NAVIGATE ESUS: Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With Recent Embolic Stroke of Undetermined Source (ESUS)
Sponsor
Bayer (Industry)
Overall Status
Terminated
CT.gov ID
NCT02313909
Collaborator
Janssen Research & Development, LLC (Industry), Population Health Research Institute (Other)
7,213
454
2
37.8
15.9
0.4
Study Details
Study Description
Brief Summary
This is a study in patients who recently had a brain attack (stroke) and in whom no clear cause of the stroke could be identified. These strokes are likely due to a blood clot and therefore, can be called embolic stroke of undetermined source. The abbreviation is ESUS. The study will compare 2 blood thinners. Patients will be randomly assigned to either Rivaroxaban 15 mg or Aspirin 100 mg and the study is intended to show, if patients given rivaroxaban have fewer blood clots in the brain (stroke) or in other blood vessels.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
7213 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Multicenter, Randomized, Double-blind, Double-dummy, Active-comparator, Event-driven, Superiority Phase III Study of Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With a Recent Embolic Stroke of Undetermined Source (ESUS), Comparing Rivaroxaban 15 mg Once Daily With Aspirin 100 mg
Actual Study Start Date
:
Dec 23, 2014
Actual Primary Completion Date
:
Feb 15, 2018
Actual Study Completion Date
:
Feb 15, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Rivaroxaban Rivaroxaban 15 mg orally once daily |
Drug: Rivaroxaban (Xarelto, BAY59-7939)
15 mg, once daily, orally, tablet
Other: Rivaroxaban-Placebo
Matching placebo, once daily, orally, tablet
|
| Active Comparator: Aspirin Aspirin 100 mg orally once daily |
Drug: Acetylsalicylic acid (Aspirin, BAY1019036)
100 mg, once daily, orally, tablet
Other: Aspirin-Placebo
Matching placebo, once daily, orally, tablet
|
Outcome Measures
Primary Outcome Measures
- Incidence Rate of the Composite Efficacy Outcome (Adjudicated) [From randomization until the efficacy cut-off date (median 326 days)]
Components of composite efficacy outcome (adjudicated) includes stroke (ischemic, hemorrhagic, and undefined stroke, TIA with positive neuroimaging) and systemic embolism. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
- Incidence Rate of a Major Bleeding Event According to the International Society on Thrombosis and Haemostasis (ISTH) Criteria (Adjudicated) [From randomization until the efficacy cut-off date (median 326 days)]
Major bleeding event (as per ISTH), defined as bleeding event that met at least one of following: fatal bleeding; symptomatic bleeding in a critical area or organ (intraarticular, intramuscular with compartment syndrome, intraocular, intraspinal, pericardial, or retroperitoneal); symptomatic intracranial haemorrhage; clinically overt bleeding associated with a recent decrease in the hemoglobin level of greater than or equal to (>=) 2 grams per decilitre (g/dL) (20 grams per liter [g/L]; 1.24 millimoles per liter [mmol/L]) compared to the most recent hemoglobin value available before the event; clinically overt bleeding leading to transfusion of 2 or more units of packed red blood cells or whole blood. The results were based on classification of events that have been positively adjudicated as major bleeding events. Incidence rate estimated as number of subjects with incident events divided by cumulative at-risk time, where subject is no longer at risk once an incident event occurred.
Secondary Outcome Measures
- Incidence Rate of Any of the Following: Cardiovascular Death, Recurrent Stroke, Systemic Embolism and Myocardial Infarction [From randomization until the efficacy cut-off date (median 326 days)]
Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred. Cardiovascular death includes death due to hemorrhage and death with undetermined/unknown cause. Systemic embolism is defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms. The diagnosis of myocardial infarction requires the combination of: 1)evidence of myocardial necrosis (either changes in cardiac biomarkers or post-mortem pathological findings); and 2)supporting information derived from the clinical presentation, electrocardiographic changes, or the results of myocardial or coronary artery imaging.
- Incidence Rate of All-Cause Mortality [From randomization until the efficacy cut-off date (median 326 days)]
All-cause mortality includes all deaths of participants due to any cause.
- Incidence Rate of the Following: Stroke, Ischemic Stroke, Disabling Stroke, Cardiovascular (CV) Death, Myocardial Infarction [From randomization until the efficacy cut-off date (median 326 days)]
Disabling stroke is defined as stroke with modified Rankin score (mRS) greater than or equal to (>=) 4 as assessed by investigator. mRS spans 0-6, running from perfect health to death. A score of 0-3 indicates functional status ranging from no symptoms to "moderate disability" (defined in the mRS as requiring some help, but able to walk without assistance); mRS 4-6 indicates functional status ranging from "moderately severe disability" (unable to walk or to attend to own bodily needs without assistance)through to death. CV death includes death due to hemorrhage and death with undetermined/unknown cause. Diagnosis of myocardial infarction requires combination of: 1) evidence of myocardial necrosis either changes in cardiac biomarkers or post-mortem pathological findings); 2) supporting information derived from clinical presentation, electrocardiographic changes, or results of myocardial or coronary artery imaging.
- Incidence Rate of Life-Threatening Bleeding Events [From randomization until the efficacy cut-off date (median 326 days)]
Life-threatening bleeding was defined as a subset of major bleeding that met at least one of the following criteria: 1) fatal bleeding; 2) symptomatic intracranial haemorrhage; 3) reduction in hemoglobin of at least 5 g/dl (50 g/l; 3.10 mmol/L); 4) transfusion of at least 4 units of packed red cells or whole blood; 5) associated with hypotension requiring the use of intravenous inotropic agents; 6) necessitated surgical intervention. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
- Incidence Rate of Clinically Relevant Non-Major Bleeding Events [From randomization until the efficacy cut-off date (median 326 days)]
Non-major clinically relevant bleeding was defined as non-major overt bleeding but required medical attention (example: hospitalization, medical treatment for bleeding), and/or was associated with the study drug interruption of more than 14 days. The results were based on the outcome events at or after randomization until the efficacy cut-off date. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
- Incidence Rate of Intracranial Hemorrhage [From randomization until the efficacy cut-off date (median 326 days)]
Intracranial hemorrhage included all bleeding events that occurred in intracerebral, sub arachnoidal as well as subdural or epidural sites. The below table displays results for all randomized participants and the outcomes at or after randomization until the efficacy cut-off date. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred.
Eligibility Criteria
Criteria
Ages Eligible for Study:
50 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Recent ESUS (between 7 days and 6 months), defined as:
-
Recent ischemic stroke (including transient ischemic attack with positive neuroimaging) visualized by brain imaging that is not lacunar, and
-
Absence of cervical carotid atherosclerotic stenosis> 50% or occlusion, and
-
No atrial fibrillation after ≥ 24-hour cardiac rhythm monitoring, and
-
No intra-cardiac thrombus on either transesophageal or transthoracic echocardiography, and
-
No other specific cause of stroke (for example, arteritis, dissection, migraine/vasospasm, drug abuse)
Exclusion Criteria:
-
Severely disabling stroke (modified Rankin score ≥4)
-
Indication for chronic anticoagulation or antiplatelet therapy
-
Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tucson | Arizona | United States | 85724 | |
| 2 | Long Beach | California | United States | 90806 | |
| 3 | Stanford | California | United States | 94305-5119 | |
| 4 | Torrance | California | United States | 90502 | |
| 5 | New Haven | Connecticut | United States | 06520-8064 | |
| 6 | Gainesville | Florida | United States | 32611 | |
| 7 | Joliet | Illinois | United States | 60435 | |
| 8 | Iowa City | Iowa | United States | 52242-1089 | |
| 9 | Lexington | Kentucky | United States | 40536 | |
| 10 | New Orleans | Louisiana | United States | 70121 | |
| 11 | Baltimore | Maryland | United States | 21210 | |
| 12 | Boston | Massachusetts | United States | 02111 | |
| 13 | Boston | Massachusetts | United States | 02118 | |
| 14 | Worcester | Massachusetts | United States | 01655 | |
| 15 | Ann Arbor | Michigan | United States | 48109-0330 | |
| 16 | Mount Clemens | Michigan | United States | 48043 | |
| 17 | New Brunswick | New Jersey | United States | 08901 | |
| 18 | Buffalo | New York | United States | 14203 | |
| 19 | New York | New York | United States | 10016-4576 | |
| 20 | Cincinnati | Ohio | United States | 45219 | |
| 21 | Cleveland | Ohio | United States | 44106-2602 | |
| 22 | Cleveland | Ohio | United States | 44195 | |
| 23 | Portland | Oregon | United States | 97225 | |
| 24 | Portland | Oregon | United States | 97239-3011 | |
| 25 | Erie | Pennsylvania | United States | 16550 | |
| 26 | Philadelphia | Pennsylvania | United States | 19104 | |
| 27 | Pittsburgh | Pennsylvania | United States | 15212 | |
| 28 | Charleston | South Carolina | United States | 29425 | |
| 29 | Columbia | South Carolina | United States | 29203-8004 | |
| 30 | Nashville | Tennessee | United States | 37232-5400 | |
| 31 | Austin | Texas | United States | 78701 | |
| 32 | Dallas | Texas | United States | 75390 | |
| 33 | El Paso | Texas | United States | 79905-2709 | |
| 34 | Houston | Texas | United States | 77030 | |
| 35 | San Antonio | Texas | United States | 78229 | |
| 36 | Temple | Texas | United States | 76504 | |
| 37 | Salt Lake City | Utah | United States | 84312 | |
| 38 | Seattle | Washington | United States | 98102 | |
| 39 | Banfield | Buenos Aires | Argentina | 1828 | |
| 40 | Ciudad Auton. de Buenos Aires | Buenos Aires | Argentina | C1405CNF | |
| 41 | Mar del Plata | Buenos Aires | Argentina | B7602CBM | |
| 42 | San Martín | Buenos Aires | Argentina | 1650 | |
| 43 | Buenos Aires | Ciudad Auton. De Buenos Aires | Argentina | 1078 | |
| 44 | Buenos Aires | Ciudad Auton. De Buenos Aires | Argentina | 1428 | |
| 45 | Buenos Aires | Ciudad Auton. De Buenos Aires | Argentina | C1039AAO | |
| 46 | Buenos Aires | Ciudad Auton. De Buenos Aires | Argentina | C1221 ADC | |
| 47 | Buenos Aires | Ciudad Auton. De Buenos Aires | Argentina | C1431FWO | |
| 48 | Buenos Aires | Ciudad Auton. De Buenos Aires | Argentina | C1437JCP | |
| 49 | Rosario | Santa Fe | Argentina | S2000DSV | |
| 50 | Rosario | Santa Fe | Argentina | ||
| 51 | Ciudad Auton. de Buenos Aires | Argentina | C1425DND | ||
| 52 | Córdoba | Argentina | X5000JHQ | ||
| 53 | Santa Fe | Argentina | 3000 | ||
| 54 | Camperdown | New South Wales | Australia | 2050 | |
| 55 | Waratah | New South Wales | Australia | 2298 | |
| 56 | Brisbane | Queensland | Australia | 4029 | |
| 57 | Southport | Queensland | Australia | 4215 | |
| 58 | Launceston | Tasmania | Australia | 7250 | |
| 59 | Clayton | Victoria | Australia | 3168 | |
| 60 | Footscray | Victoria | Australia | 3011 | |
| 61 | Murdoch | Western Australia | Australia | 6150 | |
| 62 | Elizabeth Vale | Australia | 5112 | ||
| 63 | Nedlands | Australia | 6009 | ||
| 64 | Klagenfurt | Kärnten | Austria | 9020 | |
| 65 | Villach | Kärnten | Austria | 9500 | |
| 66 | Bad Pirawarth | Niederösterreich | Austria | 2222 | |
| 67 | St. Pölten | Niederösterreich | Austria | 3100 | |
| 68 | Vöcklabruck | Oberösterreich | Austria | 4840 | |
| 69 | Feldbach | Steiermark | Austria | 8330 | |
| 70 | Feldkirch | Vorarlberg | Austria | 6807 | |
| 71 | Salzburg | Austria | 5020 | ||
| 72 | Wien | Austria | 1020 | ||
| 73 | Wien | Austria | 1090 | ||
| 74 | Brugge | West-Vlaanderen | Belgium | 8310 | |
| 75 | Antwerpen | Belgium | 2020 | ||
| 76 | Brussel | Belgium | 1090 | ||
| 77 | Bruxelles - Brussel | Belgium | 1070 | ||
| 78 | Dendermonde | Belgium | 9200 | ||
| 79 | Edegem | Belgium | 2650 | ||
| 80 | Hasselt | Belgium | 3500 | ||
| 81 | Salvador | Bahia | Brazil | 41253-190 | |
| 82 | Belo Horizonte | Minas Gerais | Brazil | 30130-100 | |
| 83 | Belo Horizonte | Minas Gerais | Brazil | 30150-221 | |
| 84 | Porto Alegre | Rio Grande Do Sul | Brazil | 90035-001 | |
| 85 | Porto Alegre | Rio Grande Do Sul | Brazil | 90110-270 | |
