An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00403767
• Collaborator: Bayer (Industry)
• Enrollment: 14,269
• Locations: 959
• Arms: 2
• Duration (Months): 45
• Patients Per Site: 14.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy and safety of rivaroxaban with warfarin for the prevention of blood clots in the brain (referred to as stroke) and blood clots in other parts of the body referred to as non-central nervous system systemic embolism) in patients with non-valvular atrial fibrillation (a heart rhythm disorder).

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation; Stroke; Embolism	Drug: Rivaroxaban; Drug: Warfarin; Drug: Matching placebo for Rivaroxaban arm (Warfarin placebo); Drug: Matching placebo for Warfarin arm (Rivaroxaban placebo)	Phase 3

Detailed Description

Patients with non-valvular atrial fibrillation who are at risk for stroke and non-central nervous system (non-CNS) systemic embolism, will be randomized (assigned by chance) to receive treatment with rivaroxaban or warfarin, two different anticoagulants (substances that prevent blood clots). Treatment will be double-blinded (neither the patient nor study staff will know which study drug is assigned to patients during the study). Patients assigned to rivaroxaban will receive rivaroxaban 20 mg orally (p.o.) once daily (OD) plus warfarin placebo p.o. OD titrated to a target sham international normalized ratio (INR) of 2.5. Patients with moderate renal impairment at screening will receive rivaroxaban 15 mg p.o. OD. Patients assigned to warfarin will receive warfarin p.o. OD titrated to a target INR of 2.5 plus rivaroxaban placebo p.o. OD. The maximum expected length of treatment is up to 32 months but may be extended up to 4 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14269 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Prospective, Randomized, Double-Blind, Parallel-Group, Multicenter, Non-inferiority Study Comparing the Efficacy and Safety of Rivaroxaban (BAY 59-7939) With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Subjects With Non-Valvular Atrial Fibrillation
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rivaroxaban	Drug: Rivaroxaban; Type=exact number, unit=mg, number=20, form=tablet, route=oral use. One 20 mg tablet once daily for an expected maximum treatment period of up to 32 months that may extend up to 4 years (Patients with moderate renal impairment at screening willl have a dose adaptation to rivaroxaban 15 mg, orally, once daily for an expected maximum treatment period of up to 32 months that may extend up to 4 years); Drug: Matching placebo for Rivaroxaban arm (Warfarin placebo); Form=tablet, route=oral. One warfarin placebo tablet taken orally once daily for up to an expected maximum treatment period of 32 months that may extend up to 4 years
Active Comparator: Warfarin	Drug: Warfarin; Type=exact number, unit=mg, number=1, 2.5, or 5 mg, form=tablet, route=oral use. Number of warfarin tablets to be determined based on target INR values once daily for an expected maximum treatment period of up to 32 months that may extend up to 4 years; Drug: Matching placebo for Warfarin arm (Rivaroxaban placebo); Form-tablet, Route=oral administration. Number of rivaroxaban placebo determined by the number of warfarin tablets taken. Duration of treatment is up to an expected maximum treatment period of 32 months that may extend up to 4 years

Outcome Measures

Primary Outcome Measures

1. The Composite Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Non-Inferiority) [Up to 4 years]

   The number of patients with the first occurrence of a stroke or non-CNS systemic embolism while on treatment (defined as the time interval from the first dose to the last dose of study drug plus 2 days). The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.

2. The Composite of Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Superiority) [Up to 4 years]

   The number of patients with the first occurrence of a stroke or non-CNS systemic embolism while on treatment (defined as the time interval from the first dose to the last dose of study drug plus 2 days). The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.

3. The Composite Event of Major/Non-major Clinically Relevant Bleeding Events: Primary Safety [Up to 4 years]

   The number of patients with the first occurrence of a major or non-major clinically relevant bleeding event while on treatment. The statistical analysis is based on time from the first dose of study drug to the first occurrence of the event while on treatment.

Secondary Outcome Measures

1. The Composite Event of Stroke/Non-CNS Systemic Embolism/Vascular Death [Up to 4 years]

   The number of patients with the first occurrence of a stroke, non-CNS systemic embolism, or vascular death while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.

2. The Composite Event of Stroke/Non-CNS Systemic Embolism/Myocardial Infarction/Vascular Death [Up to 4 years]

   The number of patients with the first occurrence of a stroke, non-CNS systemic embolism, myocardial infarction, or vascular death while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.

3. The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Stroke [Up to 4 years]

   The number of patients with the first occurrence of a stroke while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.

4. The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Non-CNS Systemic Embolism [Up to 4 years]

   The number of patients with the first occurrence of a non-CNS systemic embolism while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.

5. The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Myocardial Infarction [Up to 4 years]

   The number of patients with the first occurrence of a myocardial infarction while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.

6. The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Vascular Death [Up to 4 years]

   The number of patients with the occurrence of vascular death while on treatment. The statistical analysis is based on time from randomization to the event while on treatment.

7. All-cause Mortality [Up to 4 years]

   The number of patients who died due to any cause while on treatment. The statistical analysis is based on time from randomization to the event while on treatment.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have documented atrial fibrillation on 2 separate occasions within 6 months before screening

• History of a prior stroke, transient ischemic attack or non-neurologic systemic embolism believed to be cardiac in origin, or at least two of the following risk factors: heart failure, hypertension, age 75 years or greater, diabetes mellitus

Exclusion Criteria:

