MAGELLAN: Venous Thromboembolic Event (VTE) Prophylaxis in Medically Ill Patients

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT00571649

Collaborator

Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)

8,101

Enrollment

676

Locations

Arms

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate if extended therapy with oral rivaroxaban can prevent blood clots in the leg and lung that can occur with patients hospitalized for acute medical illness, and compare these results with those of the standard enoxaparin dose and duration regimen. The safety of rivaroxaban will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Venous Thromboembolism	Drug: Rivaroxaban (Xarelto, BAY59-7939) Drug: Enoxaparin Drug: Rivaroxaban placebo Drug: Enoxaparin placebo	Phase 3

Detailed Description

The treatment period was followed by a follow-up period starting the day after the last intake of study medication, regardless of the actual duration of study drug administration and ended on Day 90 (+ 7 days). Participants who did not complete the treatment period also entered the follow-up period. It was also possible that participants did not enter the follow-up period, e.g. due to withdrawal of consent or termination of study participation.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

8101 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Multicenter, Randomized, Parallel-group Efficacy and Safety Study for the Prevention of Venous Thromboembolism in Hospitalized Medically Ill Patients Comparing Rivaroxaban With Enoxaparin. The MAGELLAN Study

Study Start Date :

Dec 1, 2007

Actual Primary Completion Date :

Aug 1, 2010

Actual Study Completion Date :

Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rivaroxaban (Xarelto, BAY59-7939) Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days	Drug: Rivaroxaban (Xarelto, BAY59-7939) Oral rivaroxaban 10 mg once daily administered for 35 +/- 4 days Drug: Enoxaparin placebo Subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days
Active Comparator: Enoxaparin Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days	Drug: Enoxaparin Subcutaneous enoxaparin 40 mg once daily (OD) administered for 10 +/- 4 days Drug: Rivaroxaban placebo Oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days

Arm

Intervention/Treatment

Experimental: Rivaroxaban (Xarelto, BAY59-7939)

Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days

Drug: Rivaroxaban (Xarelto, BAY59-7939)

Oral rivaroxaban 10 mg once daily administered for 35 +/- 4 days

Drug: Enoxaparin placebo

Subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days

Active Comparator: Enoxaparin

Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days

Drug: Enoxaparin

Subcutaneous enoxaparin 40 mg once daily (OD) administered for 10 +/- 4 days

Drug: Rivaroxaban placebo

Oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days

Outcome Measures

Primary Outcome Measures

Percentage of Participants With Composite Endpoint of Venous Thromboembolism [VTE] (Any Deep Vein Thrombosis [DVT], Non Fatal Pulmonary Embolism [PE]) and VTE-related Death up to Day 35 + 6 Days [Up to Day 35 + 6 days]
A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death.
Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 10 + 5 Days [Up to Day 10 + 5 days]
A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death.

Secondary Outcome Measures

Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and All-cause Mortality up to Day 35 + 6 Days [Up to Day 35 + 6 days]
A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and death (VTE-related and not VTE-related).
Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 10 + 5 Days Per mITT Population [Up to Day 10 + 5 days]
A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death.
Percentage of Participants With VTE Combined With All-cause Mortality up to Day 10 + 5 Days [Up to Day 10 + 5 days]
A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and death (VTE-related and not VTE-related).
Percentage of Participants With Symptomatic VTE, Including and Excluding VTE-related Death up to Days 10, 35, and 90 [At Day 10 + 5 days, at Day 35 + 6 days, and at Day 90 + 7 days]
Symptomatic VTE (non-fatal PE and DVT in lower extremity), including and excluding VTE-related death (PE and PE cannot be excluded) up to Days 10, 35, and 90
Percentage of Participants With Net Clinical Benefit (Any DVT, Non-fatal PE, VTE-related Death, Plus Major and Clinically Relevant Non-major Bleeding Events) up to Day 35 + 6 Days [Up to Day 35 + 6 days]
Net clinical benefit is a composite of the primary efficacy endpoint (asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death) plus major and clinically relevant non-major bleeding events.
Percentage of Participants With Net Clinical Benefit (Any DVT, Non-fatal PE, VTE-related Death, Plus Major and Clinically Relevant Non-major Bleeding Events) up to Day 10 + 5 Days [Up to Day 10 + 5 days]
Net clinical benefit is a composite of the primary efficacy endpoint (asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death) plus major and clinically relevant non-major bleeding events
Percentage of Participants With Major Vascular Events up to Days 10, 35, and 90 [At Day 10 + 5 days, at Day 35 + 6 days, and at Day 90 + 7 days]
Major vascular events included cardiovascular death, acute myocardial infarction (MI), or acute ischemic stroke. Participants may have had a vascular event in more than one category.
Percentage of Participants With Each Component of the Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 35 + 6 Days [Up to Day 35 + 6 days]
The components of the composite endpoint include asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death.
Percentage of Participants With Each Component of the Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 10 + 5 Days [Up to Day 10 + 5 days]
The components of the composite endpoint include asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death.
Percentage of Participants With All-cause Mortality up to Day 90 + 7 Days [Up to Day 90 + 7 days]
All deaths, including VTE-related deaths, cardiovascular deaths, and other deaths.
Percentage of Participants With the Composite of Treatment Emergent Major Bleeding Events and Non-major Clinically Relevant Bleeding Events up to 2 Days After Last Intake of Any Study Medication (Day 35 + 6 Days) [Up to Day 35 + 6 days]
Major bleeding events were defined as events leading to >=2 g/dL fall in hemoglobin; or transfusion of >= 2 units of packed RBCs (Red blood cells) or whole blood; or leading to death. Non-major bleeding events were defined as overt bleeding not meeting the criteria of major bleeding
Percentage of Participants With the Composite of Treatment Emergent Major Bleeding Events and Non-major Clinically Relevant Bleeding Events up to 2 Days After Last Application of a Study Medication Syringe (Day 10 + 5 Days) [Up to Day 10 + 5 days]
Major bleeding events were defined as events leading to >=2 g/dL fall in hemoglobin or transfusion of >=2 units of packed RBCs or whole blood or leading to death. Non-major bleeding events were defined as overt bleeding not meeting the criteria of major bleeding.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and female patients aged 40 years or more
Patients at risk of venous thromboembolic events being hospitalized for acute medical conditions as follows:
Heart failure, New York Heart Association (NYHA) class III or IV
Active cancer
Acute ischemic stroke
Acute infectious and inflammatory diseases, including acute rheumatic diseases
Acute respiratory insufficiency
Additional risk factor for VTE, including reduced mobility

Exclusion Criteria:

