EinsteinChoice: Reduced-dosed Rivaroxaban in the Long-term Prevention of Recurrent Symptomatic VTE(Venous Thromboembolism)

Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT02064439
Collaborator
Janssen Scientific Affairs, LLC (Industry)
3,365
267
3
32
12.6
0.4

Study Details

Study Description

Brief Summary

This is a multicenter, randomized, double-blind, event-driven, superiority study for efficacy.

Patients with confirmed symptomatic DVT (Deep Vein Thrombosis) or PE (Pulmonary embolism) who completed 6 or 12 months of treatment of anticoagulation are eligible for this trial

Condition or Disease Intervention/Treatment Phase
  • Drug: BAY 59-7939
  • Drug: BAY 59-7939
  • Drug: ASA
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
3365 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Reduced-dosed Rivaroxaban and Standard-dosed Rivaroxaban Versus ASA in the Long-term Prevention of Recurrent Symptomatic Venous Thromboembolism in Patients With Symptomatic Deep-vein Thrombosis and/or Pulmonary Embolism
Actual Study Start Date :
Mar 5, 2014
Actual Primary Completion Date :
Sep 22, 2016
Actual Study Completion Date :
Nov 4, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm 1

Rivaroxaban 10 mg once daily for 12 months

Drug: BAY 59-7939
10 mg tablet once daily for 12 months

Experimental: Arm 2

Rivaroxaban 20 mg once daily for 12 months

Drug: BAY 59-7939
20 mg tablet once daily for 12 months

Active Comparator: Arm 3

ASA (Acetylsalicylic Acid) 100 mg once daily for 12 months

Drug: ASA
100 mg tablet once daily for 12 months

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With the Composite of Fatal or Non-fatal Symptomatic Recurrent Venous Thromboembolism [Up to 12 months, at least 6 months]

    The primary efficacy outcomes (i.e., recurrent venous thromboembolism [VTE] defined as composite of fatal or non-fatal symptomatic recurrent VTE, including unexplained death for which pulmonary embolism [PE] could not be ruled out) as confirmed by the central independent adjudication committee (CIAC) were considered up to the end of the individual intended duration of treatment. Incidence of the composite of the primary and secondary efficacy outcome and its components are based on the first occurrence to participant.

  2. Number of Participants With First Treatment-emergent Major Bleeding [Up to 12 months, at least 6 months]

    The principal safety outcome was major bleeding which was defined according to the criteria of the International Society on Thrombosis and Hemostasis (ISTH) as clinically overt bleeding and associated with a fall in hemoglobin of 2 gram per deciliter (g/dL) or more, or leading to a transfusion of 2 or more units of packed red blood cells or whole blood, or occurring in a critical site, e.g. intracranial, intraspinal, intraocular, pericardial, intra articular, intramuscular with compartment syndrome, retroperitoneal, or contributing to death. Incidence of the composite of the primary and secondary efficacy outcome and its components are based on the first occurrence to participant.

Secondary Outcome Measures

  1. Number of Participants With the Composite of the Primary Efficacy Outcome, Myocardial Infarction, Ischemic Stroke or Systemic Non-CNS Embolism [Up to 12 months, at least 6 months]

    The secondary efficacy outcome is the composite of the primary efficacy outcome, myocardial infarction (MI), ischemic stroke or non-central nervous system (CNS) systemic embolism. Incidence of the composite of the primary and secondary efficacy outcome and its components are based on the first occurrence to participant.

  2. Number of Participants With Non-major Bleeding Associated With Study Drug Interruption for > 14 Days [Up to 12 months, at least 6 months]

    The secondary safety outcome was clinically relevant non-major (CRNM) bleeding, which was adjudicated by the CIAC using the ASA criteria: the bleeding was non-major and the bleeding was associated with a study medication interruption of more than 14 days.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Patients with confirmed symptomatic PE and/or DVT who have been treated for 6 to 12 months and did not interrupt anticoagulation for longer than 1 week
Exclusion Criteria:
  • Legal lower age limitations (country specific) Indication for therapeutic-dosed anticoagulants Indication for antiplatelet therapy or a conventional non-steroid anti-inflammatory drug (NSAID) Hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk Calculated creatinine clearance < 30 mL/min