• Significant mitral stenosis

• Transient atrial fibrillation caused by a reversible disorder

• Active internal bleeding

• Severe disabling stroke

• History of intracranial bleeding

• Hemorrhagic disorders

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Dothan	Alabama	United States
3		Geneva	Alabama	United States
4		Mobile	Alabama	United States
5		Pell City	Alabama	United States
6		Glendale	Arizona	United States
7		Phoenix	Arizona	United States
8		Scottsdale	Arizona	United States
9		Tucson	Arizona	United States
10		Fort Smith	Arkansas	United States
11		Little Rock	Arkansas	United States
12		Anaheim	California	United States
13		Bakersfield	California	United States
14		Carmichael	California	United States
15		Corona	California	United States
16		Fair Oaks	California	United States
17		Glendale	California	United States
18		Healdsburg	California	United States
19		Laguna Hills	California	United States
20		Long Beach	California	United States
21		Los Angeles	California	United States
22		Los Gatos	California	United States
23		Mission Viejo	California	United States
24		Modesto	California	United States
25		Mountain View	California	United States
26		Northridge	California	United States
27		Oakland	California	United States
28		Orange	California	United States
29		Pismo Beach	California	United States
30		Sacramento	California	United States
31		San Diego	California	United States
32		San Leandro	California	United States
33		Santa Clara	California	United States
34		Santa Monica	California	United States
35		Santa Rosa	California	United States
36		Sylmar	California	United States
37		Torrance	California	United States
38		Ventura	California	United States
39		Yuba City	California	United States
40		Boulder	Colorado	United States
41		Denver	Colorado	United States
42		Littleton	Colorado	United States
43		Pueblo	Colorado	United States
44		Danbury	Connecticut	United States
45		Guilford	Connecticut	United States
46		Newark	Delaware	United States
47		Bradenton	Florida	United States
48		Clearwater	Florida	United States
49		Daytona Beach	Florida	United States
50		Debary	Florida	United States
51		Deerfield Beach	Florida	United States
52		Fort Lauderdale	Florida	United States
53		Fort Myers	Florida	United States
54		Fort Walton Beach	Florida	United States
55		Hialeah	Florida	United States
56		Hollywood	Florida	United States
57		Hudson	Florida	United States
58		Inverness	Florida	United States
59		Jacksonville	Florida	United States
60		Jupiter	Florida	United States
61		Kissimmee	Florida	United States
62		Largo	Florida	United States
63		Melbourne	Florida	United States
64		Miami Beach	Florida	United States
65		Miami	Florida	United States
66		Ocala	Florida	United States
67		Orange Park	Florida	United States
68		Orlando	Florida	United States
69		Ormond Beach	Florida	United States
70		Palm Beach Gardens	Florida	United States
71		Palm Harbor	Florida	United States
72		Port Charlotte	Florida	United States
73		Safety Harbor	Florida	United States
74		St. Petersburg	Florida	United States
75		Tallahassee	Florida	United States
76		Tamarac	Florida	United States
77		Tampa	Florida	United States
78		Albany	Georgia	United States
79		Atlanta	Georgia	United States
80		Augusta	Georgia	United States
81		Columbus	Georgia	United States
82		Savannah	Georgia	United States
83		Boise	Idaho	United States
84		Idaho Falls	Idaho	United States
85		Nampa	Idaho	United States
86		Aurora	Illinois	United States
87		Bannockburn	Illinois	United States
88		Chicago	Illinois	United States
89		Evergreen Park	Illinois	United States
90		Fulton	Illinois	United States
91		Lombard	Illinois	United States
92		Melrose Park	Illinois	United States
93		Moline	Illinois	United States
94		Park Ridge	Illinois	United States
95		Peoria	Illinois	United States
96		Quincy	Illinois	United States
97		Rock Island	Illinois	United States
98		Rockford	Illinois	United States
99		Springfield	Illinois	United States
100		Watseka	Illinois	United States
101		Anderson	Indiana	United States
102		Hammond	Indiana	United States
103		Indianapolis	Indiana	United States
104		Merrillville	Indiana	United States
105		Muncie	Indiana	United States
106		Munster	Indiana	United States
107		South Bend	Indiana	United States
108		Waterloo	Iowa	United States
109		Crestview Hills	Kentucky	United States
110		Edgewood	Kentucky	United States
111		Lexington	Kentucky	United States
112		Louisville	Kentucky	United States
113		Madisonville	Kentucky	United States
114		Mt Sterling	Kentucky	United States
115		Owensboro	Kentucky	United States
116		Houma	Louisiana	United States
117		Lake Charles	Louisiana	United States
118		New Orleans	Louisiana	United States
119		Thibodaux	Louisiana	United States
120		Vidalia	Louisiana	United States
121		Bangor	Maine	United States
122		Scarborough	Maine	United States
123		Annapolis	Maryland	United States
124		Beltsville	Maryland	United States
125		Columbia	Maryland	United States
126		Salisbury	Maryland	United States
127		Boston	Massachusetts	United States
128		Brighton	Massachusetts	United States
129		Framingham	Massachusetts	United States
130		Bay City	Michigan	United States
131		Bridgman	Michigan	United States
132		Chelsea	Michigan	United States
133		Dearborn	Michigan	United States
134		Detroit	Michigan	United States
135		Lansing	Michigan	United States
136		Mount Clemens	Michigan	United States
137		Petoskey	Michigan	United States
138		Traverse City	Michigan	United States
139		Troy	Michigan	United States
140		Minneapolis	Minnesota	United States
141		Saint Paul	Minnesota	United States
142		Picayune	Mississippi	United States
143		Tupelo	Mississippi	United States
144		Lexington	Missouri	United States
145		Saint Louis	Missouri	United States
146		Springfield	Missouri	United States
147		Anaconda	Montana	United States
148		Great Falls	Montana	United States
149		Beatrice	Nebraska	United States
150		Lincoln	Nebraska	United States
151		Omaha	Nebraska	United States
152		Las Vegas	Nevada	United States
153		Pahrump	Nevada	United States
154		Manchester	New Hampshire	United States
155		Bridgewater	New Jersey	United States
156		Elmer	New Jersey	United States
157		Haddon Heights	New Jersey	United States
158		New Brunswick	New Jersey	United States
159		Paterson	New Jersey	United States
160		Ridgewood	New Jersey	United States
161		Sewell	New Jersey	United States
162		Springfield	New Jersey	United States
163		Toms River	New Jersey	United States
164		Wayne	New Jersey	United States
165		Albuquerque	New Mexico	United States
166		Bronx	New York	United States
167		Brooklyn	New York	United States
168		Buffalo	New York	United States
169		Cortlandt Manor	New York	United States
170		East Syracuse	New York	United States
171		New York	New York	United States
172		Northport	New York	United States
173		Saratoga Springs	New York	United States
174		Schenectady	New York	United States
175		Staten Island	New York	United States
176		Stony Brook	New York	United States
177		Syracuse	New York	United States
178		Williamsville	New York	United States
179		Asheville	North Carolina	United States
180		Durham	North Carolina	United States
181		Greensboro	North Carolina	United States
182		Hickory	North Carolina	United States
183		Jacksonville	North Carolina	United States
184		New Bern	North Carolina	United States
185		Raleigh	North Carolina	United States
186		Reidsville	North Carolina	United States
187		Rocky Mount	North Carolina	United States
188		Statesville	North Carolina	United States
189		Winston Salem	North Carolina	United States
190		Fargo	North Dakota	United States
191		Minot	North Dakota	United States
192		Canton	Ohio	United States
193		Cincinnati	Ohio	United States
194		Columbus	Ohio	United States
195		Dayton	Ohio	United States
196		Fairfield	Ohio	United States
197		Mansfield	Ohio	United States
198		Massillon	Ohio	United States
199		Maumee	Ohio	United States
200		Toledo	Ohio	United States
201		Zanesville	Ohio	United States
202		Bartlesville	Oklahoma	United States
203		Midwest City	Oklahoma	United States
204		Norman	Oklahoma	United States
205		Oklahoma City	Oklahoma	United States
206		Yukon	Oklahoma	United States
207		Portland	Oregon	United States
208		Beaver	Pennsylvania	United States
209		Bethlehem	Pennsylvania	United States
210		Danville	Pennsylvania	United States
211		Doylestown	Pennsylvania	United States
212		Jeannette	Pennsylvania	United States
213		Jersey Shore	Pennsylvania	United States
214		Lansdale	Pennsylvania	United States
215		Leetsdale	Pennsylvania	United States
216		Lewistown	Pennsylvania	United States
217		Norristown	Pennsylvania	United States
218		North Wales	Pennsylvania	United States
219		Philadelphia	Pennsylvania	United States
220		Philipsburg	Pennsylvania	United States
221		Phoenixville	Pennsylvania	United States
222		Pittsburgh	Pennsylvania	United States
223		Sayre	Pennsylvania	United States
224		Scranton	Pennsylvania	United States
225		Shippensburg	Pennsylvania	United States
226		State College	Pennsylvania	United States
227		Topton	Pennsylvania	United States
228		Wilkes Barre	Pennsylvania	United States
229		Wormleysburg	Pennsylvania	United States
230		Wyomissing	Pennsylvania	United States
231		Pawtucket	Rhode Island	United States
232		Westerly	Rhode Island	United States
233		Anderson	South Carolina	United States
234		Charleston	South Carolina	United States
235		Columbia	South Carolina	United States
236		Easley	South Carolina	United States
237		Sumter	South Carolina	United States
238		Rapid City	South Dakota	United States
239		Athens	Tennessee	United States
240		Bristol	Tennessee	United States
241		Chattanooga	Tennessee	United States
242		Harriman	Tennessee	United States
243		Jackson	Tennessee	United States
244		Johnson City	Tennessee	United States
245		Kingsport	Tennessee	United States
246		Knoxville	Tennessee	United States
247		Lexington	Tennessee	United States
248		Memphis	Tennessee	United States
249		Nashville	Tennessee	United States
250		Amarillo	Texas	United States
251		Beaumont	Texas	United States
252		Brownsville	Texas	United States
253		Corpus Christi	Texas	United States
254		Daingerfield	Texas	United States
255		Dallas	Texas	United States
256		Desoto	Texas	United States
257		Fort Sam Houston	Texas	United States
258		Fort Worth	Texas	United States
259		Houston	Texas	United States
260		Humble	Texas	United States
261		Hurst	Texas	United States
262		Kerrville	Texas	United States
263		Kingwood	Texas	United States
264		Lubbock	Texas	United States
265		Mcallen	Texas	United States
266		Odessa	Texas	United States
267		Plano	Texas	United States
268		San Antonio	Texas	United States
269		Sugar Land	Texas	United States
270		Tomball	Texas	United States
271		Victoria	Texas	United States
272		Murray	Utah	United States
273		Salt Lake City	Utah	United States
274		Burlington	Vermont	United States
275		Blacksburg	Virginia	United States
276		Chester	Virginia	United States
277		Danville	Virginia	United States
278		Fairfax	Virginia	United States
279		Fredericksburg	Virginia	United States
280		Lynchburg	Virginia	United States
281		Richmond	Virginia	United States
282		Roanoke	Virginia	United States
283		Virginia Beach	Virginia	United States
284		Williamsburg	Virginia	United States
285		Bellingham	Washington	United States
286		Port Orchard	Washington	United States
287		Seattle	Washington	United States
288		Spokane	Washington	United States
289		Tacoma	Washington	United States
290		Vancouver	Washington	United States
291		Burlington	Wisconsin	United States
292		Elkhorn	Wisconsin	United States
293		La Crosse	Wisconsin	United States
294		Milwaukee	Wisconsin	United States
295		Wausau	Wisconsin	United States
296		Bahia Blanca		Argentina
297		Buenos Aires		Argentina
298		Cipolletti		Argentina
299		Ciudad Autonoma De Buenos Aires		Argentina
300		Cordoba		Argentina
301		Corrientes		Argentina
302		La Plata		Argentina
303		Mar Del Plata		Argentina
304		Quilmes		Argentina
305		Rosario		Argentina
306		Salta		Argentina
307		San Martin		Argentina
308		Santa Fe		Argentina
309		Tucuman		Argentina
310		Adelaide		Australia
311		Auchenflower		Australia
312		Bedford Park		Australia
313		Box Hill		Australia
314		Caboolture		Australia
315		Cairns		Australia
316		Camperdown		Australia
317		Chermside		Australia
318		Clayton		Australia
319		Coffs Harbour		Australia
320		Footscray		Australia
321		Garran		Australia
322		Geelong		Australia
323		Gosford		Australia
324		Heidelberg Heights		Australia
325		Herston		Australia
326		Hobart		Australia
327		Joondalup		Australia
328		Lismore		Australia
329		Liverpool		Australia
330		Miranda		Australia
331		Nedlands		Australia
332		New Lambton Heights		Australia
333		Parkville		Australia
334		Penrith		Australia
335		Prahran		Australia
336		Reservoir		Australia
337		Southport		Australia
338		Windsor		Australia
339		Wolloongabba		Australia
340		Feldkirch Vorarlberg Vorarlber		Austria
341		Graz		Austria
342		Tulln Niederosterreich Niedero		Austria
343		Wien N/A		Austria
344		Wien Wien		Austria
345		Wien		Austria
346		Antwerpen		Belgium
347		Bonheiden		Belgium
348		Brasschaat		Belgium
349		Brugge		Belgium
350		Brussel		Belgium
351		Bruxelles		Belgium
352		Gent		Belgium
353		Haine-Saint-Paul		Belgium
354		Leuven		Belgium
355		Mol		Belgium
356		Nivelles		Belgium
357		Ottignies		Belgium
358		Roeselare		Belgium
359		Seraing		Belgium
360		Tienen		Belgium
361		Belo Horizonte		Brazil
362		Blumenau		Brazil
363		Brasilia		Brazil
364		Campina Grande Do Sul		Brazil
365		Campinas		Brazil
366		Campo Grande		Brazil
367		Curitiba		Brazil
368		Fortaleza		Brazil
369		Goiania		Brazil
370		Goiânia		Brazil
371		Maceio		Brazil
372		Marilia		Brazil
373		Maringa		Brazil
374		Porto Alegre		Brazil
375		Recife		Brazil
376		Rio De Janeiro Br		Brazil
377		Rio De Janeiro		Brazil
378		Salvador		Brazil
379		Santo Andre		Brazil
380		Sao Caetano Do Sul		Brazil
381		Sao Paulo		Brazil
382		Sorocaba		Brazil
383		São José Do Rio Preto		Brazil
384		São Paulo		Brazil
385		Uberlandia		Brazil
386		Dimitrovgrad		Bulgaria
387		Pleven		Bulgaria
388		Plovdiv		Bulgaria
389		Russel		Bulgaria
390		Sofia		Bulgaria
391		Veliko Turnovo		Bulgaria
392		Calgary	Alberta	Canada
393		Edmonton	Alberta	Canada
394		Abbotsford	British Columbia	Canada
395		Burnaby	British Columbia	Canada
396		Campbell River	British Columbia	Canada
397		Delta	British Columbia	Canada
398		Kelowna	British Columbia	Canada
399		Langley	British Columbia	Canada
400		New Westminster	British Columbia	Canada
401		Penticton	British Columbia	Canada
402		Vancouver	British Columbia	Canada
403		Victoria	British Columbia	Canada
404		West Vancouver	British Columbia	Canada
405		Winnipeg	Manitoba	Canada
406		Moncton	New Brunswick	Canada
407		Saint John	New Brunswick	Canada
408		St. John'S	Newfoundland and Labrador	Canada
409		Halifax	Nova Scotia	Canada
410		Sydney	Nova Scotia	Canada
411		Ajax	Ontario	Canada
412		Beamsville	Ontario	Canada
413		Belleville	Ontario	Canada
414		Brampton	Ontario	Canada
415		Burlington	Ontario	Canada
416		Cambridge	Ontario	Canada
417		Corunna	Ontario	Canada
418		Courtice	Ontario	Canada
419		E. London	Ontario	Canada
420		Etobicoke	Ontario	Canada
421		Fort Erie	Ontario	Canada
422		Hamilton	Ontario	Canada
423		Kitchener	Ontario	Canada
424		Listowel	Ontario	Canada
425		London	Ontario	Canada
426		Markham	Ontario	Canada
427		Mississauga	Ontario	Canada
428		North Bay	Ontario	Canada
429		North York	Ontario	Canada
430		Oakville	Ontario	Canada
431		Oshawa	Ontario	Canada
432		Ottawa	Ontario	Canada
433		Parry Sound	Ontario	Canada
434		Richmond Hill	Ontario	Canada
435		Sarnia	Ontario	Canada
436		Sault Ste Marie	Ontario	Canada
437		Scarborough	Ontario	Canada
438		Strathroy	Ontario	Canada
439		Sudbury	Ontario	Canada
440		Thornhill	Ontario	Canada
441		Thunder Bay	Ontario	Canada
442		Toronto	Ontario	Canada
443		Waterloo	Ontario	Canada
444		Whitby	Ontario	Canada
445		York	Ontario	Canada
446		Chicoutimi	Quebec	Canada
447		Greenfield Park	Quebec	Canada
448		Joliette	Quebec	Canada
449		Jonquiere	Quebec	Canada
450		Lachine	Quebec	Canada
451		Longueuil	Quebec	Canada
452		Mirabel	Quebec	Canada
453		Montreal	Quebec	Canada
454		Pointe-Claire	Quebec	Canada
455		Saint-Jerome	Quebec	Canada
456		Saint-Lambert	Quebec	Canada
457		Sherbrooke	Quebec	Canada
458		St-Leonard	Quebec	Canada
459		North Battleford	Saskatchewan	Canada
460		Saskatoon	Saskatchewan	Canada
461		Quebec		Canada
462		Arica I Region		Chile
463		Chila		Chile
464		Concepción Viii		Chile
465		Osorno X Region		Chile
466		Osorno X Región		Chile
467		Rancagua Vi Region		Chile
468		San Felipe V Region		Chile
469		Santiago De Chile Rm		Chile
470		Santiago Rm		Chile
471		Temuco Ix		Chile
472		Valdivia X Región		Chile
473		Viña Del Mar V Región		Chile
474		Bei Jing		China
475		Beijing		China
476		Changchun		China
477		Changsha		China
478		Changzhou		China
479		Chengdu		China
480		Chongqing		China
481		Dalian		China
482		Daqing		China
483		Guangzhou		China
484		Haikou		China
485		Hangzhou		China
486		Harbin		China
487		Jinan		China
488		Nanjing		China
489		Shanghai		China
490		Shenyang		China
491		Su Zhou		China
492		Suzhou		China
493		Tianjin		China
494		Wuhan		China
495		Xian		China
496		Barranquilla Atlántico Atlanti		Colombia
497		Barranquilla		Colombia
498		Bogota D C		Colombia
499		Bogota Dc		Colombia
500		Bogotá Dc Dc		Colombia
501		Bogotá Dc		Colombia
502		Cali Valle Del Cauca		Colombia
503		Cali Valley Del Cauca		Colombia
504		Medellin Antioquia		Colombia
505		Medellin		Colombia
506		Santander		Colombia
507		Brno 2		Czech Republic
508		Chomutov		Czech Republic
509		Hradec Kralove		Czech Republic
510		Karviná 4		Czech Republic
511		Kutna Hora N/A		Czech Republic
512		Liberec		Czech Republic
513		Litomysl		Czech Republic
514		Náchod 1		Czech Republic
515		Olomouc		Czech Republic
516		Ostrava		Czech Republic
517		Pardubice		Czech Republic
518		Praha 10 N/A		Czech Republic
519		Praha 1		Czech Republic
520		Praha 2		Czech Republic
521		Praha 4		Czech Republic
522		Praha 5		Czech Republic
523		Praha 8		Czech Republic
524		Praha		Czech Republic
525		Slany		Czech Republic
526		Svitavy 2		Czech Republic
527		Svitavy		Czech Republic
528		Trutnov		Czech Republic
529		Uherské Hradistì 6		Czech Republic
530		Zlín 1		Czech Republic
531		Esbjerg		Denmark
532		Frederiksberg		Denmark
533		Gentofte		Denmark
534		Hellerup		Denmark
535		Helsingør		Denmark
536		Hvidovre		Denmark
537		Koege		Denmark
538		København		Denmark
539		Næstved		Denmark
540		Roskilde		Denmark
541		Slagelse		Denmark
542		Viborg		Denmark
543		Helsinki		Finland
544		Jyväskylä N/A		Finland
545		Kuopio		Finland
546		Mikkeli		Finland
547		Oulu		Finland
548		Turku		Finland
549		Albi		France
550		Arras		France
551		Bayonne		France
552		Belfort		France
553		Besancon N/A		France
554		Bourg En Bresse		France
555		Brest		France
556		Béziers Languedoc-Roussillon		France
557		Carcassonne		France
558		Clermont Ferrand		France
559		Corbeil Essonnes		France
560		Lille		France
561		Marseille		France
562		Montbeliard		France
563		Montpellier		France
564		Paris Cedex 14		France
565		Paris		France
566		Perpignan		France
567		Poitiers		France
568		Saint-Brieuc		France
569		St Jean De Verges		France
570		Strasbourg		France
571		Thionville		France
572		Toulouse		France
573		Trelivan		France
574		Aalen		Germany
575		Berlin/Spandau		Germany
576		Berlin		Germany
577		Biberach		Germany
578		Bochum		Germany
579		Bonn		Germany
580		Chemnitz		Germany
581		Coburg		Germany
582		Dachau		Germany
583		Dortmund		Germany
584		Dresden		Germany
585		Duisburg		Germany
586		Ebersbach		Germany
587		Eilenburg		Germany
588		Erfurt		Germany
589		Essen		Germany
590		Frankfurt		Germany
591		Freiburg		Germany
592		Greifswald		Germany
593		Halle		Germany
594		Hamburg		Germany
595		Hartmannsdorf		Germany
596		Heidelberg		Germany
597		Henstedt-Rhen		Germany
598		Herford		Germany
599		Homburg/Saar		Germany
600		Jena		Germany
601		Julich		Germany
602		Kamen		Germany
603		Karlsbad		Germany
604		Kassel		Germany
605		Kirchzarten		Germany
606		Krefeld		Germany
607		Leipzig		Germany
608		Ludwigsburg		Germany
609		Ludwigshafen		Germany
610		Lüneburg		Germany
611		Magdeburg		Germany
612		Mainz		Germany
613		Mannheim		Germany
614		Markkleeberg		Germany
615		Meißen		Germany
616		Melsungen		Germany
617		Monchengladbach		Germany
618		Munchen		Germany
619		Mühldorf		Germany
620		Mülheim		Germany
621		Münster		Germany
622		Neuwied		Germany
623		Nienburg		Germany
624		Nuernberg		Germany
625		Paderborn		Germany
626		Potsdam		Germany
627		Riesa		Germany
628		Rottweil		Germany
629		Sachsen		Germany
630		Siegen		Germany
631		Ulm		Germany
632		Wermsdorf		Germany
633		Witten		Germany
634		Wolmirstedt		Germany
635		Wuppertal		Germany
636		Athens Attica		Greece
637		Ioannina		Greece
638		Maroussi Athens		Greece
639		Patra		Greece
640		Piraeus Attica		Greece
641		Tripoli		Greece
642		Voula Attica		Greece
643		Aberdeen		Hong Kong
644		Hk		Hong Kong
645		Kln		Hong Kong
646		Sha Tin		Hong Kong
647		Budapest N/A		Hungary
648		Budapest Nap		Hungary
649		Budapest		Hungary
650		Debrecen County		Hungary
651		Eger		Hungary
652		Gyongyos		Hungary
653		Gyõr		Hungary
654		Kesckemet		Hungary
655		Miskolc		Hungary
656		Nyiregyhaza		Hungary
657		Pecs		Hungary
658		Szeged		Hungary
659		Szekszard		Hungary
660		Szombathely		Hungary
661		Veszprem		Hungary
662		Zalaegerszeg		Hungary
663		Ahmedabad		India
664		Bangalore		India
665		Bikaner		India
666		Chennai		India
667		Coimbatore		India
668		Gandhinagar Guiarat		India
669		Hyderabad Andra Pradesh		India
670		Hyderabad		India
671		Jalandhar		India
672		Madurai		India
673		Mangalore		India
674		Mumbai		India
675		Mysore		India
676		New Delhi		India
677		Pune		India
678		Suraj		India
679		Vadodara		India
680		Vishakapatnam		India
681		Afula		Israel
682		Ashkelon		Israel
683		Hadera		Israel
684		Haifa		Israel
685		Holon		Israel
686		Jerusalem		Israel
687		Nazareth		Israel
688		Netanya		Israel
689		Petach-Tikva		Israel
690		Petah-Tikva		Israel
691		Poriya		Israel
692		Rehovot		Israel
693		Safed		Israel
694		Tel Aviv		Israel
695		Tel Hashomer		Israel
696		Zerifin		Israel
697		Anyang		Korea, Republic of
698		Daegu		Korea, Republic of
699		Daejeon		Korea, Republic of
700		Goyang		Korea, Republic of
701		Kyonggi-Do		Korea, Republic of
702		Pusan		Korea, Republic of
703		Seoul		Korea, Republic of
704		Sungnam		Korea, Republic of
705		Suwon		Korea, Republic of
706		Kaunas		Lithuania
707		Klaipeda		Lithuania
708		Panevezys		Lithuania
709		Siauliai		Lithuania
710		Vilnius		Lithuania
711		Kelantan		Malaysia
712		Kuala Lumpur		Malaysia
713		Sarawak		Malaysia
714		Aguascalientes		Mexico
715		Ciudad De Mexico		Mexico
716		Culiacán Sinaloa/Mèxico		Mexico
717		Guadalajara		Mexico
718		Hermosillo		Mexico
719		Monterrey Nuevo Leòn		Mexico
720		Monterrey		Mexico
721		Queretaro		Mexico
722		San Luis Potosi		Mexico
723		Sinaloa		Mexico
724		Zapopan		Mexico
725		'S-Gravenhage		Netherlands
726		Alkmaar		Netherlands
727		Amersfoort		Netherlands
728		Amsterdam		Netherlands
729		Blaricum		Netherlands
730		Delft		Netherlands
731		Den Bosch		Netherlands
732		Den Haag		Netherlands
733		Gc Tilburg		Netherlands
734		Gouda		Netherlands
735		Groningen		Netherlands
736		Haarlem		Netherlands
737		Heerlen		Netherlands
738		Hoofddorp		Netherlands
739		Hoorn Nh		Netherlands
740		Leeuwarden		Netherlands
741		Leidschendam		Netherlands
742		Maastricht		Netherlands
743		Meppel		Netherlands
744		Nijmegen		Netherlands
745		Schiedam		Netherlands
746		Veldhoven		Netherlands
747		Christchurch		New Zealand
748		Dunedin		New Zealand
749		Grafton		New Zealand
750		Hamilton		New Zealand
751		Takapuna Auckland		New Zealand
752		Wellington		New Zealand
753		Alesund		Norway
754		Bergen		Norway
755		Elverum		Norway
756		Hamar		Norway
757		Jessheim		Norway
758		Lillehammer		Norway
759		Moss		Norway
760		Oslo		Norway
761		Sandefjord		Norway
762		Sandnes		Norway
763		Sandvika		Norway
764		Skedsmokorset		Norway
765		L41 Lima Lima		Peru
766		Lima 1 Lima Lima		Peru
767		Lima		Peru
768		Cebuu City		Philippines
769		Davao City		Philippines
770		Iloilo City		Philippines
771		Manila City		Philippines
772		Quezon City		Philippines
773		Bydgoszcz N/A		Poland
774		Bydgoszcz		Poland
775		Gdansk		Poland
776		Gdynia		Poland
777		Katowice-Ochojec		Poland
778		Katowice		Poland
779		Krakow		Poland
780		Lodz		Poland
781		Olawa		Poland
782		Olsztyn		Poland
783		Opole		Poland
784		Ostrowiec N/A		Poland
785		Piotrkow Trybunalski		Poland
786		Plock		Poland
787		Poznan		Poland
788		Siedlce		Poland
789		Sieradz N/A		Poland
790		Skierniewice		Poland
791		Starogard Gdanski Nap		Poland
792		Szczecin Nap		Poland
793		Szczecin		Poland
794		Torun		Poland
795		Warsaw		Poland
796		Warszawa N/A		Poland
797		Warszawa		Poland
798		Wloclawek		Poland
799		Wroclaw N/A		Poland
800		Wroclaw		Poland
801		Zyrardow N/A		Poland
802		Brasov		Romania
803		Bucharest		Romania
804		Bucuresti		Romania
805		Craiova		Romania
806		Focsani		Romania
807		Iasi		Romania
808		Oradea		Romania
809		Sibiu		Romania
810		Suceava		Romania
811		Tg Mures		Romania
812		Timisoara		Romania
813		Barnaul		Russian Federation
814		Chelyabinsk Chelyabinsk Region		Russian Federation
815		Chelyabinsk		Russian Federation
816		Ekaterinburg		Russian Federation
817		Kemerovo		Russian Federation
818		Krasnoyarsk		Russian Federation
819		Moscow N/A		Russian Federation
820		Moscow		Russian Federation
821		Nizhni Novgorod		Russian Federation
822		Novosibirsk Nap		Russian Federation
823		Novosibirsk		Russian Federation
824		Orenburg		Russian Federation
825		Perm		Russian Federation
826		Ryazan		Russian Federation
827		Saint Petersburg		Russian Federation
828		Saint-Petersburg		Russian Federation
829		Saratov		Russian Federation
830		Smolensk		Russian Federation
831		St Petersburg		Russian Federation
832		St. Petersburg		Russian Federation
833		Tomsk		Russian Federation
834		Tyumen Tyumen Region		Russian Federation
835		Yaroslavl Nap		Russian Federation
836		Yaroslavl		Russian Federation
837		Singapore		Singapore
838		Bloemfontein Free State		South Africa
839		Bloemfontein Orange Free State		South Africa
840		Cape Town Western Cape		South Africa
841		Cape Town		South Africa
842		Centurion Gauteng		South Africa
843		Durban Kwa Zulu Natal		South Africa
844		Johannesburg Gauteng		South Africa
845		Kempton Park Gauteng		South Africa
846		Port Elizabeth Eastern Cape		South Africa
847		Pretoria Gauteng		South Africa
848		Somerset West Western Cape		South Africa
849		Van Der Bijl Park		South Africa
850		Worcester Western Cape		South Africa
851		A Coruna		Spain
852		Alicante N/A		Spain
853		Almeria		Spain
854		Baracaldo Vizcaya		Spain
855		Barcelona		Spain
856		Burgos		Spain
857		Guadalajara		Spain
858		La Corona		Spain
859		Madrid		Spain
860		Malaga		Spain
861		Oviedo		Spain
862		Palma De Mallorca		Spain
863		Pamplona		Spain
864		Pontevedra		Spain
865		Sabadell		Spain
866		San Sebastián Guipúzcoa		Spain
867		Sevilla		Spain
868		Terrassa		Spain
869		Valencia		Spain
870		Valladolid		Spain
871		Ljungby		Sweden
872		Lund		Sweden
873		Sala		Sweden
874		Skövde		Sweden
875		Uppsala		Sweden
876		Basel Bs		Switzerland
877		Bruderholz		Switzerland
878		Geneve		Switzerland
879		Zurich		Switzerland
880		Changhua		Taiwan
881		Kaohsiung		Taiwan
882		Taichung		Taiwan
883		Tainan		Taiwan
884		Taipei		Taiwan
885		Tamshui		Taiwan
886		Tao-Yuan		Taiwan
887		Bangkok Noi		Thailand
888		Bangkok		Thailand
889		Chiang Mai		Thailand
890		Pathumthani		Thailand
891		Phathumwan		Thailand
892		Ratchatewi		Thailand
893		Adana		Turkey
894		Ankara		Turkey
895		Antalya		Turkey
896		Aydin		Turkey
897		Denizli		Turkey
898		Diyarbakir		Turkey
899		Eskisehir		Turkey
900		Görükle		Turkey
901		Istanbul		Turkey
902		Izmir		Turkey
903		Izmit		Turkey
904		Kayseri		Turkey
905		Konya		Turkey
906		Malatya Nap		Turkey
907		Mersin		Turkey
908		Samsun		Turkey
909		Cherkassy		Ukraine
910		Chernigiv		Ukraine
911		Dnepropetrovsk		Ukraine
912		Dnipropetrovsk		Ukraine
913		Donetsk		Ukraine
914		Ivano-Frankivsk		Ukraine
915		Kharkiv		Ukraine
916		Kharkov		Ukraine
917		Kirovograd		Ukraine
918		Kyiv		Ukraine
919		Lugansk		Ukraine
920		Lviv		Ukraine
921		O1103 Kyiv		Ukraine
922		Odesa		Ukraine
923		Poltava		Ukraine
924		Simferopil		Ukraine
925		Sumy		Ukraine
926		Ternopil		Ukraine
927		Uzhgorod		Ukraine
928		Vinnitsya		Ukraine
929		Vinnytsia		Ukraine
930		Zaporizhzhya		Ukraine
931		Zhytomyr		Ukraine
932		Aberdeen		United Kingdom
933		Belfast		United Kingdom
934		Birmingham		United Kingdom
935		Bournemouth		United Kingdom
936		Cambridgeshire		United Kingdom
937		Chelmsford		United Kingdom
938		Chesterfield		United Kingdom
939		Colchester		United Kingdom
940		Craigavon		United Kingdom
941		Devon		United Kingdom
942		Dundee		United Kingdom
943		Glasgow		United Kingdom
944		Harrogate		United Kingdom
945		Hull		United Kingdom
946		Leicester		United Kingdom
947		Lincoln		United Kingdom
948		Liverpool		United Kingdom
949		London		United Kingdom
950		Nottingham		United Kingdom
951		Plymouth		United Kingdom
952		Romford		United Kingdom
953		Sheffield		United Kingdom
954		Stirling		United Kingdom
955		Stoke On Trent		United Kingdom
956		York		United Kingdom
957		Caracas		Venezuela
958		Maracaibo Estado Zulia		Venezuela
959		Maracay Estado Aragua		Venezuela

Sponsors and Collaborators

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

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• ClinicalTrials.gov Identifier: NCT00403767
• Other Study ID Numbers: CR012157; 39039039AFL3001; ROCKET AF; 2006-004595-13
• First Posted: Nov 27, 2006
• Last Update Posted: Apr 29, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: Atrial Fibrillation; Stroke; Embolism; Non-central nervous system systemic embolism; Non-valvular atrial fibrillation; Blood Clot; Rivaroxaban; Warfarin; Anticoagulants; Arrhythmias, Cardiac
• Additional relevant MeSH terms: Stroke; Atrial Fibrillation; Embolism; Warfarin; Rivaroxaban

Study Results

Participant Flow

Recruitment Details	This study, an efficacy and safety study of Rivaroxaban with Warfarin for the prevention of stroke and non-central nervous system systemic embolism in patients with non-valvular atrial fibrillation, was conducted from 18 December 2006 to 07 September 2010. Patients were recruited at 1,170 study centers located in 45 countries worldwide.
Pre-assignment Detail	A total of 14,269 patients were randomized in the study. Five patients were randomized twice bringing the number of randomized unique patients to 14,264. A total of 14,236 (7111 and 7125 patients in the rivaroxaban and warfarin groups, respectively) unique patients took at least 1 dose of study medication and were included in the Safety Population.