Conditions that contraindicate the use of antithrombotic therapy with the Low Molecular-Weight Heparin (LMWH) enoxaparin
Conditions that may increase the risk of bleeding, including intracranial hemorrhage
Required drugs or procedures which may interfere with the study treatment
Concomitant conditions or diseases which may increase the risk of study subjects or interfere with the study outcome
General conditions in which subjects are not suitable to participate in the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States	35209
2		Birmingham	Alabama	United States	35235
3		Dothan	Alabama	United States	36301
4	Office of Dr. John Simmons, MD	Geneva	Alabama	United States	36340
5		Mobile	Alabama	United States	36608
6		Montgomery	Alabama	United States	36111
7		Tuscaloosa	Alabama	United States	35401
8		Tuscaloosa	Alabama	United States	35406
9		Little Rock	Arkansas	United States	72205
10		Chula Vista	California	United States	91911
11		Duarte	California	United States	91010
12		Encinitas	California	United States	92024
13		Fountain Valley	California	United States	92708
14		Fullerton	California	United States	92835
15		Glendale	California	United States	91206
16		Oceanside	California	United States	92056
17		Pasadena	California	United States	91105
18		Redlands	California	United States	92373
19		Sacramento	California	United States	95817
20		San Diego	California	United States	92120
21		Santa Barbara	California	United States	93102
22		Torrance	California	United States	90502-2004
23		Denver	Colorado	United States	80204
24		Pueblo	Colorado	United States	81003
25		Wheat Ridge	Colorado	United States	80033-6017
26		Farmington	Connecticut	United States	06030
27		Newark	Delaware	United States	19718
28		Washington	District of Columbia	United States	20037
29		Aventura	Florida	United States	33180
30		Boyton Beach	Florida	United States	33472
31		Clearwater	Florida	United States	33756
32		Delray Beach	Florida	United States	33445
33		Ft. Lauderdale	Florida	United States	33334
34		Hollywood	Florida	United States	33021
35		Jupiter	Florida	United States	33458
36		Miami Springs	Florida	United States	33166
37		Miami	Florida	United States	33136
38		Miami	Florida	United States	33173-3259
39		Pembroke Pines	Florida	United States	33024
40		Port Charlotte	Florida	United States	33952
41		Sarasota	Florida	United States	34232
42		Vero Beach	Florida	United States	32960
43		Atlanta	Georgia	United States	30342
44		Decatur	Georgia	United States	30030
45		Fort Gordon	Georgia	United States	30905
46		Savannah	Georgia	United States	31405
47		Idaho Falls	Idaho	United States	83404
48		Chicago	Illinois	United States	60611
49		Springfield	Illinois	United States	62702
50		Anderson	Indiana	United States	46011
51		Noblesville	Indiana	United States	46060
52		Des Moines	Iowa	United States	50314-2611
53		Olathe	Kansas	United States	66061
54		Lafayette	Louisiana	United States	70503
55		New Orleans	Louisiana	United States	70121
56		Shreveport	Louisiana	United States	71130-4228
57		Biddeford	Maine	United States	04005
58		Rockport	Maine	United States	04856
59		Baltimore	Maryland	United States	21215
60		Baltimore	Maryland	United States	21237
61		Framingham	Massachusetts	United States	01702
62		Ann Arbor	Michigan	United States	48106
63		Detroit	Michigan	United States	48201
64		Detroit	Michigan	United States	48202
65		Grand Rapids	Michigan	United States	49525
66		Lansing	Michigan	United States	48910
67		Petoskey	Michigan	United States	49770-2297
68		Pontiac	Michigan	United States	48341
69		St. Clair Shores	Michigan	United States	48081
70		Minneapolis	Minnesota	United States	55417
71		Kansas City	Missouri	United States	64128
72		St. Louis	Missouri	United States	63110
73		St. Louis	Missouri	United States	63141
74		Anaconda	Montana	United States	59711-2718
75		Great Falls	Montana	United States	59405
76		Omaha	Nebraska	United States	68131
77		Hackensack	New Jersey	United States	07601-1991
78		New Brunswick	New Jersey	United States	08901
79		Somerville	New Jersey	United States	08876-2598
80		Summit	New Jersey	United States	07901
81		Teaneck	New Jersey	United States	07666
82		Brooklyn	New York	United States	11215
83		Buffalo	New York	United States	14215-3021
84		Jamaica	New York	United States	11418
85		New Hyde Park	New York	United States	11040-1496
86		New York	New York	United States	10011
87		New York	New York	United States	10065
88		Stony Brook	New York	United States	11794
89		Valhalla	New York	United States	10595
90		Durham	North Carolina	United States	27710
91		Elizabeth City	North Carolina	United States	27909
92		Greensboro	North Carolina	United States	27403
93		Fargo	North Dakota	United States	58122
94		Canton	Ohio	United States	44718
95		Columbus	Ohio	United States	43215
96		Maumee	Ohio	United States	43537-1899
97		Toledo	Ohio	United States	43606
98		Bethlehem	Pennsylvania	United States	18015
99		Camp Hill	Pennsylvania	United States	17011
100		Danville	Pennsylvania	United States	17822
101		Philadelphia	Pennsylvania	United States	19107
102		Philadelphia	Pennsylvania	United States	19124
103		Scranton	Pennsylvania	United States	18510
104		Wilkes-Barre	Pennsylvania	United States	18711-3752
105		Charleston	South Carolina	United States	29425
106		Memphis	Tennessee	United States	38104
107		Nashville	Tennessee	United States	37232-2650
108		Corsicana	Texas	United States	75110
109		Dallas	Texas	United States	75216-7167
110		Edinburg	Texas	United States	78539
111		Houston	Texas	United States	77024
112		Houston	Texas	United States	77030-4009
113		Houston	Texas	United States	77030
114		McAllen	Texas	United States	78503
115		San Antonio	Texas	United States	78218
116		Ogden	Utah	United States	84403
117		Richmond	Virginia	United States	23249
118		Richmond	Virginia	United States	23298
119		Everett	Washington	United States	98201
120		Tacoma	Washington	United States	98405
121		Clarksburg	West Virginia	United States	26301
122		Avellaneda	Buenos Aires	Argentina	B1870CID
123		San Miguel	Buenos Aires	Argentina	1663
124	Hospital de Agudos "Dr. Carlos Bocalandro"	Tres de Febrero	Buenos Aires	Argentina	1657
125		Buenos Aires	Ciudad Auton. de Buenos Aires	Argentina	1221
126	Hospital Británico	Buenos Aires	Ciudad Auton. de Buenos Aires	Argentina	1280
127	Sanatorio Mitre	Buenos Aires	Ciudad Auton. de Buenos Aires	Argentina	C1039AAO
128		Buenos Aires	Ciudad Auton. de Buenos Aires	Argentina	C1431FWO
129		Vicente López		Argentina	1638
130		Garran	Australian Capital Territory	Australia	2605
131		Kogarah	New South Wales	Australia	2217
132		Lismore	New South Wales	Australia	2480
133		Sydney	New South Wales	Australia	2229
134		Auchenflower	Queensland	Australia	4066
135		Brisbane	Queensland	Australia	4066
136		Brisbane	Queensland	Australia	4101
137		Redcliffe	Queensland	Australia	4020
138		Southport	Queensland	Australia	4215
139		Woollongabba	Queensland	Australia	4102
140		Adelaide	South Australia	Australia	5042
141		Launceston	Tasmania	Australia	7250
142		Box Hill	Victoria	Australia	3128
143		Clayton	Victoria	Australia	3168
144		Melbourne	Victoria	Australia	3135
145		Melbourne	Victoria	Australia	3144
146		Perth	Western Australia	Australia	6000
147		Kittsee	Burgenland	Austria	2421
148		Oberpullendorf	Burgenland	Austria	7350
149		Wolfsberg	Kärnten	Austria	9400
150		Linz	Oberösterreich	Austria	4020
151		Gratwein	Steiermark	Austria	8113
152		Graz	Steiermark	Austria	8036
153		Hartberg	Steiermark	Austria	8230
154		Leoben	Steiermark	Austria	8700
155		Zams	Tirol	Austria	6511
156		Innsbruck		Austria	6020
157		Linz		Austria	4020
158		Mürzzuschlag		Austria	8680
159		St. Pölten		Austria	3100
160		Wien		Austria	1030
161		Wien		Austria	1100
162		Wien		Austria	1140
163		Aalst		Belgium	9300
164		Brugge		Belgium	8000
165		Bruxelles - Brussel		Belgium	1000
166		Dendermonde		Belgium	9200
167		Hasselt		Belgium	3500
168		HUY		Belgium	4500
169		Ieper		Belgium	8900
170		Leuven		Belgium	3000
171		Malmedy		Belgium	4960
172		MOL		Belgium	2400
173		Montigny S/sambre		Belgium	6061
174		Mortsel		Belgium	2640
175		Roeselare		Belgium	8800
176		Sint-niklaas		Belgium	9100
177		Tubize		Belgium	1480
178		Turnhout		Belgium	2300
179		Curitiba	Parana	Brazil	80050-350
180		Porto Alegre	Rio Grande do Sul	Brazil	90610-000
181		Campinas	Sao Paulo	Brazil	130839 970
182		Santo Andre	Sao Paulo	Brazil	09190-610
183		São Paulo	Sao Paulo	Brazil	01323-001
184		São Paulo	Sao Paulo	Brazil	04039 002
185		Sao Paulo		Brazil	05403-900
186		Sao Paulo		Brazil	05443000
187		Pleven		Bulgaria	5800
188		Ruse		Bulgaria	7002
189		Sofia		Bulgaria	1233
190		Sofia		Bulgaria	1606
191		Stara Zagora		Bulgaria	6000
192		Varna		Bulgaria	9010
193		Veliko Tarnovo		Bulgaria	5000
194		Calgary	Alberta	Canada	T2N 2T9
195		Edmonton	Alberta	Canada	T5H 3V9
196		Edmonton	Alberta	Canada	T6G 2B7
197		Edmonton	Alberta	Canada	T6L 5X8
198		Vancouver	British Columbia	Canada	V5Z 1M9
199		Saint John	New Brunswick	Canada	E2L 4L2
200		Cobourg	Ontario	Canada	K9A 5W6
201		Ottawa	Ontario	Canada	K1Y 4E9
202		Scarborough	Ontario	Canada	M1P 2V5
203		Toronto	Ontario	Canada	M5T 2S8
204	Hotel Dieu-Grace Hospital	Windsor	Ontario	Canada	N9A 1E1
205		Greenfield Park	Quebec	Canada	J4V 2H1
206	CHUM - Hopital Notre-Dame	Montreal	Quebec	Canada	H2L 4M1
207		Montreal	Quebec	Canada	H2L 4M1
208		Montreal	Quebec	Canada	H2W 1T8
209		Montreal	Quebec	Canada	H3T 1M5
210		Ste-Foy	Quebec	Canada	G1V 4G5
211		Quebec		Canada	G1J 1Z4
212		Quebec		Canada	G1V 4G5
213		Santiago		Chile	760 0448
214		Santiago		Chile
215		Viña del Mar		Chile
216		Guangzhou	Guangdong	China	510120
217		Guangzhou	Guangdong	China	510405
218		Guangzhou	Guangdong	China
219		Changsha	Hunan	China	410013
220		Nanjing	Jiangsu	China	210008
221		Nanjing	Jiangsu	China
222		Changchun	Jilin	China
223		Dalian	Liaoning	China	116027
224		Shenyang	Liaoning	China	110001
225		Shenyang	Liaoning	China	110004
226		Shenyang	Liaoning	China	110015
227	The 1st Affiliated Hosp of the 4th Military Med Uni	Xi'an	Shaanxi	China	710032
228	1st Affiliated Hosp., Med College Xi'an Jiaotong Univ.	Xi'an	Shaanxi	China	710061
229		Chengdu	Sichuan	China	610041
230		Beijing		China	100005
231		Beijing		China	100020
232		Beijing		China	100029
233		Beijing		China	100034
234		Beijing		China	100037
235		Beijing		China	100044
236	Beijing Friendship Hosp.	Beijing		China	100050
237		Beijing		China	100050
238		Beijing		China	100053
239		Beijing		China	100088
240		Beijing		China	100853
241		Chongqing		China	400038
242		Chongqing		China	400042
243		Shanghai		China	200003
244		Shanghai		China	200025
245		Shanghai		China	200127
246		Shanghai		China	200233
247		Shanghai		China
248		Medellín	Antioquia	Colombia
249		Bogotá	Distrito Capital de Bogotá	Colombia
250		Cali	Valle del Cauca	Colombia
251		Bogota		Colombia
252		Bogotá		Colombia
253		Cali		Colombia
254		Medellín		Colombia
255		Osijek		Croatia	310 00
256		Rijeka		Croatia	51000
257		Zadar		Croatia	23000
258		Zagreb		Croatia	10000
259		Zagreb		Croatia	1000
260		Brno		Czech Republic	656 91
261		Kutna Hora		Czech Republic	284 30
262		Nove Mesto na Morave		Czech Republic	592 31
263		Olomouc		Czech Republic	775 20
264		Plzen		Czech Republic	305 99
265		Praha 2		Czech Republic	128 08
266		Praha 2		Czech Republic	128 21
267		Praha 2		Czech Republic	12808
268		Ricany		Czech Republic	251 49
269		Znojmo		Czech Republic	669 02
270		Esbjerg		Denmark	6700
271		Frederiksberg C		Denmark	2000
272		Kolding		Denmark	6000
273		København NV		Denmark	2400
274		København S		Denmark	2300
275		Roskilde		Denmark	4000
276		Tallinn		Estonia	10138
277		Tallinn		Estonia	13419
278		Tallinn		Estonia	EE-10617
279		Tartu		Estonia	EE-51014
280		Helsinki		Finland	00290
281		Hämeenlinna		Finland	13530
282		Jyväskylä		Finland	40620
283		Lahti		Finland	15850
284		Lappeenranta		Finland	53130
285		Raisio		Finland	21200
286		Turku		Finland	20520
287		Turku		Finland	20700
288		Arras		France	62000
289		Besancon		France	25000
290		Brest Cedex		France	29609
291		Castelnau Le Lez		France	34170
292		Clermont Ferrand		France	63000
293		Colombes Cedex		France	92701
294		Dijon		France	21000
295		Lille		France	59037
296		Lille		France	59307
297		Limoges		France	87042
298		Lomme		France	59160
299		Lyon		France	69003
300		Montpellier Cedex		France	34295
301		Nice		France	06280
302		Nimes		France	30029
303		Paris		France	75004
304		Paris		France	75010
305		Paris		France	75475
306		Paris		France	75877
307		Pierre Benite		France	69495
308		Reims		France	51092
309		Roubaix		France	59100
310		Saint Herblain Cedex		France	44805
311		Saint-etienne		France	42000
312		Strasbourg Cedex		France	67091
313		Toulouse		France	31403
314		TOURCOING cedex		France	59208
315		Vandoeuvre Les Nancy		France	54511
316		Bad Mergentheim	Baden-Württemberg	Germany	97980
317		Esslingen	Baden-Württemberg	Germany	73730
318		Heidelberg	Baden-Württemberg	Germany	69120
319		Karlsbad	Baden-Württemberg	Germany	76307
320		Weiden	Bayern	Germany	92637
321		Beeskow	Brandenburg	Germany	15848
322		Frankfurt/Oder	Brandenburg	Germany	15236
323		Dortmund	Nordrhein-Westfalen	Germany	44137
324		Jülich	Nordrhein-Westfalen	Germany	52428
325		Köln	Nordrhein-Westfalen	Germany	50935
326		Köln	Nordrhein-Westfalen	Germany	51067
327		Köln	Nordrhein-Westfalen	Germany	51109
328		Leverkusen	Nordrhein-Westfalen	Germany	51375
329		Mönchengladbach	Nordrhein-Westfalen	Germany	41063
330		Neuss	Nordrhein-Westfalen	Germany	41464
331		Oberhausen	Nordrhein-Westfalen	Germany	46045
332		Paderborn	Nordrhein-Westfalen	Germany	33098
333		Soest	Nordrhein-Westfalen	Germany	59494
334		Stolberg	Nordrhein-Westfalen	Germany	52222
335		Troisdorf	Nordrhein-Westfalen	Germany	53844
336		Viersen	Nordrhein-Westfalen	Germany	41749
337		Wuppertal	Nordrhein-Westfalen	Germany	42109
338		Mainz	Rheinland-Pfalz	Germany	55131
339		Neuwied	Rheinland-Pfalz	Germany	56564
340		Halle	Sachsen-Anhalt	Germany	06112
341		Dresden	Sachsen	Germany	01067
342		Dresden	Sachsen	Germany	01307
343		Leipzig	Sachsen	Germany	04289
344		Pirna	Sachsen	Germany	01796
345		Berlin		Germany	10787
346		Bremen		Germany	28177
347		Elefsina	Attica	Greece	19018
348		Kifisia / Athens	Attica	Greece	14561
349		Abelokipi - Athens		Greece	115 26
350		Athens		Greece	106 76
351		Athens		Greece	115 26
352		Athens		Greece	156 69
353		Nea Ionia		Greece	14233
354		Piraeus		Greece	18536
355		Rio / Patras		Greece	265 04
356		Shatin	N.t.	Hong Kong
357		Shatin		Hong Kong
358		Baja		Hungary	6500
359		Balassagyarmat		Hungary	2660
360		Budapest		Hungary	1076
361		Budapest		Hungary	1134
362		Budapest		Hungary	1145
363		Debrecen		Hungary	4012
364		Gyor		Hungary	9024
365		Hodmezovasarhely		Hungary	6800
366		Kecskemet		Hungary	6000
367		Szekesfehervar		Hungary	8000
368		Tatabanya		Hungary	2800
369		Zalaegerszeg-Pozva		Hungary	H-8900
370		Ahmedabad	Gujar?t	India	380 054
371		Bangalore	Karn?taka	India	560052
372		Bangalore	Karn?taka	India	560099
373		Calicut	Kerala	India	673 004
374		Thiruvananthapuram	Kerala	India	695002
375		Pune	Maharashtra	India	411001
376		Pune	Maharashtra	India	411011
377		Ludhiana	Punjab	India	141001
378		Chennai	Tamil N?du	India	600081
379		Coimbatore	Tamil N?du	India	641 004
380		Kolkata	West Bengal	India	700 099
381		Hyderabad		India	500034
382		Hyderabad		India	500082
383		Hyderabad		India	600 038
384		Mumbai		India	400022
385		Noida		India
386		Jakarta		Indonesia	10430
387		Jakarta		Indonesia	11420
388		Surabaya		Indonesia	60286
389		Afula		Israel	1834111
390		Ashkelon		Israel	7830604
391		Haifa		Israel	31048
392		Haifa		Israel	3109601
393		Holon		Israel	58100
394		Kfar Saba		Israel	4428164
395		Rehovot		Israel	7610001
396		Tel Aviv		Israel	64239
397		Zefat		Israel	1311001
398		Acquaviva delle Fonti	Bari	Italy	70021
399		Napoli	Campania	Italy	80123
400		Modena	Emilia-Romagna	Italy	41100
401		Parma	Emilia-Romagna	Italy	43100
402		Piacenza	Emilia-Romagna	Italy	29121
403		Reggio Emilia	Emilia-Romagna	Italy	42123
404		Roma	Lazio	Italy	00161
405		Roma	Lazio	Italy	00168
406		Genova	Liguria	Italy	16128
407		Milano	Lombardia	Italy	20089
408		Milano	Lombardia	Italy	20133
409		Milano	Lombardia	Italy	20162
410		Varese	Lombardia	Italy	21100
411		Campobasso	Molise	Italy	86100
412		Fidenza	Parma	Italy	43036
413		Catania	Sicilia	Italy	95124
414		Palermo	Sicilia	Italy	90127
415		Terni	Trentino-Alto Adige	Italy	05019
416		Perugia	Umbria	Italy	06024
417		Perugia	Umbria	Italy	06156
418		Domodossola	Verbano-Cusio-Ossola	Italy	28845
419		Bergamo		Italy	24128
420		Latina		Italy	04100
421		Reggio Calabria		Italy	89124
422		Vicenza		Italy	36100
423		Ichinomiya	Aichi	Japan	491-8551
424		Kasugai	Aichi	Japan	487-0013
425		Obu	Aichi	Japan	474-8511
426		Matsuyama	Ehime	Japan	790-0024
427		Toon	Ehime	Japan	791-0281
428		Chikushino	Fukuoka	Japan	818-8516
429		Takasaki	Gunma	Japan	370-0829
430		Kure	Hiroshima	Japan	737-0023
431		Hakodate	Hokkaido	Japan	040-8611
432		Sapporo	Hokkaido	Japan	065-0033
433		Amagasaki	Hyogo	Japan	660-8511
434		Kanazawa	Ishikawa	Japan	920-8650
435		Hanamaki	Iwate	Japan	025-0075
436		Ebina	Kanagawa	Japan	243-0433
437		Kamakura	Kanagawa	Japan	247-8533
438		Yokohama	Kanagawa	Japan	236-0051
439		Nangoku	Kochi	Japan	783-8509
440		Matsusaka	Mie	Japan	515-8544
441		Tsu	Mie	Japan	514-1101
442		Tsu	Mie	Japan	514-8507
443		Kashiwazaki	Niigata	Japan	945-8585
444		Tomigusuku	Okinawa	Japan	901-0243
445		Urasoe	Okinawa	Japan	901-2132
446		Daito	Osaka	Japan	574-0074
447		Yao	Osaka	Japan	581-0011
448		Kusatsu	Shiga	Japan	525-8585
449		Hamamatsu	Shizuoka	Japan	432-8580
450		Meguro-ku	Tokyo	Japan	152-8902
451		Shinjuku-ku	Tokyo	Japan	162-8655
452		Shimonoseki	Yamaguchi	Japan	750-0061
453		Fukui		Japan	910-8561
454	National Hospital Organization Ibaraki Higashi Hospital	Ibaraki		Japan	319-1113
455		Kumamoto		Japan	860-0008
456		Kyoto		Japan	606-8507
457		Gyeongi-do	Korea	Korea, Republic of	463-707
458	Seoul National University Hospital	Seoul	Seoul Teugbyeolsi	Korea, Republic of	110-744
459	Seoul Metropolitan Boramae Hospital	Seoul	Seoul Teugbyeolsi	Korea, Republic of	156-707
460		Gyeonggi-do		Korea, Republic of	463-712
461		Jeollanam-do		Korea, Republic of	519-763
462		Seoul		Korea, Republic of	135-710
463		Seoul		Korea, Republic of	138736
464		Daugavpils		Latvia	LV-5417
465		Liepaja		Latvia	3402
466		Riga		Latvia	1002
467		Riga		Latvia	1005
468		Riga		Latvia	LV-1001
469		Riga		Latvia	LV-1038
470		Valmiera		Latvia	LV-4201
471		Ventspils		Latvia	LV-3601
472		Kaunas		Lithuania	LT-3000
473		Kaunas		Lithuania	LT-3002
474		Kaunas		Lithuania	LT-3026
475		Klaipeda		Lithuania	LT-5800
476		Klaipeda		Lithuania	LT-92231
477		Siauliai		Lithuania	76231
478		Utena		Lithuania	LT-28142
479		Vilnius		Lithuania	04130
480		Vilnius		Lithuania	10207
481		Vilnius		Lithuania	LT-2001
482		Kirchberg		Luxembourg	2540
483		Luxembourg		Luxembourg	1210
484		Niederkorn		Luxembourg	4602
485		Kuala Lumpur		Malaysia	59100
486		Negeri Sembilan,		Malaysia	70300
487		Sarawak		Malaysia	93400
488		Tuxtla Gutiérrez	Chiapas	Mexico	29000
489		Torreón	Coahuila	Mexico	27250
490		Mexico D. F.	Distrito Federal	Mexico	06760
491		Mexico D.F.	Distrito Federal	Mexico	11340
492		Mexico D.F.	Distrito Federal	Mexico	15900
493		México, D.F.	Distrito Federal	Mexico	06729
494		México, D.F.	Distrito Federal	Mexico	07760
495		México, D.F	Distrito Federal	Mexico	07460
496		Guadalajara	Jalisco	Mexico	44280
497		Morelia	Michoacán	Mexico	58270
498		Metepec	México	Mexico	52140
499		Monterrey	Nuevo Leon	Mexico	66480
500		Hermosillo	Sonora	Mexico	83000
501		Mérida	Yucatán	Mexico	97001
502		Aguascalientes		Mexico	20234
503		Chihuahua		Mexico	31350
504		Puebla		Mexico	72410
505		Zacatecas		Mexico	98000
506		Amersfoort		Netherlands	3816 CP
507		Amsterdam		Netherlands	1061 AE
508		Enschede		Netherlands	7511 JX
509		Heerlen		Netherlands	6401 CX
510		Maastricht		Netherlands	6229 HX
511		Nieuwegein		Netherlands	3435 CM
512		Rotterdam		Netherlands	3083 AN
513		Sittard		Netherlands	6131 BK
514		Utrecht		Netherlands	3582 KE
515		Auckland		New Zealand	0622
516		Auckland		New Zealand	1023
517		Auckland		New Zealand	2024
518		Christchurch		New Zealand	8011
519		Fredrikstad		Norway	1603
520		Gjøvik		Norway	2819
521		Hamar		Norway	2326
522		Oslo		Norway	0319
523		Oslo		Norway	0407
524		Karachi		Pakistan	74800
525		Karachi		Pakistan	75500
526		Lahore		Pakistan
527		Callao		Peru	CALLAO 2
528		Lima Cercado		Peru	LIMA 1
529		Lima		Peru	01
530		Lima		Peru	31
531		Lima		Peru	LIMA 11
532		Lima		Peru	LIMA 1
533		Bialystok		Poland	15-276
534		Bydgoszcz		Poland	85-681
535		Krakow		Poland	31-066
536		Krakow		Poland	31-121
537		Lublin		Poland	20-178
538		Olsztyn		Poland	10-228
539		Piotrkow Trybunalski		Poland	97-300
540		Siedlce		Poland	08-110
541		Starogard Gdanski		Poland	83-200
542		Szczecin		Poland	70-965
543		Tarnów		Poland	33-100
544		Warszawa		Poland	03-401
545		Warszawa		Poland	04-141
546		Warszawa		Poland	04-749
547		Wloclawek		Poland	87-800
548		S. Martinho do Bispo	Coimbra	Portugal	3041-856
549		Amadora		Portugal	2720-276
550		Cascais		Portugal	2750-349
551		Coimbra		Portugal	3000-075
552		Lisboa		Portugal	1150-199
553		Lisboa		Portugal	1349-019
554		Lisboa		Portugal	1649-035
555		Lisboa		Portugal	1849- 017
556		Matosinhos		Portugal	4454-509
557		Porto		Portugal	4099-001
558		Porto		Portugal	4200-319
559		Santarém		Portugal	2005
560		Viana do Castelo		Portugal	4901-585
561		Bucharest		Romania	014461
562		Bucharest		Romania	022328
563		Bucharest		Romania	041915
564		Constanta		Romania	900591
565		Suceava		Romania	720237
566		Moscow		Russian Federation	103030
567		Moscow		Russian Federation	115093
568		Moscow		Russian Federation	115516
569		Moscow		Russian Federation	117292
570		Moscow		Russian Federation	119048
571		Moscow		Russian Federation	119435
572		Moscow		Russian Federation	125101
573		Moscow		Russian Federation	125367
574		Nizhny Novgorod		Russian Federation	603001
575		Nizhny Novgorod		Russian Federation	603035
576		Yaroslavl		Russian Federation	150003
577		Yaroslavl		Russian Federation	150030
578		Singapore		Singapore	119074
579		Singapore		Singapore	168752
580		Singapore		Singapore	169608
581		Singapore		Singapore	308433
582	Changi General Hospital	Singapore		Singapore	529889
583		Bratislava		Slovakia	813 69
584		Bratislava		Slovakia	826 06
585		Lucenec		Slovakia	984 39
586		Martin		Slovakia	036 59
587		Zilina		Slovakia	012 07
588		Golnik		Slovenia	4204
589		Ljubljana		Slovenia	1000
590		Novo mesto		Slovenia	8000
591		Bloemfontein	Freestate	South Africa	9301
592		Johannesburg	Gauteng	South Africa	2057
593		Johannesburg	Gauteng	South Africa	2132
594		Johannesburg	Gauteng	South Africa	2196
595		Kempton Park	Gauteng	South Africa	1610
596		Pretoria	Gauteng	South Africa	0084
597		Pretoria	Gauteng	South Africa	0157
598		Pretoria	Gauteng	South Africa	0181
599		Roodepoort	Gauteng	South Africa	1724
600		Goodwood	Western Cape	South Africa	7460
601		Somerset West	Western Cape	South Africa	7130
602		Stellenbosch	Western Cape	South Africa	7505
603		Worcester	Western Cape	South Africa	6850
604		Sandton, Gauteng		South Africa	2196
605		Badalona	Barcelona	Spain	08916
606		Sabadell	Barcelona	Spain	08208
607		Cabra	Córdoba	Spain	14940
608		Olot	Girona	Spain	17800
609		Cartagena	Murcia	Spain	30202
610		Vélez	Málaga	Spain	29700
611		Vigo	Pontevedra	Spain	36214
612		Barcelona		Spain	08023
613		Barcelona		Spain	08036
614		Cuenca		Spain	16002
615		Córdoba		Spain	14004
616		Girona		Spain	17007
617		Zaragoza		Spain	50009
618		Borås		Sweden	501 82
619		Hässleholm		Sweden	281 25
620		Karlshamn		Sweden	374 80
621		Kristianstad		Sweden	29185
622		Lund		Sweden	221 85
623		Malmö		Sweden	205 02
624		Skövde		Sweden	541 85
625		Stockholm		Sweden	171 76
626		Stockholm		Sweden	182 88
627		Sundsvall		Sweden	851 86
628		Umeå		Sweden	90185
629		Visby		Sweden	62184
630		Bruderholz	Basel-Landschaft	Switzerland	4101
631		Basel	Basel-Stadt	Switzerland	4031
632		Liestal	Basel-Stadt	Switzerland	4410
633		Langenthal	Bern	Switzerland	4901
634		Baden		Switzerland	5404
635		Bern		Switzerland	3010
636		Genève		Switzerland	1211
637		Luzern		Switzerland	6000
638		Zürich		Switzerland	8091
639		Kaohsiung		Taiwan	833
640		Tainan		Taiwan	710
641		Taipei		Taiwan	10016
642		Taipei		Taiwan	114
643		Taipei		Taiwan
644		Bangkok		Thailand	10400
645		Bangkok		Thailand	10700
646		Chiangmai		Thailand	50200
647		Istanbul		Turkey	34098
648		Istanbul		Turkey	34304
649		Izmir		Turkey	35100
650		Izmir		Turkey	35340
651		Donetsk		Ukraine	83003
652		Donetsk		Ukraine	83045
653		Ivano-Frankivsk		Ukraine	76000
654		Kharkiv		Ukraine	61037
655		Kharkiv		Ukraine	61070
656		Kharkiv		Ukraine	61178
657		Kiev		Ukraine	02 091
658		Kiev		Ukraine	03680
659		Kiev		Ukraine	04112
660		Kyiv		Ukraine	01105
661		Lviv		Ukraine	790 34
662		Odessa		Ukraine	65009
663		Odessa		Ukraine	65025
664		Simferopol		Ukraine	95 026
665		Simferopol		Ukraine	95023
666		Middlesborough	Cleveland	United Kingdom	TS4 3BW
667		Dumfries	Dumfries and Galloway	United Kingdom	DG1 4EP
668		Liverpool	Merseyside	United Kingdom	L9 7JU
669		Sheffield	South Yorkshire	United Kingdom	S10 2JF
670		Glasgow	Stratchclyde	United Kingdom	G11 6NT
671		Newcastle Upon Tyne	Tyne and Wear	United Kingdom	NE1 4LP
672		Leeds	West Yorkshire	United Kingdom	LS9 7TF
673		London		United Kingdom	N18 1QX
674		London		United Kingdom	SE5 9RS
675		London		United Kingdom	W1T 4EU
676		Nottingham		United Kingdom	NG7 2UH