Contacts and Locations

Locations

Site City State Country Postal Code
1 Beverly Hills California United States 90211
2 La Jolla California United States 92037
3 Ventura California United States 93003
4 Denver Colorado United States 80262
5 Jacksonville Florida United States 32207
6 Columbus Georgia United States 31904
7 Joliet Illinois United States 60435
8 Rockport Maine United States 04856
9 Boston Massachusetts United States 02114-2696
10 Boston Massachusetts United States 02115
11 Boston Massachusetts United States 02215
12 Detroit Michigan United States 48202
13 Butte Montana United States 59701
14 Las Vegas Nevada United States 89169
15 Raleigh North Carolina United States 27607
16 Columbus Ohio United States 43210-1240
17 Toledo Ohio United States 43606
18 Philadelphia Pennsylvania United States 19104
19 San Antonio Texas United States 78229
20 Fredericksburg Virginia United States 22401
21 Bellevue Washington United States 98004
22 Seattle Washington United States 98104
23 Spokane Washington United States 99216
24 Tacoma Washington United States 98405-2433
25 Garran Australian Capital Territory Australia 2605
26 Concord New South Wales Australia 2139
27 Kogarah New South Wales Australia 2217
28 Lismore New South Wales Australia 2480
29 Randwick New South Wales Australia 2031
30 St Leonards New South Wales Australia 2065
31 Westmead New South Wales Australia 2145
32 Brisbane Queensland Australia 4029
33 Clayton Victoria Australia 3168
34 Box Hill Australia 3128
35 Melbourne Australia 3004
36 Redcliffe Australia 4020
37 Graz Steiermark Austria 8036
38 Innsbruck Tirol Austria 6020
39 Wien Austria 1090
40 Aalst Belgium 9300
41 Bruxelles - Brussel Belgium 1070
42 Bruxelles - Brussel Belgium 1200
43 Hasselt Belgium 3500
44 Leuven Belgium 3000
45 Belo Horizonte Minas Gerais Brazil 30150-221
46 Porto Alegre Rio Grande Do Sul Brazil
47 Campinas Sao Paulo Brazil 13083-970
48 Santo André Sao Paulo Brazil 09060-650
49 Santo André Sao Paulo Brazil 09190-615
50 São Paulo Sao Paulo Brazil 01323-001
51 São Paulo Sao Paulo Brazil 04039-004
52 Rio de Janeiro Brazil
53 Sao Paulo Brazil 05403-900
54 Edmonton Alberta Canada T6G 2B7
55 Victoria British Columbia Canada V8R 4R2
56 Saint John New Brunswick Canada E2L 4L2
57 Halifax Nova Scotia Canada B3H 3A7
58 Hamilton Ontario Canada L8L 2X2
59 Hamilton Ontario Canada L8N 4A6
60 Hamilton Ontario Canada L8V 1C3
61 London Ontario Canada N6A 4G5
62 Ottawa Ontario Canada K1H 8L6
63 Montreal Quebec Canada H1T 2M4
64 Montreal Quebec Canada H3T 1E2
65 Montreal Quebec Canada H3T 1M5
66 St. Jerome Quebec Canada J7Z 5T3
67 Fuzhou Fujian China 350025
68 Guangzhou Guangdong China 510080
69 Guangzhou Guangdong China 510120
70 Nanning Guangxi China 530021
71 Shijiazhuang Hebei China 050000
72 Harbin Heilongjiang China
73 Wuhan Hubei China 430032
74 Changsha Hunan China 410011
75 Changsha Hunan China 410013
76 Nantong Jiangsu China 226001
77 Suzhou Jiangsu China 215004
78 Changchun Jilin China 130000
79 Shengyang Liaoning China 110004
80 Shenyang Liaoning China 110001
81 Yinchuan Ningxia China 750004
82 Xi'an Shaanxi China 710032
83 Xi'an Shaanxi China 710061
84 Jinan Shandong China 250012
85 Qingdao Shandong China 266000
86 Taiyuan Shanxi China 030001
87 Chengdu Sichuan China 610041
88 Kunming Yunnan China 650032
89 Hangzhou Zhejiang China 310003
90 Hangzhou Zhejiang China 310016
91 Wenzhou Zhejiang China 325000
92 Beijing China 100020
93 Beijing China 100029
94 Beijing China 100037
95 Beijing China 100053
96 Beijing China 100730
97 Shanghai China 200001
98 Shanghai China 200025
99 Shanghai China 200032
100 Shanghai China 200233
101 Shanghai China 200433
102 Tianjin China 300052
103 Tianjin China 300121
104 Tianjin China 300211
105 Kladno Czechia 27259
106 Liberec Czechia 46063
107 Litomysl Czechia 570 14
108 Ostrava Czechia 708 52
109 Ostrava Czechia 728 80
110 Prague Czechia 118 33
111 Praha 1 Czechia 110 00
112 Praha 5 Czechia 150 06
113 Usti nad Labem Czechia 401 13
114 Aarhus N Denmark 8200
115 Copenhagen Denmark 2300
116 Glostrup Denmark 2600
117 Hellerup Denmark 2900
118 Herning Denmark 7400
119 København NV Denmark 2400
120 Svendborg Denmark 5700
121 Angers France 49933
122 Arras France 62000
123 Besancon France 25030
124 Bois-guillaume France 76320
125 BREST Cedex 9 France 29240
126 Brest Cedex France 29609
127 Castelnau Le Lez France 34170
128 Clermont Ferrand France 63000
129 Colombes Cedex France 92701
130 Dijon France 21000
131 Grenoble France 38043