Arm/Group Title	Rivaroxaban	Warfarin
Arm/Group Description	Rivaroxaban 15 mg p.o. once daily or Rivaroxaban 20 mg p.o. once daily	Warfarin (1 mg, 2.5 mg, or 5 mg p.o. once daily)
Period Title: Overall Study
STARTED	7111	7125
COMPLETED	4591	4657
NOT COMPLETED	2520	2468

Baseline Characteristics

Arm/Group Title	Rivaroxaban	Warfarin	Total
Arm/Group Description	Rivaroxaban 15 mg p.o. once daily or Rivaroxaban 20 mg p.o. once daily	Warfarin (1 mg, 2.5 mg, or 5 mg p.o. once daily)	Total of all reporting groups
Overall Participants	7111	7125	14236
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1646 23.1%	1642 23%	3288 23.1%
>=65 years	5465 76.9%	5483 77%	10948 76.9%
Age (years) [Mean (Standard Deviation) ]
Age Continuous	71.2 (9.45)	71.2 (9.39)	71.2 (9.42)
Sex: Female, Male (Count of Participants)
Female	2819 39.6%	2826 39.7%	5645 39.7%
Male	4292 60.4%	4299 60.3%	8591 60.3%
Region of Enrollment (participants) [Number]
Argentina	284 4%	285 4%	569 4%
Australia	120 1.7%	122 1.7%	242 1.7%
Austria	16 0.2%	16 0.2%	32 0.2%
Belgium	49 0.7%	47 0.7%	96 0.7%
Brazil	241 3.4%	242 3.4%	483 3.4%
Bulgaria	337 4.7%	339 4.8%	676 4.7%
Canada	372 5.2%	375 5.3%	747 5.2%
Chile	144 2%	142 2%	286 2%
China	249 3.5%	246 3.5%	495 3.5%
Colombia	134 1.9%	133 1.9%	267 1.9%
Czech Republic	299 4.2%	299 4.2%	598 4.2%
Denmark	60 0.8%	61 0.9%	121 0.8%
Finland	9 0.1%	7 0.1%	16 0.1%
France	35 0.5%	36 0.5%	71 0.5%
Germany	263 3.7%	265 3.7%	528 3.7%
Greece	15 0.2%	14 0.2%	29 0.2%
Hungary	119 1.7%	118 1.7%	237 1.7%
India	133 1.9%	135 1.9%	268 1.9%
Israel	94 1.3%	94 1.3%	188 1.3%
Italy	69 1%	69 1%	138 1%
Korea (South)	103 1.4%	100 1.4%	203 1.4%
Lithuania	122 1.7%	122 1.7%	244 1.7%
Malaysia	26 0.4%	25 0.4%	51 0.4%
Mexico	83 1.2%	85 1.2%	168 1.2%
Netherlands	80 1.1%	81 1.1%	161 1.1%
New Zealand	58 0.8%	58 0.8%	116 0.8%
Norway	25 0.4%	24 0.3%	49 0.3%
Peru	42 0.6%	42 0.6%	84 0.6%
Philippines	185 2.6%	183 2.6%	368 2.6%
Poland	263 3.7%	264 3.7%	527 3.7%
Romania	391 5.5%	391 5.5%	782 5.5%
Russia	645 9.1%	645 9.1%	1290 9.1%
Singapore	21 0.3%	23 0.3%	44 0.3%
South Africa	122 1.7%	125 1.8%	247 1.7%
Spain	124 1.7%	124 1.7%	248 1.7%
Sweden	12 0.2%	16 0.2%	28 0.2%
Switzerland	3 0%	4 0.1%	7 0%
Taiwan	78 1.1%	79 1.1%	157 1.1%
Thailand	43 0.6%	44 0.6%	87 0.6%
Turkey	50 0.7%	51 0.7%	101 0.7%
Ukraine	505 7.1%	504 7.1%	1009 7.1%
United Kingdom	79 1.1%	80 1.1%	159 1.1%
United States	962 13.5%	964 13.5%	1926 13.5%
Venezuela	11 0.2%	9 0.1%	20 0.1%
Hong Kong	36 0.5%	37 0.5%	73 0.5%

Outcome Measures

1. Primary Outcome

Title	The Composite Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Non-Inferiority)
Description	The number of patients with the first occurrence of a stroke or non-CNS systemic embolism while on treatment (defined as the time interval from the first dose to the last dose of study drug plus 2 days). The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

The per-protocol (PP) population consisted of all randomized unique patients excluding those who had specific pre-defined major protocol deviations that occurred by the time of enrollment into the study or during the trial. Site 042012 with GCP violation was excluded.

Arm/Group Title	Rivaroxaban	Warfarin
Arm/Group Description	Rivaroxaban 20 mg p.o. once daily or matching placebo (15 mg p.o. once daily for patients with a calculated creatinine clearance of 30 - 49 mL/min. at baseline)	Warfarin (1 mg, 2.5 mg, or 5 mg p.o. once daily)
Measure Participants	6958	7004
Number [Patients]	188	241

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Warfarin
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Alternative hypothesis of non-inferiority (NI) by a NI margin of 1.46 in hazard ratio (HR) based on on-treatment data from the per protocol population. The required number of primary efficacy endpoint events was determined based on the following assumptions: NI margin of 1.46, 1-sided alpha of 0.025, power of >95% when true HR is 1, and exponential distributions. The margin was selected based on clinical appropriateness and quantitative analysis of relevant studies in Hart et al.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The p-value is not adjusted for multiple comparisons. The alpha threshold for statistical significance is 0.025 (1-sided).
	Method	Cox Proportional Hazards model
	Comments	(non-stratified) Cox Proportional Hazards model with treatment as covariate
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.66 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	The Composite of Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Superiority)
Description	The number of patients with the first occurrence of a stroke or non-CNS systemic embolism while on treatment (defined as the time interval from the first dose to the last dose of study drug plus 2 days). The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized unique patients who took at least 1 dose of study medication after randomization during the double-blind treatment period. Site 042012 with GCP violation was excluded.

Arm/Group Title	Rivaroxaban	Warfarin
Arm/Group Description	Rivaroxaban 20 mg p.o. once daily or matching placebo (15 mg p.o. once daily for patients with a calculated creatinine clearance of 30 - 49 mL/min. at baseline)	Warfarin (1 mg, 2.5 mg, or 5 mg p.o. once daily)
Measure Participants	7061	7082
Number [Patients]	189	243

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Warfarin
	Comments	Alternative hypothesis of superiority based on on-treatment data from the safety population.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments	The p-value Is not adjusted for multiple comparisons. The alpha threshold for statistical significance is 0.05 (2-sided).
	Method	Cox Proportional Hazards model
	Comments	(non-stratified) Cox Proportional Hazards model with treatment as covariate
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.65 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	The Composite Event of Major/Non-major Clinically Relevant Bleeding Events: Primary Safety
Description	The number of patients with the first occurrence of a major or non-major clinically relevant bleeding event while on treatment. The statistical analysis is based on time from the first dose of study drug to the first occurrence of the event while on treatment.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized unique patients who took at least 1 dose of study medication after randomization during the double-blind treatment period.

Arm/Group Title	Rivaroxaban	Warfarin
Arm/Group Description	Rivaroxaban 20 mg p.o. once daily or matching placebo (15 mg p.o. once daily for patients with a calculated creatinine clearance of 30 - 49 mL/min. at baseline)	Warfarin (1 mg, 2.5 mg, or 5 mg p.o. once daily)
Measure Participants	7111	7125
Number [Patients]	1475	1449

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Warfarin
	Comments	Alternate hypothesis of superiority based on on-treatment data from the safety population.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.442
	Comments	The p-value is not adjusted for mulitple comparisons. The alpha threshold for statistical significance is 0.05 (2-sided).
	Method	Cox Proportional Hazards model
	Comments	(non-stratified) Cox Proportional Hazards model with treatment as a covariate
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.96 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	The Composite Event of Stroke/Non-CNS Systemic Embolism/Vascular Death
Description	The number of patients with the first occurrence of a stroke, non-CNS systemic embolism, or vascular death while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized unique patients who took at least 1 dose of study medication after randomization during the double-blind treatment period. Site 042012 with GCP violation was excluded.

Arm/Group Title	Rivaroxaban	Warfarin
Arm/Group Description	Rivaroxaban 20 mg p.o. once daily or matching placebo (15 mg p.o. once daily for patients with a calculated creatinine clearance of 30 - 49 mL/min. at baseline)	Warfarin (1 mg, 2.5 mg, or 5 mg p.o. once daily)
Measure Participants	7061	7125
Number [Patients]	346	410

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Warfarin
	Comments	Alternative hypothesis of superiority based on on-treatment data from the safety population.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.034
	Comments	The p-value is not adjusted for multiple comparisons. The alpha threshold for statistical significance is 0.05 (2-sided).
	Method	Cox Proportional Hazards model
	Comments	(non-stratified) Cox Proportional Hazards model with treatment as covariate
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.74 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	The Composite Event of Stroke/Non-CNS Systemic Embolism/Myocardial Infarction/Vascular Death
Description	The number of patients with the first occurrence of a stroke, non-CNS systemic embolism, myocardial infarction, or vascular death while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized unique patients who took at least 1 dose of study medication after randomization during the double-blind treatment period. Site 042012 with GCP violation was excluded.

Arm/Group Title	Rivaroxaban	Warfarin
Arm/Group Description	Rivaroxaban 20 mg p.o. once daily or matching placebo (15 mg p.o. once daily for patients with a calculated creatinine clearance of 30 - 49 mL/min. at baseline)	Warfarin (1 mg, 2.5 mg, or 5 mg p.o. once daily)
Measure Participants	7061	7082
Number [Patients]	433	519

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Warfarin
	Comments	Alternative hypothesis of superiority based on on-treatment data from the safety population.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments	The p-value is not adjusted for multiple comparisons. The alpha threshold for statistical significance is 0.05 (2-sided).
	Method	Cox Proportional Hazards model
	Comments	(non-stratified) Cox Proportional Hazards model with treatment as covariate
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.74 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Stroke
Description	The number of patients with the first occurrence of a stroke while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized unique patients who took at least 1 dose of study medication after randomization during the double-blind treatment period. Site 042012 with GCP violation was excluded.

Arm/Group Title	Rivaroxaban	Warfarin
Arm/Group Description	Rivaroxaban 20 mg p.o. once daily or matching placebo (15 mg p.o. once daily for patients with a calculated creatinine clearance of 30 - 49 mL/min. at baseline)	Warfarin (1 mg, 2.5 mg, or 5 mg p.o. once daily)
Measure Participants	7061	7082
Number [Patients]	184	221

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Warfarin
	Comments	Alternative hypothesis of superiority based on on-treatment data from the safety population.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.092
	Comments	The p-value is not adjusted for multiple comparisons. The alpha threshold for statistical significance is 0.05 (2-sided).
	Method	Cox Proportional Hazards model
	Comments	(non-stratified) Cox Proportional Hazards model with treatment as a covariate
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Non-CNS Systemic Embolism
Description	The number of patients with the first occurrence of a non-CNS systemic embolism while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized unique patients who took at least 1 dose of study medication after randomization during the double-blind treatment period. Site 042012 with GCP violation was excluded.

Arm/Group Title	Rivaroxaban	Warfarin
Arm/Group Description	Rivaroxaban 20 mg p.o. once daily or matching placebo (15 mg p.o. once daily for patients with a calculated creatinine clearance of 30 - 49 mL/min. at baseline)	Warfarin (1 mg, 2.5 mg, or 5 mg p.o. once daily)
Measure Participants	7061	7082
Number [Patients]	5	22

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Warfarin
	Comments	Alternative hypothesis of superiority based on on-treatment data from the safety population.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	The p-value is not adjusted for multiple comparisons. The alpha threshold for statistical significance is 0.05 (2-sided).
	Method	Cox Proportional Hazards model
	Comments	(non-stratified) Cox Proportional Hazards model with treatment as covariate
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.23
	Confidence Interval	(2-Sided) 95%; 0.09 to 0.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Myocardial Infarction
Description	The number of patients with the first occurrence of a myocardial infarction while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized unique patients who took at least 1 dose of study medication after randomization during the double-blind treatment period. Site 042012 with GCP violation was excluded.

Arm/Group Title	Rivaroxaban	Warfarin
Arm/Group Description	Rivaroxaban 20 mg p.o. once daily or matching placebo (15 mg p.o. once daily for patients with a calculated creatinine clearance of 30 - 49 mL/min. at baseline)	Warfarin (1 mg, 2.5 mg, or 5 mg p.o. once daily)
Measure Participants	7061	7082
Number [Patients]	101	126

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Warfarin
	Comments	Alternative hypothesis of superiority based on on-treatment data from the safety population.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.121
	Comments	The p-value is not adjusted for multiple comparisons. The alpha threshold for statistical significance is 0.05 (2-sided).
	Method	Cox Proportional Hazards model
	Comments	(non-stratified) Cox Proportional Hazards model with treatment as a covariate
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.63 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Vascular Death
Description	The number of patients with the occurrence of vascular death while on treatment. The statistical analysis is based on time from randomization to the event while on treatment.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized unique patients who took at least 1 dose of study medication after randomization during the double-blind treatment period. Site 042012 with GCP violation was excluded.

Arm/Group Title	Rivaroxaban	Warfarin
Arm/Group Description	Rivaroxaban 20 mg p.o. once daily or matching placebo (15 mg p.o. once daily for patients with a calculated creatinine clearance of 30 - 49 mL/min. at baseline)	Warfarin (1 mg, 2.5 mg, or 5 mg p.o. once daily)
Measure Participants	7061	7082
Number [Patients]	170	193

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Warfarin
	Comments	Alternative hypothesis of superiority based on on-treatment data from the safety population.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.289
	Comments	The p-value is not adjusted for multiple comparisons. The alpha threshold for statistical significance is 0.05 (2-sided).
	Method	Cox Proportional Hazards model
	Comments	(non-stratified) Cox Proportional Hazards model with treatment as a covariate
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	All-cause Mortality
Description	The number of patients who died due to any cause while on treatment. The statistical analysis is based on time from randomization to the event while on treatment.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized unique patients who took at least 1 dose of study medication after randomization during the double-blind treatment period. Site 042012 with GCP violation was excluded.

Arm/Group Title	Rivaroxaban	Warfarin
Arm/Group Description	Rivaroxaban 20 mg p.o. once daily or matching placebo (15 mg p.o. once daily for patients with a calculated creatinine clearance of 30 - 49 mL/min. at baseline)	Warfarin (1 mg, 2.5 mg, or 5 mg p.o. once daily)
Measure Participants	7061	7125
Number [Patients]	208	250