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

Additional Information:

Click here and search for results of Bayer Products provided by EMA

Publications

None provided.

Responsible Party:

Bayer

ClinicalTrials.gov Identifier:

NCT00571649

Other Study ID Numbers:

12839
2007-004614-14

First Posted:

Dec 12, 2007

Last Update Posted:

Sep 15, 2016

Last Verified:

Aug 1, 2016

Keywords provided by Bayer

Acute medical illnesses with increased risk for VTE.

Deep vein thrombosis (DVT)

Pulmonary embolism (PE),

Venous Thromboembolic disease (VTE),

Medical illness

Additional relevant MeSH terms:

Thromboembolism

Venous Thromboembolism

Enoxaparin

Rivaroxaban

Enoxaparin sodium

Study Results

Participant Flow

Recruitment Details	First patient first visit date: 04 DEC 2007; last patient last visit date 24 NOV 2010. Primary completion date: 12 AUG 2010. Participants were aged ≥40 years, hospitalized for an acute medical illness, and at risk of Venous Thromboembolism (VTE) (with heart failure, cancer, ischemic stroke, infection or inflammation, or respiratory insufficiency)
Pre-assignment Detail	A total of 8428 participants were screened; 327 failed. 8101 were randomized. 7998 (98.7%) were in the Safety Analysis Set (SAF), i.e. received study medication. 6024 (74.4%) were in the modified Intent to Treat (at Day 35) group (valid for SAF with adequate assessment of venous thromboembolism). A total of 6005 (74.1%) completed study.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Enoxaparin
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days during treatment period	Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days during treatment period
Period Title: Treatment Period
STARTED	4050	4051
Participants Received Treatment	3997	4001
Day 10	3454	3499
Day 35	3033	3115
COMPLETED	2958	3047
NOT COMPLETED	1092	1004
Period Title: Treatment Period
STARTED	3583	3635
COMPLETED	3038	3107
NOT COMPLETED	545	528

Baseline Characteristics

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Enoxaparin	Total
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days (SAF population)	Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days (SAF population)	Total of all reporting groups
Overall Participants	3997	4001	7998
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.2 (11.9)	69.2 (11.7)	69.2 (11.8)
Age, Customized (participants) [Number]
< 65 years	1323 33.1%	1363 34.1%	2686 33.6%
65 to < 75 years	1144 28.6%	1090 27.2%	2234 27.9%
>= 75 years	1530 38.3%	1548 38.7%	3078 38.5%
Sex: Female, Male (Count of Participants)
Female	1774 44.4%	1898 47.4%	3672 45.9%
Male	2223 55.6%	2103 52.6%	4326 54.1%
Race (participants) [Number]
White	2749 68.8%	2744 68.6%	5493 68.7%
Black	89 2.2%	92 2.3%	181 2.3%
Asian	793 19.8%	794 19.8%	1587 19.8%
Native American	12 0.3%	12 0.3%	24 0.3%
Hispanic	69 1.7%	70 1.7%	139 1.7%
Uncodable	106 2.7%	112 2.8%	218 2.7%
Unknown	1 0%	0 0%	1 0%
Missing	178 4.5%	177 4.4%	355 4.4%
Reason for hospitalization (participants) [Number]
Heart failure (NYHA Class III or NYHA Class IV)	1292 32.3%	1301 32.5%	2593 32.4%
Active cancer	294 7.4%	290 7.2%	584 7.3%
Acute ischemic stroke	691 17.3%	692 17.3%	1383 17.3%
Acute Infectious and Inflammatory Diseases	1904 47.6%	1876 46.9%	3780 47.3%
Acute infectious disease	1826 45.7%	1801 45%	3627 45.3%
Acute inflammatory or rheumatic disease	150 3.8%	149 3.7%	299 3.7%
Acute respiratory insufficiency	1085 27.1%	1151 28.8%	2236 28%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Composite Endpoint of Venous Thromboembolism [VTE] (Any Deep Vein Thrombosis [DVT], Non Fatal Pulmonary Embolism [PE]) and VTE-related Death up to Day 35 + 6 Days
Description	A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death.
Time Frame	Up to Day 35 + 6 days

Outcome Measure Data

Analysis Population Description
modified Intent-to-Treat (mITT) Day 35: participant was valid for the safety analysis and had an adequate assessment of VTE up to Day 35

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Enoxaparin
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days	Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days
Measure Participants	2967	3057
Number [Percentage of participants]	4.4 0.1%	5.7 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin
	Comments	A sample size of 2876 valid patients per group was estimated to obtain a joint power of at least 90% for both primary endpoints (91.4% for superiority) with 4% event rate at day 35 for comparator and 40% relative risk reduction.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0211
	Comments	Hochberg procedure: A 2-sided p-value of less than 0.05 would be considered significant, if the 1-sided p-value of the other primary efficacy outcome measure was less than 0.025, elsewise a p-value of less than 0.025 would be considered significant.
	Method	Cochran-Mantel-Haenszel
	Comments	Weighted relative risks were calculated using asymptotic methods, with weights based upon sample sizes per strata (geographic region).

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.771
	Confidence Interval	() 95% 0.618 to 0.962
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 10 + 5 Days
Description	A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death.
Time Frame	Up to Day 10 + 5 days

Outcome Measure Data

Analysis Population Description
Per Protocol (PP) Day 10: participant was valid for the safety analysis, had an adequate assessment of VTE up to Day 10 not later than 48 hours after stop of study drug, met inclusion criteria, and had no major protocol deviations.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Enoxaparin
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days	Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days
Measure Participants	2938	2993
Number [Percentage of participants]	2.7 0.1%	2.7 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin
	Comments	A sample size of 2876 valid patients per group was estimated to obtain a joint power of at least 90% for both primary endpoints (98.6% power for non-inferiority) with 1.8% event rate at day 10 for comparator and 35% relative risk reduction.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Rivaroxaban would be considered at least as effective as the comparator if the upper limit of the CI (Confidence Interval) was less than 1.5

Statistical Test of Hypothesis	p-Value	0.0025
	Comments	Hochberg procedure: A 1-sided p-value of less than 0.025 would be considered significant, if the 2-sided p-value of the other primary efficacy outcome measure was less than 0.05, elsewise a p-value of less than 0.0125 would be considered significant.
	Method	Cochran-Mantel-Haenszel
	Comments	Weighted relative risks were calculated using asymptotic methods, with weights based upon sample sizes per strata (geographic region).

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.968
	Confidence Interval	() 95% 0.713 to 1.314
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and All-cause Mortality up to Day 35 + 6 Days
Description	A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and death (VTE-related and not VTE-related).
Time Frame	Up to Day 35 + 6 days

Outcome Measure Data

Analysis Population Description
modified Intent-to-Treat (mITT) Day 35 (participant was valid for the safety analysis and had an adequate assessment of VTE up to Day 35) expanded to include participants who had an assessment of all deaths, including not VTE-related

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Enoxaparin
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days	Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days
Measure Participants	3096	3169
Number [Percentage of participants]	8.6 0.2%	9.2 0.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3758
	Comments	Test hierarchy: A p-value of less than 0.05 would be considered significant, if the tests for the two primary efficacy outcome measures were significant.
	Method	Cochran-Mantel-Haenszel
	Comments	Weighted relative risks were calculated using asymptotic methods, with weights based upon sample sizes per strata (geographic region).

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.931
	Confidence Interval	() 95% 0.795 to 1.091
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 10 + 5 Days Per mITT Population
Description	A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death.
Time Frame	Up to Day 10 + 5 days

Outcome Measure Data

Analysis Population Description
modified Intent-to-Treat (mITT) Day 10: participant was valid for the safety analysis and had an adequate assessment of VTE up to Day 10

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Enoxaparin
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days	Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days
Measure Participants	3232	3271
Number [Percentage of participants]	3.0 0.1%	3.1 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9473
	Comments	Test hierarchy: A p-value of less than 0.05 would be considered significant, if the tests for the 2 primary efficacy outcomes and for "Composite endpoint of VTE (any DVT, non fatal PE) and all-cause mortality up to Day 35 + 6 days" were significant.
	Method	Cochran-Mantel-Haenszel
	Comments	Weighted relative risks were calculated using asymptotic methods, with weights based upon sample sizes per strata (geographic region).