| 86 | Porto Alegre | Rio Grande Do Sul | Brazil | ||
| 87 | Joinville | Santa Catarina | Brazil | 89202-165 | |
| 88 | Botucatu | Sao Paulo | Brazil | 18618 970 | |
| 89 | Campinas | Sao Paulo | Brazil | 13081-000 | |
| 90 | Matão | Sao Paulo | Brazil | 15990-060 | |
| 91 | Ribeirão Preto | Sao Paulo | Brazil | 14015-130 | |
| 92 | Ribeirão Preto | Sao Paulo | Brazil | 14048-900 | |
| 93 | São Paulo | Sao Paulo | Brazil | 01228-000 | |
| 94 | São Paulo | Sao Paulo | Brazil | 08270-070 | |
| 95 | Rio de Janeiro | Brazil | 22281-100 | ||
| 96 | Calgary | Alberta | Canada | T2N 2T9 | |
| 97 | Edmonton | Alberta | Canada | T6G 2B7 | |
| 98 | Edmonton | Alberta | Canada | T6L 5X8 | |
| 99 | Lethbridge | Alberta | Canada | T1K 0C9 | |
| 100 | Vancouver | British Columbia | Canada | V5Z 1M9 | |
| 101 | Victoria | British Columbia | Canada | V8R 1J8 | |
| 102 | Brandon | Manitoba | Canada | R7A 2B3 | |
| 103 | Saint John | New Brunswick | Canada | E2L 4L2 | |
| 104 | Halifax | Nova Scotia | Canada | B3H 2Y5 | |
| 105 | Burlington | Ontario | Canada | L7M 4Y1 | |
| 106 | Hamilton | Ontario | Canada | L8L 2X2 | |
| 107 | Kingston | Ontario | Canada | K7L 2V7 | |
| 108 | London | Ontario | Canada | N6A 5A5 | |
| 109 | London | Ontario | Canada | N6G 2V4 | |
| 110 | Mississauga | Ontario | Canada | L5B 2V2 | |
| 111 | Ottawa | Ontario | Canada | K1Y 4E9 | |
| 112 | Thunder Bay | Ontario | Canada | P7K 0A4 | |
| 113 | Toronto | Ontario | Canada | M4N 3M5 | |
| 114 | Chicoutimi | Quebec | Canada | G7H 5H6 | |
| 115 | Montreal | Quebec | Canada | H2L 4M1 | |
| 116 | Montreal | Quebec | Canada | H3G 1A4 | |
| 117 | St. Jerome | Quebec | Canada | J7Z 5T3 | |
| 118 | Quebec | Canada | G1J 1Z4 | ||
| 119 | Los Angeles | Bío-Bío | Chile | ||
| 120 | Osorno | Los Lagos | Chile | ||
| 121 | Puerto Montt | Los Lagos | Chile | 5506667 | |
| 122 | Valdivia | Los Lagos | Chile | ||
| 123 | Viña del Mar | Valparaíso | Chile | ||
| 124 | Santiago | Chile | 7650567 | ||
| 125 | Santiago | Chile | 8420524 | ||
| 126 | Viña del Mar | Chile | |||
| 127 | Fuzhou | Fujian | China | 350001 | |
| 128 | Fuzhou | Fujian | China | 350005 | |
| 129 | Lanzhou | Gansu | China | 730000 | |
| 130 | Foshan | Guangdong | China | 528000 | |
| 131 | Guangzhou | Guangdong | China | 510080 | |
| 132 | Haikou | Hainan | China | 570311 | |
| 133 | Shijiazhuang | Hebei | China | 050000 | |
| 134 | Harbin | Heilongjiang | China | ||
| 135 | Zhengzhou | Henan | China | 450052 | |
| 136 | Wuhan | Hubei | China | 430014 | |
| 137 | Wuhan | Hubei | China | 430034 | |
| 138 | Wuhan | Hubei | China | 430060 | |
| 139 | Changsha | Hunan | China | 410008 | |
| 140 | Baotou | Inner Mongolia | China | 014010 | |
| 141 | Nantong | Jiangsu | China | 226001 | |
| 142 | Nanchang | Jiangxi | China | 330006 | |
| 143 | Changchun | Jilin | China | 130021 | |
| 144 | Shenyang | Liaoning | China | 110016 | |
| 145 | Qingdao | Shandong | China | 266003 | |
| 146 | Yantai | Shandong | China | 264000 | |
| 147 | Baoji | Shanxi | China | 721008 | |
| 148 | Xi'an | Shanxi | China | 710038 | |
| 149 | Kunming | Yunnan | China | 650032 | |
| 150 | Hangzhou | Zhejiang | China | 310009 | |
| 151 | Taizhou | Zhejiang | China | 317000 | |
| 152 | Wenzhou | Zhejiang | China | 325000 | |
| 153 | Beijing | China | 100050 | ||
| 154 | Beijing | China | 100730 | ||
| 155 | Chongqing | China | |||
| 156 | Guangzhou | China | |||
| 157 | Shanghai | China | 200032 | ||
| 158 | Tianjin | China | 300000 | ||
| 159 | Tianjin | China | 300052 | ||
| 160 | Blansko | Czechia | 67801 | ||
| 161 | Brno | Czechia | 625 00 | ||
| 162 | Brno | Czechia | 656 91 | ||
| 163 | Hradec Kralove | Czechia | 500 05 | ||
| 164 | Jihlava | Czechia | 58633 | ||
| 165 | Olomouc | Czechia | 775 20 | ||
| 166 | Ostrava Vitkovice | Czechia | |||
| 167 | Ostrava-Poruba | Czechia | 708 52 | ||
| 168 | Praha 2 | Czechia | 128 21 | ||
| 169 | Praha 3 | Czechia | 10034 | ||
| 170 | Vyskov | Czechia | 682 01 | ||
| 171 | Aalborg | Denmark | 9100 | ||
| 172 | Aarhus C | Denmark | 8000 | ||
| 173 | Copenhagen | Denmark | 2400 | ||
| 174 | Glostrup | Denmark | 2600 | ||
| 175 | Herlev | Denmark | 2730 | ||
| 176 | Hillerød | Denmark | 3400 | ||
| 177 | Helsinki | Finland | 00029 | ||
| 178 | Lappeenranta | Finland | FIN-53130 | ||
| 179 | OYS | Finland | 90029 | ||
| 180 | Sairaalamäki | Finland | 45750 | ||
| 181 | Tampere | Finland | FIN-33520 | ||
| 182 | Turku | Finland | 20520 | ||
| 183 | Vaasa | Finland | 65130 | ||
| 184 | Antony Cedex | France | 92166 | ||
| 185 | Bordeaux | France | 33000 | ||
| 186 | Brest Cedex | France | 29609 | ||
| 187 | Caen Cedex | France | 14033 | ||
| 188 | Dijon | France | 21033 | ||
| 189 | Le Chesnay | France | 78150 | ||
| 190 | Limoges | France | 87042 | ||
| 191 | Nantes | France | 44035 | ||
| 192 | NIMES cedex 9 | France | 30029 | ||
| 193 | PARIS cedex 14 | France | 75674 | ||
| 194 | Paris | France | 75012 | ||
| 195 | Paris | France | 75018 | ||
| 196 | Paris | France | 75475 | ||
| 197 | Paris | France | 75634 | ||
| 198 | Saint Priest En Jarez | France | 42270 | ||
| 199 | Strasbourg | France | 67091 | ||
| 200 | Freiburg | Baden-Württemberg | Germany | 79106 | |
| 201 | Mannheim | Baden-Württemberg | Germany | 68167 | |
| 202 | München | Bayern | Germany | 81675 | |
| 203 | Regensburg | Bayern | Germany | 93053 | |
| 204 | Würzburg | Bayern | Germany | 97080 | |
| 205 | Hannover | Niedersachsen | Germany | 30625 | |
| 206 | Düsseldorf | Nordrhein-Westfalen | Germany | 40225 | |
| 207 | Meerbusch | Nordrhein-Westfalen | Germany | 40670 | |
| 208 | Wuppertal | Nordrhein-Westfalen | Germany | 42283 | |
| 209 | Halle | Sachsen-Anhalt | Germany | 06120 | |
| 210 | Dresden | Sachsen | Germany | 01129 | |
| 211 | Dresden | Sachsen | Germany | 01307 | |
| 212 | Markkleeberg | Sachsen | Germany | 04416 | |
| 213 | Wermsdorf | Sachsen | Germany | 04779 | |
| 214 | Altenburg | Thüringen | Germany | 04600 | |
| 215 | Berlin | Germany | 12200 | ||
| 216 | Hamburg | Germany | 22417 | ||
| 217 | Athens | Greece | 11521 | ||
| 218 | Athens | Greece | 11528 | ||
| 219 | Ioannina | Greece | 45500 | ||
| 220 | Larissa | Greece | 41100 | ||
| 221 | Thessaloniki | Greece | 546 36 | ||
| 222 | Budapest | Hungary | 1083 | ||
| 223 | Budapest | Hungary | 1134 | ||
| 224 | Budapest | Hungary | 1204 | ||
| 225 | Debrecen | Hungary | 4012 | ||
| 226 | Eger | Hungary | 3300 | ||
| 227 | Gyor | Hungary | 9002 | ||
| 228 | Kistarcsa | Hungary | 2143 | ||
| 229 | Miskolc | Hungary | 35-26 | ||
| 230 | Nagykanizsa | Hungary | 8800 | ||
| 231 | Nyiregyhaza | Hungary | H-4400 | ||
| 232 | Sopron | Hungary | 9400 | ||
| 233 | Szeged | Hungary | 6720 | ||
| 234 | Zalaegerszeg | Hungary | 8900 | ||
| 235 | Dublin | Ireland | DUBLIN 7 | ||
| 236 | Galway | Ireland | |||
| 237 | Ashkelon | Israel | 7827804 | ||
| 238 | Beer Sheva | Israel | 8410101 | ||
| 239 | Haifa | Israel | 3339419 | ||
| 240 | Haifa | Israel | 3436212 | ||
| 241 | Jerusalem | Israel | |||
| 242 | Petah Tikva | Israel | 4941492 | ||
| 243 | Ramat Gan | Israel | 5262000 | ||
| 244 | Tel Aviv | Israel | 6423906 | ||
| 245 | L'Aquila | Abruzzo | Italy | 67100 | |
| 246 | Vibo Valentia | Calabria | Italy | 89900 | |
| 247 | Parma | Emilia-Romagna | Italy | 43126 | |
| 248 | Trieste | Friuli-Venezia Giulia | Italy | 34100 | |
| 249 | Roma | Lazio | Italy | 00133 | |
| 250 | Roma | Lazio | Italy | 00152 | |
| 251 | Roma | Lazio | Italy | 00161 | |
| 252 | Roma | Lazio | Italy | 00168 | |
| 253 | Milano | Lombardia | Italy | 20122 | |
| 254 | Milano | Lombardia | Italy | 20132 | |
| 255 | Milano | Lombardia | Italy | 20162 | |
| 256 | Pavia | Lombardia | Italy | 27100 | |
| 257 | Ancona | Marche | Italy | 60126 | |
| 258 | Isernia | Molise | Italy | 86077 | |
| 259 | Cagliari | Sardegna | Italy | 09134 | |
| 260 | Perugia | Umbria | Italy | 06012 | |
| 261 | Perugia | Umbria | Italy | 06024 | |
| 262 | Perugia | Umbria | Italy | 06156 | |
| 263 | Verona | Veneto | Italy | 37024 | |
| 264 | Verona | Veneto | Italy | 37126 | |
| 265 | Nagoya | Aichi | Japan | 454-8502 | |
| 266 | Nagoya | Aichi | Japan | 457-8511 | |
| 267 | Nagoya | Aichi | Japan | 460-0001 | |
| 268 | Okazaki | Aichi | Japan | 444-8553 | |
| 269 | Seto | Aichi | Japan | 489-8642 | |
| 270 | Toyota | Aichi | Japan | 471-8513 | |
| 271 | Kitakyushu | Fukuoka | Japan | 802-8555 | |
| 272 | Kitakyushu | Fukuoka | Japan | 805-0050 | |
| 273 | Koriyama | Fukushima | Japan | 963-8052 | |
| 274 | Fukuyama | Hiroshima | Japan | 720-0825 | |
| 275 | Asahikawa | Hokkaido | Japan | 070-8530 | |
| 276 | Hakodate | Hokkaido | Japan | 041-0802 | |
| 277 | Kushiro | Hokkaido | Japan | 085-0061 | |
| 278 | Kobe | Hyogo | Japan | 650-0047 | |
| 279 | Kobe | Hyogo | Japan | 652-0803 | |
| 280 | Kobe | Hyogo | Japan | 654-0048 | |
| 281 | Nishinomiya | Hyogo | Japan | 663-8211 | |
| 282 | Isehara | Kanagawa | Japan | 259-1193 | |
| 283 | Kawasaki | Kanagawa | Japan | 216-8511 | |
| 284 | Sendai | Miyagi | Japan | 982-8523 | |
| 285 | Sasebo | Nagasaki | Japan | 857-0134 | |
| 286 | Tenri | Nara | Japan | 632-8552 | |
| 287 | Kurashiki | Okayama | Japan | 710-8602 | |
| 288 | Matsubara | Osaka | Japan | 580-0032 | |
| 289 | Sakai | Osaka | Japan | 590-0064 | |
| 290 | Suita | Osaka | Japan | 565-8565 | |
| 291 | Hidaka | Saitama | Japan | 350-1298 | |
| 292 | Bunkyo-ku | Tokyo | Japan | 113-8603 | |
| 293 | Hachioji | Tokyo | Japan | 192-0032 | |
| 294 | Kodaira | Tokyo | Japan | 187-8510 | |
| 295 | Musashino | Tokyo | Japan | 180-8610 | |
| 296 | Shinjuku-ku | Tokyo | Japan | 162-8666 | |
| 297 | Sumida-ku | Tokyo | Japan | 130-8575 | |
| 298 | Fukuoka | Japan | 810-0001 | ||
| 299 | Fukuoka | Japan | 810-8563 | ||
| 300 | Fukuoka | Japan | 811-0213 | ||
| 301 | Hiroshima | Japan | 730-8518 | ||
| 302 | Kakogawa | Japan | 675-0122 | ||
| 303 | Kochi | Japan | 780-8522 | ||
| 304 | Kyoto | Japan | 600-8558 | ||
| 305 | Kyoto | Japan | 601-1495 | ||
| 306 | Kyoto | Japan | 602-8026 | ||
| 307 | Niigata | Japan | 950-1197 | ||
| 308 | Okayama | Japan | 700-8557 | ||
| 309 | Donggu, | Gwangju Gwang''yeogsi | Korea, Republic of | 61469 | |
| 310 | Anyang-si | Gyeonggido | Korea, Republic of | 431-070 | |
| 311 | Goyang | Gyeonggido | Korea, Republic of | 411-706 | |
| 312 | Seongnam-si | Gyeonggido | Korea, Republic of | 463-707 | |
| 313 | Seoul | Seoul Teugbyeolsi | Korea, Republic of | 152-703 | |
| 314 | Busan | Korea, Republic of | 49201 | ||
| 315 | Daegu | Korea, Republic of | 41931 | ||
| 316 | Daegu | Korea, Republic of | 42415 | ||
| 317 | Incheon | Korea, Republic of | |||
| 318 | Seoul, | Korea, Republic of | 139-872 | ||
| 319 | Seoul | Korea, Republic of | 05505 | ||
| 320 | Seoul | Korea, Republic of | 06351 | ||
| 321 | Seoul | Korea, Republic of | 110-744 | ||
| 322 | Seoul | Korea, Republic of | 120-752 | ||
| 323 | Seoul | Korea, Republic of | 130-872 | ||
| 324 | Delegación Gustavo A. Madero | Distrito Federal | Mexico | 07760 | |
| 325 | México, D.F. | Distrito Federal | Mexico | 14080 | |
| 326 | Morelia | Michoacán | Mexico | 58000 | |
| 327 | México D.F. | México | Mexico | 06720 | |
| 328 | Monterrey | Nuevo Leon | Mexico | 64460 | |
| 329 | Merida | Yucatán | Mexico | 97070 | |
| 330 | Aguascalientes | Mexico | 20127 | ||
| 331 | México D.F. | Mexico | |||
| 332 | Bialystok | Poland | 15-276 | ||
| 333 | Chelm | Poland | 22-100 | ||
| 334 | Gdansk | Poland | 80-803 | ||
| 335 | Gdansk | Poland | 80-952 | ||
| 336 | Katowice | Poland | 40-635 | ||
| 337 | Konskie | Poland | 26-200 | ||
| 338 | Lodz | Poland | 90-153 | ||
| 339 | Lodz | Poland | 90-549 | ||
| 340 | Olsztyn | Poland | 10-561 | ||
| 341 | Sandomierz | Poland | |||
| 342 | Siedlce | Poland | 08-110 | ||
| 343 | Skarzysko-Kamienna | Poland | 26-110 | ||
| 344 | Warszawa | Poland | 00-146 | ||
| 345 | Warszawa | Poland | 02957 | ||
| 346 | Warszawa | Poland | 03-242 | ||
| 347 | Vilanova De Gaia | Porto | Portugal | 4434-502 | |
| 348 | Almada | Portugal | 2801-951 | ||
| 349 | Amadora | Portugal | 2720-276 | ||
| 350 | Coimbra | Portugal | 3030-075 | ||
| 351 | Lisboa | Portugal | 1198 | ||
| 352 | Porto | Portugal | 4099-001 | ||
| 353 | Porto | Portugal | 4200-319 | ||
| 354 | Vila Franca de Xira | Portugal | P 2600-178 | ||
| 355 | Chelyabinsk | Russian Federation | 454021 | ||
| 356 | Ekaterinburg | Russian Federation | 620017 | ||
| 357 | Kaluga | Russian Federation | 248010 | ||
| 358 | Kazan | Russian Federation | 420012 | ||
| 359 | Krasnoyarsk | Russian Federation | 660022 | ||
| 360 | Moscow | Russian Federation | 117997 | ||
| 361 | Moscow | Russian Federation | 119049 | ||
| 362 | Nizhny Novgorod | Russian Federation | 603005 | ||
| 363 | St. Petersburg | Russian Federation | 190068 | ||
| 364 | St. Petersburg | Russian Federation | 191186 | ||