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban, Warfarin
	Comments	Alternative hypothesis of superiority based on on-treatment data from the safety population.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.073
	Comments	The p-value is not adjusted for multiple comparisons. The alpha threshold for statistical significance is 0.05 (2-sided).
	Method	Cox Proportional Hazards model
	Comments	(non-stratified) Cox Proportional Hazards model with treatment as covariate
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Rivaroxaban		Warfarin
Arm/Group Description	Rivaroxaban 15 mg p.o. once daily or Rivaroxaban 20 mg p.o. once daily		Warfarin (1 mg, 2.5 mg, or 5 mg p.o. once daily)
All Cause Mortality
	Rivaroxaban		Warfarin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rivaroxaban		Warfarin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2649/7111 (37.3%)		2720/7125 (38.2%)
Blood and lymphatic system disorders
Anaemia	68/7111 (1%)		31/7125 (0.4%)
Anaemia Haemolytic Autoimmune	1/7111 (0%)		0/7125 (0%)
Anaemia Vitamin B12 Deficiency	0/7111 (0%)		2/7125 (0%)
Anaemia of Malignant Disease	1/7111 (0%)		0/7125 (0%)
Coagulopathy	0/7111 (0%)		2/7125 (0%)
Febrile Neutropenia	0/7111 (0%)		1/7125 (0%)
Haemolytic Anaemia	1/7111 (0%)		1/7125 (0%)
Haemorrhagic Anaemia	5/7111 (0.1%)		5/7125 (0.1%)
Hypochromic Anaemia	0/7111 (0%)		1/7125 (0%)
Hypocoagulable State	0/7111 (0%)		1/7125 (0%)
Hypoplastic Anaemia	1/7111 (0%)		0/7125 (0%)
Idiopathic Thrombocytopenic Purpura	0/7111 (0%)		1/7125 (0%)
Iron Deficiency Anaemia	16/7111 (0.2%)		6/7125 (0.1%)
Lymphadenopathy	0/7111 (0%)		1/7125 (0%)
Microcytic Anaemia	1/7111 (0%)		0/7125 (0%)
Nephrogenic Anaemia	2/7111 (0%)		0/7125 (0%)
Normochromic Normocytic Anaemia	3/7111 (0%)		4/7125 (0.1%)
Pancytopenia	1/7111 (0%)		1/7125 (0%)
Polycythaemia	1/7111 (0%)		0/7125 (0%)
Splenic Infarction	0/7111 (0%)		1/7125 (0%)
Thrombocytopenia	6/7111 (0.1%)		3/7125 (0%)
Thrombocytopenic Purpura	1/7111 (0%)		0/7125 (0%)
Anaemia Macrocytic	0/7111 (0%)		1/7125 (0%)
Disseminated Intravascular Coagulation	0/7111 (0%)		2/7125 (0%)
Leukocytosis	0/7111 (0%)		1/7125 (0%)
Splenic Haemorrhage	0/7111 (0%)		1/7125 (0%)
Cardiac disorders
Acute Coronary Syndrome	5/7111 (0.1%)		8/7125 (0.1%)
Acute Left Ventricular Failure	5/7111 (0.1%)		4/7125 (0.1%)
Acute Myocardial Infarction	6/7111 (0.1%)		11/7125 (0.2%)
Acute Right Ventricular Failure	0/7111 (0%)		1/7125 (0%)
Adams-Stokes Syndrome	0/7111 (0%)		2/7125 (0%)
Angina Pectoris	31/7111 (0.4%)		33/7125 (0.5%)
Angina Unstable	74/7111 (1%)		92/7125 (1.3%)
Aortic Valve Disease	0/7111 (0%)		1/7125 (0%)
Aortic Valve Disease Mixed	1/7111 (0%)		0/7125 (0%)
Aortic Valve Incompetence	1/7111 (0%)		1/7125 (0%)
Aortic Valve Stenosis	4/7111 (0.1%)		8/7125 (0.1%)
Arrhythmia	9/7111 (0.1%)		6/7125 (0.1%)
Arteriosclerosis Coronary Artery	7/7111 (0.1%)		3/7125 (0%)
Atrial Fibrillation	158/7111 (2.2%)		161/7125 (2.3%)
Atrial Flutter	10/7111 (0.1%)		17/7125 (0.2%)
Atrial Tachycardia	0/7111 (0%)		1/7125 (0%)
Atrial Thrombosis	2/7111 (0%)		3/7125 (0%)
Atrioventricular Block	2/7111 (0%)		4/7125 (0.1%)
Atrioventricular Block Complete	12/7111 (0.2%)		9/7125 (0.1%)
Atrioventricular Block Second Degree	1/7111 (0%)		2/7125 (0%)
Bradyarrhythmia	3/7111 (0%)		3/7125 (0%)
Bradycardia	35/7111 (0.5%)		23/7125 (0.3%)
Cardiac Amyloidosis	1/7111 (0%)		0/7125 (0%)
Cardiac Arrest	15/7111 (0.2%)		33/7125 (0.5%)
Cardiac Asthma	3/7111 (0%)		1/7125 (0%)
Cardiac Disorder	1/7111 (0%)		1/7125 (0%)
Cardiac Failure	283/7111 (4%)		309/7125 (4.3%)
Cardiac Failure Acute	40/7111 (0.6%)		36/7125 (0.5%)
Cardiac Failure Chronic	26/7111 (0.4%)		43/7125 (0.6%)
Cardiac Failure Congestive	178/7111 (2.5%)		206/7125 (2.9%)
Cardiac Tamponade	1/7111 (0%)		2/7125 (0%)
Cardiac Valve Disease	2/7111 (0%)		0/7125 (0%)
Cardio-Respiratory Arrest	7/7111 (0.1%)		10/7125 (0.1%)
Cardiogenic Shock	14/7111 (0.2%)		10/7125 (0.1%)
Cardiomyopathy	3/7111 (0%)		6/7125 (0.1%)
Cardiopulmonary Failure	2/7111 (0%)		1/7125 (0%)
Cardiovascular Insufficiency	1/7111 (0%)		2/7125 (0%)
Congestive Cardiomyopathy	3/7111 (0%)		1/7125 (0%)
Cor Pulmonale	1/7111 (0%)		0/7125 (0%)
Coronary Artery Disease	29/7111 (0.4%)		33/7125 (0.5%)
Coronary Artery Insufficiency	1/7111 (0%)		3/7125 (0%)
Coronary Artery Stenosis	1/7111 (0%)		3/7125 (0%)
Electromechanical Dissociation	3/7111 (0%)		1/7125 (0%)
Heart Valve Stenosis	0/7111 (0%)		1/7125 (0%)
Hypertensive Heart Disease	3/7111 (0%)		0/7125 (0%)
Hypertrophic Cardiomyopathy	0/7111 (0%)		1/7125 (0%)
Ischaemic Cardiomyopathy	2/7111 (0%)		3/7125 (0%)
Left Ventricular Dysfunction	3/7111 (0%)		2/7125 (0%)
Left Ventricular Failure	11/7111 (0.2%)		12/7125 (0.2%)
Mitral Valve Incompetence	7/7111 (0.1%)		6/7125 (0.1%)
Myocardial Infarction	19/7111 (0.3%)		22/7125 (0.3%)
Myocardial Ischaemia	6/7111 (0.1%)		6/7125 (0.1%)
Myocarditis	0/7111 (0%)		1/7125 (0%)
Nodal Arrhythmia	0/7111 (0%)		2/7125 (0%)
Nodal Rhythm	1/7111 (0%)		0/7125 (0%)
Palpitations	2/7111 (0%)		3/7125 (0%)
Pericardial Effusion	4/7111 (0.1%)		1/7125 (0%)
Pericardial Haemorrhage	0/7111 (0%)		1/7125 (0%)
Pericarditis	1/7111 (0%)		1/7125 (0%)
Right Ventricular Failure	4/7111 (0.1%)		2/7125 (0%)
Sick Sinus Syndrome	37/7111 (0.5%)		25/7125 (0.4%)
Sinus Arrest	3/7111 (0%)		1/7125 (0%)
Sinus Arrhythmia	4/7111 (0.1%)		4/7125 (0.1%)
Sinus Bradycardia	1/7111 (0%)		1/7125 (0%)
Supraventricular Extrasystoles	0/7111 (0%)		1/7125 (0%)
Supraventricular Tachycardia	1/7111 (0%)		1/7125 (0%)
Tachyarrhythmia	10/7111 (0.1%)		3/7125 (0%)
Tachycardia	6/7111 (0.1%)		8/7125 (0.1%)
Tachycardia Paroxysmal	0/7111 (0%)		1/7125 (0%)
Torsade De Pointes	0/7111 (0%)		1/7125 (0%)
Ventricular Arrhythmia	1/7111 (0%)		4/7125 (0.1%)
Ventricular Asystole	0/7111 (0%)		1/7125 (0%)
Ventricular Dysfunction	0/7111 (0%)		1/7125 (0%)
Ventricular Extrasystoles	1/7111 (0%)		3/7125 (0%)
Ventricular Fibrillation	18/7111 (0.3%)		13/7125 (0.2%)
Ventricular Tachyarrhythmia	0/7111 (0%)		1/7125 (0%)
Ventricular Tachycardia	16/7111 (0.2%)		19/7125 (0.3%)
Chronotropic Incompetence	1/7111 (0%)		0/7125 (0%)
Mitral Valve Disease	1/7111 (0%)		0/7125 (0%)
Mitral Valve Stenosis	1/7111 (0%)		0/7125 (0%)
Tricuspid Valve Incompetence	0/7111 (0%)		1/7125 (0%)
Congenital, familial and genetic disorders
Gastrointestinal Angiodysplasia Haemorrhagic	1/7111 (0%)		0/7125 (0%)
Hydrocele	3/7111 (0%)		4/7125 (0.1%)
Pyloric Stenosis	1/7111 (0%)		0/7125 (0%)
Ear and labyrinth disorders
Ear Haemorrhage	2/7111 (0%)		0/7125 (0%)
External Ear Inflammation	0/7111 (0%)		1/7125 (0%)
Inner Ear Disorder	0/7111 (0%)		1/7125 (0%)
Meniere's Disease	1/7111 (0%)		0/7125 (0%)
Sudden Hearing Loss	2/7111 (0%)		2/7125 (0%)
Vertigo	10/7111 (0.1%)		10/7125 (0.1%)
Vertigo Positional	1/7111 (0%)		1/7125 (0%)
Vestibular Disorder	2/7111 (0%)		2/7125 (0%)
External Ear Disorder	0/7111 (0%)		1/7125 (0%)
Endocrine disorders
Cushing's Syndrome	0/7111 (0%)		1/7125 (0%)
Goitre	0/7111 (0%)		1/7125 (0%)
Hyperthyroidism	6/7111 (0.1%)		0/7125 (0%)
Hypothyroidism	1/7111 (0%)		0/7125 (0%)
Primary Hyperaldosteronism	1/7111 (0%)		0/7125 (0%)
Eye disorders
Amaurosis Fugax	1/7111 (0%)		0/7125 (0%)
Angle Closure Glaucoma	1/7111 (0%)		0/7125 (0%)
Cataract	13/7111 (0.2%)		31/7125 (0.4%)
Cataract Diabetic	0/7111 (0%)		1/7125 (0%)
Chorioretinal Atrophy	0/7111 (0%)		1/7125 (0%)
Conjunctival Haemorrhage	1/7111 (0%)		3/7125 (0%)
Dacryostenosis Acquired	1/7111 (0%)		0/7125 (0%)
Diabetic Retinopathy	1/7111 (0%)		0/7125 (0%)
Eye Haemorrhage	4/7111 (0.1%)		2/7125 (0%)
Glaucoma	4/7111 (0.1%)		2/7125 (0%)
Glaucomatocyclitic Crises	1/7111 (0%)		0/7125 (0%)
Hyphaema	0/7111 (0%)		1/7125 (0%)
Keratopathy	0/7111 (0%)		1/7125 (0%)
Macular Degeneration	0/7111 (0%)		1/7125 (0%)
Macular Hole	0/7111 (0%)		1/7125 (0%)
Macular Oedema	1/7111 (0%)		0/7125 (0%)
Open Angle Glaucoma	1/7111 (0%)		0/7125 (0%)
Retinal Artery Thrombosis	0/7111 (0%)		1/7125 (0%)
Retinal Detachment	2/7111 (0%)		5/7125 (0.1%)
Retinal Haemorrhage	2/7111 (0%)		3/7125 (0%)
Retinal Vein Occlusion	1/7111 (0%)		1/7125 (0%)
Retinal Vein Thrombosis	1/7111 (0%)		1/7125 (0%)
Retinopathy Haemorrhagic	0/7111 (0%)		1/7125 (0%)
Retinoschisis	0/7111 (0%)		1/7125 (0%)
Scleral Haemorrhage	1/7111 (0%)		0/7125 (0%)
Strabismus	1/7111 (0%)		0/7125 (0%)
Ulcerative Keratitis	1/7111 (0%)		0/7125 (0%)
Uveitis	0/7111 (0%)		1/7125 (0%)
Vitreous Degeneration	0/7111 (0%)		1/7125 (0%)
Vitreous Haemorrhage	3/7111 (0%)		1/7125 (0%)
Gastrointestinal disorders
Abdominal Adhesions	1/7111 (0%)		0/7125 (0%)
Abdominal Hernia	0/7111 (0%)		2/7125 (0%)
Abdominal Hernia Obstructive	1/7111 (0%)		2/7125 (0%)
Abdominal Mass	0/7111 (0%)		1/7125 (0%)
Abdominal Pain	10/7111 (0.1%)		5/7125 (0.1%)
Abdominal Pain Lower	0/7111 (0%)		1/7125 (0%)
Abdominal Pain Upper	2/7111 (0%)		2/7125 (0%)
Abdominal Strangulated Hernia	0/7111 (0%)		2/7125 (0%)
Abdominal Wall Haematoma	1/7111 (0%)		4/7125 (0.1%)
Acute Abdomen	1/7111 (0%)		2/7125 (0%)
Anal Fistula	1/7111 (0%)		2/7125 (0%)
Anal Haemorrhage	2/7111 (0%)		0/7125 (0%)
Ascites	2/7111 (0%)		4/7125 (0.1%)
Colitis Ischaemic	1/7111 (0%)		1/7125 (0%)
Colitis Ulcerative	1/7111 (0%)		0/7125 (0%)
Colonic Obstruction	0/7111 (0%)		1/7125 (0%)
Colonic Polyp	9/7111 (0.1%)		8/7125 (0.1%)
Constipation	8/7111 (0.1%)		6/7125 (0.1%)
Dental Caries	5/7111 (0.1%)		1/7125 (0%)
Diarrhoea	11/7111 (0.2%)		9/7125 (0.1%)
Diverticular Perforation	1/7111 (0%)		3/7125 (0%)
Diverticulitis Intestinal Haemorrhagic	1/7111 (0%)		0/7125 (0%)
Diverticulum	0/7111 (0%)		1/7125 (0%)
Diverticulum Intestinal	1/7111 (0%)		4/7125 (0.1%)
Diverticulum Intestinal Haemorrhagic	0/7111 (0%)		3/7125 (0%)
Duodenal Polyp	0/7111 (0%)		1/7125 (0%)
Duodenal Ulcer	4/7111 (0.1%)		3/7125 (0%)
Duodenal Ulcer Haemorrhage	4/7111 (0.1%)		4/7125 (0.1%)
Duodenitis	0/7111 (0%)		1/7125 (0%)
Dyspepsia	6/7111 (0.1%)		1/7125 (0%)
Dysphagia	0/7111 (0%)		1/7125 (0%)
Enteritis	1/7111 (0%)		3/7125 (0%)
Enterocolitis	0/7111 (0%)		2/7125 (0%)
Enterocolitis Haemorrhagic	0/7111 (0%)		1/7125 (0%)
Faecaloma	1/7111 (0%)		0/7125 (0%)
Faeces Discoloured	1/7111 (0%)		0/7125 (0%)
Femoral Hernia, Obstructive	0/7111 (0%)		1/7125 (0%)
Food Poisoning	0/7111 (0%)		1/7125 (0%)
Gastric Haemorrhage	9/7111 (0.1%)		7/7125 (0.1%)
Gastric Polyps	4/7111 (0.1%)		0/7125 (0%)
Gastric Ulcer	2/7111 (0%)		4/7125 (0.1%)
Gastric Ulcer Haemorrhage	11/7111 (0.2%)		9/7125 (0.1%)
Gastric Varices	0/7111 (0%)		1/7125 (0%)
Gastric Varices Haemorrhage	1/7111 (0%)		0/7125 (0%)
Gastritis	10/7111 (0.1%)		4/7125 (0.1%)
Gastritis Erosive	2/7111 (0%)		9/7125 (0.1%)
Gastritis Haemorrhagic	7/7111 (0.1%)		1/7125 (0%)
Gastroduodenal Haemorrhage	1/7111 (0%)		0/7125 (0%)
Gastroduodenal Ulcer	1/7111 (0%)		1/7125 (0%)
Gastrointestinal Haemorrhage	88/7111 (1.2%)		62/7125 (0.9%)
Gastrointestinal Ischaemia	1/7111 (0%)		0/7125 (0%)
Gastrointestinal Motility Disorder	1/7111 (0%)		0/7125 (0%)
Gastrointestinal Ulcer	0/7111 (0%)		1/7125 (0%)
Gastrooesophageal Reflux Disease	4/7111 (0.1%)		4/7125 (0.1%)
Gastrooesophagitis	0/7111 (0%)		1/7125 (0%)
Gingival Bleeding	5/7111 (0.1%)		3/7125 (0%)
Haematemesis	3/7111 (0%)		4/7125 (0.1%)
Haematochezia	3/7111 (0%)		4/7125 (0.1%)
Haemorrhagic Erosive Gastritis	4/7111 (0.1%)		5/7125 (0.1%)
Haemorrhoidal Haemorrhage	6/7111 (0.1%)		4/7125 (0.1%)
Haemorrhoids	7/7111 (0.1%)		4/7125 (0.1%)
Hiatus Hernia	1/7111 (0%)		2/7125 (0%)
Ileus	5/7111 (0.1%)		4/7125 (0.1%)
Ileus Paralytic	1/7111 (0%)		0/7125 (0%)
Inflammatory Bowel Disease	0/7111 (0%)		1/7125 (0%)
Inguinal Hernia	29/7111 (0.4%)		21/7125 (0.3%)
Inguinal Hernia Strangulated	1/7111 (0%)		1/7125 (0%)
Inguinal Hernia, Obstructive	3/7111 (0%)		0/7125 (0%)
Intestinal Cyst	0/7111 (0%)		1/7125 (0%)
Intestinal Dilatation	0/7111 (0%)		1/7125 (0%)
Intestinal Haemorrhage	4/7111 (0.1%)		4/7125 (0.1%)
Intestinal Infarction	2/7111 (0%)		3/7125 (0%)
Intestinal Ischaemia	2/7111 (0%)		2/7125 (0%)
Intestinal Obstruction	4/7111 (0.1%)		6/7125 (0.1%)
Intestinal Perforation	1/7111 (0%)		1/7125 (0%)
Intestinal Polyp	2/7111 (0%)		1/7125 (0%)
Intestinal Strangulation	1/7111 (0%)		0/7125 (0%)
Intra-Abdominal Haematoma	0/7111 (0%)		1/7125 (0%)