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.991
	Confidence Interval	() 95% 0.753 to 1.304
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants With VTE Combined With All-cause Mortality up to Day 10 + 5 Days
Description	A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and death (VTE-related and not VTE-related).
Time Frame	Up to Day 10 + 5 days

Outcome Measure Data

Analysis Population Description
modified Intent-to-Treat (mITT) Day 10 (participant was valid for the safety analysis and had an adequate assessment of VTE up to Day 10) expanded to include participants who had an assessment of all deaths, including not VTE-related

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Enoxaparin
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days	Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days
Measure Participants	3281	3310
Number [Percentage of participants]	4.8 0.1%	4.5 0.1%

6. Secondary Outcome

Title	Percentage of Participants With Symptomatic VTE, Including and Excluding VTE-related Death up to Days 10, 35, and 90
Description	Symptomatic VTE (non-fatal PE and DVT in lower extremity), including and excluding VTE-related death (PE and PE cannot be excluded) up to Days 10, 35, and 90
Time Frame	At Day 10 + 5 days, at Day 35 + 6 days, and at Day 90 + 7 days

Outcome Measure Data

Analysis Population Description
Safety population: Participant had at least one dose of study drug.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Enoxaparin
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days	Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days
Measure Participants	3997	4001
symptomatic VTE (incl. VTE-related death)-Day 10	0.7 0%	0.6 0%
symptomatic VTE (non fatal)-Day 10	0.5 0%	0.3 0%
symptomatic VTE (incl. VTE-related death)-Day 35	1.0 0%	1.4 0%
symptomatic VTE (non fatal)-Day 35	0.6 0%	0.7 0%
symptomatic VTE (incl. VTE-related death)-Day 90	1.7 0%	1.9 0%
symptomatic VTE (non fatal)-Day 90	0.7 0%	0.9 0%

7. Secondary Outcome

Title	Percentage of Participants With Net Clinical Benefit (Any DVT, Non-fatal PE, VTE-related Death, Plus Major and Clinically Relevant Non-major Bleeding Events) up to Day 35 + 6 Days
Description	Net clinical benefit is a composite of the primary efficacy endpoint (asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death) plus major and clinically relevant non-major bleeding events.
Time Frame	Up to Day 35 + 6 days

Outcome Measure Data

Analysis Population Description
modified Intent-to-Treat (mITT) Day 35 (participant was valid for the safety analysis and had an adequate assessment of VTE up to Day 35) expanded to include participants with major and clinically relevant bleeding events.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Enoxaparin
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days	Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days
Measure Participants	3042	3082
Number [Percentage of participants]	9.4 0.2%	7.8 0.2%

8. Secondary Outcome

Title	Percentage of Participants With Net Clinical Benefit (Any DVT, Non-fatal PE, VTE-related Death, Plus Major and Clinically Relevant Non-major Bleeding Events) up to Day 10 + 5 Days
Description	Net clinical benefit is a composite of the primary efficacy endpoint (asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death) plus major and clinically relevant non-major bleeding events
Time Frame	Up to Day 10 + 5 days

Outcome Measure Data

Analysis Population Description
Participants valid for safety analysis, with adequate assessment of VTE (to Day 10 within 48 hours of study drug), met inclusion criteria, and no major protocol deviations; expanded to include participants who had major bleeding or clinically relevant non-major bleeding events and met all criteria for PP except valid assessment of thromboembolism.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Enoxaparin
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days	Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days
Measure Participants	2950	3007
Number [Percentage of participants]	4.5 0.1%	3.9 0.1%

9. Secondary Outcome

Title	Percentage of Participants With Major Vascular Events up to Days 10, 35, and 90
Description	Major vascular events included cardiovascular death, acute myocardial infarction (MI), or acute ischemic stroke. Participants may have had a vascular event in more than one category.
Time Frame	At Day 10 + 5 days, at Day 35 + 6 days, and at Day 90 + 7 days

Outcome Measure Data

Analysis Population Description
Safety population: Participant had at least one dose of study drug.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Enoxaparin
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days	Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days
Measure Participants	3997	4001
Any event-Day 10	1.0 0%	1.0 0%
Ischemic stroke-Day 10	0.3 0%	0.3 0%
Acute MI-Day 10	0.5 0%	0.4 0%
Death (cardiovascular)-Day 10	0.4 0%	0.4 0%
Any event-Day 35	1.8 0%	1.6 0%
Ischemic stroke-Day 35	0.5 0%	0.5 0%
Acute MI-Day 35	0.6 0%	0.5 0%
Death (cardiovascular)-Day 35	0.9 0%	0.8 0%
Any event-Day 90	2.8 0.1%	2.8 0.1%
Ischemic stroke-Day 90	0.8 0%	1.1 0%
Acute MI-Day 90	0.9 0%	0.7 0%
Death (cardiovascular)-Day 90	1.4 0%	1.4 0%

10. Secondary Outcome

Title	Percentage of Participants With Each Component of the Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 35 + 6 Days
Description	The components of the composite endpoint include asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death.
Time Frame	Up to Day 35 + 6 days

Outcome Measure Data

Analysis Population Description
modified Intent-to-Treat (mITT) Day 35: participant was valid for the safety analysis and had an adequate assessment of VTE up to Day 35

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Enoxaparin
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days	Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days
Measure Participants	2967	3057
Symptomatic non-fatal PE	0.3 0%	0.5 0%
Symptomatic DVT in lower extremity	0.4 0%	0.5 0%
Asymptomatic proximal DVT in lower extremity	3.5 0.1%	4.4 0.1%
VTE related death	0.6 0%	1.0 0%

11. Secondary Outcome

Title	Percentage of Participants With Each Component of the Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 10 + 5 Days
Description	The components of the composite endpoint include asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death.
Time Frame	Up to Day 10 + 5 days

Outcome Measure Data

Analysis Population Description
Per Protocol Day 10: participant was valid for the safety analysis, had an adequate assessment of VTE up to Day 10 not later than 48 hours after stop of study drug, met inclusion criteria, and had no major protocol deviations

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Enoxaparin
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days	Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days
Measure Participants	2938	2993
Symptomatic non-fatal PE	0.2 0%	0.1 0%
Symptomatic DVT in lower extremity	0.2 0%	0.2 0%
Asymptomatic proximal DVT in lower extremity	2.4 0.1%	2.4 0.1%
VTE related death	0.1 0%	0.2 0%

12. Secondary Outcome

Title	Percentage of Participants With All-cause Mortality up to Day 90 + 7 Days
Description	All deaths, including VTE-related deaths, cardiovascular deaths, and other deaths.
Time Frame	Up to Day 90 + 7 days

Outcome Measure Data

Analysis Population Description
Safety population: Participant had at least one dose of study drug.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Enoxaparin
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days	Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days
Measure Participants	3997	4001
Any event	6.7 0.2%	6.2 0.2%
Death (cardiovascular)	1.4 0%	1.4 0%
Death (other)	4.3 0.1%	3.7 0.1%
VTE related death	1.0 0%	1.1 0%

13. Secondary Outcome

Title	Percentage of Participants With the Composite of Treatment Emergent Major Bleeding Events and Non-major Clinically Relevant Bleeding Events up to 2 Days After Last Intake of Any Study Medication (Day 35 + 6 Days)
Description	Major bleeding events were defined as events leading to >=2 g/dL fall in hemoglobin; or transfusion of >= 2 units of packed RBCs (Red blood cells) or whole blood; or leading to death. Non-major bleeding events were defined as overt bleeding not meeting the criteria of major bleeding
Time Frame	Up to Day 35 + 6 days

Outcome Measure Data

Analysis Population Description
Safety population: Participant had at least one dose of study drug.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Enoxaparin
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days	Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days
Measure Participants	3997	4001
Number [Percentage of participants]	4.1 0.1%	1.7 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin
	Comments	There was no sample size estimation as this was not planed as confirmatory analysis
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	2-sided p-value. No adjustment for multiple testing.
	Method	Cochran-Mantel-Haenszel
	Comments	Weighted relative risks were calculated using asymptotic methods, with weights based upon sample sizes per strata (geographic region).

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	2.455
	Confidence Interval	(2-Sided) 95% 1.854 to 3.251
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Percentage of Participants With the Composite of Treatment Emergent Major Bleeding Events and Non-major Clinically Relevant Bleeding Events up to 2 Days After Last Application of a Study Medication Syringe (Day 10 + 5 Days)
Description	Major bleeding events were defined as events leading to >=2 g/dL fall in hemoglobin or transfusion of >=2 units of packed RBCs or whole blood or leading to death. Non-major bleeding events were defined as overt bleeding not meeting the criteria of major bleeding.
Time Frame	Up to Day 10 + 5 days

Outcome Measure Data

Analysis Population Description
Safety population: Participant had at least one dose of study drug.

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)	Enoxaparin
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days	Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days
Measure Participants	3997	4001
Number [Percentage of participants]	2.8 0.1%	1.2 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin
	Comments	There was no sample size estimation as this was not planed as confirmatory analysis
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	2-sided p-value. No adjustment for multiple testing.
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	2.272
	Confidence Interval	(2-Sided) 95% 1.628 to 3.171
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

	Rivaroxaban (Xarelto, BAY59-7939)		Enoxaparin
Time Frame
Adverse Event Reporting Description