| 365 | St. Petersburg | Russian Federation | 194354 | ||
| 366 | St. Petersburg | Russian Federation | 196247 | ||
| 367 | Tomsk | Russian Federation | 634063 | ||
| 368 | Ulyanovsk | Russian Federation | 432063 | ||
| 369 | Volgograd | Russian Federation | 400131 | ||
| 370 | Yaroslavl | Russian Federation | 150000 | ||
| 371 | Yekaterinburg | Russian Federation | 620102 | ||
| 372 | Cape Town | Western Cape | South Africa | 7531 | |
| 373 | Somerset West | Western Cape | South Africa | 7130 | |
| 374 | Durban | South Africa | 4100 | ||
| 375 | Santiago de Compostela | A Coruña | Spain | 15706 | |
| 376 | Badalona | Barcelona | Spain | 08916 | |
| 377 | L'Hospitalet de Llobregat | Barcelona | Spain | 08907 | |
| 378 | Sant Joan Despi | Barcelona | Spain | 08970 | |
| 379 | Castellón de la Plana | Castellón | Spain | 12004 | |
| 380 | El Palmar (Murcia) | Murcia | Spain | 30120 | |
| 381 | A Coruña | Spain | 15006 | ||
| 382 | Badajoz | Spain | 06080 | ||
| 383 | Barcelona | Spain | 08003 | ||
| 384 | Barcelona | Spain | 08035 | ||
| 385 | Barcelona | Spain | 08036 | ||
| 386 | Barcelona | Spain | 08041 | ||
| 387 | Bilbao | Spain | 48013 | ||
| 388 | Cáceres | Spain | 10003 | ||
| 389 | Girona | Spain | 17007 | ||
| 390 | Granada | Spain | 18014 | ||
| 391 | León | Spain | 24008 | ||
| 392 | Lleida | Spain | 25198 | ||
| 393 | Madrid | Spain | 28006 | ||
| 394 | Madrid | Spain | 28007 | ||
| 395 | Madrid | Spain | 28046 | ||
| 396 | Sevilla | Spain | 41009 | ||
| 397 | Sevilla | Spain | 41013 | ||
| 398 | Valencia | Spain | 46026 | ||
| 399 | Valladolid | Spain | 47011 | ||
| 400 | Zaragoza | Spain | 50009 | ||
| 401 | Goteborg | Sweden | 413 45 | ||
| 402 | Hässleholm | Sweden | 281 25 | ||
| 403 | Lund | Sweden | 221 85 | ||
| 404 | Malmö | Sweden | 205 02 | ||
| 405 | Umeå | Sweden | 901 85 | ||
| 406 | Aarau | Aargau | Switzerland | 5001 | |
| 407 | Basel | Basel-Stadt | Switzerland | 4056 | |
| 408 | Lugano | Ticino | Switzerland | 6900 | |
| 409 | Baden | Switzerland | 5404 | ||
| 410 | Bern | Switzerland | 3010 | ||
| 411 | Fribourg | Switzerland | 1700 | ||
| 412 | Genève | Switzerland | 1205 | ||
| 413 | Zürich | Switzerland | 8032 | ||
| 414 | Ankara | Turkey | 06500 | ||
| 415 | Ankara | Turkey | 6100 | ||
| 416 | Antakya | Turkey | 31000 | ||
| 417 | Istanbul | Turkey | 34098 | ||
| 418 | Istanbul | Turkey | |||
| 419 | Kahramanmaras | Turkey | 46000 | ||
| 420 | Konya | Turkey | 42075 | ||
| 421 | Konya | Turkey | 42080 | ||
| 422 | High Wycombe | Buckinghamshire | United Kingdom | HP11 2TT | |
| 423 | Milton Keynes | Buckinghamshire | United Kingdom | MK6 5LD | |
| 424 | Cambridge | Cambridgeshire | United Kingdom | CB2 0QQ | |
| 425 | Exeter | Devon | United Kingdom | EX2 5DW | |
| 426 | Colchester | Essex | United Kingdom | CO4 5JR | |
| 427 | Westcliff-on-Sea | Essex | United Kingdom | SS0 0RY | |
| 428 | Gloucester | Gloucestershire | United Kingdom | GL1 3NN | |
| 429 | Watford | Hertfordshire | United Kingdom | WD1 8HB | |
| 430 | Ashford | Kent | United Kingdom | TN24 0LZ | |
| 431 | Margate | Kent | United Kingdom | CT9 4AN | |
| 432 | Leicester | Leicestershire | United Kingdom | LE2 7LX | |
| 433 | Boston | Lincolnshire | United Kingdom | PE21 9QS | |
| 434 | Harrow | London | United Kingdom | HA1 3UJ | |
| 435 | Great Yarmouth | Norfolk | United Kingdom | NR31 6LA | |
| 436 | Taunton | Somerset | United Kingdom | TA1 5DA | |
| 437 | Yeovil | Somerset | United Kingdom | BA21 4AT | |
| 438 | Sheffield | South Yorkshire | United Kingdom | S10 2JF | |
| 439 | Stoke-On-Trent | Staffordshire | United Kingdom | ST4 6QG | |
| 440 | Glasgow | Stratchclyde | United Kingdom | G51 4TF | |
| 441 | Gateshead | Tyne And Wear | United Kingdom | NE9 6SX | |
| 442 | Sunderland | Tyne And Wear | United Kingdom | SR4 7TP | |
| 443 | Wolverhampton | West Midlands | United Kingdom | WV10 0QP | |
| 444 | Leeds | West Yorkshire | United Kingdom | LS1 3EX | |
| 445 | Salisbury | Wiltshire | United Kingdom | SP2 8BJ | |
| 446 | Aberdeen | United Kingdom | AB25 2ZN | ||
| 447 | Durham | United Kingdom | DH1 5TW | ||
| 448 | Edinburgh | United Kingdom | EH16 4SA | ||
| 449 | London | United Kingdom | N18 1QX | ||
| 450 | London | United Kingdom | SE5 8AF | ||
| 451 | London | United Kingdom | W6 8RP | ||
| 452 | London | United Kingdom | WC1N 3BG | ||
| 453 | Luton | United Kingdom | LU4 0DZ | ||
| 454 | Norwich | United Kingdom | NR4 7UY |
Sponsors and Collaborators
- Bayer
- Janssen Research & Development, LLC
- Population Health Research Institute
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT02313909
Other Study ID Numbers:
- 16573
- 2013-000768-27
First Posted:
Dec 10, 2014
Last Update Posted:
Jan 9, 2019
Last Verified:
Dec 1, 2018
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Bayer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Study was conducted at multiple centers in 31 countries between 23 December 2014 (first participant first visit) and 15 February 2018 (last participant last visit). |
|---|---|
| Pre-assignment Detail | Overall, 7582 participants were screened; of these 369 participants were screen failures. A total of 7213 participants were randomized, of which 92 never took study drug; 3562 were treated with rivaroxaban(Xarelto, BAY59-7939) /placebo and 3559 were treated with acetylsalicylic acid/placebo. |
| Arm/Group Title | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Arm/Group Description | Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD). | Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD). |
| Period Title: Overall Study | ||
| STARTED | 3609 | 3604 |
| Treated | 3562 | 3559 |
| COMPLETED | 3552 | 3554 |
| NOT COMPLETED | 57 | 50 |
Baseline Characteristics
| Arm/Group Title | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD | Total |
|---|---|---|---|
| Arm/Group Description | Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD). | Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD). | Total of all reporting groups |
| Overall Participants | 3609 | 3604 | 7213 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
66.9
(9.8)
|
66.9
(9.8)
|
66.9
(9.8)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
1377
38.2%
|
1400
38.8%
|
2777
38.5%
|
| Male |
2232
61.8%
|
2204
61.2%
|
4436
61.5%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
716
19.8%
|
698
19.4%
|
1414
19.6%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
51
1.4%
|
60
1.7%
|
111
1.5%
|
| White |
2613
72.4%
|
2605
72.3%
|
5218
72.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
229
6.3%
|
241
6.7%
|
470
6.5%
|
| Stroke or TIA (prior to qualifying stroke) or Other medical history (count of participants) [Number] | |||
| Stroke or TIA |
620
17.2%
|
643
17.8%
|
1263
17.5%
|
| Other medical history |
2989
82.8%
|
2961
82.2%
|
5950
82.5%
|
| Time from qualifying stroke to randomization (days) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [days] |
38.0
|
36.0
|
37.0
|
Outcome Measures
| Title | Incidence Rate of the Composite Efficacy Outcome (Adjudicated) |
|---|---|
| Description | Components of composite efficacy outcome (adjudicated) includes stroke (ischemic, hemorrhagic, and undefined stroke, TIA with positive neuroimaging) and systemic embolism. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred. |
| Time Frame | From randomization until the efficacy cut-off date (median 326 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category. |
| Arm/Group Title | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Arm/Group Description | Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD). | Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD). |
| Measure Participants | 3609 | 3604 |
| Number (95% Confidence Interval) [event/100 participant-years] |
5.14
|
4.78
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Comments | Statistical analysis: Stroke + Systemic embolism: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.51884 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.07 | |
| Confidence Interval |
(2-Sided) 95% 0.87 to 1.33 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Incidence Rate of a Major Bleeding Event According to the International Society on Thrombosis and Haemostasis (ISTH) Criteria (Adjudicated) |
|---|---|
| Description | Major bleeding event (as per ISTH), defined as bleeding event that met at least one of following: fatal bleeding; symptomatic bleeding in a critical area or organ (intraarticular, intramuscular with compartment syndrome, intraocular, intraspinal, pericardial, or retroperitoneal); symptomatic intracranial haemorrhage; clinically overt bleeding associated with a recent decrease in the hemoglobin level of greater than or equal to (>=) 2 grams per decilitre (g/dL) (20 grams per liter [g/L]; 1.24 millimoles per liter [mmol/L]) compared to the most recent hemoglobin value available before the event; clinically overt bleeding leading to transfusion of 2 or more units of packed red blood cells or whole blood. The results were based on classification of events that have been positively adjudicated as major bleeding events. Incidence rate estimated as number of subjects with incident events divided by cumulative at-risk time, where subject is no longer at risk once an incident event occurred. |
| Time Frame | From randomization until the efficacy cut-off date (median 326 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category. |
| Arm/Group Title | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Arm/Group Description | Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD). | Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD). |
| Measure Participants | 3609 | 3604 |
| Number (95% Confidence Interval) [event/100 participant-years] |
1.82
|
0.67
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Comments | Statistical analysis: ISTH major bleeding events: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.00002 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 2.72 | |
| Confidence Interval |
(2-Sided) 95% 1.68 to 4.39 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Incidence Rate of Any of the Following: Cardiovascular Death, Recurrent Stroke, Systemic Embolism and Myocardial Infarction |
|---|---|
| Description | Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred. Cardiovascular death includes death due to hemorrhage and death with undetermined/unknown cause. Systemic embolism is defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms. The diagnosis of myocardial infarction requires the combination of: 1)evidence of myocardial necrosis (either changes in cardiac biomarkers or post-mortem pathological findings); and 2)supporting information derived from the clinical presentation, electrocardiographic changes, or the results of myocardial or coronary artery imaging. |
| Time Frame | From randomization until the efficacy cut-off date (median 326 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category. |
| Arm/Group Title | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Arm/Group Description | Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD). | Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD). |
| Measure Participants | 3609 | 3604 |
| Number (95% Confidence Interval) [event/100 participant-years] |
6.20
|
5.85
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Comments | Statistical analysis: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Confidence intervals were calculated, if at least 1 event in each treatment arm existed. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.56922 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.06 | |
| Confidence Interval |
(2-Sided) 95% 0.87 to 1.29 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Incidence Rate of All-Cause Mortality |
|---|---|
| Description | All-cause mortality includes all deaths of participants due to any cause. |
| Time Frame | From randomization until the efficacy cut-off date (median 326 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category. |
| Arm/Group Title | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Arm/Group Description | Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD). | Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD). |
| Measure Participants | 3609 | 3604 |
| Number (95% Confidence Interval) [event/100 participant-years] |
1.88
|
1.50
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Comments | Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Confidence intervals were calculated, if at least 1 event in each treatment arm existed. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.22078 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.26 | |
| Confidence Interval |
