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Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Pulmonary Embolism - The EINSTEIN PE Study

Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT00439777
Collaborator
Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
4,833
Enrollment
305
Locations
2
Arms
57
Duration (Months)
15.8
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multicenter, randomized, open-label, assessor-blind, event-driven, non-inferiority program for efficacy with a study treatment duration of 3, 6 or 12 months in patients with confirmed acute symptomatic pulmonary embolism (PE) with or without symptomatic Deep-Vein Thrombosis (DVT) (Einstein-PE).

Condition or Disease Intervention/Treatment Phase
  • Drug: Rivaroxaban (Xarelto, BAY59-7939)
  • Drug: Enoxaparin overlapping with and followed by VKA
 Phase 3

Detailed Description

Within the US 'Johnson & Johnson Pharmaceutical Research & Development, L.L.C.' is sponsor.

Study Design

Study Type:
Interventional
Actual Enrollment :
4833 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Deep-Vein Thrombosis or Pulmonary Embolism
Study Start Date :
Mar 1, 2007
Actual Primary Completion Date :
Sep 1, 2011
Actual Study Completion Date :
Dec 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: Rivaroxaban (Xarelto, BAY59-7939)

Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)

Drug: Rivaroxaban (Xarelto, BAY59-7939)
During the first 3 weeks patients will receive 15 mg rivaroxaban twice-daily. Thereafter, patients will receive rivaroxaban 20 mg once-daily. Rivaroxaban will be administered orally and should be taken with food.
Active Comparator: Enoxaparin/VKA

Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)

Drug: Enoxaparin overlapping with and followed by VKA
Enoxaparin 1.0 mg/kg twice daily with a minimal duration of 5 days. This 5 days treatment could include the period up to 36 hr before randomization if enoxaparin twice-daily was used. VKA should be started as soon as possible but not later than 48 hours after randomization.

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants With Symptomatic Recurrent Venous Thromboembolism [VTE] (i.e. the Composite of Recurrent Deep Vein Thrombosis [DVT] or Fatal or Non-fatal Pulmonary Embolism [PE]) Until the Intended End of Study Treatment [3-, 6-, or 12-month study treatment period]

    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), and/or case summaries.

Secondary Outcome Measures

  1. Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality Until the Intended End of Study Treatment [3-, 6-, or 12-month study treatment period]

    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for deaths), results/films/images of confirmatory testing, and/or case summaries.

  2. Percentage of Participants With an Event for Net Clinical Benefit 1 Until the Intended End of Study Treatment [3-, 6-, or 12-month study treatment period]

    Net clinical benefit 1: composite of recurrent DVT or non-fatal or fatal PE, and major bleeding. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death. Net clinical benefit was considered greater in those participants with fewer composite events. All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.

  3. Percentage of Participants With Recurrent PE Until the Intended End of Study Treatment [3-, 6- or 12-month study treatment period]

    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.

  4. Percentage of Participants With Recurrent DVT Until the Intended End of Study Treatment [3-, 6- or 12-month study treatment period]

    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound, venography, results/films/images of confirmatory testing, and/or case summaries.

  5. Percentage of Participants With Clinically Relevant Bleeding, Treatment-emergent (Time Window: Until 2 Days After Last Dose) [3-, 6- or 12-month study treatment period]

    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. 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.

  6. Percentage of Participants With All Deaths [3-, 6- or 12-month study treatment period]

    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either autopsy, results/films/images of confirmatory testing, and/or case summaries.

  7. Percentage of Participants With Other Vascular Events, On-treatment (Time Window: Until 1 Day After Last Dose) [3-, 6- or 12-month study treatment period]

    All pre-defined vascular events (ST segment elevation myocardial infarction, non ST segment elevation myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, non-central nervous system systemic embolism or vascular death) were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based results/films/images of confirmatory testing, and/or case summaries.

Other Outcome Measures

  1. Percentage of Participants With the Individual Components of Efficacy Outcomes Until the Intended End of Study Treatment [3-, 6- or 12-month study treatment period]

    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death.

  2. Percentage of Participants With Symptomatic Recurrent VTE (i.e. the Composite of Recurrent DVT or Fatal or Non-fatal PE) During Observational Period [Up to 30 days after the last intake of study medication]

    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), and/or case summaries.

  3. Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality During Observational Period [Up to 30 days after the last intake of study medication]

    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for deaths), results/films/images of confirmatory testing, and/or case summaries.

  4. Percentage of Participants With an Event for Net Clinical Benefit 1 During Observational Period [Up to 30 days after the last intake of study medication]

    Net clinical benefit 1: composite of recurrent DVT or non-fatal or fatal PE, and major bleeding. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death. Net clinical benefit was considered greater in those participants with fewer composite events. All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.

  5. Percentage of Participants With Recurrent DVT During Observational Period [Up to 30 days after the last intake of study medication]

    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound, venography, results/films/images of confirmatory testing, and/or case summaries.

  6. Percentage of Participants With the Individual Components of Efficacy Outcomes During Observational Period [Up to 30 days after the last intake of study medication]

    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Confirmed acute symptomatic proximal PE with or without symptomatic DVT
Exclusion Criteria:

  • Legal lower age limitations (country specific)

  • Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT and/or PE

  • Other indication for VKA than DVT and/or PE

  • The pre-randomization anti-coagulant treatment (Criteria # 4) has been prolonged from 36 hours to a maximum of 48 hours.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Little Rock Arkansas United States 72205
2 Redlands California United States 92373
3 Bay Pines Florida United States 33744
4 Miami Florida United States 33136-1096
5 Miami Florida United States 33136
6 Idaho Falls Idaho United States 83404
7 Covington Louisiana United States 70433
8 Baltimore Maryland United States 21215
9 Boston Massachusetts United States 02215
10 Chesterfield Missouri United States 63017
11 Albuquerque New Mexico United States 87108
12 Chapel Hill North Carolina United States 27599-7035
13 Greensboro North Carolina United States 27401
14 Greensboro North Carolina United States 27403
15 Oklahoma City Oklahoma United States 73104
16 Camp Hill Pennsylvania United States 17011
17 Pittsburgh Pennsylvania United States 15224
18 San Antonio Texas United States 78229
19 Murray Utah United States 84107
20 Salt Lake City Utah United States 84132
21 Fredericksburg Virginia United States 22401
22 Spokane Washington United States 99204
23 Tacoma Washington United States 98405
24 Escaldes - Engordany Andorra
25 Garran Australian Capital Territory Australia 2605
26 Gosford New South Wales Australia 2250
27 Kogarah New South Wales Australia 2217
28 Lismore New South Wales Australia 2480
29 St Leonards New South Wales Australia 2065
30 Sydney New South Wales Australia 2031
31 Sydney New South Wales Australia 2139
32 Sydney New South Wales Australia 2229
33 Brisbane Queensland Australia 4029
34 Redcliffe Queensland Australia 4020
35 Southport Queensland Australia 4215
36 Woolloongabba Queensland Australia 4102
37 Adelaide South Australia Australia 5042
38 Woodville South South Australia Australia 5011
39 Launceston Tasmania Australia 7250
40 Box Hill Victoria Australia 3128
41 Clayton Victoria Australia 3168
42 Geelong Victoria Australia 3220
43 Melbourne Victoria Australia 3135
44 Melbourne Victoria Australia 3181
45 Fremantle Western Australia Australia 6160
46 Perth Western Australia Australia 6000
47 Graz Steiermark Austria 8036
48 Feldkirch Vorarlberg Austria 6807
49 Innsbruck Austria 6020
50 Linz Austria 4010
51 Wien Austria 1090
52 Wien Austria 1140
53 Wien Austria 1171
54 Aalst Belgium 9300
55 Bruxelles - Brussel Belgium 1070
56 Bruxelles - Brussel Belgium 1200
57 Duffel Belgium 2570
58 Genk Belgium 3600
59 Gent Belgium 9000
60 Hasselt Belgium 3500
61 Leuven Belgium 3000
62 Liege Belgium 4000
63 Lier Belgium 2500
64 Namur Belgium 5000
65 Yvoir Belgium 5530
66 Zottegem Belgium 9620
67 Curitiba Parana Brazil 80050-350
68 Londrina Parana Brazil 86038440
69 Botucatu Sao Paulo Brazil 18618 000
70 Sorocaba Sao Paulo Brazil 18031-000
71 São Paulo Sao Paulo Brazil 01323-001
72 São Paulo Sao Paulo Brazil 04039-004
73 São Paulo Sao Paulo Brazil 08270-070
74 Rio de Janeiro Brazil
75 Sao Paulo Brazil 01509-900
76 Winnipeg Manitoba Canada R2H 2A6
77 London Ontario Canada N6A 4G5
78 Ottawa Ontario Canada K1Y 4E9
79 Toronto Ontario Canada M4N 3M5
80 Toronto Ontario Canada M6R 1B5
81 Guangzhou Guangdong China 510080
82 Guangzhou Guangdong China 510120
83 Guangzhou Guangdong China
84 Nanning Guangxi China 530021
85 Harbin Heilongjiang China 150086
86 Wuhan Hubei China 430022
87 Suzhou Jiangsu China 215004
88 Shenyang Liaoning China 110016
89 Hangzhou Zhejiang China 310016
90 Beijing China 100020
91 Beijing China 100029
92 Beijing China 100037
93 Beijing China 100038
94 Beijing China 100044
95 Beijing China 100730
96 Beijing China 100853
97 Shanghai China 200001
98 Shanghai China 200032
99 Shanghai China 200433
100 Kladno Czech Republic 27259
101 Ostrava-Poruba Czech Republic 708 52
102 Ostrava Czech Republic 728 80
103 Prague 5 Czech Republic 150 00
104 Praha 1 Czech Republic 110 00
105 Praha 2 Czech Republic 12800
106 Rakovnik Czech Republic 269 01
107 Usti nad Lebem Czech Republic 401 13
108 Aarhus C Denmark 8000
109 Braedstrup Denmark 8740
110 Frederiksberg Denmark 2000F
111 Tallinn Estonia 10138
112 Tampere Finland 33521
113 Turku Finland 20520
114 Agen Cedex 9 France 47923
115 Amiens France 80000
116 Angers Cedex 01 France 49033
117 Arras France 62000
118 Besancon France 25000
119 Bordeaux France 33000
120 Brest Cedex France 29609
121 Castelnau Le Lez France 34170
122 Clamart France 92141
123 Clermont Ferrand France 63000
124 Colombes Cedex France 92701
125 Dijon France 21000
126 Grenoble France 38043
127 Limoges France 87042
128 Metz-tessy France 74370
129 Montpellier Cedex France 34295
130 Nantes France 44000
131 Nice France 06002
132 Orthez France 64300
133 Paris Cedex 15 France 75908
134 Paris France 75004
135 Paris France 75015
136 Paris France 75475
137 Paris France 75877
138 Pierre Benite France 69495
139 Roanne France 42328
140 Rouen Cedex France 76031
141 Saint Etienne France 42055
142 Strasbourg Cedex France 67091
143 Toulon France 83000
144 Toulouse France 31403
145 Valenciennes Cedex France 59322
146 Vandoeuvre Les Nancy France 54511
147 Vernon France 27200
148 Bruchsal Baden-Württemberg Germany 76646
149 Heidelberg Baden-Württemberg Germany 69115
150 Heidelberg Baden-Württemberg Germany 69120
151 Karlsbad Baden-Württemberg Germany 76307
152 Neckargemünd Baden-Württemberg Germany 69151
153 Tübingen Baden-Württemberg Germany 72076
154 Augsburg Bayern Germany 86156
155 München Bayern Germany 80331
156 München Bayern Germany 81377
157 Würzburg Bayern Germany 97080
158 Darmstadt Hessen Germany 64297
159 Frankfurt Hessen Germany 60590
160 Frankfurt Hessen Germany 60596
161 Greifswald Mecklenburg-Vorpommern Germany 17475
162 Rotenburg Niedersachsen Germany 27342
163 Essen Nordrhein-Westfalen Germany 45122
164 Paderborn Nordrhein-Westfalen Germany 33098
165 Witten Nordrhein-Westfalen Germany 58455
166 Mainz Rheinland-Pfalz Germany 55131
167 Halle Sachsen-Anhalt Germany 06120
168 Magdeburg Sachsen-Anhalt Germany 39112
169 Dresden Sachsen Germany 01307
170 Nordhausen Thüringen Germany 99734
171 Berlin Germany 12099
172 Bottrop Germany 46242
173 Hamburg Germany 20251
174 Hong Kong Hong Kong
175 Wanchai Hong Kong
176 Budapest Hungary 1096
177 Budapest Hungary 1115
178 Debrecen Hungary 4032
179 Kecskemet Hungary 6000
180 Kistarcsa Hungary 2143
181 Miskolc Hungary 3526
182 Szekszard Hungary 7100
183 Szentes Hungary 6600
184 Szombathely Hungary 9700
185 Zalaegerszeg Hungary 8900
186 Kochi Kerala India 682026
187 Hyderabad India 500082
188 New Delhi India 110060
189 Pune India 411001
190 Bandung Indonesia 40161
191 Jakarta Indonesia 10330
192 Jakarta Indonesia 10430
193 Medan Indonesia 20152
194 Semarang Indonesia 50241
195 Ballinasloe Co. Galway Ireland
196 Afula Israel 18101
197 Ashkelon Israel 78278
198 Haifa Israel 31048
199 Haifa Israel 31096
200 Haifa Israel 34362
201 Holon Israel 58100
202 Jerusalem Israel 91120
203 Kfar Saba Israel 44281
204 Petach Tikva Israel 49100
205 Rehovot Israel 76100
206 Safed Israel 13100
207 Tel Aviv Israel 64239
208 Rozzano Milano Italy 20089
209 Bologna Italy 40138
210 Chieti Italy 66013
211 Milano Italy 20122
212 Milano Italy 20132
213 Milano Italy 20142
214 Padova Italy 35128
215 Palermo Italy 90127
216 Parma Italy 43100
217 Pavia Italy 27100
218 Piacenza Italy 29100
219 Reggio Emilia Italy 42100
220 Varese Italy 21100
221 Venezia Italy 30122
222 Seoul Korea Korea, Republic of 110-744
223 Daegu Korea, Republic of 705-718
224 Seoul Korea, Republic of 120-752
225 Taegu Korea, Republic of 700-712
226 Liepaja Latvia LV 3414
227 Kaunas Lithuania LT-50009
228 Vilnius Lithuania LT-08661
229 Selangor Malaysia 68000
230 Amsterdam Netherlands 1105 AZ
231 Arnhem Netherlands 6815 AD
232 Enschede Netherlands 7511 JX
233 Groningen Netherlands 9713 GZ
234 Hoofddorp Netherlands 2134 TM
235 Maastricht Netherlands 6229 HX
236 Zwolle Netherlands 8025 AB
237 Auckland New Zealand 0622
238 Auckland New Zealand 1023
239 Auckland New Zealand 2024
240 Christchurch New Zealand 8011
241 Palmerston North New Zealand 4414
242 Wellington South New Zealand 6021
243 Fredrikstad Norway 1603
244 Oslo Norway 0407
245 Rud Norway 1309
246 Trondheim Norway 7006
247 Quezon City Philippines 0850
248 Quezon City Philippines 1102
249 Bialystok Poland 15-276
250 Krakow Poland 31-066
251 Lodz Poland 90-153
252 Lublin Poland 20-081
253 Poznan Poland 60-631
254 Poznan Poland 61-848
255 Torun Poland 87-100
256 Warszawa Poland 01-138
257 Wroclaw Poland 50-326
258 Wroclaw Poland 51-124
259 San Juan Puerto Rico 00927
260 Singapore Singapore 169608
261 Singapore Singapore 308433
262 Johannesburg Gauteng South Africa 2132
263 Johannesburg Gauteng South Africa 2157
264 Johannesburg Gauteng South Africa 2191
265 Pretoria Gauteng South Africa 0084
266 Pretoria Gauteng South Africa 0157
267 Pretoria Gauteng South Africa 0181
268 Roodepoort Gauteng South Africa 1724
269 Cape Town Western Cape South Africa 7460
270 Somerset West Western Cape South Africa 7130
271 Worcester Western Cape South Africa 6850
272 Terrassa Barcelona Spain 08221
273 Valladolid Castilla - León Spain 47010
274 Palma de Mallorca Illes Baleares Spain 07010
275 Requena Valencia Spain 46340
276 Barcelona Spain 08025
277 Barcelona Spain 08036
278 Girona Spain 17007
279 Madrid Spain 28034
280 Pamplona Spain 31008
281 Borås Sweden 501 82
282 Göteborg Sweden 413 45
283 Göteborg Sweden 416 85
284 Jönköping Sweden 551 85
285 Stockholm Sweden 118 83
286 Sundsvall Sweden 851 86
287 Genéve 14 Genève 14 Switzerland 1211
288 Chur Graubünden Switzerland 7000
289 Lausanne Vaud Switzerland 1011
290 Lausanne Waadt Switzerland 1005
291 Bern Switzerland 3010
292 Luzern Switzerland 6000
293 Zürich Switzerland 8091
294 Taichung Taiwan 40705
295 Taipei Taiwan 10016
296 Taipei Taiwan 112
297 Taipei Taiwan 220
298 Bangkok Thailand 10400
299 Chiang Mai Thailand 50200
300 Pathumwan, Bangkok Thailand 10330
301 Plymouth Devon United Kingdom PL6 8DH
302 Isleworth London United Kingdom TW7 6AF
303 London United Kingdom SE1 7EH
304 London United Kingdom SE5 9RS
305 London United Kingdom

Sponsors and Collaborators

  • Bayer
  • Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

  • Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT00439777
Other Study ID Numbers:
  • 11702b
  • 2006-004495-13
First Posted:
Feb 26, 2007
Last Update Posted:
Feb 27, 2014
Last Verified:
Jan 1, 2014
Additional relevant MeSH terms:
Pulmonary Embolism
Embolism
Enoxaparin
Rivaroxaban

Study Results

Participant Flow

Recruitment Details Participants with confirmed acute symptomatic pulmonary embolism (PE) with or without symptomatic deep vein thrombosis (DVT) were recruited at specialized study sites.
Pre-assignment Detail Out of 4843 participants screened, 10 failed screening (6 due to protocol violations, 2 due to investigator decision and another 2 subjects due to technical problems [interactive voice response system did not work properly]). 4833 participants were randomized (2420 to rivaroxaban and 2413 to enoxaparin/VKA).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Period Title: Treatment Period
STARTED 2420 2413
Participants Received Treatment 2412 2405
COMPLETED 2001 1954
NOT COMPLETED 419 459
Period Title: Treatment Period
STARTED 2206 2197
COMPLETED 2165 2156
NOT COMPLETED 41 41

Baseline Characteristics

Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA Total
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0) Total of all reporting groups
Overall Participants 2419 2413 4832
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
57.9
(17.3)
57.5
(17.2)
57.7
(17.3)
Age, Customized (Number) [Number]
18 - < 40 years
410
16.9%
432
17.9%
842
17.4%
40 - < 60 years
794
32.8%
779
32.3%
1573
32.6%
60 - < 75 years
740
30.6%
754
31.2%
1494
30.9%
≥ 75 years
475
19.6%
448
18.6%
923
19.1%
Sex: Female, Male (Count of Participants)
Female
1309
54.1%
1247
51.7%
2556
52.9%
Male
1110
45.9%
1166
48.3%
2276
47.1%

Outcome Measures

1. Primary Outcome
Title Percentage of Participants With Symptomatic Recurrent Venous Thromboembolism [VTE] (i.e. the Composite of Recurrent Deep Vein Thrombosis [DVT] or Fatal or Non-fatal Pulmonary Embolism [PE]) Until the Intended End of Study Treatment
Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), and/or case summaries.
Time Frame 3-, 6-, or 12-month study treatment period