Arm/Group Title	Rivaroxaban (Xarelto, BAY59-7939)		Enoxaparin
Arm/Group Description	Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days		Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rivaroxaban (Xarelto, BAY59-7939)		Enoxaparin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1034/3997 (25.9%)		976/4001 (24.4%)
Blood and lymphatic system disorders
Agranulocytosis	0/3997 (0%)	0	1/4001 (0%)	1
Anaemia	18/3997 (0.5%)	20	13/4001 (0.3%)	13
Coagulopathy	0/3997 (0%)	0	1/4001 (0%)	1
Disseminated intravascular coagulation	2/3997 (0.1%)	2	2/4001 (0%)	2
Febrile neutropenia	4/3997 (0.1%)	5	3/4001 (0.1%)	4
Leukocytosis	1/3997 (0%)	1	0/4001 (0%)	0
Leukopenia	0/3997 (0%)	0	2/4001 (0%)	2
Lymphadenopathy	1/3997 (0%)	1	1/4001 (0%)	1
Neutropenia	0/3997 (0%)	0	3/4001 (0.1%)	3
Normochromic normocytic anaemia	0/3997 (0%)	0	1/4001 (0%)	1
Pancytopenia	1/3997 (0%)	1	0/4001 (0%)	0
Thrombocytopenia	13/3997 (0.3%)	13	9/4001 (0.2%)	9
Anaemia of malignant disease	0/3997 (0%)	0	1/4001 (0%)	1
Haemorrhagic anaemia	1/3997 (0%)	1	1/4001 (0%)	1
Heparin-induced thrombocytopenia	0/3997 (0%)	0	1/4001 (0%)	1
Cardiac disorders
Acute myocardial infarction	30/3997 (0.8%)	31	28/4001 (0.7%)	29
Angina pectoris	1/3997 (0%)	1	4/4001 (0.1%)	4
Angina unstable	6/3997 (0.2%)	7	6/4001 (0.1%)	6
Aortic valve incompetence	0/3997 (0%)	0	1/4001 (0%)	1
Aortic valve stenosis	2/3997 (0.1%)	2	0/4001 (0%)	0
Arrhythmia	2/3997 (0.1%)	2	6/4001 (0.1%)	6
Arteriosclerosis coronary artery	1/3997 (0%)	1	1/4001 (0%)	1
Atrial fibrillation	23/3997 (0.6%)	23	22/4001 (0.5%)	24
Atrial flutter	5/3997 (0.1%)	5	2/4001 (0%)	2
Atrial tachycardia	2/3997 (0.1%)	2	0/4001 (0%)	0
Atrioventricular block	1/3997 (0%)	1	0/4001 (0%)	0
Atrioventricular block complete	3/3997 (0.1%)	3	5/4001 (0.1%)	5
Bradycardia	1/3997 (0%)	1	4/4001 (0.1%)	4
Cardiac arrest	12/3997 (0.3%)	13	11/4001 (0.3%)	12
Cardiac failure	76/3997 (1.9%)	84	76/4001 (1.9%)	81
Cardiac failure acute	11/3997 (0.3%)	12	25/4001 (0.6%)	28
Cardiac failure chronic	10/3997 (0.3%)	10	10/4001 (0.2%)	11
Cardiac failure congestive	31/3997 (0.8%)	37	31/4001 (0.8%)	38
Cardiac hypertrophy	0/3997 (0%)	0	1/4001 (0%)	1
Cardio-respiratory arrest	11/3997 (0.3%)	11	12/4001 (0.3%)	12
Cardiogenic shock	6/3997 (0.2%)	6	4/4001 (0.1%)	4
Cardiomegaly	0/3997 (0%)	0	2/4001 (0%)	2
Cardiomyopathy	1/3997 (0%)	1	0/4001 (0%)	0
Cardiovascular disorder	0/3997 (0%)	0	1/4001 (0%)	2
Cor pulmonale	1/3997 (0%)	1	1/4001 (0%)	1
Cor pulmonale chronic	2/3997 (0.1%)	2	1/4001 (0%)	1
Coronary artery disease	12/3997 (0.3%)	13	7/4001 (0.2%)	8
Coronary artery occlusion	1/3997 (0%)	1	2/4001 (0%)	2
Coronary artery stenosis	1/3997 (0%)	1	3/4001 (0.1%)	3
Left ventricular failure	2/3997 (0.1%)	2	2/4001 (0%)	2
Myocardial infarction	1/3997 (0%)	1	1/4001 (0%)	1
Myocardial ischaemia	3/3997 (0.1%)	3	6/4001 (0.1%)	6
Palpitations	0/3997 (0%)	0	1/4001 (0%)	1
Pericardial effusion	1/3997 (0%)	1	0/4001 (0%)	0
Pericardial haemorrhage	1/3997 (0%)	1	0/4001 (0%)	0
Pericarditis	2/3997 (0.1%)	2	1/4001 (0%)	1
Right ventricular failure	1/3997 (0%)	1	1/4001 (0%)	1
Sick sinus syndrome	2/3997 (0.1%)	2	3/4001 (0.1%)	3
Sinus arrest	0/3997 (0%)	0	1/4001 (0%)	1
Sinus bradycardia	1/3997 (0%)	1	1/4001 (0%)	1
Supraventricular tachycardia	3/3997 (0.1%)	3	1/4001 (0%)	1
Trifascicular block	1/3997 (0%)	1	0/4001 (0%)	0
Ventricular fibrillation	4/3997 (0.1%)	6	3/4001 (0.1%)	3
Ventricular tachycardia	7/3997 (0.2%)	8	1/4001 (0%)	2
Intracardiac thrombus	1/3997 (0%)	1	3/4001 (0.1%)	3
Atrial thrombosis	4/3997 (0.1%)	4	0/4001 (0%)	0
Ischaemic cardiomyopathy	1/3997 (0%)	1	0/4001 (0%)	0
Tachyarrhythmia	1/3997 (0%)	1	0/4001 (0%)	0
Left ventricular dysfunction	1/3997 (0%)	1	1/4001 (0%)	1
Bradyarrhythmia	0/3997 (0%)	0	1/4001 (0%)	1
Electromechanical dissociation	0/3997 (0%)	0	1/4001 (0%)	1
Cardiopulmonary failure	5/3997 (0.1%)	5	8/4001 (0.2%)	8
Acute coronary syndrome	2/3997 (0.1%)	2	2/4001 (0%)	2
Haemorrhage coronary artery	1/3997 (0%)	1	0/4001 (0%)	0
Congestive cardiomyopathy	1/3997 (0%)	1	2/4001 (0%)	2
Cardiac perforation	1/3997 (0%)	1	0/4001 (0%)	0
Right ventricular dysfunction	1/3997 (0%)	1	0/4001 (0%)	0
Mitral valve disease	0/3997 (0%)	0	1/4001 (0%)	1
Cardiac fibrillation	1/3997 (0%)	1	0/4001 (0%)	0
Rheumatic heart disease	0/3997 (0%)	0	1/4001 (0%)	1
Acute left ventricular failure	1/3997 (0%)	1	0/4001 (0%)	0
Supraventricular tachyarrhythmia	1/3997 (0%)	1	0/4001 (0%)	0
Cardiovascular insufficiency	0/3997 (0%)	0	1/4001 (0%)	1
Chronotropic incompetence	1/3997 (0%)	1	0/4001 (0%)	0
Atrioventricular dissociation	0/3997 (0%)	0	1/4001 (0%)	1
Congenital, familial and genetic disorders
Atrial septal defect	1/3997 (0%)	1	1/4001 (0%)	1
Gastrointestinal angiodysplasia	1/3997 (0%)	1	0/4001 (0%)	0
Pyloric stenosis	1/3997 (0%)	1	0/4001 (0%)	0
Myotonic dystrophy	1/3997 (0%)	1	0/4001 (0%)	0
Ear and labyrinth disorders
Ear haemorrhage	1/3997 (0%)	1	0/4001 (0%)	0
Vertigo	2/3997 (0.1%)	2	2/4001 (0%)	2
Eye disorders
Cataract	1/3997 (0%)	1	1/4001 (0%)	1
Conjunctival haemorrhage	1/3997 (0%)	1	0/4001 (0%)	0
Diabetic retinopathy	1/3997 (0%)	1	0/4001 (0%)	0
Eye haemorrhage	1/3997 (0%)	1	1/4001 (0%)	1
Eye pain	0/3997 (0%)	0	1/4001 (0%)	1
Glaucoma	1/3997 (0%)	1	0/4001 (0%)	0
Keratitis	1/3997 (0%)	1	0/4001 (0%)	0
Macular degeneration	1/3997 (0%)	1	0/4001 (0%)	0
Macular oedema	0/3997 (0%)	0	1/4001 (0%)	1
Optic atrophy	0/3997 (0%)	0	1/4001 (0%)	1
Periorbital oedema	1/3997 (0%)	1	0/4001 (0%)	0
Pupils unequal	1/3997 (0%)	1	0/4001 (0%)	0
Retinopathy hypertensive	0/3997 (0%)	0	1/4001 (0%)	1
Vision blurred	1/3997 (0%)	1	0/4001 (0%)	0
Vitreous haemorrhage	0/3997 (0%)	0	1/4001 (0%)	1
Entropion	1/3997 (0%)	1	0/4001 (0%)	0
Gastrointestinal disorders
Abdominal pain	6/3997 (0.2%)	7	4/4001 (0.1%)	5
Abdominal pain upper	2/3997 (0.1%)	2	2/4001 (0%)	2
Acute abdomen	1/3997 (0%)	1	0/4001 (0%)	0
Ascites	2/3997 (0.1%)	2	0/4001 (0%)	0
Colitis	1/3997 (0%)	1	1/4001 (0%)	1
Colitis ischaemic	1/3997 (0%)	1	0/4001 (0%)	0
Colonic polyp	0/3997 (0%)	0	2/4001 (0%)	2
Constipation	2/3997 (0.1%)	2	3/4001 (0.1%)	3
Diarrhoea	5/3997 (0.1%)	6	10/4001 (0.2%)	11
Diarrhoea haemorrhagic	1/3997 (0%)	1	0/4001 (0%)	0
Diverticulum	0/3997 (0%)	0	1/4001 (0%)	1
Diverticulum intestinal	0/3997 (0%)	0	1/4001 (0%)	1
Diverticulum intestinal haemorrhagic	1/3997 (0%)	1	0/4001 (0%)	0
Duodenal ulcer	0/3997 (0%)	0	1/4001 (0%)	1
Duodenal ulcer haemorrhage	3/3997 (0.1%)	3	1/4001 (0%)	1
Duodenal ulcer perforation	0/3997 (0%)	0	1/4001 (0%)	1
Dyspepsia	0/3997 (0%)	0	2/4001 (0%)	2
Dysphagia	0/3997 (0%)	0	3/4001 (0.1%)	3
Enteritis	0/3997 (0%)	0	1/4001 (0%)	1
Enterocolitis	0/3997 (0%)	0	1/4001 (0%)	1
Femoral hernia, obstructive	0/3997 (0%)	0	1/4001 (0%)	1
Gastric haemorrhage	1/3997 (0%)	1	0/4001 (0%)	0
Gastric ulcer	1/3997 (0%)	1	2/4001 (0%)	2
Gastric ulcer haemorrhage	2/3997 (0.1%)	2	3/4001 (0.1%)	3
Gastric ulcer perforation	0/3997 (0%)	0	1/4001 (0%)	1
Gastritis	3/3997 (0.1%)	3	0/4001 (0%)	0
Gastrooesophageal reflux disease	1/3997 (0%)	1	0/4001 (0%)	0
Gastroduodenal ulcer	0/3997 (0%)	0	1/4001 (0%)	1
Gastrointestinal haemorrhage	12/3997 (0.3%)	12	7/4001 (0.2%)	8
Gastrointestinal perforation	0/3997 (0%)	0	1/4001 (0%)	1
Gingival bleeding	0/3997 (0%)	0	1/4001 (0%)	1
Haematemesis	3/3997 (0.1%)	3	4/4001 (0.1%)	4
Haematochezia	4/3997 (0.1%)	4	1/4001 (0%)	1
Ileus	6/3997 (0.2%)	6	0/4001 (0%)	0
Ileus paralytic	2/3997 (0.1%)	2	0/4001 (0%)	0
Impaired gastric emptying	0/3997 (0%)	0	1/4001 (0%)	2
Inguinal hernia	1/3997 (0%)	1	0/4001 (0%)	0
Intestinal infarction	0/3997 (0%)	0	1/4001 (0%)	1
Intestinal ischaemia	1/3997 (0%)	1	1/4001 (0%)	1
Intestinal obstruction	5/3997 (0.1%)	5	3/4001 (0.1%)	3
Large intestinal ulcer	1/3997 (0%)	1	0/4001 (0%)	0
Mallory-Weiss syndrome	1/3997 (0%)	1	0/4001 (0%)	0
Melaena	6/3997 (0.2%)	6	3/4001 (0.1%)	3
Mesenteric artery stenosis	0/3997 (0%)	0	1/4001 (0%)	1
Mouth haemorrhage	0/3997 (0%)	0	1/4001 (0%)	1
Nausea	3/3997 (0.1%)	3	5/4001 (0.1%)	7
Oesophageal haemorrhage	1/3997 (0%)	1	0/4001 (0%)	0
Oesophageal spasm	1/3997 (0%)	1	0/4001 (0%)	0
Oesophageal stenosis	0/3997 (0%)	0	1/4001 (0%)	1
Oesophageal ulcer	1/3997 (0%)	1	1/4001 (0%)	1
Oesophageal varices haemorrhage	0/3997 (0%)	0	1/4001 (0%)	1
Pancreatitis	0/3997 (0%)	0	2/4001 (0%)	2
Pancreatitis acute	1/3997 (0%)	1	0/4001 (0%)	0
Pancreatitis chronic	1/3997 (0%)	1	0/4001 (0%)	0
Peritoneal haemorrhage	2/3997 (0.1%)	2	0/4001 (0%)	0
Peritonitis	2/3997 (0.1%)	2	1/4001 (0%)	1
Proctalgia	0/3997 (0%)	0	1/4001 (0%)	1
Rectal haemorrhage	4/3997 (0.1%)	4	4/4001 (0.1%)	5
Reflux oesophagitis	1/3997 (0%)	1	0/4001 (0%)	0
Retroperitoneal haemorrhage	1/3997 (0%)	1	0/4001 (0%)	0
Small intestinal obstruction	1/3997 (0%)	1	3/4001 (0.1%)	3
Thrombosis mesenteric vessel	1/3997 (0%)	1	0/4001 (0%)	0
Upper gastrointestinal haemorrhage	4/3997 (0.1%)	4	2/4001 (0%)	2
Vomiting	7/3997 (0.2%)	7	4/4001 (0.1%)	5
Oesophagitis ulcerative	1/3997 (0%)	1	0/4001 (0%)	0
Anal haemorrhage	2/3997 (0.1%)	2	0/4001 (0%)	0
Lower gastrointestinal haemorrhage	2/3997 (0.1%)	2	2/4001 (0%)	3
Diabetic gastroparesis	1/3997 (0%)	2	0/4001 (0%)	0
Internal hernia	1/3997 (0%)	1	0/4001 (0%)	0
Oedematous pancreatitis	1/3997 (0%)	1	0/4001 (0%)	0
Small intestinal haemorrhage	1/3997 (0%)	1	0/4001 (0%)	0
Haemorrhoidal haemorrhage	1/3997 (0%)	1	2/4001 (0%)	2
Varices oesophageal	0/3997 (0%)	0	1/4001 (0%)	1
Hernial eventration	1/3997 (0%)	1	0/4001 (0%)	0
Retroperitoneal haematoma	1/3997 (0%)	1	1/4001 (0%)	1
Intestinal haemorrhage	1/3997 (0%)	2	0/4001 (0%)	0
Abdominal hernia obstructive	0/3997 (0%)	0	1/4001 (0%)	1
Diverticular perforation	1/3997 (0%)	1	1/4001 (0%)	1
General disorders
Asthenia	4/3997 (0.1%)	4	1/4001 (0%)	1
Chest pain	10/3997 (0.3%)	10	16/4001 (0.4%)	18
Chills	1/3997 (0%)	1	0/4001 (0%)	0
Death	14/3997 (0.4%)	14	9/4001 (0.2%)	9
Fatigue	2/3997 (0.1%)	2	3/4001 (0.1%)	3
Impaired healing	0/3997 (0%)	0	1/4001 (0%)	1
Malaise	1/3997 (0%)	1	1/4001 (0%)	1
Multi-organ failure	8/3997 (0.2%)	8	5/4001 (0.1%)	5
Oedema	1/3997 (0%)	1	0/4001 (0%)	0
Oedema peripheral	2/3997 (0.1%)	2	5/4001 (0.1%)	6
Pain	4/3997 (0.1%)	4	2/4001 (0%)	3
Pyrexia	8/3997 (0.2%)	8	9/4001 (0.2%)	9
Sudden death	8/3997 (0.2%)	8	5/4001 (0.1%)	5
Performance status decreased	0/3997 (0%)	0	2/4001 (0%)	3
Hernia pain	0/3997 (0%)	0	1/4001 (0%)	1
Sudden cardiac death	2/3997 (0.1%)	2	7/4001 (0.2%)	7
General physical health deterioration	5/3997 (0.1%)	5	4/4001 (0.1%)	4
Puncture site haemorrhage	0/3997 (0%)	0	1/4001 (0%)	1
Nodule	1/3997 (0%)	1	0/4001 (0%)	0
Catheter site haematoma	0/3997 (0%)	0	1/4001 (0%)	1
Ulcer haemorrhage	1/3997 (0%)	1	0/4001 (0%)	0
Drug intolerance	1/3997 (0%)	1	1/4001 (0%)	1
Unevaluable event	0/3997 (0%)	0	1/4001 (0%)	1
Non-cardiac chest pain	2/3997 (0.1%)	2	0/4001 (0%)	0
Implant site haematoma	0/3997 (0%)	0	1/4001 (0%)	1
Device malfunction	0/3997 (0%)	0	1/4001 (0%)	1
Device dislocation	1/3997 (0%)	1	0/4001 (0%)	0
Device occlusion	1/3997 (0%)	1	0/4001 (0%)	0
Disuse syndrome	0/3997 (0%)	0	1/4001 (0%)	1
Device capturing issue	1/3997 (0%)	1	0/4001 (0%)	0
Hepatobiliary disorders
Acute hepatic failure	0/3997 (0%)	0	1/4001 (0%)	1
Biliary colic	1/3997 (0%)	1	0/4001 (0%)	0
Cholecystitis	1/3997 (0%)	1	3/4001 (0.1%)	4
Cholecystitis acute	2/3997 (0.1%)	2	2/4001 (0%)	2
Cholelithiasis	2/3997 (0.1%)	2	4/4001 (0.1%)	4
Cholestasis	2/3997 (0.1%)	2	0/4001 (0%)	0