132 Le Kremlin Bicetre Cedex France 94275
133 Le Mans France 72037
134 Limoges Cedex France 87042
135 Nice France 06002
136 Paris Cedex 15 France 75908
137 Paris France 75475
138 Paris France 75674
139 Quimper France 29000
140 Saint Etienne France 42055
141 Strasbourg Cedex France 67091
142 Toulon France 83056
143 Toulouse France 31403
144 Vernon France 27200
145 Heidelberg Baden-Württemberg Germany 69120
146 München Bayern Germany 80336
147 Darmstadt Hessen Germany 64297
148 Witten Nordrhein-Westfalen Germany 58448
149 Mainz Rheinland-Pfalz Germany 55131
150 Magdeburg Sachsen-Anhalt Germany 39112
151 Dresden Sachsen Germany 01067
152 Dresden Sachsen Germany 01307
153 Erfurt Thüringen Germany 99089
154 Berlin Germany 10787
155 Karlsbad Germany 76307
156 Baja Hungary 6500
157 Budapest Hungary 1115
158 Debrecen Hungary 4032
159 Gyula Hungary 5700
160 Kecskemet Hungary 6000
161 Miskolc Hungary 3526
162 Pecs Hungary 7624
163 Szentes Hungary 6600
164 Szombathely Hungary 9700
165 Zalaegerszeg Hungary 8900
166 Afula Israel 1834111
167 Haifa Israel 3109601
168 Haifa Israel 3339419
169 Holon Israel 5810001
170 Kfar Saba Israel 4428164
171 Nahariya Israel 2210001
172 Petah Tikva Israel 4941492
173 Tel-Aviv Israel 64239
174 Zefat Israel 1311001
175 Chieti Abruzzo Italy 66013
176 Cosenza Calabria Italy 87100
177 Piacenza Emilia-Romagna Italy 29121
178 Reggio Emilia Emilia-Romagna Italy 42100
179 Varese Lombardia Italy 21100
180 Perugia Umbria Italy 06156
181 Padova Veneto Italy 35128
182 Treviso Veneto Italy 31029
183 Treviso Veneto Italy 31033
184 Donggu, Gwangju Gwang''yeogsi Korea, Republic of 501-757
185 Busan Korea, Republic of 602-739
186 Daegu Korea, Republic of 705-718
187 Seoul Korea, Republic of 03080
188 Seoul Korea, Republic of 120-752
189 Seoul Korea, Republic of 135-710
190 Leon Guanajuato Mexico 37000
191 León Guanajuato Mexico 37000
192 Guadalajara Jalisco Mexico 44280
193 Guadalajara Jalisco Mexico 44340
194 Monterrey Nuevo Leon Mexico 64718
195 Xalapa Veracruz Mexico 91020
196 Merida Yucatán Mexico 97129
197 Aguascalientes Mexico 20230
198 Chihuahua Mexico 31203
199 Alkmaar Netherlands 1815 JD
200 Almere Netherlands 1315 RA
201 Amsterdam Netherlands 1105 AZ
202 Assen Netherlands 9401 RK
203 Dordrecht Netherlands 3318 AT
204 Groningen Netherlands 9713 GZ
205 Hoofddorp Netherlands 2134 TM
206 Maastricht Netherlands 6229 HX
207 Sittard Netherlands 6131 BK
208 Zwolle Netherlands 8025 AB
209 Auckland New Zealand 1023
210 Auckland New Zealand 1309
211 Auckland New Zealand 2024
212 Christchurch New Zealand 8011
213 Palmerston North New Zealand 4414
214 Wellington New Zealand 6021
215 Fredrikstad Norway 1603
216 Oslo Norway 0450
217 Quezon City Philippines NCR 1100
218 Bialystok Poland 15-276
219 Bydgoszcz Poland 85-681
220 Poznan Poland 60-631
221 Warszawa Poland 01-138
222 Wroclaw Poland 51-124
223 Barnaul Russian Federation 656045
224 Moscow Russian Federation 111539
225 Moscow Russian Federation 121552
226 Novosibirsk Russian Federation 630055
227 Novosibirsk Russian Federation 630087
228 Rostov-on-Don Russian Federation 344022
229 Ryazan Russian Federation 390026
230 Sochi Russian Federation 354057
231 St. Petersburg Russian Federation 197022
232 St. Petersburg Russian Federation
233 Tver Russian Federation 170036
234 Johannesburg Gauteng South Africa 2132
235 Johannesburg Gauteng South Africa 2191
236 Pretoria West Gauteng South Africa 0082
237 Pretoria Gauteng South Africa 0181
238 Roodepoort Gauteng South Africa 1724
239 Worcester Western Cape South Africa 6850
240 Bloemfontein South Africa 9301
241 Torrevieja Alicante Spain 03186
242 L'Hospitalet de Llobregat Barcelona Spain 08907
243 San Sebastián de los Reyes Madrid Spain 28702
244 Girona Spain 17007
245 Madrid Spain 28007
246 Göteborg Sweden 416 85
247 Kristianstad Sweden 29185
248 Basel Basel-Stadt Switzerland 4031
249 Lausanne Vaud Switzerland 1011
250 Bern Switzerland 3010
251 Fribourg Switzerland 1700
252 Genève Switzerland 1205
253 Luzern Switzerland 6000
254 New Taipei City Taiwan 220
255 Taichung Taiwan 40447
256 Taipei Taiwan 11217
257 Bangkok Thailand 10400
258 Khon Kaen Thailand 40002
259 Istanbul Turkey 34-300
260 Istanbul Turkey 34760
261 Plymouth Devon United Kingdom PL6 8DH
262 Hull Humberside United Kingdom HU3 2JZ
263 Newcastle Upon Tyne Tyne And Wear United Kingdom NE1 4LP
264 Cardiff United Kingdom CF14 4XW
265 London United Kingdom SE1 7EH
266 Ha Noi Vietnam
267 Ho Chi Minh Vietnam 70000