Outcome Measure Data

Analysis Population Description
The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Measure Participants 2419 2413
Number [Percentage of participants]
2.1
0.1%
1.8
0.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin/VKA
Comments The rivaroxaban to comparator hazard ratio was computed with a 95% CI (confidence interval) (two-sided testing). Based on this model, rivaroxaban would be considered at least as effective as the comparator if the upper limit of the CI was less than 2.0.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Assuming equal efficacy, a total of 88 events will give a power of 90% to demonstrate that rivaroxaban is at least as effective as the comparator, considering a relative non-inferiority upper CI margin for the hazard ratio of 2.0 (two-sided alpha=0.05). The mean overall incidence for the primary efficacy outcome of 3% was expected and therefore 1465 patients per group would be needed. This number was to be adjusted based on the observed overall incidence of symptomatic recurrent VTE.
Statistical Test of Hypothesis p-Value 0.0026
Comments
Method Regression, Cox
Comments Stratified by intend treatment duration, adjusted for presence of active malignancy at baseline
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.75 to 1.68
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.2067
Estimation Comments The standard error of the log hazard ratio was estimated.
2. Secondary Outcome
Title Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality Until the Intended End of Study Treatment
Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for deaths), results/films/images of confirmatory testing, and/or case summaries.
Time Frame 3-, 6-, or 12-month study treatment period

Outcome Measure Data

Analysis Population Description
The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Measure Participants 2419 2413
Number [Percentage of participants]
4.0
0.2%
3.4
0.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin/VKA
Comments Stratified by intend treatment duration, adjusted for presence of active malignancy at baseline.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.33
Comments Nominal p-value
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.86 to 1.56
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.1500
Estimation Comments The standard error of the log hazard ratio was estimated.
3. Secondary Outcome
Title Percentage of Participants With an Event for Net Clinical Benefit 1 Until the Intended End of Study Treatment
Description Net clinical benefit 1: composite of recurrent DVT or non-fatal or fatal PE, and major bleeding. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death. Net clinical benefit was considered greater in those participants with fewer composite events. All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.
Time Frame 3-, 6-, or 12-month study treatment period

Outcome Measure Data

Analysis Population Description
The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Measure Participants 2419 2413
Number [Percentage of participants]
3.4
0.1%
4.0
0.2%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin/VKA
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.275
Comments Nominal p-value
Method Regression, Cox
Comments Stratified by intend treatment duration, adjusted for presence of active malignancy at baseline
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.63 to 1.14
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.1499
Estimation Comments The standard error of the log hazard ratio was estimated.
4. Secondary Outcome
Title Percentage of Participants With Recurrent PE Until the Intended End of Study Treatment
Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.
Time Frame 3-, 6- or 12-month study treatment period

Outcome Measure Data

Analysis Population Description
The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Measure Participants 2419 2413
Number [Percentage of participants]
1.4
0.1%
1.2
0%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin/VKA
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.55
Comments nominal p-value
Method Regression, Cox
Comments Stratified by intend treatment duration, adjusted for presence of active malignancy at baseline.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.70 to 1.93
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.2570
Estimation Comments The standard error of the log hazard ratio was estimated.
5. Secondary Outcome
Title Percentage of Participants With Recurrent DVT Until the Intended End of Study Treatment
Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound, venography, results/films/images of confirmatory testing, and/or case summaries.
Time Frame 3-, 6- or 12-month study treatment period

Outcome Measure Data

Analysis Population Description
The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Measure Participants 2419 2413
Number [Percentage of participants]
0.7
0%
0.8
0%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin/VKA
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.85
Comments Nominal p-value
Method Regression, Cox
Comments Stratified by intend treatment duration, adjusted for presence of active malignancy at baseline.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.49 to 1.79
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.3289
Estimation Comments The standard error of the log hazard ratio was estimated.
6. Secondary Outcome
Title Percentage of Participants With Clinically Relevant Bleeding, Treatment-emergent (Time Window: Until 2 Days After Last Dose)
Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. 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.
Time Frame 3-, 6- or 12-month study treatment period

Outcome Measure Data

Analysis Population Description
The valid-for-safety analysis population consisted of all participants who were randomized with valid informed consent and received at least one dose of anticoagulant study treatment after randomization (i.e. enoxaparin, warfarin, acenocoumarol, rivaroxaban). Participants were analyzed according to the treatment they actually received.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Measure Participants 2412 2405
Number [Percentage of participants]
10.3
0.4%
11.4
0.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin/VKA
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.23
Comments If the primary efficacy analysis shows that rivaroxaban is non-inferior to the comparator, the principal safety outcome was to be compared between treatment groups to maintain the overall type I error of 0.05 (2-sided) (a closed testing procedure).
Method Regression, Cox
Comments Stratified by intend treatment duration, adjusted for presence of active malignancy at baseline.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.76 to 1.07
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.08756
Estimation Comments The standard error of the log hazard ratio was estimated.
7. Secondary Outcome
Title Percentage of Participants With All Deaths
Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either autopsy, results/films/images of confirmatory testing, and/or case summaries.
Time Frame 3-, 6- or 12-month study treatment period

Outcome Measure Data

Analysis Population Description
The valid-for-safety analysis population consisted of all participants who were randomized with valid informed consent and received at least one dose of anticoagulant study treatment after randomization (i.e. enoxaparin, warfarin, acenocoumarol, rivaroxaban). Participants were analyzed according to the treatment they actually received.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Measure Participants 2412 2405
All post-randomization
2.6
0.1%
2.1
0.1%
Treatment-emergent (time window: 2 days)
1.2
0%
0.8
0%
Treatment-emergent (time window: 7 days)
1.5
0.1%
1.1
0%
8. Secondary Outcome
Title Percentage of Participants With Other Vascular Events, On-treatment (Time Window: Until 1 Day After Last Dose)
Description All pre-defined vascular events (ST segment elevation myocardial infarction, non ST segment elevation myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, non-central nervous system systemic embolism or vascular death) were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based results/films/images of confirmatory testing, and/or case summaries.
Time Frame 3-, 6- or 12-month study treatment period

Outcome Measure Data

Analysis Population Description
The valid-for-safety analysis population consisted of all participants who were randomized with valid informed consent and received at least one dose of anticoagulant study treatment after randomization (i.e. enoxaparin, warfarin, acenocoumarol, rivaroxaban). Participants were analyzed according to the treatment they actually received.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Measure Participants 2412 2405
Number [Percentage of participants]
1.5
0.1%
1.5
0.1%
9. Other Pre-specified Outcome
Title Percentage of Participants With the Individual Components of Efficacy Outcomes Until the Intended End of Study Treatment
Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death.
Time Frame 3-, 6- or 12-month study treatment period

Outcome Measure Data

Analysis Population Description
The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Measure Participants 2419 2413
Death (PE)
0.1
0%
0.04
0%
Death (PE cannot be excluded)
0.3
0%
0.2
0%
Symptomatic PE and DVT
0.0
0%
0.1
0%
Symptomatic recurrent PE only
1.0
0%
0.8
0%
Symptomatic recurrent DVT only
0.7
0%
0.7
0%
Death (bleeding)
0.2
0%
0.2
0%
Death (cardiovascular)
0.4
0%
0.1
0%
Death (other)
1.3
0.1%
1.5
0.1%
Major bleeding
1.4
0.1%
2.4
0.1%
10. Other Pre-specified Outcome
Title Percentage of Participants With Symptomatic Recurrent VTE (i.e. the Composite of Recurrent DVT or Fatal or Non-fatal PE) During Observational Period
Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), and/or case summaries.
Time Frame Up to 30 days after the last intake of study medication

Outcome Measure Data

Analysis Population Description
Participants entering the observational period were participants for whom the investigator indicated on the eCRF (electronic case report form) that the participant entered the observational period or had a confirmed event more than one day and up to 30 days after the last dose as a component of the respective composite outcome.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Measure Participants 2211 2201
Number [Percentage of participants]
0.9
0%
0.7
0%
11. Other Pre-specified Outcome
Title Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality During Observational Period
Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for deaths), results/films/images of confirmatory testing, and/or case summaries.
Time Frame Up to 30 days after the last intake of study medication

Outcome Measure Data

Analysis Population Description
Participants entering the observational period were participants for whom the investigator indicated on the eCRF that the participant entered the observational period or had a confirmed event more than one day and up to 30 days after the last dose as a component of the respective composite outcome.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Measure Participants 2213 2203
Number [Percentage of participants]
2.1
0.1%
1.5
0.1%
12. Other Pre-specified Outcome
Title Percentage of Participants With an Event for Net Clinical Benefit 1 During Observational Period
Description Net clinical benefit 1: composite of recurrent DVT or non-fatal or fatal PE, and major bleeding. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death. Net clinical benefit was considered greater in those participants with fewer composite events. All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.
Time Frame Up to 30 days after the last intake of study medication

Outcome Measure Data

Analysis Population Description
Participants entering the observational period were participants for whom the investigator indicated on the eCRF that the participant entered the observational period or had a confirmed event more than one day and up to 30 days after the last dose as a component of the respective composite outcome.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Measure Participants 2212 2201
Number [Percentage of participants]
1.2
0%
1.2
0%
13. Other Pre-specified Outcome
Title Percentage of Participants With Recurrent DVT During Observational Period
Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound, venography, results/films/images of confirmatory testing, and/or case summaries.
Time Frame Up to 30 days after the last intake of study medication

Outcome Measure Data

Analysis Population Description
Participants entering the observational period were participants for whom the investigator indicated on the eCRF that the participant entered the observational period or had a confirmed event more than one day and up to 30 days after the last dose as a component of the respective composite outcome.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Measure Participants 2210 2201
Number [Percentage of participants]
0.3
0%
0.1
0%
14. Other Pre-specified Outcome
Title Percentage of Participants With the Individual Components of Efficacy Outcomes During Observational Period
Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death.
Time Frame Up to 30 days after the last intake of study medication