(2-Sided) 95% 0.87 to 1.81 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Incidence Rate of the Following: Stroke, Ischemic Stroke, Disabling Stroke, Cardiovascular (CV) Death, Myocardial Infarction |
|---|---|
| Description | Disabling stroke is defined as stroke with modified Rankin score (mRS) greater than or equal to (>=) 4 as assessed by investigator. mRS spans 0-6, running from perfect health to death. A score of 0-3 indicates functional status ranging from no symptoms to "moderate disability" (defined in the mRS as requiring some help, but able to walk without assistance); mRS 4-6 indicates functional status ranging from "moderately severe disability" (unable to walk or to attend to own bodily needs without assistance)through to death. CV death includes death due to hemorrhage and death with undetermined/unknown cause. Diagnosis of myocardial infarction requires combination of: 1) evidence of myocardial necrosis either changes in cardiac biomarkers or post-mortem pathological findings); 2) supporting information derived from clinical presentation, electrocardiographic changes, or results of myocardial or coronary artery imaging. |
| Time Frame | From randomization until the efficacy cut-off date (median 326 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category. |
| Arm/Group Title | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Arm/Group Description | Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD). | Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD). |
| Measure Participants | 3609 | 3604 |
| Stroke |
5.11
|
4.71
|
| Ischemic stroke |
4.71
|
4.56
|
| Disabling stroke |
1.20
|
0.84
|
| CV death(includes death due to hemorrhage) |
0.99
|
0.66
|
| Myocardial infarction |
0.49
|
0.67
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Comments | Statistical analysis 1: Stroke: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.47970 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.08 | |
| Confidence Interval |
(2-Sided) 95% 0.87 to 1.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Comments | Statistical analysis 2: Ischemic stroke: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.78738 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.03 | |
| Confidence Interval |
(2-Sided) 95% 0.83 to 1.29 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Comments | Statistical analysis 3: Disabling stroke: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.14822 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.42 | |
| Confidence Interval |
(2-Sided) 95% 0.88 to 2.28 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Comments | Statistical analysis 4:CV death: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.14051 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.48 | |
| Confidence Interval |
(2-Sided) 95% 0.87 to 2.52 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Comments | Statistical analysis 5: Myocardial infarction: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.34284 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.74 | |
| Confidence Interval |
(2-Sided) 95% 0.39 to 1.38 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Incidence Rate of Life-Threatening Bleeding Events |
|---|---|
| Description | Life-threatening bleeding was defined as a subset of major bleeding that met at least one of the following criteria: 1) fatal bleeding; 2) symptomatic intracranial haemorrhage; 3) reduction in hemoglobin of at least 5 g/dl (50 g/l; 3.10 mmol/L); 4) transfusion of at least 4 units of packed red cells or whole blood; 5) associated with hypotension requiring the use of intravenous inotropic agents; 6) necessitated surgical intervention. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred. |
| Time Frame | From randomization until the efficacy cut-off date (median 326 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category. |
| Arm/Group Title | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Arm/Group Description | Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD). | Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD). |
| Measure Participants | 3609 | 3604 |
| Number (95% Confidence Interval) [event/100 participant-years] |
1.02
|
0.43
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Comments | Statistical analysis: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.00443 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 2.34 | |
| Confidence Interval |
(2-Sided) 95% 1.28 to 4.29 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Incidence Rate of Clinically Relevant Non-Major Bleeding Events |
|---|---|
| Description | Non-major clinically relevant bleeding was defined as non-major overt bleeding but required medical attention (example: hospitalization, medical treatment for bleeding), and/or was associated with the study drug interruption of more than 14 days. The results were based on the outcome events at or after randomization until the efficacy cut-off date. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred. |
| Time Frame | From randomization until the efficacy cut-off date (median 326 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category. |
| Arm/Group Title | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Arm/Group Description | Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD). | Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD). |
| Measure Participants | 3609 | 3604 |
| Number (95% Confidence Interval) [event/100 participant-years] |
3.52
|
2.32
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Comments | Statistical analysis: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.00451 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.51 | |
| Confidence Interval |
(2-Sided) 95% 1.13 to 2.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Incidence Rate of Intracranial Hemorrhage |
|---|---|
| Description | Intracranial hemorrhage included all bleeding events that occurred in intracerebral, sub arachnoidal as well as subdural or epidural sites. The below table displays results for all randomized participants and the outcomes at or after randomization until the efficacy cut-off date. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred. |
| Time Frame | From randomization until the efficacy cut-off date (median 326 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat analysis set included all randomized participants. Participants who were evaluable for this measure at given time period for the arm were included in the category. |
| Arm/Group Title | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Arm/Group Description | Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD). | Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD). |
| Measure Participants | 3609 | 3604 |
| Number (95% Confidence Interval) [event/100 participant-years] |
0.70
|
0.35
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 15 mg OD, Acetylsalicylic Acid 100 mg OD |
|---|---|---|
| Comments | Statistical analysis 1: Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.04409 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 2.01 | |
| Confidence Interval |
(2-Sided) 95% 1.00 to 4.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | From start of study drug administration until 2 days after the last dose of study drug, an average of 279 days | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety analysis set included all randomized participants who received at least one dose of study drug. | |||
| Arm/Group Title | Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD | ||
| Arm/Group Description | Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD). | Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally once daily (OD). | ||
All Cause Mortality |
||||
| Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 73/3562 (2%) | 58/3559 (1.6%) | ||
Serious Adverse Events |
||||
| Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 466/3562 (13.1%) | 434/3559 (12.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 8/3562 (0.2%) | 8 | 3/3559 (0.1%) | 3 |
| Anaemia macrocytic | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Antiphospholipid syndrome | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Febrile neutropenia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Iron deficiency anaemia | 4/3562 (0.1%) | 4 | 1/3559 (0%) | 1 |
| Microcytic anaemia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Pancytopenia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Thrombocytopenia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Thrombotic thrombocytopenic purpura | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Cardiac disorders | ||||
| Angina pectoris | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Aortic valve stenosis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Arrhythmia | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Arrhythmia supraventricular | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Atrial fibrillation | 36/3562 (1%) | 36 | 37/3559 (1%) | 37 |
| Atrial flutter | 5/3562 (0.1%) | 5 | 3/3559 (0.1%) | 3 |
| Atrioventricular block complete | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Atrioventricular block second degree | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Bradycardia | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Cardiac amyloidosis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Cardiac failure | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Cardiac failure chronic | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Cardiac failure congestive | 3/3562 (0.1%) | 3 | 3/3559 (0.1%) | 3 |
| Conduction disorder | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Coronary artery disease | 3/3562 (0.1%) | 3 | 2/3559 (0.1%) | 2 |
| Coronary artery occlusion | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Coronary artery stenosis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hypertensive heart disease | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Myocardial ischaemia | 1/3562 (0%) | 1 | 3/3559 (0.1%) | 3 |
| Myocarditis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Palpitations | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Pericardial effusion | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Sinus bradycardia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Supraventricular tachycardia | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Ventricular tachycardia | 3/3562 (0.1%) | 3 | 0/3559 (0%) | 0 |
| Atrial thrombosis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Ventricular hypokinesia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Coronary artery insufficiency | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Endocarditis noninfective | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||
| Atrial septal defect | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Bicuspid aortic valve | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Hydrocele | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Pulmonary arteriovenous fistula | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Meniere's disease | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Vertigo | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Vertigo positional | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Endocrine disorders | ||||
| Basedow's disease | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Goitre | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Hyperparathyroidism | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hyperthyroidism | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Thyroiditis subacute | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Eye disorders | ||||
| Blindness | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Cataract | 4/3562 (0.1%) | 5 | 8/3559 (0.2%) | 10 |
| Diplopia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Eyelid ptosis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Glaucoma | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Macular oedema | 1/3562 (0%) | 2 | 0/3559 (0%) | 0 |
| Retinal detachment | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Visual impairment | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Macular fibrosis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Ophthalmic vein thrombosis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Colitis ischaemic | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Constipation | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Crohn's disease | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Dental caries | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Diarrhoea | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Diverticulum intestinal | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Duodenal ulcer | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Dyspepsia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Gastric haemorrhage | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Gastric ulcer | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Gastric ulcer haemorrhage | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Gastrointestinal fistula | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Gastrooesophageal reflux disease | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Haemorrhoids | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Hiatus hernia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Ileus | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Inguinal hernia | 7/3562 (0.2%) | 7 | 5/3559 (0.1%) | 5 |