Sponsors and Collaborators

  • Bayer
  • Janssen Scientific Affairs, LLC

Investigators

  • Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT02064439
Other Study ID Numbers:
  • 16416
  • 2013-000619-26
First Posted:
Feb 17, 2014
Last Update Posted:
Dec 19, 2017
Last Verified:
Nov 1, 2017
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Bayer
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details In total 3439 participants were screened at 244 sites in 31 countries from 05-Mar-2014 (First Patient First Visit) to 15-Mar-2016 (Last Patient First Visit).
Pre-assignment Detail Of the 3439 participants screened 43 did not complete screening. Thus, 3396 participants were randomly assigned to treatment, 31 of the randomized participants never received study medication because either withdrew consent or were withdrawn from the study based on protocol violations.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD Acetylsalicylic (ASA) 100 mg, OD
Arm/Group Description Participants were randomized, stratified by country and by index event, to receive rivaroxaban 10 mg tablet or matching placebo once daily (OD) with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized. Participants were randomized, stratified by country and by index event, to receive rivaroxaban 20 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized. Participants were randomized, stratified by country and by index event, to receive ASA 100 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.
Period Title: Overall Study
STARTED 1127 1107 1131
COMPLETED 984 969 949
NOT COMPLETED 143 138 182

Baseline Characteristics

Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD Acetylsalicylic (ASA) 100 mg, OD Total
Arm/Group Description Participants were randomized, stratified by country and by index event, to receive rivaroxaban 10 mg tablet or matching placebo once daily (OD) with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized. Participants were randomized, stratified by country and by index event, to receive rivaroxaban 20 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized. Participants were randomized, stratified by country and by index event, to receive ASA 100 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized. Total of all reporting groups
Overall Participants 1127 1107 1131 3365
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
58.8
(14.7)
57.9
(14.7)
58.8
(14.7)
58.5
(14.7)
Sex: Female, Male (Count of Participants)
Female
507
45%
505
45.6%
488
43.1%
1500
44.6%
Male
620
55%
602
54.4%
643
56.9%
1865
55.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
31
2.8%
31
2.8%
30
2.7%
92
2.7%
Not Hispanic or Latino
892
79.1%
899
81.2%
889
78.6%
2680
79.6%
Unknown or Not Reported
204
18.1%
177
16%
212
18.7%
593
17.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
2
0.2%
0
0%
2
0.2%
4
0.1%
Asian
161
14.3%
159
14.4%
159
14.1%
479
14.2%
Native Hawaiian or Other Pacific Islander
1
0.1%
1
0.1%
2
0.2%
4
0.1%
Black or African American
41
3.6%
49
4.4%
36
3.2%
126
3.7%
White
786
69.7%
772
69.7%
786
69.5%
2344
69.7%
More than one race
1
0.1%
0
0%
5
0.4%
6
0.2%
Unknown or Not Reported
135
12%
126
11.4%
141
12.5%
402
11.9%