Intra-Abdominal Haemorrhage	1/7111 (0%)		1/7125 (0%)
Irritable Bowel Syndrome	2/7111 (0%)		2/7125 (0%)
Large Intestinal Haemorrhage	2/7111 (0%)		0/7125 (0%)
Large Intestinal Obstruction	1/7111 (0%)		0/7125 (0%)
Large Intestine Perforation	1/7111 (0%)		1/7125 (0%)
Lower Gastrointestinal Haemorrhage	19/7111 (0.3%)		15/7125 (0.2%)
Lumbar Hernia	1/7111 (0%)		0/7125 (0%)
Mallory-Weiss Syndrome	2/7111 (0%)		0/7125 (0%)
Mechanical Ileus	1/7111 (0%)		1/7125 (0%)
Melaena	29/7111 (0.4%)		18/7125 (0.3%)
Mesenteric Artery Thrombosis	0/7111 (0%)		2/7125 (0%)
Mesenteric Vein Thrombosis	0/7111 (0%)		1/7125 (0%)
Mouth Haemorrhage	2/7111 (0%)		4/7125 (0.1%)
Nausea	3/7111 (0%)		2/7125 (0%)
Oesophageal Disorder	1/7111 (0%)		0/7125 (0%)
Oesophageal Haemorrhage	2/7111 (0%)		0/7125 (0%)
Oesophageal Rupture	1/7111 (0%)		0/7125 (0%)
Oesophageal Spasm	1/7111 (0%)		0/7125 (0%)
Oesophageal Stenosis	0/7111 (0%)		1/7125 (0%)
Oesophageal Ulcer	1/7111 (0%)		1/7125 (0%)
Oesophageal Varices Haemorrhage	1/7111 (0%)		1/7125 (0%)
Oesophagitis Haemorrhagic	1/7111 (0%)		1/7125 (0%)
Pancreatic Cyst	0/7111 (0%)		1/7125 (0%)
Pancreatic Mass	2/7111 (0%)		1/7125 (0%)
Pancreatitis	6/7111 (0.1%)		2/7125 (0%)
Pancreatitis Acute	7/7111 (0.1%)		6/7125 (0.1%)
Pancreatitis Haemorrhagic	0/7111 (0%)		1/7125 (0%)
Pancreatitis Relapsing	0/7111 (0%)		1/7125 (0%)
Peptic Ulcer	2/7111 (0%)		0/7125 (0%)
Peptic Ulcer Haemorrhage	3/7111 (0%)		4/7125 (0.1%)
Peritoneal Necrosis	0/7111 (0%)		1/7125 (0%)
Peritonitis	1/7111 (0%)		1/7125 (0%)
Pneumoperitoneum	0/7111 (0%)		1/7125 (0%)
Rectal Haemorrhage	24/7111 (0.3%)		26/7125 (0.4%)
Rectal Polyp	1/7111 (0%)		2/7125 (0%)
Rectal Ulcer	1/7111 (0%)		0/7125 (0%)
Rectal Ulcer Haemorrhage	0/7111 (0%)		1/7125 (0%)
Regurgitation	0/7111 (0%)		1/7125 (0%)
Retroperitoneal Haematoma	0/7111 (0%)		2/7125 (0%)
Retroperitoneal Haemorrhage	1/7111 (0%)		1/7125 (0%)
Small Intestinal Haemorrhage	0/7111 (0%)		2/7125 (0%)
Small Intestinal Obstruction	2/7111 (0%)		4/7125 (0.1%)
Subileus	1/7111 (0%)		2/7125 (0%)
Tongue Haemorrhage	1/7111 (0%)		0/7125 (0%)
Umbilical Hernia	1/7111 (0%)		3/7125 (0%)
Umbilical Hernia, Obstructive	1/7111 (0%)		0/7125 (0%)
Upper Gastrointestinal Haemorrhage	53/7111 (0.7%)		34/7125 (0.5%)
Varices Oesophageal	1/7111 (0%)		1/7125 (0%)
Volvulus	1/7111 (0%)		1/7125 (0%)
Vomiting	3/7111 (0%)		3/7125 (0%)
Anal Fissure	1/7111 (0%)		0/7125 (0%)
Barrett's Oesophagus	1/7111 (0%)		0/7125 (0%)
Colitis	0/7111 (0%)		1/7125 (0%)
Erosive Oesophagitis	0/7111 (0%)		1/7125 (0%)
Oesophagitis	0/7111 (0%)		1/7125 (0%)
Pancreatitis Chronic	1/7111 (0%)		0/7125 (0%)
Peritoneal Haemorrhage	2/7111 (0%)		0/7125 (0%)
Small Intestinal Perforation	0/7111 (0%)		1/7125 (0%)
General disorders
Asthenia	4/7111 (0.1%)		3/7125 (0%)
Cardiac Death	0/7111 (0%)		2/7125 (0%)
Catheter Site Haemorrhage	1/7111 (0%)		0/7125 (0%)
Chest Discomfort	0/7111 (0%)		4/7125 (0.1%)
Chest Pain	37/7111 (0.5%)		44/7125 (0.6%)
Chills	1/7111 (0%)		0/7125 (0%)
Death	19/7111 (0.3%)		23/7125 (0.3%)
Device Capturing Issue	1/7111 (0%)		0/7125 (0%)
Device Dislocation	2/7111 (0%)		1/7125 (0%)
Device Lead Damage	1/7111 (0%)		0/7125 (0%)
Device Malfunction	6/7111 (0.1%)		5/7125 (0.1%)
Device Occlusion	4/7111 (0.1%)		0/7125 (0%)
Device Power Source Issue	1/7111 (0%)		1/7125 (0%)
Gait Disturbance	1/7111 (0%)		1/7125 (0%)
General Physical Health Deterioration	0/7111 (0%)		3/7125 (0%)
Generalised Oedema	3/7111 (0%)		1/7125 (0%)
Hernia	0/7111 (0%)		2/7125 (0%)
Hernia Pain	1/7111 (0%)		0/7125 (0%)
Hyperthermia	0/7111 (0%)		1/7125 (0%)
Impaired Healing	1/7111 (0%)		1/7125 (0%)
Implant Site Haemorrhage	0/7111 (0%)		1/7125 (0%)
Implant Site Reaction	0/7111 (0%)		1/7125 (0%)
Injury Associated with Device	0/7111 (0%)		1/7125 (0%)
Malaise	0/7111 (0%)		3/7125 (0%)
Medical Device Complication	2/7111 (0%)		1/7125 (0%)
Multi-Organ Failure	10/7111 (0.1%)		6/7125 (0.1%)
Non-Cardiac Chest Pain	15/7111 (0.2%)		16/7125 (0.2%)
Oedema	0/7111 (0%)		1/7125 (0%)
Oedema Peripheral	5/7111 (0.1%)		4/7125 (0.1%)
Pelvic Mass	0/7111 (0%)		1/7125 (0%)
Pyrexia	3/7111 (0%)		6/7125 (0.1%)
Sudden Cardiac Death	12/7111 (0.2%)		13/7125 (0.2%)
Sudden Death	80/7111 (1.1%)		68/7125 (1%)
Systemic Inflammatory Response Syndrome	1/7111 (0%)		0/7125 (0%)
Thrombosis in Device	0/7111 (0%)		1/7125 (0%)
Vessel Puncture Site Haemorrhage	1/7111 (0%)		0/7125 (0%)
Feeling Abnormal	0/7111 (0%)		1/7125 (0%)
Implant Site Effusion	1/7111 (0%)		0/7125 (0%)
Mucosal Inflammation	1/7111 (0%)		0/7125 (0%)
Hepatobiliary disorders
Bile Duct Obstruction	2/7111 (0%)		1/7125 (0%)
Bile Duct Stone	5/7111 (0.1%)		7/7125 (0.1%)
Biliary Colic	2/7111 (0%)		2/7125 (0%)
Cardiac Cirrhosis	2/7111 (0%)		1/7125 (0%)
Cholangitis	7/7111 (0.1%)		2/7125 (0%)
Cholangitis Acute	1/7111 (0%)		0/7125 (0%)
Cholangitis Sclerosing	0/7111 (0%)		1/7125 (0%)
Cholecystitis	9/7111 (0.1%)		13/7125 (0.2%)
Cholecystitis Acute	23/7111 (0.3%)		15/7125 (0.2%)
Cholecystitis Chronic	6/7111 (0.1%)		0/7125 (0%)
Cholelithiasis	20/7111 (0.3%)		16/7125 (0.2%)
Cholelithiasis Obstructive	0/7111 (0%)		1/7125 (0%)
Cryptogenic Cirrhosis	0/7111 (0%)		2/7125 (0%)
Cytolytic Hepatitis	2/7111 (0%)		0/7125 (0%)
Gallbladder Fistula	1/7111 (0%)		0/7125 (0%)
Hepatic Cirrhosis	3/7111 (0%)		2/7125 (0%)
Hepatic Congestion	1/7111 (0%)		0/7125 (0%)
Hepatic Failure	0/7111 (0%)		1/7125 (0%)
Hepatic Function Abnormal	1/7111 (0%)		0/7125 (0%)
Hepatic Haemorrhage	1/7111 (0%)		0/7125 (0%)
Hepatic Steatosis	2/7111 (0%)		2/7125 (0%)
Hepatitis	1/7111 (0%)		1/7125 (0%)
Hepatitis Acute	1/7111 (0%)		1/7125 (0%)
Ischaemic Hepatitis	1/7111 (0%)		3/7125 (0%)
Jaundice	0/7111 (0%)		2/7125 (0%)
Jaundice Cholestatic	1/7111 (0%)		2/7125 (0%)
Jaundice Hepatocellular	0/7111 (0%)		1/7125 (0%)
Liver Disorder	1/7111 (0%)		0/7125 (0%)
Portal Vein Thrombosis	1/7111 (0%)		0/7125 (0%)
Acute Hepatic Failure	0/7111 (0%)		1/7125 (0%)
Cholestasis	0/7111 (0%)		1/7125 (0%)
Haemorrhagic Hepatic Cyst	0/7111 (0%)		1/7125 (0%)
Immune system disorders
Anaphylactic Reaction	1/7111 (0%)		0/7125 (0%)
Anaphylactic Shock	1/7111 (0%)		0/7125 (0%)
Drug Hypersensitivity	2/7111 (0%)		1/7125 (0%)
Hypersensitivity	3/7111 (0%)		0/7125 (0%)
Skin Graft Rejection	0/7111 (0%)		1/7125 (0%)
Infections and infestations
Abdominal Abscess	2/7111 (0%)		1/7125 (0%)
Abscess	0/7111 (0%)		1/7125 (0%)
Abscess Limb	1/7111 (0%)		1/7125 (0%)
Abscess Neck	1/7111 (0%)		0/7125 (0%)
Abscess of External Auditory Meatus	0/7111 (0%)		1/7125 (0%)
Amoebiasis	1/7111 (0%)		0/7125 (0%)
Amoebic Dysentery	1/7111 (0%)		0/7125 (0%)
Anal Abscess	3/7111 (0%)		0/7125 (0%)
Appendiceal Abscess	0/7111 (0%)		1/7125 (0%)
Appendicitis	12/7111 (0.2%)		7/7125 (0.1%)
Appendicitis Perforated	2/7111 (0%)		1/7125 (0%)
Arthritis Bacterial	2/7111 (0%)		1/7125 (0%)
Arthritis Infective	2/7111 (0%)		1/7125 (0%)
Bacteraemia	2/7111 (0%)		2/7125 (0%)
Bacterial Infection	0/7111 (0%)		1/7125 (0%)
Bacterial Pyelonephritis	0/7111 (0%)		1/7125 (0%)
Bacterial Sepsis	1/7111 (0%)		0/7125 (0%)
Blister Infected	1/7111 (0%)		0/7125 (0%)
Breast Cellulitis	1/7111 (0%)		0/7125 (0%)
Bronchiectasis	2/7111 (0%)		1/7125 (0%)
Bronchitis	38/7111 (0.5%)		32/7125 (0.4%)
Bronchitis Bacterial	1/7111 (0%)		1/7125 (0%)
Bronchitis Viral	1/7111 (0%)		0/7125 (0%)
Bronchopneumonia	11/7111 (0.2%)		12/7125 (0.2%)
Bursitis Infective Staphylococcal	1/7111 (0%)		0/7125 (0%)
Cellulitis	42/7111 (0.6%)		64/7125 (0.9%)
Cellulitis Pharyngeal	1/7111 (0%)		0/7125 (0%)
Cellulitis of Male External Genital Organ	1/7111 (0%)		0/7125 (0%)
Cervicitis	0/7111 (0%)		1/7125 (0%)
Cholecystitis Infective	2/7111 (0%)		1/7125 (0%)
Clostridial Infection	1/7111 (0%)		0/7125 (0%)
Cystitis	2/7111 (0%)		1/7125 (0%)
Dengue Fever	0/7111 (0%)		4/7125 (0.1%)
Device Related Infection	3/7111 (0%)		1/7125 (0%)
Diabetic Foot Infection	2/7111 (0%)		0/7125 (0%)
Diabetic Gangrene	0/7111 (0%)		2/7125 (0%)
Diarrhoea Infectious	0/7111 (0%)		1/7125 (0%)
Diverticulitis	7/7111 (0.1%)		10/7125 (0.1%)
Ear Infection	0/7111 (0%)		1/7125 (0%)
Empyema	0/7111 (0%)		1/7125 (0%)
Encephalitis Herpes	1/7111 (0%)		0/7125 (0%)
Endocarditis	3/7111 (0%)		0/7125 (0%)
Endocarditis Bacterial	1/7111 (0%)		0/7125 (0%)
Enterococcal Bacteraemia	0/7111 (0%)		1/7125 (0%)
Erysipelas	17/7111 (0.2%)		15/7125 (0.2%)
Escherichia Urinary Tract Infection	0/7111 (0%)		1/7125 (0%)
Extradural Abscess	1/7111 (0%)		0/7125 (0%)
Furuncle	0/7111 (0%)		1/7125 (0%)
Gangrene	4/7111 (0.1%)		5/7125 (0.1%)
Gastroenteritis	18/7111 (0.3%)		38/7125 (0.5%)
Gastroenteritis Norovirus	1/7111 (0%)		1/7125 (0%)
Gastroenteritis Salmonella	1/7111 (0%)		0/7125 (0%)
Gastroenteritis Viral	1/7111 (0%)		0/7125 (0%)
Gastrointestinal Infection	0/7111 (0%)		1/7125 (0%)
Groin Abscess	0/7111 (0%)		1/7125 (0%)
Haematoma Infection	1/7111 (0%)		1/7125 (0%)
Helicobacter Gastritis	2/7111 (0%)		1/7125 (0%)
Hepatitis B	1/7111 (0%)		2/7125 (0%)
Hepatitis C	3/7111 (0%)		5/7125 (0.1%)
Hepatitis E	1/7111 (0%)		0/7125 (0%)
Hepatitis Viral	0/7111 (0%)		1/7125 (0%)
Herpes Zoster	6/7111 (0.1%)		6/7125 (0.1%)
Herpes Zoster Ophthalmic	0/7111 (0%)		1/7125 (0%)
Herpes Zoster Oticus	1/7111 (0%)		0/7125 (0%)
Implant Site Infection	3/7111 (0%)		2/7125 (0%)
Incision Site Abscess	1/7111 (0%)		0/7125 (0%)
Infected Epidermal Cyst	0/7111 (0%)		1/7125 (0%)
Infected Sebaceous Cyst	0/7111 (0%)		1/7125 (0%)
Infected Skin Ulcer	3/7111 (0%)		1/7125 (0%)
Infection	2/7111 (0%)		1/7125 (0%)
Infective Exacerbation of Chronic Obstructive Airways Disease	1/7111 (0%)		2/7125 (0%)
Influenza	5/7111 (0.1%)		3/7125 (0%)
Infusion Site Infection	1/7111 (0%)		0/7125 (0%)
Intertrigo Candida	0/7111 (0%)		1/7125 (0%)
Intervertebral Discitis	1/7111 (0%)		0/7125 (0%)
Kidney Infection	0/7111 (0%)		2/7125 (0%)
Labyrinthitis	2/7111 (0%)		1/7125 (0%)
Laryngitis Bacterial	0/7111 (0%)		1/7125 (0%)
Leptospirosis	0/7111 (0%)		1/7125 (0%)
Liver Abscess	1/7111 (0%)		0/7125 (0%)
Lobar Pneumonia	16/7111 (0.2%)		13/7125 (0.2%)
Localised Infection	3/7111 (0%)		2/7125 (0%)
Lower Respiratory Tract Infection	4/7111 (0.1%)		4/7125 (0.1%)
Lower Respiratory Tract Infection Viral	1/7111 (0%)		0/7125 (0%)
Lung Infection	13/7111 (0.2%)		7/7125 (0.1%)
Lung Infection Pseudomonal	1/7111 (0%)		0/7125 (0%)
Lyme Disease	1/7111 (0%)		0/7125 (0%)
Malaria	1/7111 (0%)		0/7125 (0%)
Meningitis	0/7111 (0%)		1/7125 (0%)
Meningitis Bacterial	1/7111 (0%)		0/7125 (0%)
Meningitis Pneumococcal	1/7111 (0%)		0/7125 (0%)
Meningitis Viral	0/7111 (0%)		1/7125 (0%)
Nasal Abscess	0/7111 (0%)		1/7125 (0%)
Neuroborreliosis	1/7111 (0%)		0/7125 (0%)
Oesophageal Candidiasis	0/7111 (0%)		1/7125 (0%)
Orchitis	3/7111 (0%)		1/7125 (0%)
Osteomyelitis	6/7111 (0.1%)		4/7125 (0.1%)
Otitis Externa	2/7111 (0%)		0/7125 (0%)
Otitis Media	1/7111 (0%)		1/7125 (0%)
Otitis Media Chronic	0/7111 (0%)		1/7125 (0%)
Paronychia	1/7111 (0%)		1/7125 (0%)
Parotitis	0/7111 (0%)		1/7125 (0%)
Pelvic Abscess	1/7111 (0%)		0/7125 (0%)
Peridiverticular Abscess	0/7111 (0%)		1/7125 (0%)
Perihepatic Abscess	1/7111 (0%)		0/7125 (0%)
Perirectal Abscess	1/7111 (0%)		0/7125 (0%)
Peritoneal Abscess	1/7111 (0%)		0/7125 (0%)
Peritonsillar Abscess	2/7111 (0%)		0/7125 (0%)
Periumbilical Abscess	0/7111 (0%)		1/7125 (0%)
Pharyngitis	1/7111 (0%)		1/7125 (0%)
Pneumococcal Sepsis	0/7111 (0%)		1/7125 (0%)
Pneumonia	157/7111 (2.2%)		197/7125 (2.8%)
Pneumonia Bacterial	5/7111 (0.1%)		6/7125 (0.1%)
Pneumonia Pneumococcal	1/7111 (0%)		0/7125 (0%)
Pneumonia Staphylococcal	1/7111 (0%)		0/7125 (0%)
Post Procedural Cellulitis	1/7111 (0%)		0/7125 (0%)
Post Procedural Infection	5/7111 (0.1%)		2/7125 (0%)
Postoperative Wound Infection	5/7111 (0.1%)		2/7125 (0%)
Pulmonary Tuberculosis	0/7111 (0%)		2/7125 (0%)
Pyelonephritis	3/7111 (0%)		4/7125 (0.1%)
Pyelonephritis Acute	4/7111 (0.1%)		4/7125 (0.1%)
Pyelonephritis Chronic	0/7111 (0%)		1/7125 (0%)
Pyoderma	1/7111 (0%)		0/7125 (0%)
Pyothorax	0/7111 (0%)		1/7125 (0%)
Rectal Abscess	0/7111 (0%)		1/7125 (0%)
Respiratory Tract Infection	8/7111 (0.1%)		9/7125 (0.1%)
Salmonellosis	0/7111 (0%)		2/7125 (0%)
Scrotal Infection	1/7111 (0%)		0/7125 (0%)
Sepsis	28/7111 (0.4%)		29/7125 (0.4%)
Septic Shock	11/7111 (0.2%)		7/7125 (0.1%)