| Intestinal obstruction | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Intestinal perforation | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Large intestinal ulcer | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Nausea | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Pancreatitis | 0/3562 (0%) | 0 | 3/3559 (0.1%) | 3 |
| Pancreatitis acute | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Small intestinal obstruction | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Vomiting | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Pancreatolithiasis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Large intestine polyp | 4/3562 (0.1%) | 4 | 3/3559 (0.1%) | 3 |
| Gastric volvulus | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Abdominal hernia | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Gastric mucosal lesion | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Erosive duodenitis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Rectal fissure | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| General disorders | ||||
| Asthenia | 0/3562 (0%) | 0 | 3/3559 (0.1%) | 3 |
| Fatigue | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Gait disturbance | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hernia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Influenza like illness | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Oedema peripheral | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Pyrexia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Peripheral swelling | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| General physical health deterioration | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Non-cardiac chest pain | 3/3562 (0.1%) | 3 | 4/3559 (0.1%) | 4 |
| Multiple organ dysfunction syndrome | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Hepatobiliary disorders | ||||
| Bile duct stone | 4/3562 (0.1%) | 4 | 1/3559 (0%) | 1 |
| Biliary colic | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Cholangitis | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Cholangitis acute | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Cholecystitis | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Cholecystitis acute | 3/3562 (0.1%) | 3 | 4/3559 (0.1%) | 4 |
| Cholelithiasis | 6/3562 (0.2%) | 6 | 3/3559 (0.1%) | 3 |
| Hepatic cirrhosis | 0/3562 (0%) | 0 | 1/3559 (0%) | 2 |
| Hepatitis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hepatitis acute | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Drug-induced liver injury | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Immune system disorders | ||||
| Anaphylactic reaction | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Anaphylactic shock | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Corneal graft rejection | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Hypersensitivity | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Infections and infestations | ||||
| Appendicitis | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Appendicitis perforated | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Atypical pneumonia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Bacteraemia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Brain abscess | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Bronchitis | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Cellulitis | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Clostridium difficile colitis | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Corneal abscess | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Cystitis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Diabetic gangrene | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Diverticulitis | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Encephalitis viral | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Endophthalmitis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Erysipelas | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Gastroenteritis | 6/3562 (0.2%) | 6 | 3/3559 (0.1%) | 3 |
| Gastroenteritis viral | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Gastrointestinal infection | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hepatitis A | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Infected skin ulcer | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Influenza | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Kidney infection | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Liver abscess | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Localised infection | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Lower respiratory tract infection | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Meningitis | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Orchitis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Osteomyelitis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Otitis externa | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Paronychia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Peritoneal abscess | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Peritonitis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Pneumonia | 14/3562 (0.4%) | 14 | 14/3559 (0.4%) | 14 |
| Postoperative wound infection | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Pyelonephritis chronic | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Renal abscess | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Sepsis | 3/3562 (0.1%) | 3 | 1/3559 (0%) | 1 |
| Septic shock | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Sinusitis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Tooth abscess | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Upper respiratory tract infection | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Urinary tract infection | 6/3562 (0.2%) | 6 | 6/3559 (0.2%) | 7 |
| Vestibular neuronitis | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Viral infection | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Urosepsis | 3/3562 (0.1%) | 3 | 4/3559 (0.1%) | 5 |
| Rectal abscess | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Escherichia bacteraemia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Pneumonia necrotising | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Abdominal infection | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Infective exacerbation of chronic obstructive airways disease | 3/3562 (0.1%) | 4 | 0/3559 (0%) | 0 |
| Neurocysticercosis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Enteritis infectious | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Abdominal abscess | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Bursitis infective | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Lung infection | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Perichondritis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Respiratory tract infection | 3/3562 (0.1%) | 3 | 1/3559 (0%) | 1 |
| Acarodermatitis | 1/3562 (0%) | 2 | 0/3559 (0%) | 0 |
| Herpes zoster oticus | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Lower respiratory tract infection viral | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Biliary tract infection bacterial | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Pneumocystis jirovecii pneumonia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Accidental overdose | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Anastomotic ulcer haemorrhage | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Ankle fracture | 3/3562 (0.1%) | 3 | 2/3559 (0.1%) | 2 |
| Carbon monoxide poisoning | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Compression fracture | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Facial bones fracture | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Fall | 3/3562 (0.1%) | 5 | 2/3559 (0.1%) | 2 |
| Femoral neck fracture | 6/3562 (0.2%) | 6 | 0/3559 (0%) | 0 |
| Femur fracture | 5/3562 (0.1%) | 5 | 2/3559 (0.1%) | 2 |
| Foot fracture | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Head injury | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hip fracture | 1/3562 (0%) | 1 | 5/3559 (0.1%) | 5 |
| Humerus fracture | 2/3562 (0.1%) | 2 | 3/3559 (0.1%) | 3 |
| Intentional overdose | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Joint dislocation | 1/3562 (0%) | 1 | 1/3559 (0%) | 2 |
| Laceration | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Ligament sprain | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Medication error | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Overdose | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Radius fracture | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Rib fracture | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Road traffic accident | 0/3562 (0%) | 0 | 4/3559 (0.1%) | 4 |
| Spinal compression fracture | 3/3562 (0.1%) | 3 | 3/3559 (0.1%) | 3 |
| Spinal fracture | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Subarachnoid haemorrhage | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Wrist fracture | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Traumatic fracture | 0/3562 (0%) | 0 | 3/3559 (0.1%) | 3 |
| Cervical vertebral fracture | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Muscle strain | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Face injury | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Contusion | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Arterial restenosis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Brain contusion | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Thermal burn | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Transplant failure | 0/3562 (0%) | 0 | 1/3559 (0%) | 2 |
| Limb injury | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Traumatic intracranial haemorrhage | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Upper limb fracture | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Ligament rupture | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Bone contusion | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Spinal column injury | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Pubis fracture | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Craniocerebral injury | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Meniscus injury | 0/3562 (0%) | 0 | 3/3559 (0.1%) | 3 |
| Incorrect dosage administered | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Traumatic haemothorax | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Limb fracture | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Investigations | ||||
| Blood creatinine increased | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| C-reactive protein increased | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Eosinophil count increased | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Haemoglobin decreased | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Prostatic specific antigen increased | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Influenza A virus test positive | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Liver function test increased | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Diabetes mellitus | 4/3562 (0.1%) | 4 | 1/3559 (0%) | 1 |
| Diabetic ketoacidosis | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Failure to thrive | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Gout | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Hyperglycaemia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hyponatraemia | 1/3562 (0%) | 2 | 6/3559 (0.2%) | 6 |
| Obesity | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Shock hypoglycaemic | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Diabetic complication | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Diabetic metabolic decompensation | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Adult failure to thrive | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Back pain | 1/3562 (0%) | 1 | 3/3559 (0.1%) | 4 |