Outcome Measures

1. Primary Outcome
Title Number of Participants With the Composite of Fatal or Non-fatal Symptomatic Recurrent Venous Thromboembolism
Description The primary efficacy outcomes (i.e., recurrent venous thromboembolism [VTE] defined as composite of fatal or non-fatal symptomatic recurrent VTE, including unexplained death for which pulmonary embolism [PE] could not be ruled out) as confirmed by the central independent adjudication committee (CIAC) were considered up to the end of the individual intended duration of treatment. Incidence of the composite of the primary and secondary efficacy outcome and its components are based on the first occurrence to participant.
Time Frame Up to 12 months, at least 6 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD Acetylsalicylic (ASA) 100 mg, OD
Arm/Group Description Participants were randomized, stratified by country and by index event, to receive rivaroxaban 10 mg tablet or matching placebo once daily (OD) with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized. Participants were randomized, stratified by country and by index event, to receive rivaroxaban 20 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized. Participants were randomized, stratified by country and by index event, to receive ASA 100 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.
Measure Participants 1127 1107 1131
Composite
13
1.2%
17
1.5%
50
4.4%
Symptomatic recurrent Deep vein thrombosis (DVT)
8
0.7%
9
0.8%
29
2.6%
Symptomatic recurrent PE
5
0.4%
6
0.5%
19
1.7%
Death (PE)
0
0%
0
0%
1
0.1%
Death (unexplained and PE cannot be ruled out)
0
0%
2
0.2%
1
0.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD, Acetylsalicylic (ASA) 100 mg, OD
Comments Statistical analysis was performed on the first occurrence of the composite outcome.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0001
Comments P-value and hazard ratio estimates based on stratified proportional hazards model, with stratification based index event (DVT or PE with or without DVT).
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
0.20 to 0.59
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD, Acetylsalicylic (ASA) 100 mg, OD
Comments Statistical analysis was performed on the first occurrence of the composite outcome.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments P-value and hazard ratio estimates based on stratified proportional hazards model, with stratification based index event (DVT or PE with or without DVT).
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.26
Confidence Interval (2-Sided) 98%
0.14 to 0.47
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD, Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD
Comments Statistical analysis was performed on the first occurrence of the composite outcome.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4328
Comments P-value and hazard ratio estimates based on stratified proportional hazards model, with stratification based index event (DVT or PE with or without DVT).
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.34
Confidence Interval (2-Sided) 95%
0.65 to 2.75
Parameter Dispersion Type:
Value:
Estimation Comments
2. Primary Outcome
Title Number of Participants With First Treatment-emergent Major Bleeding
Description The principal safety outcome was major bleeding which was defined according to the criteria of the International Society on Thrombosis and Hemostasis (ISTH) as clinically overt bleeding and associated with a fall in hemoglobin of 2 gram per deciliter (g/dL) or more, or leading to a transfusion of 2 or more units of packed red blood cells or whole blood, or occurring in a critical site, e.g. intracranial, intraspinal, intraocular, pericardial, intra articular, intramuscular with compartment syndrome, retroperitoneal, or contributing to death. Incidence of the composite of the primary and secondary efficacy outcome and its components are based on the first occurrence to participant.
Time Frame Up to 12 months, at least 6 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD Acetylsalicylic (ASA) 100 mg, OD
Arm/Group Description Participants were randomized, stratified by country and by index event, to receive rivaroxaban 10 mg tablet or matching placebo once daily (OD) with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized. Participants were randomized, stratified by country and by index event, to receive rivaroxaban 20 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized. Participants were randomized, stratified by country and by index event, to receive ASA 100 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.
Measure Participants 1127 1107 1131
Any major bleeding
5
0.4%
6
0.5%
3
0.3%
Fatal bleeding
0
0%
1
0.1%
1
0.1%
Non-fatal critical organ bleed
2
0.2%
4
0.4%
1
0.1%
Non-fatal non-critical organ bleeding
3
0.3%
1
0.1%
1
0.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD, Acetylsalicylic (ASA) 100 mg, OD
Comments Statistical analysis was performed on the first occurrence of the composite outcome.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3235
Comments P-value and hazard ratio estimates based on stratified proportional hazards model, with stratification based index event (DVT or PE with or without DVT).
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.01
Confidence Interval (2-Sided) 95%
0.50 to 8.04
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD, Acetylsalicylic (ASA) 100 mg, OD
Comments Statistical analysis was performed on the first occurrence of the composite outcome.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5005
Comments P-value and hazard ratio estimates based on stratified proportional hazards model, with stratification based index event (DVT or PE with or without DVT).
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.64
Confidence Interval (2-Sided) 95%
0.39 to 6.84
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD, Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD
Comments Statistical analysis was performed on the first occurrence of the composite outcome.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7337
Comments P-value and hazard ratio estimates based on stratified proportional hazards model, with stratification based index event (DVT or PE with or without DVT).
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.23
Confidence Interval (2-Sided) 95%
0.37 to 4.03
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Number of Participants With the Composite of the Primary Efficacy Outcome, Myocardial Infarction, Ischemic Stroke or Systemic Non-CNS Embolism
Description The secondary efficacy outcome is the composite of the primary efficacy outcome, myocardial infarction (MI), ischemic stroke or non-central nervous system (CNS) systemic embolism. Incidence of the composite of the primary and secondary efficacy outcome and its components are based on the first occurrence to participant.
Time Frame Up to 12 months, at least 6 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD Acetylsalicylic (ASA) 100 mg, OD
Arm/Group Description Participants were randomized, stratified by country and by index event, to receive rivaroxaban 10 mg tablet or matching placebo once daily (OD) with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized. Participants were randomized, stratified by country and by index event, to receive rivaroxaban 20 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized. Participants were randomized, stratified by country and by index event, to receive ASA 100 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.
Measure Participants 1127 1107 1131
Composite
18
1.6%
19
1.7%
56
5%
Ischemic stroke
4
0.4%
2
0.2%
2
0.2%
Non-CNS systemic embolism
1
0.1%
0
0%
1
0.1%
Myocardial infarction
0
0%
1
0.1%
4
0.4%
Symptomatic recurrent DVT
8
0.7%
9
0.8%
29
2.6%
Symptomatic recurrent PE
5
0.4%
6
0.5%
18
1.6%
Death (PE)
0
0%
0
0%
1
0.1%
Death (unexplained and PE cannot be ruled out)
0
0%
1
0.1%
1
0.1%
Death (cardiovascular: myocardial infarction)
0
0%
0
0%
0
0%
Death (cardiovascular: ischemic stroke)
0
0%
0
0%
0
0%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD, Acetylsalicylic (ASA) 100 mg, OD
Comments Statistical analysis was performed on the first occurrence of the composite outcome.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments P-value and hazard ratio estimates based on stratified proportional hazards model, with stratification based index event (DVT or PE with or without DVT).
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
0.20 to 0.57
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD, Acetylsalicylic (ASA) 100 mg, OD
Comments Statistical analysis was performed on the first occurrence of the composite outcome.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments P-value and hazard ratio estimates based on stratified proportional hazards model, with stratification based index event (DVT or PE with or without DVT).
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.32
Confidence Interval (2-Sided) 95%
0.19 to 0.54
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD, Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD
Comments Statistical analysis was performed on the first occurrence of the composite outcome.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8172
Comments P-value and hazard ratio estimates based on stratified proportional hazards model, with stratification based index event (DVT or PE with or without DVT).
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.57 to 2.06
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
Title Number of Participants With Non-major Bleeding Associated With Study Drug Interruption for > 14 Days
Description The secondary safety outcome was clinically relevant non-major (CRNM) bleeding, which was adjudicated by the CIAC using the ASA criteria: the bleeding was non-major and the bleeding was associated with a study medication interruption of more than 14 days.
Time Frame Up to 12 months, at least 6 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD Acetylsalicylic (ASA) 100 mg, OD
Arm/Group Description Participants were randomized, stratified by country and by index event, to receive rivaroxaban 10 mg tablet or matching placebo once daily (OD) with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized. Participants were randomized, stratified by country and by index event, to receive rivaroxaban 20 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized. Participants were randomized, stratified by country and by index event, to receive ASA 100 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.
Measure Participants 1127 1107 1131
Number [participants]
12
1.1%
17
1.5%
12
1.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD, Acetylsalicylic (ASA) 100 mg, OD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3318
Comments P-value and hazard ratio estimates based on stratified proportional hazards model, with stratification based index event (DVT or PE with or without DVT).
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.44
Confidence Interval (2-Sided) 95%
0.69 to 3.02
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD, Acetylsalicylic (ASA) 100 mg, OD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9726
Comments P-value and hazard ratio estimates based on stratified proportional hazards model, with stratification based index event (DVT or PE with or without DVT).
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.44 to 2.20
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD, Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3137
Comments P-value and hazard ratio estimates based on stratified proportional hazards model, with stratification based index event (DVT or PE with or without DVT).
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.46
Confidence Interval (2-Sided) 95%
0.70 to 3.06
Parameter Dispersion Type:
Value:
Estimation Comments