Outcome Measure Data

Analysis Population Description
Participants entering the observational period were participants for whom the investigator indicated on the eCRF that the participant entered the observational period or had a confirmed event more than one day and up to 30 days after the last dose as a component of the respective composite outcome.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Measure Participants 2213 2203
Death (PE)
0.09
0%
0
0%
Death (PE cannot be excluded)
0
0%
0.05
0%
Symptomatic PE and DVT
0.09
0%
0
0%
Symptomatic recurrent PE only
0.5
0%
0.5
0%
Symptomatic recurrent DVT only
0.2
0%
0.1
0%
Death (bleeding)
0.09
0%
0.09
0%
Death (cardiovascular)
0.3
0%
0.05
0%
Death (other)
0.8
0%
0.7
0%
Major bleeding
0.3
0%
0.5
0%
15. Post-Hoc Outcome
Title Percentage of Participants With an Event for Net Clinical Benefit 2 Until the Intended End of Study Treatment
Description Net clinical benefit 2: composite of recurrent DVT or non-fatal or fatal PE, major bleeding (associated with 2 g/dL or greater fall in hemoglobin, leading to transfusion of ≥2 units, occurring in a critical site or contributing to death), cardiovascular death, myocardial infarction, stroke, and non CNS (central nervous system) systemic embolism. Net clinical benefit was considered greater in those participants with fewer composite events. All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound (DVT), venography (DVT), spiral CT scanning (PE), pulmonary angiography (PE), ventilation/perfusion lung scan (PE), lung scintigraphy (PE), autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.
Time Frame 3-, 6- or 12-month study treatment period

Outcome Measure Data

Analysis Population Description
The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Measure Participants 2419 2413
Number [Percentage of participants]
4.5
0.2%
4.8
0.2%
16. Post-Hoc Outcome
Title Percentage of Participants With an Event for Net Clinical Benefit 2 During Observational Period
Description Net clinical benefit 2: composite of recurrent DVT or non-fatal or fatal PE, major bleeding (associated with 2 g/dL or greater fall in hemoglobin, leading to transfusion of ≥2 units, occurring in a critical site or contributing to death), cardiovascular death, myocardial infarction, stroke, and non CNS (central nervous system) systemic embolism. Net clinical benefit was considered greater in those participants with fewer composite events. All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound (DVT), venography (DVT), spiral CT scanning (PE), pulmonary angiography (PE), ventilation/perfusion lung scan (PE), lung scintigraphy (PE), autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.
Time Frame Up to 30 days after the last intake of study medication

Outcome Measure Data

Analysis Population Description
Participants entering the observational period were participants for whom the investigator indicated on the eCRF that the participant entered the observational period or had a confirmed event more than one day and up to 30 days after the last dose as a component of the respective composite outcome.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Measure Participants 2213 2201
Number [Percentage of participants]
1.5
0.1%
1.4
0.1%