Sialoadenitis	1/7111 (0%)		0/7125 (0%)
Skin Bacterial Infection	0/7111 (0%)		1/7125 (0%)
Staphylococcal Bacteraemia	1/7111 (0%)		1/7125 (0%)
Staphylococcal Infection	1/7111 (0%)		3/7125 (0%)
Streptococcal Bacteraemia	0/7111 (0%)		2/7125 (0%)
Streptococcal Sepsis	1/7111 (0%)		0/7125 (0%)
Subacute Endocarditis	1/7111 (0%)		0/7125 (0%)
Subcutaneous Abscess	1/7111 (0%)		3/7125 (0%)
Syphilis	0/7111 (0%)		1/7125 (0%)
Tooth Abscess	1/7111 (0%)		1/7125 (0%)
Tracheobronchitis	1/7111 (0%)		4/7125 (0.1%)
Tuberculosis	0/7111 (0%)		1/7125 (0%)
Tuberculous Pleurisy	0/7111 (0%)		1/7125 (0%)
Upper Respiratory Tract Infection	7/7111 (0.1%)		12/7125 (0.2%)
Urinary Tract Infection	35/7111 (0.5%)		47/7125 (0.7%)
Urinary Tract Infection Bacterial	0/7111 (0%)		1/7125 (0%)
Urinary Tract Infection Staphylococcal	2/7111 (0%)		0/7125 (0%)
Urosepsis	8/7111 (0.1%)		11/7125 (0.2%)
Varicella	0/7111 (0%)		1/7125 (0%)
Vestibular Neuronitis	1/7111 (0%)		0/7125 (0%)
Viral Infection	2/7111 (0%)		2/7125 (0%)
Viral Labyrinthitis	1/7111 (0%)		0/7125 (0%)
West Nile Viral Infection	0/7111 (0%)		1/7125 (0%)
Wound Infection	3/7111 (0%)		5/7125 (0.1%)
Wound Sepsis	1/7111 (0%)		0/7125 (0%)
Clostridium Difficile Colitis	0/7111 (0%)		1/7125 (0%)
Febrile Infection	0/7111 (0%)		1/7125 (0%)
Haemophilus Infection	1/7111 (0%)		0/7125 (0%)
Mediastinitis	0/7111 (0%)		1/7125 (0%)
Necrotising Fasciitis	0/7111 (0%)		1/7125 (0%)
Neutropenic Sepsis	0/7111 (0%)		1/7125 (0%)
Pharyngeal Abscess	0/7111 (0%)		1/7125 (0%)
Pseudomembranous Colitis	1/7111 (0%)		0/7125 (0%)
Respiratory Tract Infection Bacterial	0/7111 (0%)		1/7125 (0%)
Sepsis Syndrome	0/7111 (0%)		1/7125 (0%)
Injury, poisoning and procedural complications
Accident	0/7111 (0%)		1/7125 (0%)
Accidental Overdose	2/7111 (0%)		1/7125 (0%)
Alcohol Poisoning	0/7111 (0%)		1/7125 (0%)
Ankle Fracture	5/7111 (0.1%)		6/7125 (0.1%)
Avulsion Fracture	1/7111 (0%)		0/7125 (0%)
Back Injury	0/7111 (0%)		1/7125 (0%)
Brain Contusion	0/7111 (0%)		1/7125 (0%)
Burns Third Degree	1/7111 (0%)		1/7125 (0%)
Carbon Monoxide Poisoning	1/7111 (0%)		1/7125 (0%)
Cardiac Valve Rupture	0/7111 (0%)		1/7125 (0%)
Cervical Vertebral Fracture	1/7111 (0%)		2/7125 (0%)
Chest Injury	2/7111 (0%)		2/7125 (0%)
Clavicle Fracture	0/7111 (0%)		2/7125 (0%)
Compression Fracture	0/7111 (0%)		2/7125 (0%)
Concussion	2/7111 (0%)		6/7125 (0.1%)
Contusion	4/7111 (0.1%)		6/7125 (0.1%)
Drug Toxicity	0/7111 (0%)		1/7125 (0%)
Extradural Haematoma	1/7111 (0%)		1/7125 (0%)
Face Injury	0/7111 (0%)		2/7125 (0%)
Facial Bones Fracture	2/7111 (0%)		1/7125 (0%)
Fall	15/7111 (0.2%)		11/7125 (0.2%)
Femoral Neck Fracture	10/7111 (0.1%)		15/7125 (0.2%)
Femur Fracture	10/7111 (0.1%)		14/7125 (0.2%)
Fibula Fracture	2/7111 (0%)		0/7125 (0%)
Foot Fracture	2/7111 (0%)		1/7125 (0%)
Fracture	0/7111 (0%)		1/7125 (0%)
Gun Shot Wound	0/7111 (0%)		1/7125 (0%)
Hand Fracture	1/7111 (0%)		1/7125 (0%)
Head Injury	8/7111 (0.1%)		6/7125 (0.1%)
Hip Fracture	15/7111 (0.2%)		16/7125 (0.2%)
Humerus Fracture	7/7111 (0.1%)		5/7125 (0.1%)
In-Stent Coronary Artery Restenosis	1/7111 (0%)		3/7125 (0%)
Incision Site Haemorrhage	1/7111 (0%)		1/7125 (0%)
Incisional Hernia	2/7111 (0%)		2/7125 (0%)
Injury	1/7111 (0%)		1/7125 (0%)
Joint Dislocation	5/7111 (0.1%)		2/7125 (0%)
Joint Injury	0/7111 (0%)		3/7125 (0%)
Limb Injury	1/7111 (0%)		0/7125 (0%)
Lower Limb Fracture	2/7111 (0%)		2/7125 (0%)
Lumbar Vertebral Fracture	2/7111 (0%)		2/7125 (0%)
Meniscus Lesion	1/7111 (0%)		0/7125 (0%)
Multiple Fractures	0/7111 (0%)		1/7125 (0%)
Multiple Injuries	3/7111 (0%)		0/7125 (0%)
Muscle Rupture	1/7111 (0%)		3/7125 (0%)
Muscle Strain	1/7111 (0%)		1/7125 (0%)
Neck Injury	1/7111 (0%)		0/7125 (0%)
Operative Haemorrhage	1/7111 (0%)		9/7125 (0.1%)
Overdose	4/7111 (0.1%)		0/7125 (0%)
Patella Fracture	0/7111 (0%)		2/7125 (0%)
Pelvic Fracture	3/7111 (0%)		3/7125 (0%)
Periorbital Haematoma	1/7111 (0%)		0/7125 (0%)
Post Procedural Haematoma	2/7111 (0%)		2/7125 (0%)
Post Procedural Haemorrhage	11/7111 (0.2%)		10/7125 (0.1%)
Postoperative Respiratory Distress	0/7111 (0%)		1/7125 (0%)
Postoperative Wound Complication	0/7111 (0%)		1/7125 (0%)
Procedural Complication	1/7111 (0%)		0/7125 (0%)
Pubis Fracture	0/7111 (0%)		4/7125 (0.1%)
Radius Fracture	3/7111 (0%)		2/7125 (0%)
Rib Fracture	6/7111 (0.1%)		12/7125 (0.2%)
Road Traffic Accident	0/7111 (0%)		1/7125 (0%)
Seroma	1/7111 (0%)		0/7125 (0%)
Skeletal Injury	2/7111 (0%)		0/7125 (0%)
Skin Injury	0/7111 (0%)		1/7125 (0%)
Skin Laceration	1/7111 (0%)		4/7125 (0.1%)
Skull Fractured Base	0/7111 (0%)		1/7125 (0%)
Soft Tissue Injury	0/7111 (0%)		1/7125 (0%)
Spinal Column Injury	0/7111 (0%)		1/7125 (0%)
Spinal Compression Fracture	3/7111 (0%)		6/7125 (0.1%)
Spinal Fracture	1/7111 (0%)		2/7125 (0%)
Splenic Rupture	0/7111 (0%)		2/7125 (0%)
Subcutaneous Haematoma	2/7111 (0%)		2/7125 (0%)
Subdural Haematoma	15/7111 (0.2%)		16/7125 (0.2%)
Subdural Haemorrhage	2/7111 (0%)		6/7125 (0.1%)
Tendon Rupture	2/7111 (0%)		0/7125 (0%)
Therapeutic Agent Toxicity	8/7111 (0.1%)		4/7125 (0.1%)
Thoracic Vertebral Fracture	1/7111 (0%)		2/7125 (0%)
Tibia Fracture	0/7111 (0%)		4/7125 (0.1%)
Traumatic Brain Injury	3/7111 (0%)		3/7125 (0%)
Traumatic Fracture	1/7111 (0%)		0/7125 (0%)
Traumatic Haematoma	2/7111 (0%)		2/7125 (0%)
Traumatic Haemorrhage	1/7111 (0%)		0/7125 (0%)
Traumatic Intracranial Haemorrhage	0/7111 (0%)		1/7125 (0%)
Upper Limb Fracture	3/7111 (0%)		5/7125 (0.1%)
Vascular Graft Occlusion	0/7111 (0%)		1/7125 (0%)
Vascular Pseudoaneurysm	1/7111 (0%)		0/7125 (0%)
Wound Dehiscence	2/7111 (0%)		0/7125 (0%)
Wound Haemorrhage	3/7111 (0%)		6/7125 (0.1%)
Wrist Fracture	1/7111 (0%)		2/7125 (0%)
Cardiac Function Disturbance Postoperative	1/7111 (0%)		0/7125 (0%)
Eschar	1/7111 (0%)		0/7125 (0%)
Foreign Body	0/7111 (0%)		1/7125 (0%)
Nerve Injury	0/7111 (0%)		1/7125 (0%)
Traumatic Lung Injury	0/7111 (0%)		1/7125 (0%)
Venous Injury	1/7111 (0%)		0/7125 (0%)
Investigations
Alanine Aminotransferase Increased	7/7111 (0.1%)		2/7125 (0%)
Arteriogram	1/7111 (0%)		0/7125 (0%)
Arteriogram Coronary	0/7111 (0%)		3/7125 (0%)
Aspartate Aminotransferase Increased	5/7111 (0.1%)		1/7125 (0%)
Bilirubin Conjugated Increased	2/7111 (0%)		0/7125 (0%)
Blood Alkaline Phosphatase Increased	1/7111 (0%)		0/7125 (0%)
Blood Amylase Increased	0/7111 (0%)		1/7125 (0%)
Blood Bilirubin Increased	4/7111 (0.1%)		1/7125 (0%)
Blood Creatinine Increased	0/7111 (0%)		1/7125 (0%)
Blood Glucose Increased	1/7111 (0%)		1/7125 (0%)
Blood Potassium Decreased	0/7111 (0%)		1/7125 (0%)
Blood Pressure Increased	2/7111 (0%)		4/7125 (0.1%)
C-Reactive Protein Increased	0/7111 (0%)		1/7125 (0%)
Chest X-Ray Abnormal	0/7111 (0%)		1/7125 (0%)
Coagulation Time Prolonged	0/7111 (0%)		1/7125 (0%)
Dexamethasone Suppression Test Positive	0/7111 (0%)		1/7125 (0%)
Ejection Fraction Decreased	1/7111 (0%)		0/7125 (0%)
Haemoglobin Decreased	1/7111 (0%)		1/7125 (0%)
Heart Rate Decreased	1/7111 (0%)		1/7125 (0%)
Heart Rate Increased	0/7111 (0%)		1/7125 (0%)
Heart Rate Irregular	1/7111 (0%)		0/7125 (0%)
Hepatic Enzyme Abnormal	0/7111 (0%)		2/7125 (0%)
Hepatic Enzyme Increased	8/7111 (0.1%)		13/7125 (0.2%)
International Normalised Ratio Abnormal	0/7111 (0%)		2/7125 (0%)
International Normalised Ratio Increased	16/7111 (0.2%)		23/7125 (0.3%)
Intraocular Pressure Increased	1/7111 (0%)		0/7125 (0%)
Laboratory Test Interference	0/7111 (0%)		1/7125 (0%)
Lipase Increased	1/7111 (0%)		0/7125 (0%)
Liver Function Test Abnormal	10/7111 (0.1%)		14/7125 (0.2%)
Occult Blood	1/7111 (0%)		2/7125 (0%)
Occult Blood Positive	1/7111 (0%)		1/7125 (0%)
Pancreatic Enzymes Increased	0/7111 (0%)		1/7125 (0%)
Transaminases Increased	1/7111 (0%)		2/7125 (0%)
Weight Decreased	1/7111 (0%)		0/7125 (0%)
Aspiration Bronchial	0/7111 (0%)		1/7125 (0%)
Prothrombin Level Decreased	0/7111 (0%)		1/7125 (0%)
Prothrombin Time Prolonged	1/7111 (0%)		0/7125 (0%)
Metabolism and nutrition disorders
Cachexia	1/7111 (0%)		0/7125 (0%)
Decreased Appetite	1/7111 (0%)		1/7125 (0%)
Dehydration	18/7111 (0.3%)		16/7125 (0.2%)
Diabetes Mellitus	32/7111 (0.5%)		23/7125 (0.3%)
Diabetes Mellitus Inadequate Control	9/7111 (0.1%)		8/7125 (0.1%)
Diabetic Foot	5/7111 (0.1%)		4/7125 (0.1%)
Diabetic Ketoacidosis	0/7111 (0%)		2/7125 (0%)
Electrolyte Imbalance	1/7111 (0%)		0/7125 (0%)
Gout	6/7111 (0.1%)		4/7125 (0.1%)
Haemochromatosis	1/7111 (0%)		0/7125 (0%)
Hypercalcaemia	1/7111 (0%)		1/7125 (0%)
Hyperglycaemia	10/7111 (0.1%)		7/7125 (0.1%)
Hyperkalaemia	2/7111 (0%)		3/7125 (0%)
Hyperosmolar State	0/7111 (0%)		1/7125 (0%)
Hypocalcaemia	2/7111 (0%)		0/7125 (0%)
Hypoglycaemia	19/7111 (0.3%)		14/7125 (0.2%)
Hypokalaemia	5/7111 (0.1%)		8/7125 (0.1%)
Hypomagnesaemia	0/7111 (0%)		1/7125 (0%)
Hyponatraemia	5/7111 (0.1%)		6/7125 (0.1%)
Hypoproteinaemia	0/7111 (0%)		1/7125 (0%)
Hypovolaemia	0/7111 (0%)		3/7125 (0%)
Neuroglycopenia	0/7111 (0%)		1/7125 (0%)
Obesity	0/7111 (0%)		1/7125 (0%)
Podagra	0/7111 (0%)		1/7125 (0%)
Shock Hypoglycaemic	0/7111 (0%)		2/7125 (0%)
Type 1 Diabetes Mellitus	1/7111 (0%)		0/7125 (0%)
Type 2 Diabetes Mellitus	6/7111 (0.1%)		5/7125 (0.1%)
Vitamin B12 Deficiency	0/7111 (0%)		2/7125 (0%)
Failure to Thrive	1/7111 (0%)		0/7125 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/7111 (0.1%)		5/7125 (0.1%)
Arthritis	4/7111 (0.1%)		3/7125 (0%)
Back Pain	15/7111 (0.2%)		13/7125 (0.2%)
Bone Pain	1/7111 (0%)		1/7125 (0%)
Bursitis	0/7111 (0%)		2/7125 (0%)
Coccydynia	0/7111 (0%)		1/7125 (0%)
Compartment Syndrome	1/7111 (0%)		0/7125 (0%)
Costochondritis	1/7111 (0%)		3/7125 (0%)
Dupuytren's Contracture	1/7111 (0%)		0/7125 (0%)
Fracture Nonunion	2/7111 (0%)		0/7125 (0%)
Gouty Arthritis	3/7111 (0%)		4/7125 (0.1%)
Groin Pain	0/7111 (0%)		1/7125 (0%)
Haemarthrosis	9/7111 (0.1%)		10/7125 (0.1%)
Inguinal Mass	0/7111 (0%)		1/7125 (0%)
Intervertebral Disc Degeneration	2/7111 (0%)		1/7125 (0%)
Intervertebral Disc Disorder	0/7111 (0%)		2/7125 (0%)
Intervertebral Disc Protrusion	5/7111 (0.1%)		4/7125 (0.1%)
Jaw Cyst	0/7111 (0%)		1/7125 (0%)
Joint Effusion	1/7111 (0%)		1/7125 (0%)
Joint Range of Motion Decreased	1/7111 (0%)		0/7125 (0%)
Knee Deformity	1/7111 (0%)		0/7125 (0%)
Lumbar Spinal Stenosis	0/7111 (0%)		2/7125 (0%)
Mobility Decreased	0/7111 (0%)		2/7125 (0%)
Monarthritis	0/7111 (0%)		1/7125 (0%)
Muscle Atrophy	0/7111 (0%)		1/7125 (0%)
Muscle Haemorrhage	2/7111 (0%)		2/7125 (0%)
Muscle Spasms	1/7111 (0%)		1/7125 (0%)
Muscular Weakness	0/7111 (0%)		1/7125 (0%)
Musculoskeletal Chest Pain	9/7111 (0.1%)		5/7125 (0.1%)
Musculoskeletal Pain	2/7111 (0%)		0/7125 (0%)
Myalgia	3/7111 (0%)		1/7125 (0%)
Neck Pain	4/7111 (0.1%)		1/7125 (0%)
Neuropathic Arthropathy	0/7111 (0%)		1/7125 (0%)
Osteitis	0/7111 (0%)		1/7125 (0%)
Osteoarthritis	29/7111 (0.4%)		48/7125 (0.7%)
Osteochondrosis	1/7111 (0%)		0/7125 (0%)
Osteoporosis	1/7111 (0%)		0/7125 (0%)
Pathological Fracture	0/7111 (0%)		2/7125 (0%)
Periarthritis	1/7111 (0%)		0/7125 (0%)
Periostitis	1/7111 (0%)		0/7125 (0%)
Polyarthritis	0/7111 (0%)		4/7125 (0.1%)
Polymyalgia Rheumatica	0/7111 (0%)		2/7125 (0%)
Psoriatic Arthropathy	0/7111 (0%)		1/7125 (0%)
Rhabdomyolysis	0/7111 (0%)		2/7125 (0%)
Rheumatoid Arthritis	1/7111 (0%)		2/7125 (0%)
Rotator Cuff Syndrome	2/7111 (0%)		2/7125 (0%)
Soft Tissue Haemorrhage	0/7111 (0%)		1/7125 (0%)
Spinal Column Stenosis	3/7111 (0%)		3/7125 (0%)
Spinal Disorder	1/7111 (0%)		1/7125 (0%)
Spinal Osteoarthritis	4/7111 (0.1%)		5/7125 (0.1%)
Spondylolisthesis	0/7111 (0%)		2/7125 (0%)
Sympathetic Posterior Cervical Syndrome	0/7111 (0%)		1/7125 (0%)
Synovial Cyst	2/7111 (0%)		0/7125 (0%)
Systemic Lupus Erythematosus	0/7111 (0%)		2/7125 (0%)
Tendonitis	0/7111 (0%)		1/7125 (0%)
Tenosynovitis	0/7111 (0%)		1/7125 (0%)
Trismus	1/7111 (0%)		0/7125 (0%)
Arthropathy	0/7111 (0%)		1/7125 (0%)
Fistula	1/7111 (0%)		0/7125 (0%)
Pain in Extremity	1/7111 (0%)		1/7125 (0%)
Trigger Finger	0/7111 (0%)		1/7125 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	3/7111 (0%)		1/7125 (0%)
Adrenal Adenoma	0/7111 (0%)		1/7125 (0%)
B-Cell Lymphoma	1/7111 (0%)		3/7125 (0%)
Basal Cell Carcinoma	5/7111 (0.1%)		8/7125 (0.1%)
Benign Colonic Neoplasm	1/7111 (0%)		0/7125 (0%)