Adverse Events

Time Frame From after start of study medication but not more than 2 days after stop of study medication.
Adverse Event Reporting Description
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD Acetylsalicylic (ASA) 100 mg, OD
Arm/Group Description Participants were randomized, stratified by country and by index event, to receive rivaroxaban 10 mg tablet or matching placebo once daily (OD) with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized. Participants were randomized, stratified by country and by index event, to receive rivaroxaban 20 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized. Participants were randomized, stratified by country and by index event, to receive ASA 100 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.
All Cause Mortality
Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD Acetylsalicylic (ASA) 100 mg, OD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN)
Serious Adverse Events
Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD Acetylsalicylic (ASA) 100 mg, OD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 78/1127 (6.9%) 82/1107 (7.4%) 79/1131 (7%)
Blood and lymphatic system disorders
Anaemia 0/1127 (0%) 0 2/1107 (0.2%) 2 0/1131 (0%) 0
Iron deficiency anaemia 0/1127 (0%) 0 2/1107 (0.2%) 2 0/1131 (0%) 0
Thrombocytopenia 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Cardiac disorders
Arteriosclerosis coronary artery 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Atrial fibrillation 1/1127 (0.1%) 1 3/1107 (0.3%) 3 1/1131 (0.1%) 1
Atrial flutter 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Atrioventricular block second degree 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Bradycardia 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Cardiac failure 1/1127 (0.1%) 1 0/1107 (0%) 0 1/1131 (0.1%) 1
Cardiac failure chronic 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Cardiac failure congestive 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Coronary artery disease 0/1127 (0%) 0 0/1107 (0%) 0 2/1131 (0.2%) 2
Mitral valve incompetence 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Myocardial ischaemia 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Pericarditis 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Pericarditis constrictive 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Tachycardia 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Ear and labyrinth disorders
Vertigo 0/1127 (0%) 0 1/1107 (0.1%) 1 1/1131 (0.1%) 1
Vestibular disorder 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Sudden hearing loss 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Endocrine disorders
Cushing's syndrome 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Eye disorders
Corneal degeneration 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Gastrointestinal disorders
Ascites 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Diverticulum 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Diverticulum intestinal 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Gastritis 1/1127 (0.1%) 1 1/1107 (0.1%) 1 0/1131 (0%) 0
Haemorrhoids 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Inguinal hernia 1/1127 (0.1%) 1 2/1107 (0.2%) 2 0/1131 (0%) 0
Intestinal obstruction 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Pancreatitis acute 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Pancreatitis relapsing 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Umbilical hernia 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Subileus 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Hypertrophic anal papilla 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Abdominal hernia 1/1127 (0.1%) 1 0/1107 (0%) 0 1/1131 (0.1%) 1
Eosinophilic oesophagitis 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Colon dysplasia 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
General disorders
Chest pain 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Hepatobiliary disorders
Bile duct stone 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Biliary colic 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Cholecystitis 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Cholecystitis acute 0/1127 (0%) 0 1/1107 (0.1%) 1 2/1131 (0.2%) 2
Cholelithiasis 1/1127 (0.1%) 2 0/1107 (0%) 0 0/1131 (0%) 0
Immune system disorders
Overlap syndrome 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Infections and infestations
Appendicitis 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Cellulitis 1/1127 (0.1%) 1 2/1107 (0.2%) 2 1/1131 (0.1%) 1
Clostridium difficile colitis 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Diarrhoea infectious 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Diverticulitis 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Erysipelas 2/1127 (0.2%) 2 0/1107 (0%) 0 2/1131 (0.2%) 2
Gastroenteritis 2/1127 (0.2%) 2 1/1107 (0.1%) 1 1/1131 (0.1%) 1
Influenza 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Nasopharyngitis 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Orchitis 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Peritonitis 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Plasmodium falciparum infection 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Pneumonia 2/1127 (0.2%) 2 5/1107 (0.5%) 6 3/1131 (0.3%) 3
Pseudomembranous colitis 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Pyelitis 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Pyelonephritis acute 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Sepsis 1/1127 (0.1%) 1 3/1107 (0.3%) 3 2/1131 (0.2%) 2
Septic shock 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Urethral abscess 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Urinary tract infection 2/1127 (0.2%) 2 4/1107 (0.4%) 6 0/1131 (0%) 0
Wound infection 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Urosepsis 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Abscess limb 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Arthritis bacterial 0/1127 (0%) 0 2/1107 (0.2%) 3 0/1131 (0%) 0
Infective exacerbation of chronic obstructive airways disease 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Pseudomonal sepsis 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Pneumonia bacterial 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Lung infection 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Borrelia infection 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Post procedural infection 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Injury, poisoning and procedural complications
Ankle fracture 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Clavicle fracture 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Fall 1/1127 (0.1%) 1 0/1107 (0%) 0 3/1131 (0.3%) 3
Femoral neck fracture 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Femur fracture 0/1127 (0%) 0 0/1107 (0%) 0 3/1131 (0.3%) 3
Fibula fracture 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Head injury 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Humerus fracture 2/1127 (0.2%) 2 0/1107 (0%) 0 1/1131 (0.1%) 1
Injury 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Joint dislocation 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Overdose 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Radius fracture 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Road traffic accident 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Spinal compression fracture 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Tendon rupture 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Tibia fracture 1/1127 (0.1%) 1 1/1107 (0.1%) 1 0/1131 (0%) 0
Cervical vertebral fracture 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Lumbar vertebral fracture 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Lower limb fracture 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Stomal hernia 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Pubis fracture 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Craniocerebral injury 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Investigations
Cystoscopy 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Haemoglobin decreased 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
White blood cell count decreased 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
B-lymphocyte count increased 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Metabolism and nutrition disorders
Diabetes mellitus inadequate control 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Obesity 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Type 2 diabetes mellitus 2/1127 (0.2%) 2 0/1107 (0%) 0 0/1131 (0%) 0