Adverse Events

Time Frame
Adverse Event Reporting Description
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
All Cause Mortality
Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN)
Serious Adverse Events
Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 504/2412 (20.9%) 495/2405 (20.6%)
Blood and lymphatic system disorders
Anaemia 14/2412 (0.6%) 6/2405 (0.2%)
Anaemia folate deficiency 1/2412 (0%) 0/2405 (0%)
Coagulopathy 0/2412 (0%) 2/2405 (0.1%)
Disseminated intravascular coagulation 1/2412 (0%) 0/2405 (0%)
Eosinophilia 0/2412 (0%) 1/2405 (0%)
Febrile neutropenia 0/2412 (0%) 1/2405 (0%)
Haemolytic anaemia 1/2412 (0%) 0/2405 (0%)
Hypercoagulation 1/2412 (0%) 0/2405 (0%)
Idiopathic thrombocytopenic purpura 0/2412 (0%) 1/2405 (0%)
Leukopenia 0/2412 (0%) 1/2405 (0%)
Lymphadenopathy 1/2412 (0%) 1/2405 (0%)
Neutropenia 0/2412 (0%) 2/2405 (0.1%)
Pancytopenia 0/2412 (0%) 1/2405 (0%)
Pernicious anaemia 1/2412 (0%) 0/2405 (0%)
Splenic haemorrhage 0/2412 (0%) 1/2405 (0%)
Splenic infarction 0/2412 (0%) 1/2405 (0%)
Thrombocytopenia 2/2412 (0.1%) 0/2405 (0%)
Haemorrhagic anaemia 1/2412 (0%) 2/2405 (0.1%)
Cardiac disorders
Acute myocardial infarction 6/2412 (0.2%) 10/2405 (0.4%)
Angina pectoris 3/2412 (0.1%) 4/2405 (0.2%)
Angina unstable 7/2412 (0.3%) 2/2405 (0.1%)
Arrhythmia 2/2412 (0.1%) 1/2405 (0%)
Atrial fibrillation 8/2412 (0.3%) 11/2405 (0.5%)
Atrial flutter 1/2412 (0%) 1/2405 (0%)
Atrioventricular block 0/2412 (0%) 1/2405 (0%)
Cardiac arrest 1/2412 (0%) 0/2405 (0%)
Cardiac failure 9/2412 (0.4%) 7/2405 (0.3%)
Cardiac failure acute 4/2412 (0.2%) 2/2405 (0.1%)
Cardiac failure congestive 4/2412 (0.2%) 5/2405 (0.2%)
Cardio-respiratory arrest 1/2412 (0%) 0/2405 (0%)
Cardiogenic shock 1/2412 (0%) 0/2405 (0%)
Cardiomyopathy 0/2412 (0%) 1/2405 (0%)
Cor pulmonale 3/2412 (0.1%) 1/2405 (0%)
Cor pulmonale acute 1/2412 (0%) 0/2405 (0%)
Cor pulmonale chronic 1/2412 (0%) 1/2405 (0%)
Coronary artery disease 1/2412 (0%) 8/2405 (0.3%)
Coronary artery stenosis 0/2412 (0%) 1/2405 (0%)
Left ventricular failure 1/2412 (0%) 0/2405 (0%)
Mitral valve incompetence 1/2412 (0%) 0/2405 (0%)
Myocardial infarction 0/2412 (0%) 1/2405 (0%)
Myocardial ischaemia 0/2412 (0%) 2/2405 (0.1%)
Myocarditis 0/2412 (0%) 1/2405 (0%)
Palpitations 2/2412 (0.1%) 2/2405 (0.1%)
Pericardial effusion 1/2412 (0%) 1/2405 (0%)
Pericardial haemorrhage 1/2412 (0%) 2/2405 (0.1%)
Pericarditis 2/2412 (0.1%) 0/2405 (0%)
Right ventricular failure 3/2412 (0.1%) 0/2405 (0%)
Sick sinus syndrome 0/2412 (0%) 1/2405 (0%)
Sinus tachycardia 0/2412 (0%) 2/2405 (0.1%)
Supraventricular tachycardia 1/2412 (0%) 4/2405 (0.2%)
Tachycardia 1/2412 (0%) 2/2405 (0.1%)
Ventricular fibrillation 1/2412 (0%) 0/2405 (0%)
Ventricular tachycardia 3/2412 (0.1%) 1/2405 (0%)
Coronary artery dissection 0/2412 (0%) 1/2405 (0%)
Acute coronary syndrome 0/2412 (0%) 1/2405 (0%)
Congestive cardiomyopathy 2/2412 (0.1%) 0/2405 (0%)
Acute left ventricular failure 1/2412 (0%) 0/2405 (0%)
Congenital, familial and genetic disorders
Atrial septal defect 1/2412 (0%) 0/2405 (0%)
Hydrocele 1/2412 (0%) 0/2405 (0%)
Phimosis 0/2412 (0%) 1/2405 (0%)
Ear and labyrinth disorders
Vertigo 3/2412 (0.1%) 4/2405 (0.2%)
Vertigo positional 1/2412 (0%) 0/2405 (0%)
Deafness unilateral 0/2412 (0%) 1/2405 (0%)
Sudden hearing loss 1/2412 (0%) 1/2405 (0%)
Endocrine disorders
Addison's disease 1/2412 (0%) 0/2405 (0%)
Adrenal haemorrhage 1/2412 (0%) 1/2405 (0%)
Diabetes insipidus 0/2412 (0%) 1/2405 (0%)
Goitre 0/2412 (0%) 2/2405 (0.1%)
Hyperparathyroidism primary 0/2412 (0%) 1/2405 (0%)
Hyperthyroidism 0/2412 (0%) 1/2405 (0%)
Eye disorders
Amaurosis 0/2412 (0%) 1/2405 (0%)
Cataract 0/2412 (0%) 1/2405 (0%)
Diplopia 1/2412 (0%) 0/2405 (0%)
Eye haemorrhage 0/2412 (0%) 3/2405 (0.1%)
Eye pain 0/2412 (0%) 1/2405 (0%)
Optic ischaemic neuropathy 1/2412 (0%) 0/2405 (0%)
Retinal degeneration 0/2412 (0%) 1/2405 (0%)
Retinal haemorrhage 0/2412 (0%) 1/2405 (0%)
Vision blurred 0/2412 (0%) 1/2405 (0%)
Age-related macular degeneration 0/2412 (0%) 1/2405 (0%)
Gastrointestinal disorders
Abdominal pain 1/2412 (0%) 4/2405 (0.2%)
Abdominal pain upper 1/2412 (0%) 4/2405 (0.2%)
Acute abdomen 0/2412 (0%) 1/2405 (0%)
Anorectal disorder 0/2412 (0%) 1/2405 (0%)
Ascites 0/2412 (0%) 1/2405 (0%)
Colitis 1/2412 (0%) 1/2405 (0%)
Colitis ischaemic 1/2412 (0%) 0/2405 (0%)
Colonic polyp 2/2412 (0.1%) 0/2405 (0%)
Colonic stenosis 1/2412 (0%) 0/2405 (0%)
Dental caries 1/2412 (0%) 0/2405 (0%)
Diarrhoea 1/2412 (0%) 0/2405 (0%)
Diarrhoea haemorrhagic 1/2412 (0%) 0/2405 (0%)
Diverticulum 1/2412 (0%) 1/2405 (0%)
Diverticulum intestinal 1/2412 (0%) 0/2405 (0%)
Diverticulum oesophageal 1/2412 (0%) 0/2405 (0%)
Duodenal ulcer 2/2412 (0.1%) 0/2405 (0%)
Dyspepsia 2/2412 (0.1%) 0/2405 (0%)
Dysphagia 1/2412 (0%) 0/2405 (0%)
Gastric haemorrhage 0/2412 (0%) 1/2405 (0%)
Gastric perforation 1/2412 (0%) 0/2405 (0%)
Gastric ulcer 1/2412 (0%) 0/2405 (0%)
Gastric ulcer haemorrhage 1/2412 (0%) 1/2405 (0%)
Gastritis 1/2412 (0%) 2/2405 (0.1%)
Gastritis haemorrhagic 1/2412 (0%) 1/2405 (0%)
Gastrooesophageal reflux disease 1/2412 (0%) 1/2405 (0%)
Gastrointestinal haemorrhage 7/2412 (0.3%) 5/2405 (0.2%)
Haematemesis 4/2412 (0.2%) 2/2405 (0.1%)
Haematochezia 0/2412 (0%) 1/2405 (0%)
Haemorrhoids 1/2412 (0%) 0/2405 (0%)
Hiatus hernia 1/2412 (0%) 0/2405 (0%)
Ileus 0/2412 (0%) 1/2405 (0%)
Inguinal hernia 1/2412 (0%) 0/2405 (0%)
Intestinal fistula 1/2412 (0%) 0/2405 (0%)
Intestinal infarction 1/2412 (0%) 0/2405 (0%)
Intestinal obstruction 0/2412 (0%) 1/2405 (0%)
Large intestine perforation 1/2412 (0%) 2/2405 (0.1%)
Melaena 2/2412 (0.1%) 7/2405 (0.3%)
Nausea 2/2412 (0.1%) 0/2405 (0%)
Oesophageal ulcer 1/2412 (0%) 0/2405 (0%)
Oesophageal ulcer haemorrhage 0/2412 (0%) 1/2405 (0%)
Pancreatitis 0/2412 (0%) 1/2405 (0%)
Pancreatitis acute 0/2412 (0%) 1/2405 (0%)
Rectal haemorrhage 6/2412 (0.2%) 6/2405 (0.2%)
Retroperitoneal haemorrhage 0/2412 (0%) 1/2405 (0%)
Small intestinal obstruction 1/2412 (0%) 1/2405 (0%)
Small intestinal perforation 0/2412 (0%) 1/2405 (0%)
Tooth loss 1/2412 (0%) 0/2405 (0%)
Umbilical hernia 1/2412 (0%) 0/2405 (0%)
Upper gastrointestinal haemorrhage 2/2412 (0.1%) 2/2405 (0.1%)
Vomiting 3/2412 (0.1%) 3/2405 (0.1%)
Intestinal polyp 0/2412 (0%) 1/2405 (0%)
Gastrointestinal dysplasia 1/2412 (0%) 0/2405 (0%)
Subileus 1/2412 (0%) 1/2405 (0%)
Lower gastrointestinal haemorrhage 2/2412 (0.1%) 3/2405 (0.1%)
Haemorrhoidal haemorrhage 1/2412 (0%) 2/2405 (0.1%)
Retroperitoneal haematoma 0/2412 (0%) 2/2405 (0.1%)
Intestinal haemorrhage 1/2412 (0%) 3/2405 (0.1%)
Abdominal hernia 1/2412 (0%) 0/2405 (0%)
Large intestinal obstruction 1/2412 (0%) 0/2405 (0%)
Abdominal wall haematoma 0/2412 (0%) 2/2405 (0.1%)
General disorders
Asthenia 1/2412 (0%) 0/2405 (0%)
Chest discomfort 1/2412 (0%) 0/2405 (0%)
Chest pain 21/2412 (0.9%) 27/2405 (1.1%)
Cyst 0/2412 (0%) 1/2405 (0%)
Death 4/2412 (0.2%) 2/2405 (0.1%)
Fatigue 2/2412 (0.1%) 0/2405 (0%)
Gait disturbance 1/2412 (0%) 0/2405 (0%)
Granuloma 0/2412 (0%) 1/2405 (0%)
Impaired healing 0/2412 (0%) 1/2405 (0%)
Malaise 1/2412 (0%) 0/2405 (0%)
Multi-organ failure 1/2412 (0%) 0/2405 (0%)
Oedema peripheral 1/2412 (0%) 2/2405 (0.1%)
Pyrexia 4/2412 (0.2%) 2/2405 (0.1%)
Sudden death 3/2412 (0.1%) 1/2405 (0%)
General physical health deterioration 3/2412 (0.1%) 2/2405 (0.1%)