Benign Neoplasm of Bladder	0/7111 (0%)		1/7125 (0%)
Benign Neoplasm of Prostate	1/7111 (0%)		0/7125 (0%)
Bile Duct Cancer	2/7111 (0%)		1/7125 (0%)
Bladder Cancer	2/7111 (0%)		4/7125 (0.1%)
Bladder Neoplasm	6/7111 (0.1%)		5/7125 (0.1%)
Bladder Papilloma	0/7111 (0%)		1/7125 (0%)
Bladder Transitional Cell Carcinoma	2/7111 (0%)		0/7125 (0%)
Bone Sarcoma	1/7111 (0%)		0/7125 (0%)
Bowen's Disease	2/7111 (0%)		0/7125 (0%)
Brain Cancer Metastatic	1/7111 (0%)		0/7125 (0%)
Brain Neoplasm	2/7111 (0%)		2/7125 (0%)
Brain Neoplasm Benign	0/7111 (0%)		1/7125 (0%)
Breast Cancer	13/7111 (0.2%)		15/7125 (0.2%)
Breast Cancer Metastatic	1/7111 (0%)		0/7125 (0%)
Breast Cancer in Situ	1/7111 (0%)		0/7125 (0%)
Breast Neoplasm	0/7111 (0%)		2/7125 (0%)
Bronchial Carcinoma	0/7111 (0%)		1/7125 (0%)
Cervix Carcinoma	1/7111 (0%)		1/7125 (0%)
Colon Adenoma	2/7111 (0%)		0/7125 (0%)
Colon Cancer	21/7111 (0.3%)		14/7125 (0.2%)
Colon Cancer Metastatic	3/7111 (0%)		8/7125 (0.1%)
Colon Cancer Recurrent	0/7111 (0%)		1/7125 (0%)
Colon Cancer Stage Iii	1/7111 (0%)		0/7125 (0%)
Colon Neoplasm	3/7111 (0%)		1/7125 (0%)
Colorectal Cancer	0/7111 (0%)		5/7125 (0.1%)
Endometrial Cancer	7/7111 (0.1%)		0/7125 (0%)
Endometrial Cancer Metastatic	1/7111 (0%)		0/7125 (0%)
Epiglottic Carcinoma	1/7111 (0%)		0/7125 (0%)
Gallbladder Cancer	0/7111 (0%)		1/7125 (0%)
Gastric Cancer	7/7111 (0.1%)		6/7125 (0.1%)
Gastric Cancer Stage I	1/7111 (0%)		0/7125 (0%)
Gastric Cancer Stage Iv	0/7111 (0%)		1/7125 (0%)
Gastrointestinal Carcinoma	1/7111 (0%)		1/7125 (0%)
Glioblastoma	1/7111 (0%)		0/7125 (0%)
Glioblastoma Multiforme	1/7111 (0%)		0/7125 (0%)
Glioma	0/7111 (0%)		1/7125 (0%)
Haemangioma	1/7111 (0%)		0/7125 (0%)
Hepatic Adenoma	0/7111 (0%)		1/7125 (0%)
Hepatic Cancer Metastatic	1/7111 (0%)		2/7125 (0%)
Hepatic Neoplasm	0/7111 (0%)		1/7125 (0%)
Hepatic Neoplasm Malignant	2/7111 (0%)		2/7125 (0%)
Infected Neoplasm	0/7111 (0%)		1/7125 (0%)
Intra-Abdominal Haemangioma	1/7111 (0%)		0/7125 (0%)
Intracranial Tumour Haemorrhage	1/7111 (0%)		0/7125 (0%)
Keratoacanthoma	1/7111 (0%)		0/7125 (0%)
Large Cell Carcinoma of the Respiratory Tract Stage Unspecified	2/7111 (0%)		0/7125 (0%)
Laryngeal Cancer	1/7111 (0%)		0/7125 (0%)
Leiomyosarcoma	1/7111 (0%)		0/7125 (0%)
Leiomyosarcoma Recurrent	1/7111 (0%)		0/7125 (0%)
Lentigo Maligna Stage Unspecified	0/7111 (0%)		1/7125 (0%)
Leukaemia	0/7111 (0%)		1/7125 (0%)
Lip And/Or Oral Cavity Cancer	1/7111 (0%)		1/7125 (0%)
Lipoma	2/7111 (0%)		3/7125 (0%)
Liposarcoma	1/7111 (0%)		1/7125 (0%)
Lung Adenocarcinoma	0/7111 (0%)		1/7125 (0%)
Lung Adenocarcinoma Metastatic	2/7111 (0%)		1/7125 (0%)
Lung Cancer Metastatic	3/7111 (0%)		2/7125 (0%)
Lung Carcinoma Cell Type Unspecified Stage Iv	2/7111 (0%)		0/7125 (0%)
Lung Neoplasm	3/7111 (0%)		4/7125 (0.1%)
Lung Neoplasm Malignant	11/7111 (0.2%)		10/7125 (0.1%)
Lung Squamous Cell Carcinoma Stage Unspecified	3/7111 (0%)		1/7125 (0%)
Lymphoma	2/7111 (0%)		4/7125 (0.1%)
Malignant Melanoma	5/7111 (0.1%)		7/7125 (0.1%)
Malignant Palate Neoplasm	1/7111 (0%)		0/7125 (0%)
Malignant Urinary Tract Neoplasm	1/7111 (0%)		0/7125 (0%)
Meningioma	0/7111 (0%)		1/7125 (0%)
Mesothelioma	2/7111 (0%)		1/7125 (0%)
Mesothelioma Malignant	1/7111 (0%)		0/7125 (0%)
Metastases to Central Nervous System	0/7111 (0%)		1/7125 (0%)
Metastases to Liver	5/7111 (0.1%)		1/7125 (0%)
Metastases to Lung	1/7111 (0%)		1/7125 (0%)
Metastasis	0/7111 (0%)		1/7125 (0%)
Metastatic Bronchial Carcinoma	0/7111 (0%)		1/7125 (0%)
Metastatic Carcinoma of the Bladder	1/7111 (0%)		0/7125 (0%)
Metastatic Malignant Melanoma	2/7111 (0%)		3/7125 (0%)
Metastatic Neoplasm	2/7111 (0%)		2/7125 (0%)
Multiple Myeloma	1/7111 (0%)		2/7125 (0%)
Myelodysplastic Syndrome	2/7111 (0%)		0/7125 (0%)
Myeloproliferative Disorder	0/7111 (0%)		1/7125 (0%)
Neoplasm Malignant	1/7111 (0%)		0/7125 (0%)
Neoplasm Prostate	1/7111 (0%)		1/7125 (0%)
Neurilemmoma Malignant	1/7111 (0%)		0/7125 (0%)
Neuroendocrine Carcinoma of the Skin	0/7111 (0%)		1/7125 (0%)
Non-Hodgkin's Lymphoma	2/7111 (0%)		2/7125 (0%)
Non-Hodgkin's Lymphoma Recurrent	2/7111 (0%)		0/7125 (0%)
Non-Small Cell Lung Cancer	1/7111 (0%)		0/7125 (0%)
Oesophageal Adenocarcinoma	1/7111 (0%)		2/7125 (0%)
Oesophageal Carcinoma	2/7111 (0%)		3/7125 (0%)
Ovarian Cancer	0/7111 (0%)		1/7125 (0%)
Ovarian Fibroma	1/7111 (0%)		0/7125 (0%)
Ovarian Neoplasm	1/7111 (0%)		0/7125 (0%)
Pancreatic Carcinoma	3/7111 (0%)		4/7125 (0.1%)
Pancreatic Carcinoma Metastatic	3/7111 (0%)		2/7125 (0%)
Pancreatic Neoplasm	1/7111 (0%)		1/7125 (0%)
Paraneoplastic Syndrome	1/7111 (0%)		0/7125 (0%)
Pituitary Tumour Benign	1/7111 (0%)		0/7125 (0%)
Polycythaemia Vera	1/7111 (0%)		1/7125 (0%)
Prostate Cancer	15/7111 (0.2%)		16/7125 (0.2%)
Prostate Cancer Metastatic	3/7111 (0%)		1/7125 (0%)
Prostate Cancer Recurrent	1/7111 (0%)		0/7125 (0%)
Prostatic Adenoma	8/7111 (0.1%)		3/7125 (0%)
Rectal Cancer	3/7111 (0%)		4/7125 (0.1%)
Rectal Neoplasm	3/7111 (0%)		2/7125 (0%)
Renal Cancer	2/7111 (0%)		4/7125 (0.1%)
Renal Cell Carcinoma	2/7111 (0%)		3/7125 (0%)
Renal Neoplasm	2/7111 (0%)		2/7125 (0%)
Salivary Gland Cancer	1/7111 (0%)		0/7125 (0%)
Salivary Gland Neoplasm	0/7111 (0%)		1/7125 (0%)
Skin Cancer	0/7111 (0%)		1/7125 (0%)
Small Cell Lung Cancer Stage Unspecified	0/7111 (0%)		1/7125 (0%)
Small Intestine Carcinoma	0/7111 (0%)		1/7125 (0%)
Squamous Cell Carcinoma	5/7111 (0.1%)		5/7125 (0.1%)
Squamous Cell Carcinoma of Skin	2/7111 (0%)		2/7125 (0%)
Testis Cancer	1/7111 (0%)		0/7125 (0%)
Throat Cancer	0/7111 (0%)		1/7125 (0%)
Thyroid Adenoma	1/7111 (0%)		0/7125 (0%)
Thyroid Cancer	2/7111 (0%)		3/7125 (0%)
Thyroid Neoplasm	0/7111 (0%)		1/7125 (0%)
Transitional Cell Carcinoma	2/7111 (0%)		2/7125 (0%)
Ureteric Cancer	0/7111 (0%)		1/7125 (0%)
Ureteric Cancer Metastatic	0/7111 (0%)		1/7125 (0%)
Uterine Cancer	2/7111 (0%)		1/7125 (0%)
Vulval Cancer	1/7111 (0%)		0/7125 (0%)
Adenocarcinoma Pancreas	0/7111 (0%)		1/7125 (0%)
Benign Soft Tissue Neoplasm	1/7111 (0%)		0/7125 (0%)
Colon Cancer Stage I	1/7111 (0%)		0/7125 (0%)
Colon Cancer Stage Iv	1/7111 (0%)		0/7125 (0%)
Gastric Neoplasm	1/7111 (0%)		0/7125 (0%)
Gastrointestinal Neoplasm	1/7111 (0%)		0/7125 (0%)
Gastrointestinal Stromal Tumour	1/7111 (0%)		0/7125 (0%)
Lymphangiosis Carcinomatosa	0/7111 (0%)		1/7125 (0%)
Mediastinum Neoplasm	0/7111 (0%)		1/7125 (0%)
Metastases to Bone	1/7111 (0%)		0/7125 (0%)
Neoplasm Skin	1/7111 (0%)		1/7125 (0%)
Oesophageal Neoplasm	1/7111 (0%)		0/7125 (0%)
Oesophageal Squamous Cell Carcinoma	2/7111 (0%)		0/7125 (0%)
Rectal Cancer Stage Iii	0/7111 (0%)		1/7125 (0%)
Refractory Anaemia with An Excess of Blasts	1/7111 (0%)		0/7125 (0%)
Retroperitoneal Cancer	1/7111 (0%)		0/7125 (0%)
Ureteral Neoplasm	0/7111 (0%)		1/7125 (0%)
Nervous system disorders
Anoxic Encephalopathy	1/7111 (0%)		3/7125 (0%)
Aphasia	2/7111 (0%)		1/7125 (0%)
Balance Disorder	0/7111 (0%)		2/7125 (0%)
Basal Ganglia Haemorrhage	2/7111 (0%)		0/7125 (0%)
Brachial Plexopathy	1/7111 (0%)		0/7125 (0%)
Brain Oedema	0/7111 (0%)		1/7125 (0%)
Brain Stem Infarction	0/7111 (0%)		1/7125 (0%)
Carotid Arteriosclerosis	1/7111 (0%)		0/7125 (0%)
Carotid Artery Disease	1/7111 (0%)		0/7125 (0%)
Carotid Artery Occlusion	1/7111 (0%)		1/7125 (0%)
Carotid Artery Stenosis	5/7111 (0.1%)		6/7125 (0.1%)
Carpal Tunnel Syndrome	2/7111 (0%)		1/7125 (0%)
Cauda Equina Syndrome	1/7111 (0%)		0/7125 (0%)
Central Pain Syndrome	0/7111 (0%)		1/7125 (0%)
Cerebellar Haemorrhage	0/7111 (0%)		2/7125 (0%)
Cerebral Arteriosclerosis	3/7111 (0%)		0/7125 (0%)
Cerebral Haematoma	1/7111 (0%)		1/7125 (0%)
Cerebral Haemorrhage	7/7111 (0.1%)		9/7125 (0.1%)
Cerebral Infarction	2/7111 (0%)		2/7125 (0%)
Cerebral Ischaemia	0/7111 (0%)		1/7125 (0%)
Cerebrovascular Accident	14/7111 (0.2%)		8/7125 (0.1%)
Cerebrovascular Disorder	1/7111 (0%)		1/7125 (0%)
Cerebrovascular Insufficiency	1/7111 (0%)		1/7125 (0%)
Cervicobrachial Syndrome	0/7111 (0%)		1/7125 (0%)
Chorea	0/7111 (0%)		1/7125 (0%)
Clonic Convulsion	1/7111 (0%)		0/7125 (0%)
Cognitive Disorder	0/7111 (0%)		1/7125 (0%)
Coma	1/7111 (0%)		0/7125 (0%)
Complex Partial Seizures	0/7111 (0%)		1/7125 (0%)
Convulsion	11/7111 (0.2%)		12/7125 (0.2%)
Dementia	3/7111 (0%)		5/7125 (0.1%)
Dementia Alzheimer's Type	0/7111 (0%)		1/7125 (0%)
Diabetic Autonomic Neuropathy	0/7111 (0%)		1/7125 (0%)
Diabetic Neuropathy	3/7111 (0%)		9/7125 (0.1%)
Dizziness	4/7111 (0.1%)		4/7125 (0.1%)
Dysarthria	0/7111 (0%)		1/7125 (0%)
Dyskinesia	1/7111 (0%)		0/7125 (0%)
Encephalopathy	3/7111 (0%)		3/7125 (0%)
Epilepsy	11/7111 (0.2%)		12/7125 (0.2%)
Facial Palsy	0/7111 (0%)		1/7125 (0%)
Facial Paresis	0/7111 (0%)		1/7125 (0%)
Grand Mal Convulsion	2/7111 (0%)		2/7125 (0%)
Haemorrhage Intracranial	13/7111 (0.2%)		34/7125 (0.5%)
Haemorrhagic Cerebral Infarction	1/7111 (0%)		2/7125 (0%)
Haemorrhagic Stroke	16/7111 (0.2%)		14/7125 (0.2%)
Haemorrhagic Transformation Stroke	6/7111 (0.1%)		11/7125 (0.2%)
Headache	1/7111 (0%)		2/7125 (0%)
Hemiparesis	1/7111 (0%)		1/7125 (0%)
Hepatic Encephalopathy	1/7111 (0%)		0/7125 (0%)
Hypertensive Encephalopathy	0/7111 (0%)		1/7125 (0%)
Hypoaesthesia	0/7111 (0%)		1/7125 (0%)
Hypoglycaemic Coma	0/7111 (0%)		1/7125 (0%)
Hypotonia	1/7111 (0%)		0/7125 (0%)
Hypoxic Encephalopathy	0/7111 (0%)		3/7125 (0%)
Iiird Nerve Paralysis	0/7111 (0%)		1/7125 (0%)
Intercostal Neuralgia	0/7111 (0%)		2/7125 (0%)
Intracranial Aneurysm	0/7111 (0%)		1/7125 (0%)
Intracranial Haematoma	1/7111 (0%)		2/7125 (0%)
Intraventricular Haemorrhage	0/7111 (0%)		1/7125 (0%)
Ischaemic Neuropathy	0/7111 (0%)		1/7125 (0%)
Ischaemic Stroke	18/7111 (0.3%)		26/7125 (0.4%)
Lacunar Infarction	0/7111 (0%)		1/7125 (0%)
Loss of Consciousness	1/7111 (0%)		1/7125 (0%)
Lumbar Radiculopathy	1/7111 (0%)		1/7125 (0%)
Metabolic Encephalopathy	2/7111 (0%)		1/7125 (0%)
Migraine	0/7111 (0%)		1/7125 (0%)
Myasthenia Gravis	1/7111 (0%)		0/7125 (0%)
Nerve Compression	1/7111 (0%)		0/7125 (0%)
Neuralgia	0/7111 (0%)		1/7125 (0%)
Neuritis	0/7111 (0%)		1/7125 (0%)
Neuropathy Peripheral	2/7111 (0%)		3/7125 (0%)
Paraesthesia	3/7111 (0%)		1/7125 (0%)
Parkinson's Disease	2/7111 (0%)		3/7125 (0%)
Parkinsonism	1/7111 (0%)		1/7125 (0%)
Partial Seizures	2/7111 (0%)		1/7125 (0%)
Partial Seizures with Secondary Generalisation	1/7111 (0%)		0/7125 (0%)
Petit Mal Epilepsy	0/7111 (0%)		1/7125 (0%)
Polyneuropathy	2/7111 (0%)		1/7125 (0%)
Postictal Paralysis	0/7111 (0%)		1/7125 (0%)
Presyncope	6/7111 (0.1%)		5/7125 (0.1%)
Radicular Syndrome	1/7111 (0%)		0/7125 (0%)
Radiculitis	0/7111 (0%)		1/7125 (0%)
Radiculitis Lumbosacral	0/7111 (0%)		1/7125 (0%)
Sciatica	4/7111 (0.1%)		4/7125 (0.1%)
Senile Dementia	1/7111 (0%)		0/7125 (0%)
Sensory Disturbance	1/7111 (0%)		0/7125 (0%)
Simple Partial Seizures	0/7111 (0%)		1/7125 (0%)
Status Epilepticus	1/7111 (0%)		0/7125 (0%)
Subarachnoid Haemorrhage	4/7111 (0.1%)		5/7125 (0.1%)
Syncope	55/7111 (0.8%)		42/7125 (0.6%)
Toxic Encephalopathy	0/7111 (0%)		1/7125 (0%)
Transient Global Amnesia	0/7111 (0%)		1/7125 (0%)
Transient Ischaemic Attack	50/7111 (0.7%)		71/7125 (1%)
Vascular Dementia	0/7111 (0%)		1/7125 (0%)
Vascular Encephalopathy	5/7111 (0.1%)		3/7125 (0%)
Vertebrobasilar Insufficiency	6/7111 (0.1%)		4/7125 (0.1%)
Vith Nerve Disorder	0/7111 (0%)		1/7125 (0%)
Cerebellar Atrophy	1/7111 (0%)		0/7125 (0%)
Diabetic Hyperosmolar Coma	0/7111 (0%)		1/7125 (0%)
Embolic Stroke	1/7111 (0%)		0/7125 (0%)
Hydrocephalus	1/7111 (0%)		0/7125 (0%)
Myoclonus	1/7111 (0%)		0/7125 (0%)
Paraplegia	1/7111 (0%)		0/7125 (0%)
Pregnancy, puerperium and perinatal conditions
Cephalhaematoma	1/7111 (0%)		0/7125 (0%)
Psychiatric disorders
Acute Psychosis	2/7111 (0%)		0/7125 (0%)
Agitation	0/7111 (0%)		1/7125 (0%)
Alcohol Abuse	1/7111 (0%)		1/7125 (0%)
Alcoholism	0/7111 (0%)		1/7125 (0%)
Anxiety	1/7111 (0%)		2/7125 (0%)
Completed Suicide	1/7111 (0%)		2/7125 (0%)
Confusional State	4/7111 (0.1%)		5/7125 (0.1%)
Delirium	2/7111 (0%)		1/7125 (0%)
Delusion	0/7111 (0%)		1/7125 (0%)
Depression	3/7111 (0%)		9/7125 (0.1%)
Disorientation	1/7111 (0%)		1/7125 (0%)
Generalised Anxiety Disorder	1/7111 (0%)		0/7125 (0%)
Hallucination	0/7111 (0%)		2/7125 (0%)
Hallucination, Visual	1/7111 (0%)		0/7125 (0%)