Granulomatous liver disease	1/3997 (0%)	1	0/4001 (0%)	0
Hepatic cirrhosis	0/3997 (0%)	0	2/4001 (0%)	2
Hepatic congestion	1/3997 (0%)	1	1/4001 (0%)	1
Hepatic failure	1/3997 (0%)	1	2/4001 (0%)	2
Hepatic function abnormal	7/3997 (0.2%)	7	5/4001 (0.1%)	5
Hepatic steatosis	2/3997 (0.1%)	2	0/4001 (0%)	0
Hepatitis acute	1/3997 (0%)	1	1/4001 (0%)	1
Hepatitis alcoholic	0/3997 (0%)	0	1/4001 (0%)	1
Hepatitis toxic	0/3997 (0%)	0	1/4001 (0%)	1
Hepatorenal syndrome	1/3997 (0%)	1	1/4001 (0%)	1
Hyperbilirubinaemia	0/3997 (0%)	0	1/4001 (0%)	1
Ischaemic hepatitis	2/3997 (0.1%)	2	1/4001 (0%)	1
Jaundice	2/3997 (0.1%)	2	0/4001 (0%)	0
Cytolytic hepatitis	2/3997 (0.1%)	2	1/4001 (0%)	1
Bile duct obstruction	1/3997 (0%)	1	0/4001 (0%)	0
Haemobilia	1/3997 (0%)	1	0/4001 (0%)	0
Hepatic lesion	0/3997 (0%)	0	2/4001 (0%)	2
Cryptogenic cirrhosis	0/3997 (0%)	0	1/4001 (0%)	1
Liver injury	0/3997 (0%)	0	1/4001 (0%)	1
Immune system disorders
Amyloidosis	0/3997 (0%)	0	1/4001 (0%)	1
Anaphylactic reaction	1/3997 (0%)	1	0/4001 (0%)	0
Drug hypersensitivity	0/3997 (0%)	0	2/4001 (0%)	2
Hypersensitivity	0/3997 (0%)	0	2/4001 (0%)	2
Sarcoidosis	0/3997 (0%)	0	1/4001 (0%)	1
Infections and infestations
Abscess	1/3997 (0%)	1	0/4001 (0%)	0
Acquired immunodeficiency syndrome	1/3997 (0%)	1	0/4001 (0%)	0
Appendicitis	1/3997 (0%)	1	1/4001 (0%)	1
Appendicitis perforated	1/3997 (0%)	1	0/4001 (0%)	0
Bacteraemia	1/3997 (0%)	1	0/4001 (0%)	0
Bronchiectasis	3/3997 (0.1%)	3	2/4001 (0%)	2
Bronchiolitis	1/3997 (0%)	1	0/4001 (0%)	0
Bronchitis	18/3997 (0.5%)	18	4/4001 (0.1%)	4
Bronchopneumonia	8/3997 (0.2%)	8	10/4001 (0.2%)	10
Cellulitis	20/3997 (0.5%)	23	9/4001 (0.2%)	10
Cellulitis streptococcal	1/3997 (0%)	1	0/4001 (0%)	0
Diarrhoea infectious	0/3997 (0%)	0	1/4001 (0%)	1
Disseminated tuberculosis	1/3997 (0%)	1	0/4001 (0%)	0
Diverticulitis	5/3997 (0.1%)	5	1/4001 (0%)	1
Empyema	1/3997 (0%)	1	1/4001 (0%)	1
Endocarditis	1/3997 (0%)	1	2/4001 (0%)	3
Enteritis necroticans	1/3997 (0%)	1	0/4001 (0%)	0
Enterococcal bacteraemia	0/3997 (0%)	0	1/4001 (0%)	1
Erysipelas	4/3997 (0.1%)	4	2/4001 (0%)	2
Furuncle	1/3997 (0%)	1	0/4001 (0%)	0
Gangrene	0/3997 (0%)	0	2/4001 (0%)	3
Gastroenteritis	12/3997 (0.3%)	12	4/4001 (0.1%)	4
Gastroenteritis viral	0/3997 (0%)	0	1/4001 (0%)	1
Gastrointestinal infection	1/3997 (0%)	1	0/4001 (0%)	0
Hepatitis C	1/3997 (0%)	1	0/4001 (0%)	0
Herpes zoster	2/3997 (0.1%)	2	2/4001 (0%)	2
Impetigo	1/3997 (0%)	1	0/4001 (0%)	0
Infected skin ulcer	1/3997 (0%)	1	1/4001 (0%)	1
Infection	1/3997 (0%)	1	0/4001 (0%)	0
Liver abscess	1/3997 (0%)	1	1/4001 (0%)	1
Lobar pneumonia	4/3997 (0.1%)	4	1/4001 (0%)	1
Localised infection	3/3997 (0.1%)	3	0/4001 (0%)	0
Lower respiratory tract infection	4/3997 (0.1%)	4	3/4001 (0.1%)	3
Lung abscess	2/3997 (0.1%)	2	1/4001 (0%)	1
Meningitis	0/3997 (0%)	0	2/4001 (0%)	2
Necrotising fasciitis	0/3997 (0%)	0	1/4001 (0%)	1
Oesophageal candidiasis	1/3997 (0%)	1	1/4001 (0%)	1
Oral candidiasis	0/3997 (0%)	0	1/4001 (0%)	1
Osteomyelitis	4/3997 (0.1%)	4	1/4001 (0%)	1
Peridiverticular abscess	1/3997 (0%)	1	0/4001 (0%)	0
Perinephric abscess	0/3997 (0%)	0	1/4001 (0%)	1
Peritoneal abscess	0/3997 (0%)	0	1/4001 (0%)	1
Pneumonia	74/3997 (1.9%)	78	76/4001 (1.9%)	78
Pneumonia klebsiella	1/3997 (0%)	1	0/4001 (0%)	0
Pneumonia pneumococcal	2/3997 (0.1%)	2	0/4001 (0%)	0
Pneumonia primary atypical	0/3997 (0%)	0	1/4001 (0%)	1
Postoperative wound infection	0/3997 (0%)	0	1/4001 (0%)	1
Pseudomembranous colitis	1/3997 (0%)	1	1/4001 (0%)	1
Pulmonary tuberculosis	0/3997 (0%)	0	1/4001 (0%)	1
Pyelonephritis	1/3997 (0%)	1	1/4001 (0%)	1
Pyelonephritis acute	1/3997 (0%)	1	2/4001 (0%)	2
Pyometra	0/3997 (0%)	0	1/4001 (0%)	1
Pyothorax	1/3997 (0%)	1	1/4001 (0%)	1
Retroperitoneal abscess	1/3997 (0%)	1	0/4001 (0%)	0
Salmonellosis	0/3997 (0%)	0	1/4001 (0%)	1
Sepsis	29/3997 (0.7%)	30	14/4001 (0.3%)	14
Septic shock	15/3997 (0.4%)	16	18/4001 (0.4%)	20
Sinusitis	1/3997 (0%)	1	1/4001 (0%)	1
Subcutaneous abscess	0/3997 (0%)	0	1/4001 (0%)	1
Tuberculosis	1/3997 (0%)	2	0/4001 (0%)	0
Upper respiratory tract infection	0/3997 (0%)	0	1/4001 (0%)	1
Urinary tract infection	17/3997 (0.4%)	20	13/4001 (0.3%)	14
Viral infection	1/3997 (0%)	1	1/4001 (0%)	1
Viral upper respiratory tract infection	0/3997 (0%)	0	2/4001 (0%)	2
Wound infection	0/3997 (0%)	0	1/4001 (0%)	1
Urosepsis	4/3997 (0.1%)	4	6/4001 (0.1%)	6
Abscess limb	1/3997 (0%)	1	1/4001 (0%)	1
Staphylococcal bacteraemia	2/3997 (0.1%)	2	0/4001 (0%)	0
Burn infection	1/3997 (0%)	1	0/4001 (0%)	0
Haematoma infection	1/3997 (0%)	1	0/4001 (0%)	0
Pulmonary sepsis	0/3997 (0%)	0	1/4001 (0%)	1
Bacterial sepsis	1/3997 (0%)	1	2/4001 (0%)	2
Sepsis syndrome	1/3997 (0%)	1	1/4001 (0%)	1
Psoas abscess	1/3997 (0%)	1	1/4001 (0%)	1
Phlebitis infective	1/3997 (0%)	1	0/4001 (0%)	0
Infective exacerbation of chronic obstructive airways disease	10/3997 (0.3%)	10	12/4001 (0.3%)	12
Lung infection pseudomonal	0/3997 (0%)	0	1/4001 (0%)	1
Abdominal sepsis	3/3997 (0.1%)	3	0/4001 (0%)	0
Wound sepsis	1/3997 (0%)	1	0/4001 (0%)	0
Staphylococcal infection	0/3997 (0%)	0	1/4001 (0%)	1
Tuberculosis liver	1/3997 (0%)	1	0/4001 (0%)	0
Enterocolitis infectious	2/3997 (0.1%)	2	0/4001 (0%)	0
Wound infection staphylococcal	1/3997 (0%)	1	1/4001 (0%)	1
Implant site infection	0/3997 (0%)	0	1/4001 (0%)	1
Intervertebral discitis	1/3997 (0%)	2	0/4001 (0%)	0
Diabetic foot infection	1/3997 (0%)	1	2/4001 (0%)	2
Abdominal abscess	0/3997 (0%)	0	1/4001 (0%)	1
Pneumonia bacterial	0/3997 (0%)	0	1/4001 (0%)	1
Arthritis infective	1/3997 (0%)	1	0/4001 (0%)	0
Lung infection	2/3997 (0.1%)	2	4/4001 (0.1%)	4
Pneumonia fungal	2/3997 (0.1%)	2	1/4001 (0%)	1
Bronchitis bacterial	0/3997 (0%)	0	1/4001 (0%)	1
Respiratory tract infection	10/3997 (0.3%)	12	6/4001 (0.1%)	6
Cholecystitis infective	1/3997 (0%)	1	0/4001 (0%)	0
Infective spondylitis	0/3997 (0%)	0	1/4001 (0%)	1
Device related infection	2/3997 (0.1%)	2	2/4001 (0%)	2
Staphylococcal skin infection	0/3997 (0%)	0	1/4001 (0%)	1
Post procedural infection	1/3997 (0%)	1	0/4001 (0%)	0
H1N1 influenza	1/3997 (0%)	1	0/4001 (0%)	0
Device related sepsis	1/3997 (0%)	1	1/4001 (0%)	1
Injury, poisoning and procedural complications
Alcohol poisoning	1/3997 (0%)	1	0/4001 (0%)	0
Ankle fracture	0/3997 (0%)	0	1/4001 (0%)	1
Burns second degree	1/3997 (0%)	1	0/4001 (0%)	0
Clavicle fracture	1/3997 (0%)	1	0/4001 (0%)	0
Drug toxicity	0/3997 (0%)	0	1/4001 (0%)	1
Eye penetration	0/3997 (0%)	0	1/4001 (0%)	1
Fall	5/3997 (0.1%)	5	3/4001 (0.1%)	3
Femoral neck fracture	2/3997 (0.1%)	2	4/4001 (0.1%)	4
Femur fracture	2/3997 (0.1%)	2	3/4001 (0.1%)	3
Foot fracture	1/3997 (0%)	1	1/4001 (0%)	1
Head injury	1/3997 (0%)	1	2/4001 (0%)	2
Hip fracture	5/3997 (0.1%)	5	0/4001 (0%)	0
Humerus fracture	4/3997 (0.1%)	4	2/4001 (0%)	2
Incisional hernia, obstructive	0/3997 (0%)	0	1/4001 (0%)	1
Operative haemorrhage	1/3997 (0%)	1	1/4001 (0%)	1
Overdose	1/3997 (0%)	1	1/4001 (0%)	1
Periorbital haematoma	0/3997 (0%)	0	1/4001 (0%)	1
Pneumoconiosis	0/3997 (0%)	0	1/4001 (0%)	1
Radius fracture	1/3997 (0%)	1	0/4001 (0%)	0
Rib fracture	1/3997 (0%)	1	0/4001 (0%)	0
Spinal compression fracture	0/3997 (0%)	0	1/4001 (0%)	1
Spinal cord injury cervical	1/3997 (0%)	1	0/4001 (0%)	0
Spinal fracture	0/3997 (0%)	0	1/4001 (0%)	1
Subdural haematoma	0/3997 (0%)	0	1/4001 (0%)	1
Subdural haemorrhage	1/3997 (0%)	1	1/4001 (0%)	1
Therapeutic agent toxicity	0/3997 (0%)	0	2/4001 (0%)	2
Tibia fracture	0/3997 (0%)	0	1/4001 (0%)	1
Wound dehiscence	1/3997 (0%)	1	0/4001 (0%)	0
Suture rupture	0/3997 (0%)	0	1/4001 (0%)	1
Vascular graft occlusion	0/3997 (0%)	0	1/4001 (0%)	1
Traumatic fracture	1/3997 (0%)	1	0/4001 (0%)	0
Cervical vertebral fracture	1/3997 (0%)	1	0/4001 (0%)	0
Lumbar vertebral fracture	1/3997 (0%)	1	1/4001 (0%)	1
Contusion	1/3997 (0%)	1	1/4001 (0%)	1
Post procedural haemorrhage	4/3997 (0.1%)	4	1/4001 (0%)	1
Wound	0/3997 (0%)	0	1/4001 (0%)	1
Traumatic haemorrhage	1/3997 (0%)	1	0/4001 (0%)	0
Exposure to toxic agent	1/3997 (0%)	1	0/4001 (0%)	0
Thermal burn	1/3997 (0%)	1	0/4001 (0%)	0
Wound necrosis	0/3997 (0%)	0	1/4001 (0%)	1
Multiple drug overdose	0/3997 (0%)	0	1/4001 (0%)	1
Poisoning	1/3997 (0%)	1	0/4001 (0%)	0
Chest injury	0/3997 (0%)	0	1/4001 (0%)	1
Upper limb fracture	1/3997 (0%)	1	1/4001 (0%)	1
Procedural pain	1/3997 (0%)	1	0/4001 (0%)	0
Gastrointestinal stoma complication	1/3997 (0%)	1	0/4001 (0%)	0
Procedural nausea	0/3997 (0%)	0	1/4001 (0%)	1
Foreign body	0/3997 (0%)	0	1/4001 (0%)	1
Investigations
Alanine aminotransferase increased	20/3997 (0.5%)	20	23/4001 (0.6%)	26
Arteriogram coronary	1/3997 (0%)	1	2/4001 (0%)	2
Aspartate aminotransferase increased	1/3997 (0%)	1	5/4001 (0.1%)	7
Biopsy lymph gland	0/3997 (0%)	0	1/4001 (0%)	1
Blood bilirubin increased	4/3997 (0.1%)	4	1/4001 (0%)	1
Blood creatinine increased	1/3997 (0%)	1	0/4001 (0%)	0
Blood glucose abnormal	1/3997 (0%)	1	0/4001 (0%)	0
Blood glucose decreased	1/3997 (0%)	1	0/4001 (0%)	0
Blood glucose increased	1/3997 (0%)	2	0/4001 (0%)	0
Creatinine renal clearance decreased	4/3997 (0.1%)	4	3/4001 (0.1%)	3
Gamma-glutamyltransferase increased	1/3997 (0%)	1	1/4001 (0%)	1
Haemoglobin decreased	2/3997 (0.1%)	3	1/4001 (0%)	1
Immunoglobulins increased	0/3997 (0%)	0	1/4001 (0%)	1
Liver function test abnormal	8/3997 (0.2%)	8	5/4001 (0.1%)	5
Prothrombin time prolonged	1/3997 (0%)	1	0/4001 (0%)	0
Weight decreased	2/3997 (0.1%)	2	0/4001 (0%)	0
Aspiration bronchial	1/3997 (0%)	1	0/4001 (0%)	0
Transaminases increased	3/3997 (0.1%)	3	2/4001 (0%)	2
Blood alkaline phosphatase increased	1/3997 (0%)	1	0/4001 (0%)	0
Hepatic enzyme increased	10/3997 (0.3%)	10	11/4001 (0.3%)	11
Occult blood positive	1/3997 (0%)	1	2/4001 (0%)	2
Coagulation test	1/3997 (0%)	1	0/4001 (0%)	0
False positive investigation result	1/3997 (0%)	1	0/4001 (0%)	0
Metabolism and nutrition disorders
Abnormal loss of weight	0/3997 (0%)	0	1/4001 (0%)	1
Cachexia	2/3997 (0.1%)	2	0/4001 (0%)	0
Dehydration	9/3997 (0.2%)	9	5/4001 (0.1%)	5
Diabetes mellitus	2/3997 (0.1%)	2	3/4001 (0.1%)	3
Diabetes mellitus inadequate control	3/3997 (0.1%)	3	1/4001 (0%)	1
Diabetic ketoacidosis	1/3997 (0%)	1	0/4001 (0%)	0
Fluid overload	1/3997 (0%)	1	0/4001 (0%)	0
Hyperammonaemia	0/3997 (0%)	0	1/4001 (0%)	1
Hypercalcaemia	2/3997 (0.1%)	2	0/4001 (0%)	0
Hyperglycaemia	1/3997 (0%)	1	4/4001 (0.1%)	4
Hyperkalaemia	2/3997 (0.1%)	2	3/4001 (0.1%)	3
Hyperosmolar state	0/3997 (0%)	0	1/4001 (0%)	1
Hypoglycaemia	3/3997 (0.1%)	3	7/4001 (0.2%)	7
Hypokalaemia	0/3997 (0%)	0	3/4001 (0.1%)	3
Hyponatraemia	4/3997 (0.1%)	5	4/4001 (0.1%)	4
Hypovolaemia	1/3997 (0%)	1	1/4001 (0%)	1
Lactic acidosis	2/3997 (0.1%)	2	0/4001 (0%)	0
Metabolic acidosis	3/3997 (0.1%)	3	3/4001 (0.1%)	3
Diabetic foot	3/3997 (0.1%)	3	4/4001 (0.1%)	4
Malnutrition	1/3997 (0%)	1	0/4001 (0%)	0
Decreased appetite	2/3997 (0.1%)	2	0/4001 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/3997 (0.1%)	2	0/4001 (0%)	0
Back pain	1/3997 (0%)	1	3/4001 (0.1%)	3
Gouty arthritis	1/3997 (0%)	1	0/4001 (0%)	0
Groin pain	0/3997 (0%)	0	1/4001 (0%)	1
Lumbar spinal stenosis	1/3997 (0%)	1	0/4001 (0%)	0
Muscle haemorrhage	2/3997 (0.1%)	2	1/4001 (0%)	1
Muscular weakness	2/3997 (0.1%)	2	1/4001 (0%)	1
Musculoskeletal pain	0/3997 (0%)	0	1/4001 (0%)	1
Myopathy	1/3997 (0%)	1	2/4001 (0%)	2
Osteoarthritis	1/3997 (0%)	1	0/4001 (0%)	0
Osteonecrosis	1/3997 (0%)	1	0/4001 (0%)	0