Adverse drug reaction 0/2412 (0%) 1/2405 (0%)
Drug intolerance 0/2412 (0%) 1/2405 (0%)
Non-cardiac chest pain 6/2412 (0.2%) 3/2405 (0.1%)
Implant site thrombosis 0/2412 (0%) 1/2405 (0%)
Device deposit issue 0/2412 (0%) 1/2405 (0%)
Hepatobiliary disorders
Bile duct stone 1/2412 (0%) 1/2405 (0%)
Biliary colic 1/2412 (0%) 0/2405 (0%)
Cholangitis 1/2412 (0%) 1/2405 (0%)
Cholecystitis 2/2412 (0.1%) 1/2405 (0%)
Cholecystitis acute 0/2412 (0%) 1/2405 (0%)
Cholelithiasis 4/2412 (0.2%) 5/2405 (0.2%)
Hepatic failure 1/2412 (0%) 2/2405 (0.1%)
Hepatic function abnormal 0/2412 (0%) 1/2405 (0%)
Hepatic pain 1/2412 (0%) 0/2405 (0%)
Hepatic steatosis 0/2412 (0%) 1/2405 (0%)
Hepatitis 0/2412 (0%) 1/2405 (0%)
Hepatitis acute 1/2412 (0%) 0/2405 (0%)
Hepatitis chronic active 1/2412 (0%) 0/2405 (0%)
Ischaemic hepatitis 1/2412 (0%) 0/2405 (0%)
Jaundice 1/2412 (0%) 0/2405 (0%)
Cytolytic hepatitis 1/2412 (0%) 0/2405 (0%)
Immune system disorders
Antiphospholipid syndrome 1/2412 (0%) 1/2405 (0%)
Drug hypersensitivity 0/2412 (0%) 1/2405 (0%)
Hypersensitivity 1/2412 (0%) 0/2405 (0%)
Sarcoidosis 1/2412 (0%) 0/2405 (0%)
Infections and infestations
Appendicitis 0/2412 (0%) 2/2405 (0.1%)
Bacteraemia 0/2412 (0%) 1/2405 (0%)
Bronchitis 5/2412 (0.2%) 8/2405 (0.3%)
Bronchopneumonia 4/2412 (0.2%) 4/2405 (0.2%)
Bronchopulmonary aspergillosis 1/2412 (0%) 0/2405 (0%)
Cellulitis 4/2412 (0.2%) 5/2405 (0.2%)
Cystitis 0/2412 (0%) 1/2405 (0%)
Diverticulitis 1/2412 (0%) 0/2405 (0%)
Endocarditis 1/2412 (0%) 0/2405 (0%)
Endocarditis bacterial 1/2412 (0%) 0/2405 (0%)
Gastroenteritis 3/2412 (0.1%) 0/2405 (0%)
Gastroenteritis salmonella 1/2412 (0%) 0/2405 (0%)
Hepatitis A 0/2412 (0%) 1/2405 (0%)
Herpes simplex 1/2412 (0%) 0/2405 (0%)
Herpes zoster 0/2412 (0%) 2/2405 (0.1%)
Lobar pneumonia 4/2412 (0.2%) 1/2405 (0%)
Localised infection 0/2412 (0%) 1/2405 (0%)
Lower respiratory tract infection 3/2412 (0.1%) 4/2405 (0.2%)
Lung abscess 0/2412 (0%) 1/2405 (0%)
Mastitis 1/2412 (0%) 0/2405 (0%)
Osteomyelitis 0/2412 (0%) 2/2405 (0.1%)
Pneumonia 22/2412 (0.9%) 21/2405 (0.9%)
Pneumonia mycoplasmal 0/2412 (0%) 1/2405 (0%)
Pneumonia primary atypical 0/2412 (0%) 1/2405 (0%)
Postoperative wound infection 0/2412 (0%) 1/2405 (0%)
Pyelonephritis 3/2412 (0.1%) 2/2405 (0.1%)
Pyelonephritis acute 0/2412 (0%) 1/2405 (0%)
Sepsis 13/2412 (0.5%) 2/2405 (0.1%)
Sinusitis 1/2412 (0%) 0/2405 (0%)
Skin infection 0/2412 (0%) 1/2405 (0%)
Tracheobronchitis 1/2412 (0%) 0/2405 (0%)
Tuberculosis 1/2412 (0%) 0/2405 (0%)
Urinary tract infection 7/2412 (0.3%) 4/2405 (0.2%)
Viral rash 0/2412 (0%) 1/2405 (0%)
Wound infection 2/2412 (0.1%) 0/2405 (0%)
Urosepsis 2/2412 (0.1%) 2/2405 (0.1%)
Anal abscess 1/2412 (0%) 0/2405 (0%)
Neutropenic sepsis 1/2412 (0%) 0/2405 (0%)
Appendiceal abscess 0/2412 (0%) 1/2405 (0%)
Groin abscess 0/2412 (0%) 1/2405 (0%)
Abscess limb 0/2412 (0%) 1/2405 (0%)
Abscess soft tissue 1/2412 (0%) 0/2405 (0%)
Prostate infection 0/2412 (0%) 1/2405 (0%)
Skin bacterial infection 0/2412 (0%) 1/2405 (0%)
Abscess neck 0/2412 (0%) 1/2405 (0%)
Pneumonia necrotising 1/2412 (0%) 0/2405 (0%)
Subdiaphragmatic abscess 1/2412 (0%) 0/2405 (0%)
Infective exacerbation of chronic obstructive airways disease 1/2412 (0%) 2/2405 (0.1%)
Biliary sepsis 0/2412 (0%) 1/2405 (0%)
Joint abscess 1/2412 (0%) 0/2405 (0%)
Wound infection staphylococcal 1/2412 (0%) 0/2405 (0%)
Intervertebral discitis 1/2412 (0%) 0/2405 (0%)
Lung infection 3/2412 (0.1%) 4/2405 (0.2%)
Respiratory tract infection 1/2412 (0%) 2/2405 (0.1%)
Cholecystitis infective 1/2412 (0%) 0/2405 (0%)
Device related infection 1/2412 (0%) 0/2405 (0%)
Infectious peritonitis 4/2412 (0.2%) 0/2405 (0%)
Injury, poisoning and procedural complications
Alcohol poisoning 1/2412 (0%) 0/2405 (0%)
Ankle fracture 3/2412 (0.1%) 0/2405 (0%)
Cerebral haemorrhage traumatic 1/2412 (0%) 0/2405 (0%)
Concussion 1/2412 (0%) 0/2405 (0%)
Facial bones fracture 2/2412 (0.1%) 0/2405 (0%)
Fall 4/2412 (0.2%) 1/2405 (0%)
Femoral neck fracture 1/2412 (0%) 0/2405 (0%)
Femur fracture 1/2412 (0%) 0/2405 (0%)
Fibula fracture 1/2412 (0%) 1/2405 (0%)
Foot fracture 0/2412 (0%) 1/2405 (0%)
Hip fracture 1/2412 (0%) 0/2405 (0%)
Humerus fracture 0/2412 (0%) 2/2405 (0.1%)
Joint dislocation 0/2412 (0%) 1/2405 (0%)
Kidney rupture 0/2412 (0%) 1/2405 (0%)
Multiple injuries 0/2412 (0%) 1/2405 (0%)
Operative haemorrhage 1/2412 (0%) 0/2405 (0%)
Overdose 2/2412 (0.1%) 2/2405 (0.1%)
Rib fracture 1/2412 (0%) 0/2405 (0%)
Road traffic accident 0/2412 (0%) 1/2405 (0%)
Soft tissue injury 0/2412 (0%) 2/2405 (0.1%)
Spinal compression fracture 1/2412 (0%) 0/2405 (0%)
Splenic haematoma 0/2412 (0%) 1/2405 (0%)
Sternal fracture 0/2412 (0%) 1/2405 (0%)
Subcutaneous haematoma 1/2412 (0%) 3/2405 (0.1%)
Subdural haematoma 1/2412 (0%) 3/2405 (0.1%)
Subdural haemorrhage 0/2412 (0%) 3/2405 (0.1%)
Tendon rupture 1/2412 (0%) 0/2405 (0%)
Tibia fracture 1/2412 (0%) 0/2405 (0%)
Traumatic haematoma 0/2412 (0%) 2/2405 (0.1%)
Anaemia postoperative 0/2412 (0%) 1/2405 (0%)
Vascular pseudoaneurysm 0/2412 (0%) 1/2405 (0%)
Perirenal haematoma 0/2412 (0%) 1/2405 (0%)
Traumatic fracture 1/2412 (0%) 0/2405 (0%)
Cervical vertebral fracture 0/2412 (0%) 1/2405 (0%)
Lumbar vertebral fracture 1/2412 (0%) 0/2405 (0%)
Thoracic vertebral fracture 0/2412 (0%) 2/2405 (0.1%)
Contusion 1/2412 (0%) 0/2405 (0%)
Post procedural haemorrhage 2/2412 (0.1%) 3/2405 (0.1%)
Incision site haemorrhage 0/2412 (0%) 1/2405 (0%)
Brain contusion 0/2412 (0%) 1/2405 (0%)
Cardiac valve replacement complication 0/2412 (0%) 1/2405 (0%)
Postoperative ileus 1/2412 (0%) 0/2405 (0%)
Procedural complication 0/2412 (0%) 1/2405 (0%)
Joint injury 2/2412 (0.1%) 0/2405 (0%)
Limb injury 1/2412 (0%) 0/2405 (0%)
Chest injury 0/2412 (0%) 1/2405 (0%)
Upper limb fracture 1/2412 (0%) 1/2405 (0%)
Toxicity to various agents 0/2412 (0%) 1/2405 (0%)
Craniocerebral injury 0/2412 (0%) 1/2405 (0%)
Investigations
Activated partial thromboplastin time prolonged 1/2412 (0%) 0/2405 (0%)
Alanine aminotransferase increased 6/2412 (0.2%) 9/2405 (0.4%)
Aspartate aminotransferase increased 1/2412 (0%) 1/2405 (0%)
Blood amylase increased 1/2412 (0%) 0/2405 (0%)
Blood potassium increased 1/2412 (0%) 0/2405 (0%)
C-reactive protein increased 0/2412 (0%) 1/2405 (0%)
Coagulation time prolonged 0/2412 (0%) 1/2405 (0%)
Coagulation time shortened 0/2412 (0%) 1/2405 (0%)
Gamma-glutamyltransferase increased 0/2412 (0%) 1/2405 (0%)
Haemoglobin decreased 1/2412 (0%) 0/2405 (0%)
International normalised ratio abnormal 0/2412 (0%) 1/2405 (0%)
International normalised ratio increased 1/2412 (0%) 4/2405 (0.2%)
Liver function test abnormal 4/2412 (0.2%) 9/2405 (0.4%)
Prostatic specific antigen increased 1/2412 (0%) 1/2405 (0%)
Ultrasound liver abnormal 1/2412 (0%) 0/2405 (0%)
Ejection fraction decreased 0/2412 (0%) 1/2405 (0%)
Medical observation 1/2412 (0%) 0/2405 (0%)
Transaminases increased 2/2412 (0.1%) 2/2405 (0.1%)
Hepatic enzyme increased 3/2412 (0.1%) 1/2405 (0%)
Metabolism and nutrition disorders
Acidosis 1/2412 (0%) 0/2405 (0%)
Dehydration 1/2412 (0%) 2/2405 (0.1%)
Diabetes mellitus 1/2412 (0%) 0/2405 (0%)
Failure to thrive 0/2412 (0%) 1/2405 (0%)
Gout 0/2412 (0%) 1/2405 (0%)
Hypercalcaemia 0/2412 (0%) 1/2405 (0%)
Hyperglycaemia 1/2412 (0%) 0/2405 (0%)