| Fasciitis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Gouty arthritis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Groin pain | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Lumbar spinal stenosis | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Muscle spasms | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Musculoskeletal pain | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Myalgia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Neck pain | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Osteoarthritis | 11/3562 (0.3%) | 12 | 3/3559 (0.1%) | 3 |
| Osteonecrosis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Pain in extremity | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Periarthritis | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Rheumatoid arthritis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Rotator cuff syndrome | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Spinal column stenosis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Spinal osteoarthritis | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Synovial cyst | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Myofascial pain syndrome | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Muscle tightness | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Intervertebral disc protrusion | 3/3562 (0.1%) | 3 | 0/3559 (0%) | 0 |
| Musculoskeletal chest pain | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Limb discomfort | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Intervertebral disc disorder | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Plica syndrome | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Vertebral foraminal stenosis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Acute lymphocytic leukaemia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Adenocarcinoma | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Adenocarcinoma gastric | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Adenocarcinoma of colon | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| B-cell lymphoma | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Basal cell carcinoma | 3/3562 (0.1%) | 3 | 2/3559 (0.1%) | 2 |
| Bile duct adenocarcinoma | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Bladder cancer | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Bladder neoplasm | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Bladder transitional cell carcinoma | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Brain neoplasm malignant | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Cervix carcinoma | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Chronic lymphocytic leukaemia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Colon cancer | 3/3562 (0.1%) | 3 | 2/3559 (0.1%) | 2 |
| Colorectal cancer stage IV | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Essential thrombocythaemia | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Fallopian tube cancer | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Gallbladder cancer | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Gastric cancer | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Gastrointestinal carcinoma | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hodgkin's disease | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Kaposi's sarcoma | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Lung adenocarcinoma | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Lung adenocarcinoma stage IV | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Lung carcinoma cell type unspecified stage IV | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Lymphoma | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Malignant melanoma | 1/3562 (0%) | 2 | 0/3559 (0%) | 0 |
| Metastases to bone | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Myelodysplastic syndrome | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Non-Hodgkin's lymphoma | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Oesophageal adenocarcinoma | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Oesophageal carcinoma | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Oropharyngeal cancer | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Pancreatic carcinoma | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Pancreatic carcinoma metastatic | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Papillary thyroid cancer | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Parathyroid tumour | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Plasma cell myeloma | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Rectal adenocarcinoma | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Rectal cancer | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Rectal cancer stage III | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Spinal meningioma benign | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Squamous cell carcinoma of lung | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Squamous cell carcinoma of the tongue | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Transitional cell carcinoma | 3/3562 (0.1%) | 3 | 0/3559 (0%) | 0 |
| Uterine leiomyoma | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Rectal adenoma | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Lung cancer metastatic | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Metastases to peritoneum | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Intestinal adenocarcinoma | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Neuroendocrine tumour | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Lung neoplasm malignant | 1/3562 (0%) | 1 | 5/3559 (0.1%) | 5 |
| Pancreatic carcinoma stage IV | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Prostate cancer | 1/3562 (0%) | 1 | 8/3559 (0.2%) | 8 |
| Benign bone neoplasm | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Brain neoplasm | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Renal neoplasm | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Oesophageal squamous cell carcinoma | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Pituitary tumour benign | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Non-small cell lung cancer | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Pancreatic neoplasm | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Lung neoplasm | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Thyroid cancer | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Renal cell carcinoma | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Metastatic uterine cancer | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Inflammatory pseudotumour | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Malignant neoplasm of unknown primary site | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hepatic cancer | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Invasive breast carcinoma | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Nervous system disorders | ||||
| Amyotrophic lateral sclerosis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Autonomic nervous system imbalance | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Brain stem haemorrhage | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Carotid artery stenosis | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Cerebellar haemorrhage | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Cerebral haemorrhage | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Cerebral venous thrombosis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Cerebrovascular accident | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Chorea | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Demyelination | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Diabetic neuropathy | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Dizziness | 2/3562 (0.1%) | 2 | 4/3559 (0.1%) | 4 |
| Dysarthria | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Epilepsy | 7/3562 (0.2%) | 8 | 8/3559 (0.2%) | 8 |
| Facial paralysis | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Generalised tonic-clonic seizure | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Headache | 2/3562 (0.1%) | 2 | 3/3559 (0.1%) | 3 |
| Hemiparesis | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Hypoaesthesia | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Intracranial aneurysm | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Loss of consciousness | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Migraine | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Migraine with aura | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Multiple sclerosis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Myelopathy | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Nervous system disorder | 1/3562 (0%) | 1 | 4/3559 (0.1%) | 4 |
| Paraesthesia | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Polyneuropathy | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Post herpetic neuralgia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Presyncope | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Sciatica | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Seizure | 9/3562 (0.3%) | 10 | 9/3559 (0.3%) | 9 |
| Status epilepticus | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Syncope | 10/3562 (0.3%) | 10 | 8/3559 (0.2%) | 8 |
| Tension headache | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Transient global amnesia | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Vertebrobasilar insufficiency | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Cervical radiculopathy | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Thalamus haemorrhage | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Putamen haemorrhage | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Stroke in evolution | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Partial seizures | 5/3562 (0.1%) | 5 | 2/3559 (0.1%) | 2 |
| Parkinson's disease | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Metabolic encephalopathy | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Cerebral artery stenosis | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Central pain syndrome | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Cerebral arteriosclerosis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Post stroke seizure | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 3 |
| Hemianaesthesia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Pseudostroke | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Hemiparaesthesia | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Focal dyscognitive seizures | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Product Issues | ||||
| Device malfunction | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Psychiatric disorders | ||||
| Adjustment disorder with mixed anxiety and depressed mood | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Alcohol abuse | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Alcoholism | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Anxiety | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Completed suicide | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Conversion disorder | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Delirium | 2/3562 (0.1%) | 2 | 3/3559 (0.1%) | 3 |
| Depression | 3/3562 (0.1%) | 3 | 1/3559 (0%) | 1 |
| Depression suicidal | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Disorientation | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hallucination, visual | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Intentional self-injury | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Mania | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Obsessive-compulsive personality disorder | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Panic disorder | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Panic reaction | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Schizophrenia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Somnambulism | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Suicide attempt | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Alcohol withdrawal syndrome | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Major depression | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Neurologic somatic symptom disorder | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Alcohol use disorder | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Renal and urinary disorders | ||||