Pain in extremity	1/3997 (0%)	1	3/4001 (0.1%)	3
Pathological fracture	0/3997 (0%)	0	1/4001 (0%)	1
Rhabdomyolysis	2/3997 (0.1%)	2	1/4001 (0%)	1
Spinal column stenosis	0/3997 (0%)	0	1/4001 (0%)	1
Systemic lupus erythematosus	1/3997 (0%)	1	1/4001 (0%)	1
Tendon disorder	0/3997 (0%)	0	1/4001 (0%)	1
Trismus	1/3997 (0%)	1	0/4001 (0%)	0
Intervertebral disc protrusion	2/3997 (0.1%)	2	0/4001 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	0/3997 (0%)	0	2/4001 (0%)	2
Basal cell carcinoma	0/3997 (0%)	0	1/4001 (0%)	1
Bile duct cancer	2/3997 (0.1%)	2	0/4001 (0%)	0
Bladder cancer	1/3997 (0%)	1	0/4001 (0%)	0
Bladder neoplasm	2/3997 (0.1%)	3	0/4001 (0%)	0
Breast cancer	2/3997 (0.1%)	3	4/4001 (0.1%)	4
Breast cancer in situ	1/3997 (0%)	1	0/4001 (0%)	0
Breast neoplasm	1/3997 (0%)	1	0/4001 (0%)	0
Bronchial carcinoma	3/3997 (0.1%)	3	1/4001 (0%)	1
Cervix carcinoma	1/3997 (0%)	1	0/4001 (0%)	0
Colon cancer	5/3997 (0.1%)	5	3/4001 (0.1%)	3
Colorectal cancer stage IV	1/3997 (0%)	1	0/4001 (0%)	0
Gastric cancer	1/3997 (0%)	1	3/4001 (0.1%)	3
Hepatic neoplasm malignant	3/3997 (0.1%)	3	0/4001 (0%)	0
Hodgkin's disease	1/3997 (0%)	1	2/4001 (0%)	3
Laryngeal cancer	1/3997 (0%)	1	2/4001 (0%)	2
Lung adenocarcinoma	2/3997 (0.1%)	2	1/4001 (0%)	1
Lung adenocarcinoma recurrent	0/3997 (0%)	0	1/4001 (0%)	1
Lung carcinoma cell type unspecified stage IV	1/3997 (0%)	1	0/4001 (0%)	0
Lung squamous cell carcinoma stage unspecified	4/3997 (0.1%)	4	2/4001 (0%)	2
Lymphoma	3/3997 (0.1%)	3	0/4001 (0%)	0
Malignant pleural effusion	0/3997 (0%)	0	3/4001 (0.1%)	3
Mediastinum neoplasm	0/3997 (0%)	0	1/4001 (0%)	1
Meningioma	1/3997 (0%)	1	0/4001 (0%)	0
Mesothelioma malignant	1/3997 (0%)	1	1/4001 (0%)	1
Metastases to adrenals	2/3997 (0.1%)	2	1/4001 (0%)	1
Metastases to bone	1/3997 (0%)	1	3/4001 (0.1%)	3
Metastases to liver	6/3997 (0.2%)	6	3/4001 (0.1%)	3
Metastases to lung	2/3997 (0.1%)	3	1/4001 (0%)	1
Metastases to lymph nodes	1/3997 (0%)	1	0/4001 (0%)	0
Metastases to pleura	1/3997 (0%)	1	1/4001 (0%)	1
Metastases to spine	0/3997 (0%)	0	2/4001 (0%)	2
Metastatic malignant melanoma	0/3997 (0%)	0	1/4001 (0%)	1
Metastatic pain	1/3997 (0%)	1	0/4001 (0%)	0
Multiple myeloma	2/3997 (0.1%)	2	1/4001 (0%)	1
Myeloproliferative disorder	1/3997 (0%)	1	0/4001 (0%)	0
Neoplasm malignant	1/3997 (0%)	1	0/4001 (0%)	0
Non-small cell lung cancer stage IV	2/3997 (0.1%)	2	1/4001 (0%)	1
Oesophageal carcinoma	0/3997 (0%)	0	1/4001 (0%)	1
Ovarian cancer	1/3997 (0%)	1	4/4001 (0.1%)	4
Ovarian epithelial cancer metastatic	2/3997 (0.1%)	2	1/4001 (0%)	1
Pancreatic carcinoma	1/3997 (0%)	1	0/4001 (0%)	0
Pancreatic carcinoma metastatic	1/3997 (0%)	1	0/4001 (0%)	0
Plasmacytoma	0/3997 (0%)	0	1/4001 (0%)	1
Prostate cancer metastatic	1/3997 (0%)	1	0/4001 (0%)	0
Rectal cancer recurrent	1/3997 (0%)	1	0/4001 (0%)	0
Renal cancer	1/3997 (0%)	1	0/4001 (0%)	0
Sarcoma	1/3997 (0%)	1	0/4001 (0%)	0
Small cell lung cancer stage unspecified	1/3997 (0%)	1	3/4001 (0.1%)	3
Tongue neoplasm malignant stage unspecified	1/3997 (0%)	1	0/4001 (0%)	0
Uterine cancer	3/3997 (0.1%)	3	0/4001 (0%)	0
Metastases to pancreas	0/3997 (0%)	0	1/4001 (0%)	1
Tumour haemorrhage	1/3997 (0%)	1	0/4001 (0%)	0
Lung cancer metastatic	0/3997 (0%)	0	1/4001 (0%)	1
Myeloma recurrence	1/3997 (0%)	2	0/4001 (0%)	0
Malignant neoplasm progression	3/3997 (0.1%)	3	4/4001 (0.1%)	4
Metastases to peritoneum	2/3997 (0.1%)	2	0/4001 (0%)	0
Metastases to meninges	1/3997 (0%)	1	1/4001 (0%)	1
Colorectal cancer metastatic	0/3997 (0%)	0	1/4001 (0%)	1
Small intestine carcinoma	0/3997 (0%)	0	1/4001 (0%)	1
Anal cancer metastatic	1/3997 (0%)	1	0/4001 (0%)	0
Hepatic cancer metastatic	0/3997 (0%)	0	2/4001 (0%)	2
Biliary cancer metastatic	0/3997 (0%)	0	1/4001 (0%)	1
Colon cancer metastatic	0/3997 (0%)	0	1/4001 (0%)	1
Ovarian cancer metastatic	0/3997 (0%)	0	1/4001 (0%)	1
Cancer pain	1/3997 (0%)	1	1/4001 (0%)	1
Lung neoplasm malignant	16/3997 (0.4%)	18	11/4001 (0.3%)	11
Metastases to central nervous system	4/3997 (0.1%)	4	3/4001 (0.1%)	3
Paraneoplastic syndrome	1/3997 (0%)	1	0/4001 (0%)	0
Prostate cancer	1/3997 (0%)	1	1/4001 (0%)	1
Brain neoplasm	2/3997 (0.1%)	2	2/4001 (0%)	3
Colon neoplasm	0/3997 (0%)	0	1/4001 (0%)	1
Metastatic neoplasm	3/3997 (0.1%)	4	2/4001 (0%)	2
Nasopharyngeal cancer	0/3997 (0%)	0	1/4001 (0%)	1
Neoplasm progression	1/3997 (0%)	1	2/4001 (0%)	2
Paraproteinaemia	0/3997 (0%)	0	1/4001 (0%)	1
Pleural neoplasm	1/3997 (0%)	1	0/4001 (0%)	0
Renal neoplasm	1/3997 (0%)	1	1/4001 (0%)	1
Salivary gland neoplasm	0/3997 (0%)	0	1/4001 (0%)	1
Non-small cell lung cancer	1/3997 (0%)	1	1/4001 (0%)	1
Lung neoplasm	4/3997 (0.1%)	5	1/4001 (0%)	1
Lung adenocarcinoma metastatic	1/3997 (0%)	1	0/4001 (0%)	0
Renal cell carcinoma	0/3997 (0%)	0	1/4001 (0%)	1
Sarcoma metastatic	1/3997 (0%)	1	0/4001 (0%)	0
Nervous system disorders
Altered state of consciousness	0/3997 (0%)	0	2/4001 (0%)	2
Amyotrophic lateral sclerosis	0/3997 (0%)	0	1/4001 (0%)	1
Ataxia	0/3997 (0%)	0	1/4001 (0%)	1
Autonomic nervous system imbalance	1/3997 (0%)	1	0/4001 (0%)	0
Carotid artery stenosis	4/3997 (0.1%)	4	0/4001 (0%)	0
Cauda equina syndrome	1/3997 (0%)	1	0/4001 (0%)	0
Cerebellar haemorrhage	0/3997 (0%)	0	1/4001 (0%)	1
Cerebral atrophy	1/3997 (0%)	1	0/4001 (0%)	0
Cerebral circulatory failure	0/3997 (0%)	0	1/4001 (0%)	1
Cerebral haemorrhage	4/3997 (0.1%)	4	2/4001 (0%)	2
Cerebral infarction	0/3997 (0%)	0	2/4001 (0%)	2
Cerebral ischaemia	3/3997 (0.1%)	3	1/4001 (0%)	1
Cerebrovascular accident	5/3997 (0.1%)	5	1/4001 (0%)	1
Cervical myelopathy	0/3997 (0%)	0	1/4001 (0%)	1
Coma	2/3997 (0.1%)	2	1/4001 (0%)	1
Convulsion	2/3997 (0.1%)	2	3/4001 (0.1%)	3
Dementia	1/3997 (0%)	1	0/4001 (0%)	0
Dementia Alzheimer's type	0/3997 (0%)	0	2/4001 (0%)	2
Diabetic hyperglycaemic coma	1/3997 (0%)	1	0/4001 (0%)	0
Dizziness	0/3997 (0%)	0	1/4001 (0%)	1
Dysarthria	0/3997 (0%)	0	2/4001 (0%)	2
Embolic stroke	1/3997 (0%)	1	0/4001 (0%)	0
Encephalopathy	0/3997 (0%)	0	1/4001 (0%)	1
Epilepsy	2/3997 (0.1%)	2	0/4001 (0%)	0
Extrapyramidal disorder	0/3997 (0%)	0	1/4001 (0%)	1
Grand mal convulsion	0/3997 (0%)	0	1/4001 (0%)	1
Guillain-Barre syndrome	1/3997 (0%)	1	1/4001 (0%)	1
Haemorrhage intracranial	3/3997 (0.1%)	3	1/4001 (0%)	1
Haemorrhagic stroke	1/3997 (0%)	1	0/4001 (0%)	0
Hemiparesis	0/3997 (0%)	0	1/4001 (0%)	1
Hepatic encephalopathy	1/3997 (0%)	1	2/4001 (0%)	2
Hydrocephalus	1/3997 (0%)	1	1/4001 (0%)	1
Hypoaesthesia	1/3997 (0%)	1	0/4001 (0%)	0
Hypoglycaemic coma	0/3997 (0%)	0	1/4001 (0%)	1
Intracranial aneurysm	0/3997 (0%)	0	1/4001 (0%)	1
Lethargy	0/3997 (0%)	0	1/4001 (0%)	1
Loss of consciousness	3/3997 (0.1%)	3	1/4001 (0%)	1
Myoclonus	1/3997 (0%)	1	0/4001 (0%)	0
Nerve compression	0/3997 (0%)	0	1/4001 (0%)	1
Neuropathy peripheral	1/3997 (0%)	1	0/4001 (0%)	0
Parkinsonism	0/3997 (0%)	0	1/4001 (0%)	1
Peripheral sensory neuropathy	0/3997 (0%)	0	1/4001 (0%)	1
Presyncope	1/3997 (0%)	1	0/4001 (0%)	0
Radiculopathy	1/3997 (0%)	1	0/4001 (0%)	0
Sciatica	0/3997 (0%)	0	2/4001 (0%)	2
Somnolence	0/3997 (0%)	0	1/4001 (0%)	1
Speech disorder	1/3997 (0%)	1	0/4001 (0%)	0
Spinal cord compression	4/3997 (0.1%)	4	0/4001 (0%)	0
Subarachnoid haemorrhage	0/3997 (0%)	0	1/4001 (0%)	1
Syncope	15/3997 (0.4%)	18	10/4001 (0.2%)	10
Tension headache	0/3997 (0%)	0	1/4001 (0%)	1
Transient ischaemic attack	4/3997 (0.1%)	4	10/4001 (0.2%)	10
Unresponsive to stimuli	1/3997 (0%)	1	0/4001 (0%)	0
Carotid artery occlusion	1/3997 (0%)	1	0/4001 (0%)	0
Psychomotor skills impaired	0/3997 (0%)	0	1/4001 (0%)	1
Quadriparesis	1/3997 (0%)	1	0/4001 (0%)	0
VIIth nerve paralysis	0/3997 (0%)	0	1/4001 (0%)	1
Lacunar infarction	0/3997 (0%)	0	1/4001 (0%)	1
Haemorrhagic transformation stroke	2/3997 (0.1%)	2	3/4001 (0.1%)	3
Vascular dementia	1/3997 (0%)	1	2/4001 (0%)	2
Intracranial venous sinus thrombosis	0/3997 (0%)	0	1/4001 (0%)	1
Ischaemic stroke	30/3997 (0.8%)	31	39/4001 (1%)	40
Partial seizures	1/3997 (0%)	1	0/4001 (0%)	0
Parkinson's disease	0/3997 (0%)	0	1/4001 (0%)	1
Metabolic encephalopathy	1/3997 (0%)	1	1/4001 (0%)	1
Critical illness polyneuropathy	0/3997 (0%)	0	1/4001 (0%)	1
Acute polyneuropathy	1/3997 (0%)	3	0/4001 (0%)	0
Brain stem stroke	0/3997 (0%)	0	1/4001 (0%)	1
Hypoxic-ischaemic encephalopathy	3/3997 (0.1%)	3	0/4001 (0%)	0
Psychiatric disorders
Anorexia nervosa	1/3997 (0%)	1	0/4001 (0%)	0
Anxiety	1/3997 (0%)	1	1/4001 (0%)	1
Completed suicide	0/3997 (0%)	0	1/4001 (0%)	1
Confusional state	2/3997 (0.1%)	2	1/4001 (0%)	1
Delirium	0/3997 (0%)	0	1/4001 (0%)	1
Depression	1/3997 (0%)	1	5/4001 (0.1%)	5
Disorientation	1/3997 (0%)	1	0/4001 (0%)	0
Panic attack	2/3997 (0.1%)	2	1/4001 (0%)	1
Somatisation disorder	1/3997 (0%)	1	0/4001 (0%)	0
Suicide attempt	1/3997 (0%)	1	1/4001 (0%)	1
Mental status changes	1/3997 (0%)	1	1/4001 (0%)	1
Bipolar disorder	1/3997 (0%)	1	0/4001 (0%)	0
Major depression	1/3997 (0%)	1	1/4001 (0%)	2
Mental disorder	0/3997 (0%)	0	1/4001 (0%)	1
Psychotic disorder	1/3997 (0%)	1	1/4001 (0%)	2
Psychiatric decompensation	0/3997 (0%)	0	1/4001 (0%)	1
Renal and urinary disorders
Acute prerenal failure	0/3997 (0%)	0	1/4001 (0%)	1
Anuria	1/3997 (0%)	1	0/4001 (0%)	0
Azotaemia	0/3997 (0%)	0	1/4001 (0%)	1
Calculus ureteric	0/3997 (0%)	0	1/4001 (0%)	1
Calculus urinary	0/3997 (0%)	0	1/4001 (0%)	2
Cystitis haemorrhagic	1/3997 (0%)	1	0/4001 (0%)	0
Haematuria	9/3997 (0.2%)	9	7/4001 (0.2%)	7
Nephritis	1/3997 (0%)	1	0/4001 (0%)	0
Nephrolithiasis	0/3997 (0%)	0	1/4001 (0%)	1
Nephrotic syndrome	0/3997 (0%)	0	2/4001 (0%)	2
Obstructive uropathy	1/3997 (0%)	1	0/4001 (0%)	0
Proteinuria	1/3997 (0%)	1	0/4001 (0%)	0
Renal failure	12/3997 (0.3%)	12	14/4001 (0.3%)	14
Renal failure acute	31/3997 (0.8%)	32	16/4001 (0.4%)	16
Renal failure chronic	1/3997 (0%)	1	1/4001 (0%)	1
Urinary bladder haemorrhage	1/3997 (0%)	1	0/4001 (0%)	0
Urinary retention	2/3997 (0.1%)	2	0/4001 (0%)	0
Cystitis glandularis	1/3997 (0%)	1	0/4001 (0%)	0
Urethral haemorrhage	0/3997 (0%)	0	1/4001 (0%)	1
Renal impairment	2/3997 (0.1%)	2	1/4001 (0%)	1
Pulmonary renal syndrome	1/3997 (0%)	1	0/4001 (0%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/3997 (0%)	1	1/4001 (0%)	1
Epididymitis	1/3997 (0%)	1	1/4001 (0%)	1
Penile haemorrhage	1/3997 (0%)	1	0/4001 (0%)	0
Prostatitis	1/3997 (0%)	1	0/4001 (0%)	0
Vaginal haemorrhage	1/3997 (0%)	1	0/4001 (0%)	0
Postmenopausal haemorrhage	1/3997 (0%)	1	0/4001 (0%)	0
Perineal fistula	1/3997 (0%)	1	0/4001 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	8/3997 (0.2%)	8	5/4001 (0.1%)	5
Acute respiratory distress syndrome	1/3997 (0%)	1	5/4001 (0.1%)	5
Acute respiratory failure	35/3997 (0.9%)	37	12/4001 (0.3%)	13
Apnoeic attack	1/3997 (0%)	1	0/4001 (0%)	0
Aspiration	0/3997 (0%)	0	1/4001 (0%)	1
Asthma	8/3997 (0.2%)	9	6/4001 (0.1%)	7
Atelectasis	1/3997 (0%)	1	0/4001 (0%)	0
Bronchitis chronic	3/3997 (0.1%)	3	2/4001 (0%)	2
Chronic obstructive pulmonary disease	109/3997 (2.7%)	138	104/4001 (2.6%)	131
Chronic respiratory failure	2/3997 (0.1%)	2	4/4001 (0.1%)	4
Dyspnoea	19/3997 (0.5%)	20	17/4001 (0.4%)	18
Dyspnoea paroxysmal nocturnal	1/3997 (0%)	1	0/4001 (0%)	0
Epistaxis	4/3997 (0.1%)	4	4/4001 (0.1%)	4
Haemoptysis	9/3997 (0.2%)	9	2/4001 (0%)	2
Haemothorax	1/3997 (0%)	1	1/4001 (0%)	1
Hypercapnia	1/3997 (0%)	1	2/4001 (0%)	2
Hypoxia	2/3997 (0.1%)	2	3/4001 (0.1%)	3
Interstitial lung disease	2/3997 (0.1%)	2	2/4001 (0%)	2