Hyperkalaemia 0/2412 (0%) 1/2405 (0%)
Hypoalbuminaemia 0/2412 (0%) 1/2405 (0%)
Hypocalcaemia 0/2412 (0%) 1/2405 (0%)
Hypoglycaemia 2/2412 (0.1%) 0/2405 (0%)
Hypokalaemia 0/2412 (0%) 1/2405 (0%)
Hyponatraemia 1/2412 (0%) 2/2405 (0.1%)
Hypovolaemia 0/2412 (0%) 1/2405 (0%)
Shock hypoglycaemic 1/2412 (0%) 0/2405 (0%)
Metabolic disorder 0/2412 (0%) 1/2405 (0%)
Malnutrition 0/2412 (0%) 1/2405 (0%)
Decreased appetite 1/2412 (0%) 1/2405 (0%)
Type 2 diabetes mellitus 2/2412 (0.1%) 0/2405 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia 2/2412 (0.1%) 2/2405 (0.1%)
Back pain 5/2412 (0.2%) 6/2405 (0.2%)
Bone pain 0/2412 (0%) 3/2405 (0.1%)
Cervical spinal stenosis 1/2412 (0%) 0/2405 (0%)
Groin pain 1/2412 (0%) 0/2405 (0%)
Haemarthrosis 0/2412 (0%) 1/2405 (0%)
Joint stiffness 0/2412 (0%) 1/2405 (0%)
Muscle haemorrhage 1/2412 (0%) 9/2405 (0.4%)
Muscle twitching 0/2412 (0%) 1/2405 (0%)
Muscular weakness 4/2412 (0.2%) 3/2405 (0.1%)
Musculoskeletal pain 3/2412 (0.1%) 1/2405 (0%)
Myalgia 2/2412 (0.1%) 0/2405 (0%)
Osteoarthritis 4/2412 (0.2%) 6/2405 (0.2%)
Osteolysis 1/2412 (0%) 0/2405 (0%)
Osteonecrosis 1/2412 (0%) 1/2405 (0%)
Pain in extremity 4/2412 (0.2%) 1/2405 (0%)
Rheumatoid arthritis 1/2412 (0%) 0/2405 (0%)
Rotator cuff syndrome 2/2412 (0.1%) 0/2405 (0%)
Scoliosis 0/2412 (0%) 1/2405 (0%)
Spinal column stenosis 0/2412 (0%) 1/2405 (0%)
Spinal osteoarthritis 0/2412 (0%) 1/2405 (0%)
Systemic lupus erythematosus 0/2412 (0%) 1/2405 (0%)
Temporomandibular joint syndrome 0/2412 (0%) 1/2405 (0%)
Pseudarthrosis 0/2412 (0%) 1/2405 (0%)
Musculoskeletal chest pain 3/2412 (0.1%) 1/2405 (0%)
Intervertebral disc compression 0/2412 (0%) 1/2405 (0%)
Intervertebral disc degeneration 0/2412 (0%) 1/2405 (0%)
Spinal disorder 1/2412 (0%) 0/2405 (0%)
Intervertebral disc disorder 1/2412 (0%) 0/2405 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia 0/2412 (0%) 1/2405 (0%)
Acute promyelocytic leukaemia 1/2412 (0%) 0/2405 (0%)
Adenocarcinoma 1/2412 (0%) 0/2405 (0%)
B-cell lymphoma 1/2412 (0%) 1/2405 (0%)
Basal cell carcinoma 0/2412 (0%) 1/2405 (0%)
Benign oesophageal neoplasm 1/2412 (0%) 0/2405 (0%)
Bile duct cancer non-resectable 0/2412 (0%) 1/2405 (0%)
Bladder cancer 1/2412 (0%) 2/2405 (0.1%)
Bladder neoplasm 0/2412 (0%) 2/2405 (0.1%)
Breast cancer 1/2412 (0%) 1/2405 (0%)
Breast cancer recurrent 1/2412 (0%) 1/2405 (0%)
Breast neoplasm 1/2412 (0%) 0/2405 (0%)
Bronchial carcinoma 0/2412 (0%) 1/2405 (0%)
Cervix carcinoma 0/2412 (0%) 1/2405 (0%)
Colon cancer 8/2412 (0.3%) 1/2405 (0%)
Fibroadenoma of breast 1/2412 (0%) 0/2405 (0%)
Gallbladder cancer 1/2412 (0%) 0/2405 (0%)
Gastric cancer 3/2412 (0.1%) 0/2405 (0%)
Glioblastoma multiforme 0/2412 (0%) 1/2405 (0%)
Lung adenocarcinoma 3/2412 (0.1%) 4/2405 (0.2%)
Lung carcinoma cell type unspecified recurrent 1/2412 (0%) 1/2405 (0%)
Lung squamous cell carcinoma stage unspecified 1/2412 (0%) 1/2405 (0%)
Lymphoma 0/2412 (0%) 1/2405 (0%)
Malignant ascites 1/2412 (0%) 1/2405 (0%)
Malignant melanoma 1/2412 (0%) 0/2405 (0%)
Malignant pleural effusion 0/2412 (0%) 1/2405 (0%)
Meningioma 1/2412 (0%) 0/2405 (0%)
Mesothelioma malignant 0/2412 (0%) 1/2405 (0%)
Metastases to liver 2/2412 (0.1%) 4/2405 (0.2%)
Metastases to lung 0/2412 (0%) 1/2405 (0%)
Metastases to lymph nodes 0/2412 (0%) 1/2405 (0%)
Metastases to pleura 0/2412 (0%) 2/2405 (0.1%)
Metastases to spine 1/2412 (0%) 0/2405 (0%)
Multiple myeloma 1/2412 (0%) 1/2405 (0%)
Myelodysplastic syndrome 0/2412 (0%) 1/2405 (0%)
Myelofibrosis 1/2412 (0%) 0/2405 (0%)
Neoplasm malignant 0/2412 (0%) 1/2405 (0%)
Neoplasm prostate 1/2412 (0%) 0/2405 (0%)
Ovarian cancer 1/2412 (0%) 0/2405 (0%)
Ovarian germ cell teratoma benign 1/2412 (0%) 0/2405 (0%)
Pancreatic carcinoma 1/2412 (0%) 0/2405 (0%)
Pancreatic carcinoma metastatic 1/2412 (0%) 0/2405 (0%)
Parathyroid tumour benign 0/2412 (0%) 1/2405 (0%)
Polycythaemia vera 0/2412 (0%) 1/2405 (0%)
Prostate cancer recurrent 0/2412 (0%) 1/2405 (0%)
Prostatic adenoma 2/2412 (0.1%) 2/2405 (0.1%)
Rectal cancer 2/2412 (0.1%) 1/2405 (0%)
Renal cancer 1/2412 (0%) 3/2405 (0.1%)
Small cell lung cancer stage unspecified 1/2412 (0%) 0/2405 (0%)
Squamous cell carcinoma of skin 0/2412 (0%) 1/2405 (0%)
T-cell lymphoma 1/2412 (0%) 0/2405 (0%)
Uterine leiomyoma 4/2412 (0.2%) 2/2405 (0.1%)
Histiocytosis haematophagic 1/2412 (0%) 1/2405 (0%)
Tumour haemorrhage 1/2412 (0%) 1/2405 (0%)
Lung cancer metastatic 1/2412 (0%) 2/2405 (0.1%)
Gastrointestinal stromal tumour 0/2412 (0%) 1/2405 (0%)
Metastases to peritoneum 1/2412 (0%) 0/2405 (0%)
Rectal cancer metastatic 0/2412 (0%) 1/2405 (0%)
Breast cancer metastatic 1/2412 (0%) 0/2405 (0%)
Colon cancer metastatic 0/2412 (0%) 1/2405 (0%)
Lung neoplasm malignant 5/2412 (0.2%) 4/2405 (0.2%)
Metastases to central nervous system 0/2412 (0%) 1/2405 (0%)
Prostate cancer 3/2412 (0.1%) 7/2405 (0.3%)
Brain neoplasm 2/2412 (0.1%) 0/2405 (0%)
Colon neoplasm 2/2412 (0.1%) 0/2405 (0%)
Mantle cell lymphoma 0/2412 (0%) 1/2405 (0%)
Metastatic neoplasm 0/2412 (0%) 2/2405 (0.1%)
Ovarian epithelial cancer 2/2412 (0.1%) 0/2405 (0%)
Pelvic neoplasm 0/2412 (0%) 1/2405 (0%)
Colorectal cancer 2/2412 (0.1%) 0/2405 (0%)
Renal neoplasm 1/2412 (0%) 1/2405 (0%)
Adrenal neoplasm 0/2412 (0%) 1/2405 (0%)
Extranodal marginal zone B-cell lymphoma (MALT type) 1/2412 (0%) 0/2405 (0%)
Non-small cell lung cancer 1/2412 (0%) 0/2405 (0%)
Gastric neoplasm 0/2412 (0%) 1/2405 (0%)
Lung neoplasm 0/2412 (0%) 2/2405 (0.1%)
Rectal neoplasm 1/2412 (0%) 0/2405 (0%)
Metastasis 0/2412 (0%) 1/2405 (0%)
Metastatic gastric cancer 0/2412 (0%) 1/2405 (0%)
Thyroid cancer 0/2412 (0%) 2/2405 (0.1%)
Renal cell carcinoma 1/2412 (0%) 0/2405 (0%)
Inflammatory pseudotumour 1/2412 (0%) 0/2405 (0%)
Nervous system disorders
Altered state of consciousness 1/2412 (0%) 0/2405 (0%)
Amyotrophic lateral sclerosis 1/2412 (0%) 1/2405 (0%)
Ataxia 0/2412 (0%) 1/2405 (0%)
Carotid artery stenosis 0/2412 (0%) 1/2405 (0%)
Cauda equina syndrome 1/2412 (0%) 0/2405 (0%)
Cerebellar haemorrhage 1/2412 (0%) 0/2405 (0%)
Cerebral haemorrhage 0/2412 (0%) 4/2405 (0.2%)
Cerebral infarction 0/2412 (0%) 1/2405 (0%)
Cerebrovascular accident 1/2412 (0%) 0/2405 (0%)
Clumsiness 1/2412 (0%) 0/2405 (0%)
Coma 1/2412 (0%) 0/2405 (0%)
Convulsion 2/2412 (0.1%) 3/2405 (0.1%)
Dementia Alzheimer's type 0/2412 (0%) 1/2405 (0%)
Depressed level of consciousness 1/2412 (0%) 0/2405 (0%)
Dizziness 3/2412 (0.1%) 3/2405 (0.1%)
Encephalopathy 0/2412 (0%) 1/2405 (0%)
Epilepsy 2/2412 (0.1%) 1/2405 (0%)
Guillain-Barre syndrome 1/2412 (0%) 0/2405 (0%)
Haemorrhage intracranial 0/2412 (0%) 2/2405 (0.1%)
Headache 3/2412 (0.1%) 4/2405 (0.2%)
Hepatic encephalopathy 1/2412 (0%) 0/2405 (0%)
Leukoencephalopathy 1/2412 (0%) 0/2405 (0%)
Loss of consciousness 0/2412 (0%) 1/2405 (0%)
Migraine 0/2412 (0%) 1/2405 (0%)
Nervous system disorder 1/2412 (0%) 0/2405 (0%)
Neuropathy peripheral 2/2412 (0.1%) 0/2405 (0%)
Parkinsonism 1/2412 (0%) 0/2405 (0%)
Presyncope 0/2412 (0%) 1/2405 (0%)
Sciatica 2/2412 (0.1%) 1/2405 (0%)
Spinal cord compression 0/2412 (0%) 1/2405 (0%)
Subarachnoid haemorrhage 0/2412 (0%) 1/2405 (0%)
Syncope 8/2412 (0.3%) 6/2405 (0.2%)
Tension headache 0/2412 (0%) 1/2405 (0%)
Transient ischaemic attack 3/2412 (0.1%) 3/2405 (0.1%)
Balance disorder 1/2412 (0%) 0/2405 (0%)
VIIth nerve paralysis 0/2412 (0%) 1/2405 (0%)
