (0.4%)		1/499 (0.2%)
Pulmonary alveolar haemorrhage	0/988 (0%)		1/499 (0.2%)
Pulmonary congestion	0/988 (0%)		1/499 (0.2%)
Pulmonary fibrosis	1/988 (0.1%)		0/499 (0%)
Pulmonary hypertension	1/988 (0.1%)		0/499 (0%)
Pulmonary oedema	1/988 (0.1%)		0/499 (0%)
Respiratory disorder	1/988 (0.1%)		0/499 (0%)
Sleep apnoea syndrome	1/988 (0.1%)		0/499 (0%)
Surgical and medical procedures
Bladder catheterisation	0/988 (0%)		1/499 (0.2%)
Cardiac ablation	3/988 (0.3%)		1/499 (0.2%)
Implantable defibrillator insertion	1/988 (0.1%)		0/499 (0%)
Plastic surgery	0/988 (0%)		1/499 (0.2%)
Shoulder arthroplasty	1/988 (0.1%)		0/499 (0%)
Vascular disorders
Hypotension	2/988 (0.2%)		0/499 (0%)
Other (Not Including Serious) Adverse Events
	Rivaroxaban (Xarelto; BAY59-7939)		Vitamin K Antagonist
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	272/988 (27.5%)		126/499 (25.3%)
Cardiac disorders
Atrial fibrillation	2/988 (0.2%)		7/499 (1.4%)
Atrial thrombosis	16/988 (1.6%)		6/499 (1.2%)
Atrioventricular block first degree	40/988 (4%)		25/499 (5%)
Bradycardia	30/988 (3%)		13/499 (2.6%)
Sinus bradycardia	25/988 (2.5%)		12/499 (2.4%)
Gastrointestinal disorders
Constipation	10/988 (1%)		3/499 (0.6%)
Diarrhoea	18/988 (1.8%)		3/499 (0.6%)
Nausea	17/988 (1.7%)		1/499 (0.2%)
General disorders
Fatigue	14/988 (1.4%)		9/499 (1.8%)
Oedema peripheral	20/988 (2%)		5/499 (1%)
Infections and infestations
Influenza	3/988 (0.3%)		5/499 (1%)
Nasopharyngitis	12/988 (1.2%)		5/499 (1%)
Urinary tract infection	7/988 (0.7%)		5/499 (1%)
Injury, poisoning and procedural complications
Contusion	3/988 (0.3%)		5/499 (1%)
Investigations
International normalised ratio increased	1/988 (0.1%)		9/499 (1.8%)
Nervous system disorders
Dizziness	25/988 (2.5%)		9/499 (1.8%)
Headache	25/988 (2.5%)		7/499 (1.4%)
Respiratory, thoracic and mediastinal disorders
Cough	13/988 (1.3%)		3/499 (0.6%)
Dyspnoea	16/988 (1.6%)		12/499 (2.4%)
Epistaxis	30/988 (3%)		9/499 (1.8%)
Skin and subcutaneous tissue disorders
Rash	12/988 (1.2%)		5/499 (1%)
Vascular disorders
Hypertension	22/988 (2.2%)		4/499 (0.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

The Consultant agrees not to publish or cause to be published any works of authorship relating to the Project rendered pursuant to this Agreement without first notifying Bayer in writing and obtaining Bayer's written consent. Bayer will respond to such notification within sixty (60) days of receipt.Bayer reserves the right to insist on the removal of all or any of its Confidential Information from any such work prior to publication