Lung disorder	1/3997 (0%)	1	5/4001 (0.1%)	5
Lung infiltration	0/3997 (0%)	0	2/4001 (0%)	2
Obliterative bronchiolitis	1/3997 (0%)	1	0/4001 (0%)	0
Pleural effusion	9/3997 (0.2%)	11	10/4001 (0.2%)	11
Pleurisy	1/3997 (0%)	1	1/4001 (0%)	1
Pneumonia aspiration	4/3997 (0.1%)	4	11/4001 (0.3%)	12
Pneumonitis	1/3997 (0%)	1	1/4001 (0%)	1
Pneumothorax	1/3997 (0%)	1	4/4001 (0.1%)	4
Productive cough	1/3997 (0%)	1	0/4001 (0%)	0
Pulmonary congestion	1/3997 (0%)	1	2/4001 (0%)	2
Pulmonary embolism	4/3997 (0.1%)	4	4/4001 (0.1%)	4
Pulmonary fibrosis	3/3997 (0.1%)	4	3/4001 (0.1%)	3
Pulmonary haemorrhage	1/3997 (0%)	1	0/4001 (0%)	0
Pulmonary hypertension	3/3997 (0.1%)	3	2/4001 (0%)	2
Pulmonary oedema	9/3997 (0.2%)	9	14/4001 (0.3%)	14
Respiratory acidosis	1/3997 (0%)	1	0/4001 (0%)	0
Respiratory disorder	0/3997 (0%)	0	1/4001 (0%)	1
Respiratory distress	1/3997 (0%)	1	1/4001 (0%)	1
Respiratory failure	56/3997 (1.4%)	59	40/4001 (1%)	41
Hydrothorax	0/3997 (0%)	0	1/4001 (0%)	1
Pneumomediastinum	0/3997 (0%)	0	1/4001 (0%)	1
Tracheal stenosis	1/3997 (0%)	1	0/4001 (0%)	0
Bronchopleural fistula	1/3997 (0%)	1	0/4001 (0%)	0
Obstructive airways disorder	1/3997 (0%)	1	0/4001 (0%)	0
Asthmatic crisis	0/3997 (0%)	0	1/4001 (0%)	1
Bronchial hyperreactivity	1/3997 (0%)	1	0/4001 (0%)	0
Lung cyst	0/3997 (0%)	0	1/4001 (0%)	1
Skin and subcutaneous tissue disorders
Angioedema	3/3997 (0.1%)	4	1/4001 (0%)	1
Dermatitis contact	0/3997 (0%)	0	1/4001 (0%)	1
Ecchymosis	2/3997 (0.1%)	2	0/4001 (0%)	0
Erythema	1/3997 (0%)	1	0/4001 (0%)	0
Haemorrhage subcutaneous	1/3997 (0%)	1	0/4001 (0%)	0
Purpura	1/3997 (0%)	1	0/4001 (0%)	0
Rash	0/3997 (0%)	0	1/4001 (0%)	1
Skin ulcer	6/3997 (0.2%)	6	3/4001 (0.1%)	3
Swelling face	0/3997 (0%)	0	1/4001 (0%)	1
Urticaria	1/3997 (0%)	1	0/4001 (0%)	0
Skin ulcer haemorrhage	1/3997 (0%)	1	0/4001 (0%)	0
Neuropathic ulcer	1/3997 (0%)	1	0/4001 (0%)	0
Social circumstances
Disability	1/3997 (0%)	1	0/4001 (0%)	0
Social problem	1/3997 (0%)	1	0/4001 (0%)	0
Surgical and medical procedures
Angioplasty	0/3997 (0%)	0	1/4001 (0%)	1
Cardiac pacemaker insertion	0/3997 (0%)	0	1/4001 (0%)	1
Radical hysterectomy	1/3997 (0%)	1	0/4001 (0%)	0
Toe amputation	0/3997 (0%)	0	1/4001 (0%)	1
Central venous catheterisation	0/3997 (0%)	0	1/4001 (0%)	1
Peripheral artery angioplasty	0/3997 (0%)	0	1/4001 (0%)	1
Tumour excision	1/3997 (0%)	1	0/4001 (0%)	0
Chemotherapy	2/3997 (0.1%)	2	2/4001 (0%)	2
Mitral valve repair	1/3997 (0%)	1	0/4001 (0%)	0
Vascular disorders
Aortic aneurysm	0/3997 (0%)	0	1/4001 (0%)	1
Aortic aneurysm rupture	1/3997 (0%)	1	0/4001 (0%)	0
Aortic stenosis	3/3997 (0.1%)	5	3/4001 (0.1%)	3
Aortic thrombosis	0/3997 (0%)	0	1/4001 (0%)	1
Arterial rupture	1/3997 (0%)	2	0/4001 (0%)	0
Arterial thrombosis limb	1/3997 (0%)	1	2/4001 (0%)	2
Arteriosclerosis	3/3997 (0.1%)	3	0/4001 (0%)	0
Arteritis	1/3997 (0%)	1	1/4001 (0%)	1
Bleeding varicose vein	1/3997 (0%)	1	0/4001 (0%)	0
Circulatory collapse	1/3997 (0%)	1	1/4001 (0%)	1
Essential hypertension	1/3997 (0%)	1	0/4001 (0%)	0
Femoral arterial stenosis	0/3997 (0%)	0	2/4001 (0%)	2
Femoral artery aneurysm	1/3997 (0%)	1	0/4001 (0%)	0
Haematoma	1/3997 (0%)	1	0/4001 (0%)	0
Hypertension	7/3997 (0.2%)	7	4/4001 (0.1%)	4
Hypertensive crisis	3/3997 (0.1%)	3	1/4001 (0%)	1
Hypotension	10/3997 (0.3%)	10	7/4001 (0.2%)	7
Hypovolaemic shock	2/3997 (0.1%)	2	2/4001 (0%)	2
Iliac artery thrombosis	0/3997 (0%)	0	1/4001 (0%)	1
Lymphoedema	1/3997 (0%)	1	1/4001 (0%)	1
Orthostatic hypotension	2/3997 (0.1%)	2	0/4001 (0%)	0
Peripheral ischaemia	3/3997 (0.1%)	3	5/4001 (0.1%)	5
Shock	2/3997 (0.1%)	2	3/4001 (0.1%)	3
Thrombophlebitis	0/3997 (0%)	0	1/4001 (0%)	1
Thrombosis	2/3997 (0.1%)	2	0/4001 (0%)	0
Vasculitis	1/3997 (0%)	1	0/4001 (0%)	0
Venous thrombosis	0/3997 (0%)	0	1/4001 (0%)	1
Subclavian vein thrombosis	0/3997 (0%)	0	1/4001 (0%)	1
Shock haemorrhagic	2/3997 (0.1%)	2	1/4001 (0%)	1
Subclavian artery stenosis	0/3997 (0%)	0	1/4001 (0%)	1
Deep vein thrombosis	4/3997 (0.1%)	4	5/4001 (0.1%)	5
Haemorrhage	2/3997 (0.1%)	2	0/4001 (0%)	0
Neurogenic shock	0/3997 (0%)	0	1/4001 (0%)	1
Superior vena caval occlusion	1/3997 (0%)	1	0/4001 (0%)	0
Extremity necrosis	1/3997 (0%)	1	0/4001 (0%)	0
Peripheral embolism	1/3997 (0%)	1	2/4001 (0%)	2
Venous thrombosis limb	0/3997 (0%)	0	1/4001 (0%)	1
Peripheral arterial occlusive disease	2/3997 (0.1%)	3	2/4001 (0%)	2
Arteriosclerosis obliterans	0/3997 (0%)	0	1/4001 (0%)	1
Aortic dissection rupture	2/3997 (0.1%)	2	0/4001 (0%)	0
Other (Not Including Serious) Adverse Events
	Rivaroxaban (Xarelto, BAY59-7939)		Enoxaparin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2297/3997 (57.5%)		2291/4001 (57.3%)
Blood and lymphatic system disorders
Anaemia	87/3997 (2.2%)	93	85/4001 (2.1%)	87
Neutropenia	20/3997 (0.5%)	32	16/4001 (0.4%)	20
Thrombocytopenia	29/3997 (0.7%)	32	25/4001 (0.6%)	27
Cardiac disorders
Atrial fibrillation	74/3997 (1.9%)	82	61/4001 (1.5%)	65
Cardiac failure	43/3997 (1.1%)	46	38/4001 (0.9%)	44
Mitral valve incompetence	36/3997 (0.9%)	36	32/4001 (0.8%)	33
Tachycardia	32/3997 (0.8%)	33	43/4001 (1.1%)	49
Tricuspid valve incompetence	19/3997 (0.5%)	19	22/4001 (0.5%)	22
Ventricular extrasystoles	24/3997 (0.6%)	26	17/4001 (0.4%)	17
Ear and labyrinth disorders
Vertigo	26/3997 (0.7%)	26	25/4001 (0.6%)	26
Eye disorders
Conjunctivitis	16/3997 (0.4%)	16	24/4001 (0.6%)	24
Gastrointestinal disorders
Abdominal pain	89/3997 (2.2%)	109	56/4001 (1.4%)	64
Abdominal pain upper	59/3997 (1.5%)	63	53/4001 (1.3%)	62
Constipation	362/3997 (9.1%)	418	346/4001 (8.6%)	375
Diarrhoea	214/3997 (5.4%)	238	230/4001 (5.7%)	256
Dyspepsia	53/3997 (1.3%)	54	62/4001 (1.5%)	69
Gastritis	36/3997 (0.9%)	37	38/4001 (0.9%)	38
Gastritis erosive	20/3997 (0.5%)	21	19/4001 (0.5%)	19
Gingival bleeding	20/3997 (0.5%)	22	9/4001 (0.2%)	9
Hiatus hernia	20/3997 (0.5%)	20	16/4001 (0.4%)	16
Nausea	207/3997 (5.2%)	242	226/4001 (5.6%)	253
Vomiting	170/3997 (4.3%)	205	149/4001 (3.7%)	175
Haemorrhoidal haemorrhage	22/3997 (0.6%)	23	12/4001 (0.3%)	12
General disorders
Asthenia	52/3997 (1.3%)	54	31/4001 (0.8%)	32
Chest pain	89/3997 (2.2%)	102	77/4001 (1.9%)	82
Fatigue	33/3997 (0.8%)	35	35/4001 (0.9%)	35
Injection site haemorrhage	8/3997 (0.2%)	8	21/4001 (0.5%)	23
Oedema peripheral	132/3997 (3.3%)	153	115/4001 (2.9%)	127
Pain	42/3997 (1.1%)	46	39/4001 (1%)	40
Pyrexia	132/3997 (3.3%)	158	131/4001 (3.3%)	162
Hepatobiliary disorders
Cholelithiasis	49/3997 (1.2%)	50	47/4001 (1.2%)	48
Hepatic function abnormal	17/3997 (0.4%)	18	24/4001 (0.6%)	24
Hepatic steatosis	48/3997 (1.2%)	48	61/4001 (1.5%)	61
Infections and infestations
Bronchitis	64/3997 (1.6%)	65	47/4001 (1.2%)	48
Cellulitis	22/3997 (0.6%)	22	18/4001 (0.4%)	19
Nasopharyngitis	37/3997 (0.9%)	38	36/4001 (0.9%)	36
Oral candidiasis	31/3997 (0.8%)	31	34/4001 (0.8%)	35
Pneumonia	73/3997 (1.8%)	75	65/4001 (1.6%)	68
Upper respiratory tract infection	30/3997 (0.8%)	33	26/4001 (0.6%)	27
Urinary tract infection	138/3997 (3.5%)	148	142/4001 (3.5%)	151
Injury, poisoning and procedural complications
Fall	33/3997 (0.8%)	38	40/4001 (1%)	40
Contusion	38/3997 (1%)	50	42/4001 (1%)	63
Investigations
Alanine aminotransferase increased	32/3997 (0.8%)	32	61/4001 (1.5%)	66
Aspartate aminotransferase increased	23/3997 (0.6%)	23	35/4001 (0.9%)	36
Blood creatinine increased	38/3997 (1%)	40	36/4001 (0.9%)	39
Blood urea increased	24/3997 (0.6%)	27	23/4001 (0.6%)	24
Creatinine renal clearance decreased	36/3997 (0.9%)	40	35/4001 (0.9%)	35
Gamma-glutamyltransferase increased	31/3997 (0.8%)	31	32/4001 (0.8%)	32
Haemoglobin decreased	23/3997 (0.6%)	26	12/4001 (0.3%)	12
Metabolism and nutrition disorders
Dehydration	43/3997 (1.1%)	49	30/4001 (0.7%)	30
Diabetes mellitus	39/3997 (1%)	40	34/4001 (0.8%)	34
Hyperglycaemia	46/3997 (1.2%)	54	50/4001 (1.2%)	63
Hyperkalaemia	62/3997 (1.6%)	66	51/4001 (1.3%)	57
Hypoglycaemia	37/3997 (0.9%)	46	39/4001 (1%)	48
Hypokalaemia	191/3997 (4.8%)	219	184/4001 (4.6%)	219
Hyponatraemia	35/3997 (0.9%)	38	34/4001 (0.8%)	34
Decreased appetite	38/3997 (1%)	42	40/4001 (1%)	44
Musculoskeletal and connective tissue disorders
Arthralgia	62/3997 (1.6%)	68	76/4001 (1.9%)	87
Back pain	97/3997 (2.4%)	105	82/4001 (2%)	85
Muscle spasms	25/3997 (0.6%)	25	28/4001 (0.7%)	30
Musculoskeletal pain	46/3997 (1.2%)	50	61/4001 (1.5%)	66
Neck pain	14/3997 (0.4%)	14	22/4001 (0.5%)	25
Osteoarthritis	29/3997 (0.7%)	30	22/4001 (0.5%)	24
Pain in extremity	110/3997 (2.8%)	127	103/4001 (2.6%)	113
Nervous system disorders
Dizziness	81/3997 (2%)	83	72/4001 (1.8%)	80
Headache	205/3997 (5.1%)	237	185/4001 (4.6%)	221
Syncope	23/3997 (0.6%)	24	19/4001 (0.5%)	21
Psychiatric disorders
Anxiety	89/3997 (2.2%)	99	94/4001 (2.3%)	98
Confusional state	28/3997 (0.7%)	28	23/4001 (0.6%)	24
Depression	68/3997 (1.7%)	68	73/4001 (1.8%)	77
Insomnia	172/3997 (4.3%)	199	185/4001 (4.6%)	202
Sleep disorder	25/3997 (0.6%)	25	16/4001 (0.4%)	18
Renal and urinary disorders
Dysuria	22/3997 (0.6%)	23	15/4001 (0.4%)	15
Haematuria	65/3997 (1.6%)	68	48/4001 (1.2%)	53
Renal cyst	65/3997 (1.6%)	65	61/4001 (1.5%)	63
Renal failure	52/3997 (1.3%)	55	47/4001 (1.2%)	48
Renal failure acute	25/3997 (0.6%)	26	19/4001 (0.5%)	19
Urinary retention	22/3997 (0.6%)	23	17/4001 (0.4%)	19
Renal impairment	39/3997 (1%)	40	29/4001 (0.7%)	31
Reproductive system and breast disorders
Benign prostatic hyperplasia	44/3997 (1.1%)	45	20/4001 (0.5%)	20
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	71/3997 (1.8%)	92	59/4001 (1.5%)	84
Cough	107/3997 (2.7%)	118	94/4001 (2.3%)	100
Dyspnoea	107/3997 (2.7%)	120	99/4001 (2.5%)	112
Epistaxis	123/3997 (3.1%)	145	66/4001 (1.6%)	83
Haemoptysis	37/3997 (0.9%)	40	32/4001 (0.8%)	37
Pleural effusion	28/3997 (0.7%)	32	31/4001 (0.8%)	32
Oropharyngeal pain	27/3997 (0.7%)	28	27/4001 (0.7%)	28
Skin and subcutaneous tissue disorders
Decubitus ulcer	21/3997 (0.5%)	22	18/4001 (0.4%)	23
Ecchymosis	42/3997 (1.1%)	47	39/4001 (1%)	42
Erythema	27/3997 (0.7%)	30	37/4001 (0.9%)	41
Pruritus	47/3997 (1.2%)	47	50/4001 (1.2%)	51
Rash	41/3997 (1%)	44	50/4001 (1.2%)	51
Vascular disorders
Haematoma	24/3997 (0.6%)	29	24/4001 (0.6%)	26
Hypertension	154/3997 (3.9%)	177	156/4001 (3.9%)	178
Hypertensive crisis	20/3997 (0.5%)	23	16/4001 (0.4%)	18
Hypotension	82/3997 (2.1%)	91	93/4001 (2.3%)	102
Phlebitis	37/3997 (0.9%)	38	38/4001 (0.9%)	41
Aortic arteriosclerosis	25/3997 (0.6%)	25	19/4001 (0.5%)	19

Limitations/Caveats

A heterogeneous population (with different acute medical illnesses and severity of illness) was included in the trial. VTE risk in acute medical illnesses is moderate [with no thromboprophylaxis] .

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 more than 60 days but less than or equal to 180 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:

NCT00571649

Other Study ID Numbers:

12839
2007-004614-14

First Posted:

Dec 12, 2007

Last Update Posted:

Sep 15, 2016

Last Verified:

Aug 1, 2016

MAGELLAN: Venous Thromboembolic Event (VTE) Prophylaxis in Medically Ill Patients

Study Details

Study Description

Brief Summary

Detailed Description

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Additional Information:

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

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Certain Agreements

Results Point of Contact