Lacunar infarction 0/2412 (0%) 1/2405 (0%)
Haemorrhagic transformation stroke 1/2412 (0%) 0/2405 (0%)
Cerebrovascular insufficiency 1/2412 (0%) 0/2405 (0%)
Radicular pain 1/2412 (0%) 0/2405 (0%)
Ischaemic stroke 13/2412 (0.5%) 5/2405 (0.2%)
Parkinson's disease 1/2412 (0%) 0/2405 (0%)
Complex regional pain syndrome 0/2412 (0%) 1/2405 (0%)
Pregnancy, puerperium and perinatal conditions
Post abortion haemorrhage 0/2412 (0%) 1/2405 (0%)
Pregnancy 0/2412 (0%) 2/2405 (0.1%)
Psychiatric disorders
Alcohol abuse 0/2412 (0%) 1/2405 (0%)
Alcoholism 0/2412 (0%) 1/2405 (0%)
Anxiety 5/2412 (0.2%) 3/2405 (0.1%)
Bipolar I disorder 1/2412 (0%) 1/2405 (0%)
Confusional state 0/2412 (0%) 1/2405 (0%)
Delusion 1/2412 (0%) 0/2405 (0%)
Depression 4/2412 (0.2%) 3/2405 (0.1%)
Mania 1/2412 (0%) 0/2405 (0%)
Panic attack 1/2412 (0%) 0/2405 (0%)
Suicide attempt 1/2412 (0%) 1/2405 (0%)
Mental status changes 0/2412 (0%) 1/2405 (0%)
Somatoform disorder 1/2412 (0%) 0/2405 (0%)
Mental disorder 0/2412 (0%) 1/2405 (0%)
Mental disorder due to a general medical condition 0/2412 (0%) 1/2405 (0%)
Renal and urinary disorders
Acute prerenal failure 1/2412 (0%) 0/2405 (0%)
Anuria 0/2412 (0%) 1/2405 (0%)
Bladder dilatation 0/2412 (0%) 1/2405 (0%)
Dysuria 1/2412 (0%) 0/2405 (0%)
Glomerulonephritis membranous 1/2412 (0%) 0/2405 (0%)
Haematuria 8/2412 (0.3%) 11/2405 (0.5%)
Nephritis 1/2412 (0%) 0/2405 (0%)
Nephrolithiasis 0/2412 (0%) 3/2405 (0.1%)
Nephropathy toxic 0/2412 (0%) 1/2405 (0%)
Nephrotic syndrome 1/2412 (0%) 0/2405 (0%)
Renal colic 0/2412 (0%) 3/2405 (0.1%)
Renal cyst 0/2412 (0%) 1/2405 (0%)
Renal failure acute 2/2412 (0.1%) 4/2405 (0.2%)
Urinary retention 2/2412 (0.1%) 0/2405 (0%)
Urinary tract disorder 1/2412 (0%) 0/2405 (0%)
Urinary bladder polyp 1/2412 (0%) 0/2405 (0%)
Renal mass 0/2412 (0%) 1/2405 (0%)
Renal impairment 1/2412 (0%) 1/2405 (0%)
Urethral stenosis 0/2412 (0%) 2/2405 (0.1%)
Reproductive system and breast disorders
Benign prostatic hyperplasia 0/2412 (0%) 1/2405 (0%)
Cervical dysplasia 0/2412 (0%) 1/2405 (0%)
Cervical polyp 0/2412 (0%) 1/2405 (0%)
Dysfunctional uterine bleeding 1/2412 (0%) 0/2405 (0%)
Menorrhagia 9/2412 (0.4%) 2/2405 (0.1%)
Metrorrhagia 4/2412 (0.2%) 2/2405 (0.1%)
Ovarian cyst 0/2412 (0%) 1/2405 (0%)
Priapism 0/2412 (0%) 1/2405 (0%)
Prostatitis 0/2412 (0%) 1/2405 (0%)
Uterine polyp 0/2412 (0%) 1/2405 (0%)
Uterine prolapse 1/2412 (0%) 0/2405 (0%)
Vaginal haemorrhage 4/2412 (0.2%) 0/2405 (0%)
Vulval disorder 1/2412 (0%) 0/2405 (0%)
Genital haemorrhage 1/2412 (0%) 0/2405 (0%)
Prostatic mass 0/2412 (0%) 1/2405 (0%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema 1/2412 (0%) 0/2405 (0%)
Acute respiratory distress syndrome 2/2412 (0.1%) 1/2405 (0%)
Acute respiratory failure 1/2412 (0%) 4/2405 (0.2%)
Asthma 4/2412 (0.2%) 2/2405 (0.1%)
Bronchial obstruction 0/2412 (0%) 1/2405 (0%)
Bronchiectasis 0/2412 (0%) 1/2405 (0%)
Bronchospasm 0/2412 (0%) 1/2405 (0%)
Chronic obstructive pulmonary disease 9/2412 (0.4%) 5/2405 (0.2%)
Cough 1/2412 (0%) 0/2405 (0%)
Dyspnoea 17/2412 (0.7%) 13/2405 (0.5%)
Emphysema 1/2412 (0%) 0/2405 (0%)
Epistaxis 3/2412 (0.1%) 2/2405 (0.1%)
Haemoptysis 6/2412 (0.2%) 8/2405 (0.3%)
Haemothorax 1/2412 (0%) 2/2405 (0.1%)
Hyperventilation 0/2412 (0%) 1/2405 (0%)
Interstitial lung disease 1/2412 (0%) 0/2405 (0%)
Lung disorder 3/2412 (0.1%) 2/2405 (0.1%)
Pharyngeal cyst 0/2412 (0%) 1/2405 (0%)
Pleural effusion 9/2412 (0.4%) 11/2405 (0.5%)
Pleurisy 0/2412 (0%) 4/2405 (0.2%)
Pleuritic pain 4/2412 (0.2%) 8/2405 (0.3%)
Pneumothorax 1/2412 (0%) 3/2405 (0.1%)
Pulmonary congestion 1/2412 (0%) 1/2405 (0%)
Pulmonary embolism 6/2412 (0.2%) 1/2405 (0%)
Pulmonary fibrosis 0/2412 (0%) 1/2405 (0%)
Pulmonary haemorrhage 2/2412 (0.1%) 0/2405 (0%)
Pulmonary hypertension 4/2412 (0.2%) 1/2405 (0%)
Pulmonary infarction 3/2412 (0.1%) 2/2405 (0.1%)
Pulmonary oedema 1/2412 (0%) 1/2405 (0%)
Pulmonary venous thrombosis 1/2412 (0%) 0/2405 (0%)
Respiratory arrest 1/2412 (0%) 1/2405 (0%)
Respiratory failure 3/2412 (0.1%) 5/2405 (0.2%)
Sleep apnoea syndrome 0/2412 (0%) 1/2405 (0%)
Mediastinal haemorrhage 0/2412 (0%) 1/2405 (0%)
Pulmonary arterial hypertension 0/2412 (0%) 1/2405 (0%)
Skin and subcutaneous tissue disorders
Angioedema 1/2412 (0%) 1/2405 (0%)
Dermatitis 0/2412 (0%) 1/2405 (0%)
Dermatitis exfoliative 1/2412 (0%) 0/2405 (0%)
Dermatomyositis 1/2412 (0%) 0/2405 (0%)
Drug eruption 0/2412 (0%) 1/2405 (0%)
Haemorrhage subcutaneous 0/2412 (0%) 1/2405 (0%)
Hyperkeratosis 0/2412 (0%) 1/2405 (0%)
Lichen planus 1/2412 (0%) 0/2405 (0%)
Purpura 1/2412 (0%) 0/2405 (0%)
Rash morbilliform 1/2412 (0%) 0/2405 (0%)
Skin lesion 0/2412 (0%) 1/2405 (0%)
Skin necrosis 0/2412 (0%) 1/2405 (0%)
Skin ulcer 1/2412 (0%) 1/2405 (0%)
Urticaria 2/2412 (0.1%) 0/2405 (0%)
Social circumstances
Miscarriage of partner 1/2412 (0%) 0/2405 (0%)
Surgical and medical procedures
Abortion induced 2/2412 (0.1%) 3/2405 (0.1%)
Vascular disorders
Aortic aneurysm 1/2412 (0%) 2/2405 (0.1%)
Aortic aneurysm rupture 0/2412 (0%) 2/2405 (0.1%)
Aortic dissection 2/2412 (0.1%) 0/2405 (0%)
Aortic thrombosis 0/2412 (0%) 1/2405 (0%)
Circulatory collapse 1/2412 (0%) 0/2405 (0%)
Embolism arterial 0/2412 (0%) 1/2405 (0%)
Haematoma 4/2412 (0.2%) 4/2405 (0.2%)
Hypertension 1/2412 (0%) 3/2405 (0.1%)
Hypertensive crisis 0/2412 (0%) 1/2405 (0%)
Hypotension 3/2412 (0.1%) 1/2405 (0%)
Hypovolaemic shock 0/2412 (0%) 1/2405 (0%)
Iliac artery thrombosis 0/2412 (0%) 1/2405 (0%)
Orthostatic hypotension 1/2412 (0%) 0/2405 (0%)
Peripheral ischaemia 1/2412 (0%) 0/2405 (0%)
Temporal arteritis 0/2412 (0%) 1/2405 (0%)
Thrombophlebitis superficial 1/2412 (0%) 0/2405 (0%)
Vena cava thrombosis 1/2412 (0%) 0/2405 (0%)
Lymphocele 1/2412 (0%) 0/2405 (0%)
Intra-abdominal haematoma 0/2412 (0%) 1/2405 (0%)
Varicophlebitis 1/2412 (0%) 0/2405 (0%)
Arterial haemorrhage 0/2412 (0%) 1/2405 (0%)
Intra-abdominal haemorrhage 1/2412 (0%) 2/2405 (0.1%)
Paradoxical embolism 1/2412 (0%) 0/2405 (0%)
Distributive shock 0/2412 (0%) 1/2405 (0%)
Other (Not Including Serious) Adverse Events
Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1053/2412 (43.7%) 1065/2405 (44.3%)
Gastrointestinal disorders
Constipation 146/2412 (6.1%) 141/2405 (5.9%)
Diarrhoea 128/2412 (5.3%) 132/2405 (5.5%)
Nausea 113/2412 (4.7%) 131/2405 (5.4%)
General disorders
Chest pain 179/2412 (7.4%) 181/2405 (7.5%)
Infections and infestations
Nasopharyngitis 188/2412 (7.8%) 195/2405 (8.1%)
Injury, poisoning and procedural complications
Contusion 95/2412 (3.9%) 133/2405 (5.5%)
Musculoskeletal and connective tissue disorders
Back pain 87/2412 (3.6%) 134/2405 (5.6%)
Pain in extremity 172/2412 (7.1%) 162/2405 (6.7%)
Nervous system disorders
Headache 196/2412 (8.1%) 177/2405 (7.4%)
Respiratory, thoracic and mediastinal disorders
Cough 160/2412 (6.6%) 179/2405 (7.4%)
Dyspnoea 156/2412 (6.5%) 147/2405 (6.1%)
Epistaxis 229/2412 (9.5%) 205/2405 (8.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Results Point of Contact

Name/Title Therapeutic Area Head
Organization BAYER
Phone
Email clinical-trials-contact@bayerhealthcare.com
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT00439777
Other Study ID Numbers:
  • 11702b
  • 2006-004495-13
First Posted:
Feb 26, 2007
Last Update Posted:
Feb 27, 2014
Last Verified:
Jan 1, 2014