Musculoskeletal and connective tissue disorders
Joint ankylosis 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Osteitis 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 2
Osteoarthritis 3/1127 (0.3%) 3 0/1107 (0%) 0 5/1131 (0.4%) 6
Pain in extremity 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Rheumatoid arthritis 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Spinal column stenosis 0/1127 (0%) 0 2/1107 (0.2%) 2 1/1131 (0.1%) 1
Mobility decreased 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Intervertebral disc protrusion 1/1127 (0.1%) 1 0/1107 (0%) 0 1/1131 (0.1%) 1
Musculoskeletal chest pain 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Meniscal degeneration 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Spinal pain 0/1127 (0%) 0 1/1107 (0.1%) 2 0/1131 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon 1/1127 (0.1%) 1 1/1107 (0.1%) 1 0/1131 (0%) 0
Basal cell carcinoma 0/1127 (0%) 0 1/1107 (0.1%) 1 1/1131 (0.1%) 1
Benign gastric neoplasm 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Bladder cancer 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Bladder cancer recurrent 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Bladder transitional cell carcinoma 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Breast cancer 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Cervix carcinoma 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Cervix carcinoma recurrent 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Endometrial cancer 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Gastric cancer 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Leiomyosarcoma 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Lung carcinoma cell type unspecified stage IV 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Malignant melanoma stage I 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Malignant melanoma stage IV 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Meningioma 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Metastases to lung 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Metastases to lymph nodes 1/1127 (0.1%) 1 1/1107 (0.1%) 1 0/1131 (0%) 0
Oesophageal carcinoma 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Oesophageal carcinoma stage 0 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Plasma cell myeloma 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Rectal cancer recurrent 1/1127 (0.1%) 1 1/1107 (0.1%) 1 0/1131 (0%) 0
Ureteric cancer 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Uterine cancer 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Uterine leiomyoma 1/1127 (0.1%) 1 1/1107 (0.1%) 1 0/1131 (0%) 0
Colon cancer metastatic 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Prostate cancer 3/1127 (0.3%) 3 1/1107 (0.1%) 1 1/1131 (0.1%) 1
Cervix warts 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Malignant glioma 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Ovarian cancer stage IV 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Nervous system disorders
Axonal neuropathy 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Dizziness 1/1127 (0.1%) 2 0/1107 (0%) 0 0/1131 (0%) 0
Dyskinesia 2/1127 (0.2%) 2 0/1107 (0%) 0 0/1131 (0%) 0
Headache 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Migraine 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Presyncope 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Sciatica 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Seizure 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Syncope 0/1127 (0%) 0 1/1107 (0.1%) 1 2/1131 (0.2%) 2
Facial paresis 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Psychiatric disorders
Adjustment disorder with depressed mood 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Alcohol abuse 1/1127 (0.1%) 1 0/1107 (0%) 0 1/1131 (0.1%) 2
Alcoholism 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 2
Anxiety 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Depression 0/1127 (0%) 0 1/1107 (0.1%) 1 2/1131 (0.2%) 2
Paranoia 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Suicide attempt 3/1127 (0.3%) 3 0/1107 (0%) 0 0/1131 (0%) 0
Renal and urinary disorders
Nephrolithiasis 2/1127 (0.2%) 2 1/1107 (0.1%) 1 0/1131 (0%) 0
Neurogenic bladder 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Renal colic 0/1127 (0%) 0 1/1107 (0.1%) 1 1/1131 (0.1%) 1
Renal failure 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Urinary retention 0/1127 (0%) 0 1/1107 (0.1%) 1 1/1131 (0.1%) 1
Tubulointerstitial nephritis 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Urethral stenosis 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Acute kidney injury 0/1127 (0%) 0 0/1107 (0%) 0 2/1131 (0.2%) 2
End stage renal disease 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Ureterolithiasis 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Reproductive system and breast disorders
Prostatitis 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Asthma 1/1127 (0.1%) 1 1/1107 (0.1%) 1 0/1131 (0%) 0
Chronic obstructive pulmonary disease 1/1127 (0.1%) 1 3/1107 (0.3%) 4 3/1131 (0.3%) 3
Dyspnoea 1/1127 (0.1%) 1 2/1107 (0.2%) 4 1/1131 (0.1%) 1
Interstitial lung disease 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Nasal polyps 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Pleural effusion 0/1127 (0%) 0 1/1107 (0.1%) 2 0/1131 (0%) 0
Pleurisy 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Pulmonary hypertension 1/1127 (0.1%) 1 0/1107 (0%) 0 1/1131 (0.1%) 1
Respiratory failure 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Pulmonary mass 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Organising pneumonia 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Skin and subcutaneous tissue disorders
Rash 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Seborrhoea 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Urticaria 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Pruritus generalised 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Cutaneous lupus erythematosus 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Surgical and medical procedures
Hysterectomy 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Meningioma surgery 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Vascular disorders
Aortic aneurysm 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Aortic dissection 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Aortic stenosis 0/1127 (0%) 0 1/1107 (0.1%) 1 0/1131 (0%) 0
Hypertension 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Hypertensive crisis 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Thrombophlebitis 0/1127 (0%) 0 0/1107 (0%) 0 1/1131 (0.1%) 1
Peripheral arterial occlusive disease 1/1127 (0.1%) 1 0/1107 (0%) 0 0/1131 (0%) 0
Other (Not Including Serious) Adverse Events
Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD Acetylsalicylic (ASA) 100 mg, OD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 40/1127 (3.5%) 35/1107 (3.2%) 38/1131 (3.4%)
Cardiac disorders
Atrial fibrillation 6/1127 (0.5%) 6 2/1107 (0.2%) 2 3/1131 (0.3%) 3
Gastrointestinal disorders
Abdominal pain upper 2/1127 (0.2%) 3 2/1107 (0.2%) 2 5/1131 (0.4%) 5
Constipation 2/1127 (0.2%) 2 0/1107 (0%) 0 7/1131 (0.6%) 8
Diarrhoea 4/1127 (0.4%) 4 4/1107 (0.4%) 5 1/1131 (0.1%) 1
Dyspepsia 1/1127 (0.1%) 1 3/1107 (0.3%) 3 4/1131 (0.4%) 4
Gastrooesophageal reflux disease 1/1127 (0.1%) 1 5/1107 (0.5%) 5 6/1131 (0.5%) 6
Vomiting 0/1127 (0%) 0 4/1107 (0.4%) 4 2/1131 (0.2%) 2
Infections and infestations
Nasopharyngitis 4/1127 (0.4%) 4 2/1107 (0.2%) 2 0/1131 (0%) 0
Upper respiratory tract infection 1/1127 (0.1%) 1 4/1107 (0.4%) 6 3/1131 (0.3%) 4
Musculoskeletal and connective tissue disorders
Back pain 3/1127 (0.3%) 3 3/1107 (0.3%) 3 4/1131 (0.4%) 4
Myalgia 2/1127 (0.2%) 2 2/1107 (0.2%) 2 4/1131 (0.4%) 4
Nervous system disorders
Dizziness 4/1127 (0.4%) 5 4/1107 (0.4%) 4 3/1131 (0.3%) 3
Skin and subcutaneous tissue disorders
Pruritus 8/1127 (0.7%) 8 3/1107 (0.3%) 3 3/1131 (0.3%) 3
Rash 5/1127 (0.4%) 5 3/1107 (0.3%) 3 3/1131 (0.3%) 3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The steering committee will be responsible for the publication and presentation strategy. All publications will be based on data released or agreed by Bayer, verified by the steering committee.

Results Point of Contact

Name/Title Therapeutic Area Head
Organization Bayer AG
Phone
Email clinical-trials-contact@bayer.com
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT02064439
Other Study ID Numbers:
  • 16416
  • 2013-000619-26
First Posted:
Feb 17, 2014
Last Update Posted:
Dec 19, 2017
Last Verified:
Nov 1, 2017