Mental Disorder Due to A General Medical Condition	1/7111 (0%)		0/7125 (0%)
Mental Status Changes	3/7111 (0%)		4/7125 (0.1%)
Mood Disorder Due to A General Medical Condition	1/7111 (0%)		0/7125 (0%)
Neurosis	0/7111 (0%)		1/7125 (0%)
Panic Disorder	0/7111 (0%)		2/7125 (0%)
Post-Traumatic Stress Disorder	0/7111 (0%)		1/7125 (0%)
Psychotic Disorder	1/7111 (0%)		0/7125 (0%)
Schizophrenia	1/7111 (0%)		0/7125 (0%)
Suicide Attempt	1/7111 (0%)		0/7125 (0%)
Bipolar Disorder	1/7111 (0%)		0/7125 (0%)
Renal and urinary disorders
Acute Prerenal Failure	1/7111 (0%)		1/7125 (0%)
Bladder Neck Obstruction	0/7111 (0%)		1/7125 (0%)
Bladder Prolapse	1/7111 (0%)		0/7125 (0%)
Calculus Bladder	4/7111 (0.1%)		1/7125 (0%)
Calculus Ureteric	2/7111 (0%)		3/7125 (0%)
Calculus Urethral	1/7111 (0%)		0/7125 (0%)
Calculus Urinary	1/7111 (0%)		1/7125 (0%)
Cystitis Erosive	1/7111 (0%)		0/7125 (0%)
Cystitis Haemorrhagic	1/7111 (0%)		0/7125 (0%)
Focal Segmental Glomerulosclerosis	1/7111 (0%)		0/7125 (0%)
Haematuria	62/7111 (0.9%)		46/7125 (0.6%)
Haemorrhage Urinary Tract	3/7111 (0%)		1/7125 (0%)
Hydronephrosis	0/7111 (0%)		2/7125 (0%)
Hypertensive Nephropathy	0/7111 (0%)		1/7125 (0%)
Kidney Enlargement	1/7111 (0%)		0/7125 (0%)
Nephritis	0/7111 (0%)		1/7125 (0%)
Nephrolithiasis	9/7111 (0.1%)		9/7125 (0.1%)
Nephropathy	1/7111 (0%)		0/7125 (0%)
Nephropathy Toxic	2/7111 (0%)		0/7125 (0%)
Nephrotic Syndrome	0/7111 (0%)		1/7125 (0%)
Obstructive Uropathy	0/7111 (0%)		1/7125 (0%)
Polyuria	0/7111 (0%)		1/7125 (0%)
Renal Artery Arteriosclerosis	0/7111 (0%)		1/7125 (0%)
Renal Artery Stenosis	1/7111 (0%)		1/7125 (0%)
Renal Colic	1/7111 (0%)		3/7125 (0%)
Renal Cyst	1/7111 (0%)		2/7125 (0%)
Renal Failure	27/7111 (0.4%)		18/7125 (0.3%)
Renal Failure Acute	37/7111 (0.5%)		46/7125 (0.6%)
Renal Failure Chronic	9/7111 (0.1%)		8/7125 (0.1%)
Renal Haemorrhage	0/7111 (0%)		1/7125 (0%)
Renal Impairment	5/7111 (0.1%)		8/7125 (0.1%)
Ureteric Haemorrhage	0/7111 (0%)		2/7125 (0%)
Urethral Haemorrhage	2/7111 (0%)		0/7125 (0%)
Urethral Stenosis	5/7111 (0.1%)		2/7125 (0%)
Urinary Bladder Haemorrhage	0/7111 (0%)		2/7125 (0%)
Urinary Bladder Polyp	1/7111 (0%)		1/7125 (0%)
Urinary Incontinence	2/7111 (0%)		1/7125 (0%)
Urinary Retention	12/7111 (0.2%)		7/7125 (0.1%)
Urinary Tract Obstruction	2/7111 (0%)		0/7125 (0%)
Urogenital Haemorrhage	0/7111 (0%)		1/7125 (0%)
Azotaemia	0/7111 (0%)		1/7125 (0%)
Reproductive system and breast disorders
Benign Prostatic Hyperplasia	15/7111 (0.2%)		15/7125 (0.2%)
Endometrial Hyperplasia	2/7111 (0%)		1/7125 (0%)
Endometrial Hypertrophy	1/7111 (0%)		0/7125 (0%)
Epididymitis	3/7111 (0%)		1/7125 (0%)
Erectile Dysfunction	1/7111 (0%)		0/7125 (0%)
Female Genital Tract Fistula	1/7111 (0%)		0/7125 (0%)
Genital Haemorrhage	0/7111 (0%)		1/7125 (0%)
Haemorrhagic Ovarian Cyst	0/7111 (0%)		1/7125 (0%)
Menorrhagia	1/7111 (0%)		0/7125 (0%)
Metrorrhagia	4/7111 (0.1%)		3/7125 (0%)
Oedema Genital	0/7111 (0%)		1/7125 (0%)
Postmenopausal Haemorrhage	2/7111 (0%)		2/7125 (0%)
Prostatic Obstruction	1/7111 (0%)		0/7125 (0%)
Prostatitis	1/7111 (0%)		1/7125 (0%)
Prostatomegaly	1/7111 (0%)		0/7125 (0%)
Scrotal Oedema	1/7111 (0%)		0/7125 (0%)
Uterine Haemorrhage	2/7111 (0%)		1/7125 (0%)
Uterine Polyp	4/7111 (0.1%)		2/7125 (0%)
Uterine Prolapse	1/7111 (0%)		0/7125 (0%)
Vaginal Haemorrhage	6/7111 (0.1%)		2/7125 (0%)
Vulval Ulceration	0/7111 (0%)		1/7125 (0%)
Fibrocystic Breast Disease	1/7111 (0%)		0/7125 (0%)
Prostatic Atrophy	0/7111 (0%)		1/7125 (0%)
Prostatic Intraepithelial Neoplasia	0/7111 (0%)		1/7125 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Pulmonary Oedema	13/7111 (0.2%)		9/7125 (0.1%)
Acute Respiratory Distress Syndrome	1/7111 (0%)		0/7125 (0%)
Acute Respiratory Failure	7/7111 (0.1%)		9/7125 (0.1%)
Aspiration	0/7111 (0%)		2/7125 (0%)
Asthma	6/7111 (0.1%)		11/7125 (0.2%)
Brain Hypoxia	0/7111 (0%)		1/7125 (0%)
Bronchitis Chronic	10/7111 (0.1%)		9/7125 (0.1%)
Bronchospasm	1/7111 (0%)		1/7125 (0%)
Choking	1/7111 (0%)		0/7125 (0%)
Chronic Obstructive Pulmonary Disease	59/7111 (0.8%)		56/7125 (0.8%)
Chronic Respiratory Failure	0/7111 (0%)		2/7125 (0%)
Cough	1/7111 (0%)		1/7125 (0%)
Diaphragmatic Hernia	1/7111 (0%)		0/7125 (0%)
Dyspnoea	9/7111 (0.1%)		25/7125 (0.4%)
Dyspnoea Exertional	1/7111 (0%)		0/7125 (0%)
Emphysema	0/7111 (0%)		1/7125 (0%)
Epistaxis	39/7111 (0.5%)		41/7125 (0.6%)
Foreign Body Aspiration	0/7111 (0%)		1/7125 (0%)
Haemoptysis	10/7111 (0.1%)		9/7125 (0.1%)
Haemothorax	4/7111 (0.1%)		3/7125 (0%)
Hydrothorax	2/7111 (0%)		1/7125 (0%)
Hyperventilation	1/7111 (0%)		1/7125 (0%)
Hypoxia	1/7111 (0%)		0/7125 (0%)
Interstitial Lung Disease	5/7111 (0.1%)		2/7125 (0%)
Laryngeal Polyp	0/7111 (0%)		1/7125 (0%)
Lung Disorder	3/7111 (0%)		2/7125 (0%)
Mediastinal Haematoma	1/7111 (0%)		0/7125 (0%)
Nasal Polyps	2/7111 (0%)		0/7125 (0%)
Nasal Septum Deviation	1/7111 (0%)		0/7125 (0%)
Paranasal Cyst	0/7111 (0%)		1/7125 (0%)
Pharyngeal Oedema	1/7111 (0%)		0/7125 (0%)
Pleural Effusion	16/7111 (0.2%)		12/7125 (0.2%)
Pleurisy	2/7111 (0%)		1/7125 (0%)
Pleuritic Pain	0/7111 (0%)		1/7125 (0%)
Pneumonia Aspiration	4/7111 (0.1%)		3/7125 (0%)
Pneumonitis	5/7111 (0.1%)		2/7125 (0%)
Pneumothorax	3/7111 (0%)		1/7125 (0%)
Pulmonary Amyloidosis	0/7111 (0%)		1/7125 (0%)
Pulmonary Arterial Hypertension	1/7111 (0%)		0/7125 (0%)
Pulmonary Congestion	2/7111 (0%)		2/7125 (0%)
Pulmonary Embolism	15/7111 (0.2%)		18/7125 (0.3%)
Pulmonary Fibrosis	1/7111 (0%)		0/7125 (0%)
Pulmonary Haemorrhage	3/7111 (0%)		1/7125 (0%)
Pulmonary Hypertension	3/7111 (0%)		3/7125 (0%)
Pulmonary Mass	1/7111 (0%)		0/7125 (0%)
Pulmonary Microemboli	1/7111 (0%)		0/7125 (0%)
Pulmonary Oedema	15/7111 (0.2%)		7/7125 (0.1%)
Respiratory Arrest	2/7111 (0%)		2/7125 (0%)
Respiratory Disorder	1/7111 (0%)		0/7125 (0%)
Respiratory Distress	2/7111 (0%)		1/7125 (0%)
Respiratory Failure	18/7111 (0.3%)		18/7125 (0.3%)
Sleep Apnoea Syndrome	1/7111 (0%)		1/7125 (0%)
Status Asthmaticus	0/7111 (0%)		1/7125 (0%)
Hydropneumothorax	0/7111 (0%)		1/7125 (0%)
Respiratory Tract Haemorrhage	1/7111 (0%)		0/7125 (0%)
Skin and subcutaneous tissue disorders
Angioedema	1/7111 (0%)		0/7125 (0%)
Blood Blister	1/7111 (0%)		0/7125 (0%)
Dermal Cyst	1/7111 (0%)		1/7125 (0%)
Dermatitis	2/7111 (0%)		0/7125 (0%)
Dermatitis Allergic	1/7111 (0%)		0/7125 (0%)
Dermatitis Atopic	1/7111 (0%)		2/7125 (0%)
Dry Gangrene	1/7111 (0%)		0/7125 (0%)
Ecchymosis	4/7111 (0.1%)		5/7125 (0.1%)
Eczema	0/7111 (0%)		1/7125 (0%)
Erythema Multiforme	1/7111 (0%)		0/7125 (0%)
Leukocytoclastic Vasculitis	2/7111 (0%)		0/7125 (0%)
Panniculitis	1/7111 (0%)		0/7125 (0%)
Prurigo	1/7111 (0%)		0/7125 (0%)
Pruritus	0/7111 (0%)		2/7125 (0%)
Psoriasis	0/7111 (0%)		1/7125 (0%)
Purpura	0/7111 (0%)		1/7125 (0%)
Rash	2/7111 (0%)		1/7125 (0%)
Seborrhoeic Dermatitis	1/7111 (0%)		0/7125 (0%)
Skin Disorder	1/7111 (0%)		0/7125 (0%)
Skin Haemorrhage	2/7111 (0%)		0/7125 (0%)
Skin Lesion	1/7111 (0%)		0/7125 (0%)
Skin Ulcer	5/7111 (0.1%)		8/7125 (0.1%)
Skin Ulcer Haemorrhage	0/7111 (0%)		2/7125 (0%)
Stevens-Johnson Syndrome	0/7111 (0%)		1/7125 (0%)
Umbilical Haemorrhage	0/7111 (0%)		1/7125 (0%)
Urticaria Chronic	0/7111 (0%)		1/7125 (0%)
Decubitus Ulcer	1/7111 (0%)		0/7125 (0%)
Surgical and medical procedures
Cardiac Pacemaker Battery Replacement	0/7111 (0%)		2/7125 (0%)
Cardiac Pacemaker Insertion	3/7111 (0%)		1/7125 (0%)
Cardiac Pacemaker Replacement	3/7111 (0%)		2/7125 (0%)
Cardiac Pacemaker Revision	0/7111 (0%)		1/7125 (0%)
Cardioversion	0/7111 (0%)		1/7125 (0%)
Carpal Tunnel Decompression	1/7111 (0%)		1/7125 (0%)
Cataract Operation	2/7111 (0%)		1/7125 (0%)
Finger Amputation	2/7111 (0%)		0/7125 (0%)
Foot Amputation	1/7111 (0%)		0/7125 (0%)
Haemorrhoid Operation	1/7111 (0%)		0/7125 (0%)
Hip Arthroplasty	3/7111 (0%)		1/7125 (0%)
Implantable Defibrillator Insertion	0/7111 (0%)		1/7125 (0%)
Inguinal Hernia Repair	2/7111 (0%)		0/7125 (0%)
Knee Arthroplasty	1/7111 (0%)		1/7125 (0%)
Knee Operation	0/7111 (0%)		1/7125 (0%)
Limb Operation	1/7111 (0%)		0/7125 (0%)
Penile Repair	1/7111 (0%)		0/7125 (0%)
Percutaneous Coronary Intervention	2/7111 (0%)		0/7125 (0%)
Polypectomy	1/7111 (0%)		1/7125 (0%)
Prostatectomy	0/7111 (0%)		1/7125 (0%)
Skin Graft	0/7111 (0%)		1/7125 (0%)
Skin Neoplasm Excision	0/7111 (0%)		1/7125 (0%)
Tooth Extraction	3/7111 (0%)		1/7125 (0%)
Transurethral Prostatectomy	2/7111 (0%)		0/7125 (0%)
Varicose Vein Operation	0/7111 (0%)		1/7125 (0%)
Wound Drainage	1/7111 (0%)		0/7125 (0%)
Abdominal Hernia Repair	0/7111 (0%)		1/7125 (0%)
Colostomy Closure	1/7111 (0%)		0/7125 (0%)
Ileostomy	1/7111 (0%)		0/7125 (0%)
Malignant Tumour Excision	1/7111 (0%)		0/7125 (0%)
Vascular disorders
Accelerated Hypertension	1/7111 (0%)		0/7125 (0%)
Angiopathy	0/7111 (0%)		1/7125 (0%)
Aortic Aneurysm	6/7111 (0.1%)		7/7125 (0.1%)
Aortic Aneurysm Rupture	2/7111 (0%)		6/7125 (0.1%)
Aortic Dilatation	1/7111 (0%)		0/7125 (0%)
Aortic Disorder	0/7111 (0%)		1/7125 (0%)
Aortic Dissection	1/7111 (0%)		2/7125 (0%)
Aortic Stenosis	1/7111 (0%)		0/7125 (0%)
Arterial Occlusive Disease	1/7111 (0%)		2/7125 (0%)
Arterial Stenosis Limb	2/7111 (0%)		0/7125 (0%)
Arterial Thrombosis Limb	0/7111 (0%)		1/7125 (0%)
Arteriosclerosis	2/7111 (0%)		2/7125 (0%)
Arteriosclerosis Obliterans	4/7111 (0.1%)		3/7125 (0%)
Arteriovenous Fistula	0/7111 (0%)		1/7125 (0%)
Bleeding Varicose Vein	4/7111 (0.1%)		1/7125 (0%)
Circulatory Collapse	3/7111 (0%)		1/7125 (0%)
Deep Vein Thrombosis	12/7111 (0.2%)		15/7125 (0.2%)
Diabetic Vascular Disorder	1/7111 (0%)		1/7125 (0%)
Diastolic Hypertension	0/7111 (0%)		1/7125 (0%)
Essential Hypertension	0/7111 (0%)		2/7125 (0%)
Extremity Necrosis	2/7111 (0%)		1/7125 (0%)
Femoral Arterial Stenosis	1/7111 (0%)		1/7125 (0%)
Femoral Artery Occlusion	1/7111 (0%)		2/7125 (0%)
Haematoma	32/7111 (0.5%)		42/7125 (0.6%)
Haemodynamic Instability	1/7111 (0%)		0/7125 (0%)
Haemorrhage	1/7111 (0%)		5/7125 (0.1%)
Haemorrhagic Infarction	0/7111 (0%)		1/7125 (0%)
Hypertension	26/7111 (0.4%)		28/7125 (0.4%)
Hypertensive Crisis	16/7111 (0.2%)		16/7125 (0.2%)
Hypertensive Emergency	1/7111 (0%)		2/7125 (0%)
Hypotension	13/7111 (0.2%)		15/7125 (0.2%)
Hypovolaemic Shock	4/7111 (0.1%)		2/7125 (0%)
Intermittent Claudication	2/7111 (0%)		0/7125 (0%)
Jugular Vein Distension	0/7111 (0%)		1/7125 (0%)
Lymphoedema	1/7111 (0%)		0/7125 (0%)
Microangiopathy	0/7111 (0%)		1/7125 (0%)
Orthostatic Hypotension	4/7111 (0.1%)		8/7125 (0.1%)
Peripheral Arterial Occlusive Disease	8/7111 (0.1%)		8/7125 (0.1%)
Peripheral Ischaemia	10/7111 (0.1%)		2/7125 (0%)
Peripheral Vascular Disorder	7/7111 (0.1%)		3/7125 (0%)
Phlebitis	1/7111 (0%)		1/7125 (0%)
Raynaud's Phenomenon	0/7111 (0%)		1/7125 (0%)
Shock Haemorrhagic	1/7111 (0%)		1/7125 (0%)
Thrombophlebitis	0/7111 (0%)		1/7125 (0%)
Thrombophlebitis Migrans	1/7111 (0%)		0/7125 (0%)
Thrombophlebitis Superficial	0/7111 (0%)		3/7125 (0%)
Varicose Ulceration	0/7111 (0%)		1/7125 (0%)
Varicose Vein	3/7111 (0%)		2/7125 (0%)
Vasculitis	0/7111 (0%)		1/7125 (0%)
Vasculitis Necrotising	1/7111 (0%)		0/7125 (0%)
Venous Insufficiency	0/7111 (0%)		2/7125 (0%)
Venous Thrombosis	1/7111 (0%)		0/7125 (0%)
Venous Thrombosis Limb	0/7111 (0%)		2/7125 (0%)
Lymphatic Fistula	1/7111 (0%)		0/7125 (0%)
Subclavian Vein Thrombosis	0/7111 (0%)		1/7125 (0%)
Vena Cava Thrombosis	0/7111 (0%)		1/7125 (0%)
Other (Not Including Serious) Adverse Events
	Rivaroxaban		Warfarin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2537/7111 (35.7%)		2573/7125 (36.1%)
Gastrointestinal disorders
Diarrhoea	384/7111 (5.4%)		401/7125 (5.6%)
General disorders
Oedema Peripheral	443/7111 (6.2%)		451/7125 (6.3%)
Infections and infestations
Bronchitis	377/7111 (5.3%)		401/7125 (5.6%)
Nasopharyngitis	430/7111 (6%)		464/7125 (6.5%)
Nervous system disorders
Dizziness	445/7111 (6.3%)		453/7125 (6.4%)
Headache	332/7111 (4.7%)		367/7125 (5.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	389/7111 (5.5%)		382/7125 (5.4%)
Epistaxis	705/7111 (9.9%)		594/7125 (8.3%)
Cough	356/7111 (5%)		363/7125 (5.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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