| Acute prerenal failure | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hydronephrosis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Nephrolithiasis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Renal colic | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 3 |
| Renal cyst | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Renal failure | 2/3562 (0.1%) | 2 | 3/3559 (0.1%) | 3 |
| Renal haematoma | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Renal hypertension | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Urinary retention | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Costovertebral angle tenderness | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Renal impairment | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Chronic kidney disease | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Urethral stenosis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Acute kidney injury | 4/3562 (0.1%) | 4 | 6/3559 (0.2%) | 6 |
| Ureterolithiasis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 4/3562 (0.1%) | 4 | 2/3559 (0.1%) | 2 |
| Menorrhagia | 0/3562 (0%) | 0 | 1/3559 (0%) | 2 |
| Peyronie's disease | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Prostatitis | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Uterine prolapse | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Endometrial dysplasia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Genital haemorrhage | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Asthma | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Chronic obstructive pulmonary disease | 3/3562 (0.1%) | 3 | 3/3559 (0.1%) | 4 |
| Dyspnoea | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Hiccups | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Idiopathic pulmonary fibrosis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Lung disorder | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Pleural effusion | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Pneumonia aspiration | 3/3562 (0.1%) | 3 | 0/3559 (0%) | 0 |
| Pulmonary embolism | 1/3562 (0%) | 1 | 8/3559 (0.2%) | 8 |
| Pulmonary oedema | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Respiratory failure | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Sleep apnoea syndrome | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Pulmonary mass | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Bronchial disorder | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Dermatomyositis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Erythema multiforme | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Psoriasis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Rash | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Skin reaction | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Diabetic foot | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Surgical and medical procedures | ||||
| Atrial septal defect repair | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Finger amputation | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Vascular disorders | ||||
| Aortic aneurysm | 3/3562 (0.1%) | 3 | 2/3559 (0.1%) | 2 |
| Aortic aneurysm rupture | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Aortic stenosis | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Embolism venous | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Hypertension | 4/3562 (0.1%) | 4 | 6/3559 (0.2%) | 6 |
| Hypertensive crisis | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Hypotension | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Lymphoedema | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Orthostatic hypotension | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Peripheral ischaemia | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Peripheral vascular disorder | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Temporal arteritis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Thrombophlebitis superficial | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Varicose vein | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Post thrombotic syndrome | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Deep vein thrombosis | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Peripheral artery occlusion | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Peripheral arterial occlusive disease | 5/3562 (0.1%) | 5 | 5/3559 (0.1%) | 6 |
| May-Thurner syndrome | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Peripheral artery stenosis | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Rivaroxaban 15 mg OD | Acetylsalicylic Acid 100 mg OD | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 308/3562 (8.6%) | 294/3559 (8.3%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Antiphospholipid syndrome | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Iron deficiency anaemia | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Thrombocytopenia | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Thrombocytosis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Cardiac disorders | ||||
| Angina pectoris | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Atrial fibrillation | 60/3562 (1.7%) | 60 | 60/3559 (1.7%) | 60 |
| Atrial flutter | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Atrial tachycardia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Cardiac failure | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Cardiac failure congestive | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Coronary artery disease | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Myocardial ischaemia | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Palpitations | 3/3562 (0.1%) | 3 | 1/3559 (0%) | 1 |
| Sinus arrhythmia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Sinus tachycardia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Supraventricular extrasystoles | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Supraventricular tachycardia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Tachycardia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Ventricular fibrillation | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Intracardiac thrombus | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Cardiac flutter | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||
| Atrial septal defect | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Fabry's disease | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Factor V Leiden mutation | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Ear and labyrinth disorders | ||||
| Tinnitus | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Vertigo | 2/3562 (0.1%) | 2 | 4/3559 (0.1%) | 4 |
| Vertigo positional | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Endocrine disorders | ||||
| Hypothyroidism | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Thyroiditis subacute | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Thyroid mass | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Eye disorders | ||||
| Cataract | 1/3562 (0%) | 2 | 2/3559 (0.1%) | 2 |
| Conjunctival haemorrhage | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Diabetic retinopathy | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Dry eye | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Episcleritis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Eyelid ptosis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Keratitis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Pterygium | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Retinal vein occlusion | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Vision blurred | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Conjunctival hyperaemia | 1/3562 (0%) | 2 | 0/3559 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Abdominal pain | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Abdominal pain lower | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Abdominal pain upper | 5/3562 (0.1%) | 5 | 7/3559 (0.2%) | 7 |
| Cheilitis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Chronic gastritis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Constipation | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Defaecation urgency | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Diarrhoea | 8/3562 (0.2%) | 8 | 3/3559 (0.1%) | 3 |
| Dyspepsia | 2/3562 (0.1%) | 2 | 3/3559 (0.1%) | 4 |
| Eructation | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Gastric ulcer | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Gastritis | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Gastritis erosive | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Gastrooesophageal reflux disease | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Gastrointestinal disorder | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Gingival bleeding | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Gingival swelling | 0/3562 (0%) | 0 | 1/3559 (0%) | 2 |
| Haemorrhoids | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hyperchlorhydria | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Inflammatory bowel disease | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Inguinal hernia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Lip swelling | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Nausea | 5/3562 (0.1%) | 5 | 1/3559 (0%) | 1 |
| Oesophagitis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Retching | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Toothache | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Vomiting | 2/3562 (0.1%) | 2 | 4/3559 (0.1%) | 4 |
| Palatal disorder | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Colitis microscopic | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| General disorders | ||||
| Asthenia | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Chest discomfort | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Chest pain | 3/3562 (0.1%) | 3 | 4/3559 (0.1%) | 4 |
| Chills | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Discomfort | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Fatigue | 2/3562 (0.1%) | 2 | 3/3559 (0.1%) | 3 |
| Gait disturbance | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Malaise | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Oedema peripheral | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Peripheral swelling | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Non-cardiac chest pain | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Biliary colic | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hepatic function abnormal | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Hepatitis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Hypertransaminasaemia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Immune system disorders | ||||
| Hypersensitivity | 3/3562 (0.1%) | 3 | 1/3559 (0%) | 3 |
| Allergy to arthropod sting | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Infections and infestations | ||||
| Bronchitis | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Cystitis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Diarrhoea infectious | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Gastroenteritis | 3/3562 (0.1%) | 3 | 1/3559 (0%) | 1 |
| Herpes zoster | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Influenza | 1/3562 (0%) | 1 | 1/3559 (0%) | 2 |
| Lower respiratory tract infection | 1/3562 (0%) | 2 | 0/3559 (0%) | 0 |
| Oesophageal candidiasis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Pneumonia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Pneumonia viral | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Upper respiratory tract infection | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 2 |
| Urinary tract infection | 3/3562 (0.1%) | 3 | 4/3559 (0.1%) | 4 |
| Vaginal infection | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Vulvovaginitis trichomonal | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Helicobacter infection | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Lung infection | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Respiratory tract infection viral | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Alveolar osteitis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Accident | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Alcohol poisoning | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Concussion | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Fall | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Foot fracture | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Head injury | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Humerus fracture | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Inappropriate schedule of drug administration | 1/3562 (0%) | 2 | 0/3559 (0%) | 0 |
| Medication error | 10/3562 (0.3%) | 10 | 9/3559 (0.3%) | 9 |
| Overdose | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Radius fracture | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Rib fracture | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Tendon rupture | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Face injury | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Contusion | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Post procedural haemorrhage | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Limb injury | 3/3562 (0.1%) | 3 | 1/3559 (0%) | 1 |
| Upper limb fracture | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Drug administration error | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Incorrect dose administered | 6/3562 (0.2%) | 6 | 4/3559 (0.1%) | 4 |
| Labelled drug-drug interaction medication error | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Skin wound | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Incorrect dosage administered | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Medication monitoring error | 1/3562 (0%) | 1 | 3/3559 (0.1%) | 3 |
| Intentional product misuse | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Investigations | ||||
| Alanine aminotransferase increased | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Blood creatine phosphokinase increased | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Blood creatinine increased | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Coagulation factor VIII level increased | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Glomerular filtration rate decreased | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Haemoglobin decreased | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Heart rate increased | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Visual acuity tests abnormal | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Weight decreased | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Transaminases increased | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Blood alkaline phosphatase increased | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Hepatic enzyme increased | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Liver function test increased | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Diabetes mellitus | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Electrolyte imbalance | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Gout | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Haemochromatosis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hypercholesterolaemia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Hyperglycaemia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Decreased appetite | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Type 2 diabetes mellitus | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/3562 (0%) | 1 | 4/3559 (0.1%) | 4 |
| Arthritis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Back pain | 4/3562 (0.1%) | 4 | 3/3559 (0.1%) | 3 |
| Bursitis | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Chondrocalcinosis pyrophosphate | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Gouty arthritis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Haemarthrosis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Joint swelling | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Metatarsalgia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Muscle spasms | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Muscular weakness | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Musculoskeletal pain | 1/3562 (0%) | 1 | 4/3559 (0.1%) | 4 |
| Myalgia | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Myopathy | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Osteoarthritis | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Osteochondrosis | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Pain in extremity | 3/3562 (0.1%) | 3 | 1/3559 (0%) | 1 |
| Periostitis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Plantar fasciitis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Spinal osteoarthritis | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Synovial cyst | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Tendonitis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Tenosynovitis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Limb mass | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Basosquamous carcinoma | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Breast cancer | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Breast neoplasm | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Essential thrombocythaemia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Metastases to bone | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Superficial spreading melanoma stage unspecified | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Nervous system disorders | ||||
| Amnesia | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Aphasia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Cerebrovascular accident | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Dementia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Dizziness | 5/3562 (0.1%) | 6 | 7/3559 (0.2%) | 7 |
| Dizziness postural | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Dysarthria | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Dysgeusia | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Epilepsy | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Facial paralysis | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Headache | 10/3562 (0.3%) | 10 | 8/3559 (0.2%) | 9 |
| Hypoaesthesia | 1/3562 (0%) | 1 | 3/3559 (0.1%) | 3 |
| Lethargy | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Migraine | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Paraesthesia | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Parkinsonism | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Presyncope | 1/3562 (0%) | 1 | 2/3559 (0.1%) | 2 |
| Sciatica | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Seizure | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Sensory disturbance | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Somnolence | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Speech disorder | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Syncope | 2/3562 (0.1%) | 2 | 3/3559 (0.1%) | 4 |
| Vertebral artery occlusion | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Cervical radiculopathy | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hyposmia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Facial paresis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| IIIrd nerve paresis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Cognitive disorder | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Vascular dementia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Stroke in evolution | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Partial seizures | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Parkinson's disease | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Autonomic neuropathy | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Cerebral artery stenosis | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Occipital neuralgia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Psychiatric disorders | ||||
| Anxiety | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Depression | 3/3562 (0.1%) | 3 | 2/3559 (0.1%) | 2 |
| Insomnia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Panic attack | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Impatience | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Abulia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Anxiety disorder | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Mental disorder due to a general medical condition | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Adjustment disorder | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Post stroke depression | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Renal and urinary disorders | ||||
| Haematuria | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Nephrolithiasis | 2/3562 (0.1%) | 2 | 0/3559 (0%) | 0 |
| Renal colic | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Renal failure | 3/3562 (0.1%) | 3 | 0/3559 (0%) | 0 |
| Urinary incontinence | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Renal impairment | 2/3562 (0.1%) | 2 | 2/3559 (0.1%) | 2 |
| Chronic kidney disease | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Ureterolithiasis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Breast mass | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Prostatitis | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Prostatomegaly | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Cough | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Dry throat | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Dyspnoea | 4/3562 (0.1%) | 4 | 1/3559 (0%) | 1 |
| Epistaxis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hiccups | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Pharyngeal ulceration | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Pulmonary embolism | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Pulmonary microemboli | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Acne | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Alopecia | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Angioedema | 0/3562 (0%) | 0 | 1/3559 (0%) | 2 |
| Dermatitis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Dermatitis allergic | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Drug eruption | 0/3562 (0%) | 0 | 3/3559 (0.1%) | 3 |
| Eczema | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Erythema | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Pruritus | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Rash | 4/3562 (0.1%) | 4 | 4/3559 (0.1%) | 4 |
| Rash erythematous | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Rash papular | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Rash pruritic | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Skin lesion | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Urticaria | 2/3562 (0.1%) | 2 | 3/3559 (0.1%) | 3 |
| Precancerous skin lesion | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Skin swelling | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Solar lentigo | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Social circumstances | ||||
| Treatment noncompliance | 2/3562 (0.1%) | 2 | 5/3559 (0.1%) | 5 |
| Surgical and medical procedures | ||||
| Tooth extraction | 2/3562 (0.1%) | 3 | 2/3559 (0.1%) | 2 |
| Cataract operation | 1/3562 (0%) | 1 | 1/3559 (0%) | 1 |
| Implantable cardiac monitor insertion | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Vascular disorders | ||||
| Aortic aneurysm | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Flushing | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Hypertension | 11/3562 (0.3%) | 11 | 7/3559 (0.2%) | 8 |
| Hypertensive crisis | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Hypotension | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Intermittent claudication | 1/3562 (0%) | 1 | 0/3559 (0%) | 0 |
| Phlebitis superficial | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Thrombophlebitis superficial | 0/3562 (0%) | 0 | 2/3559 (0.1%) | 2 |
| Varicose vein | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Vascular pain | 0/3562 (0%) | 0 | 1/3559 (0%) | 1 |
| Deep vein thrombosis | 2/3562 (0.1%) | 2 | 1/3559 (0%) | 1 |
| Peripheral arterial occlusive disease | 3/3562 (0.1%) | 3 | 0/3559 (0%) | 0 |
Limitations/Caveats
Study terminated early due to no efficacy improvement over aspirin at the second interim analysis and very little chance of showing overall benefit if the study were completed.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Global PI to provide to Bayer for review any proposed Publication/oral presentation relating to Study/Study Drug/Results at least 20 days prior to submission or presentation of the Publication. Abstracts/posters/oral presentations to be provided to Bayer 5 working days before Publication/presentation. Bayer may provide comments within the applicable period. Under certain circumstances Bayer may request a further delay of publications to avoid adverse effects on a Bayer patent application.
Results Point of Contact
| Name/Title | Therapeutic Area Head |
|---|---|
| Organization | Bayer |
| Phone | 1-888-8422937 |
| clinical-trials-contact@bayer.com |
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT02313909
Other Study ID Numbers:
- 16573
- 2013-000768-27
First Posted:
Dec 10, 2014
Last Update Posted:
Jan 9, 2019
Last Verified:
Dec 1, 2018