COMPASS: Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease
Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT01776424
Collaborator
Population Health Research Institute (Other), Janssen Research & Development, LLC (Industry)
27,395
565
3
99.5
48.5
0.5
Study Details
Study Description
Brief Summary
The primary objectives of this study are:
-
To determine whether rivaroxaban 2.5 mg twice daily (bid) + aspirin 100 mg once daily (od) compared with aspirin 100 mg od reduces the risk of a composite of myocardial infarction, stroke, or cardiovascular death in subjects with coronary artery disease (CAD) or peripheral artery disease (PAD);
-
To determine whether rivaroxaban 5 mg bid compared with aspirin 100 mg od reduces the risk of a composite of myocardial infarction, stroke or cardiovascular death in subjects with CAD or PAD.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
27395 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
A Randomized Controlled Trial of Rivaroxaban for the Prevention of Major Cardiovascular Events in Patients With Coronary or Peripheral Artery Disease (COMPASS - Cardiovascular OutcoMes for People Using Anticoagulation StrategieS).
Actual Study Start Date
:
Feb 28, 2013
Actual Primary Completion Date
:
Jul 21, 2017
Actual Study Completion Date
:
Jun 15, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Rivaroxaban [2.5mg] + Aspirin Rivaroxaban 2.5 mg twice daily and Aspirin 100 mg once daily. (Long-term open-label extension was added to make rivaroxaban 2.5 mg twice daily + aspirin 100 mg once daily available to COMPASS trial subjects until the rivaroxaban treatment is commercially available for this indication or for approximately 3 years from regulatory approval of the long term open label extension in a country, whichever comes first.) |
Drug: Rivaroxaban (Xarelto, BAY59-7939)
Rivaroxaban 2.5 mg twice daily, tablet
Drug: Aspirin
Aspirin 100 mg once daily, tablet
Drug: Pantoprazole
Subjects who are not on a proton pump inhibitor (PPI) will also be randomized to pantoprazole or pantoprazole placebo
|
| Experimental: Rivaroxaban [5mg] + Placebo(1) Rivaroxaban 5 mg twice daily and Aspirin Placebo once daily |
Drug: Rivaroxaban (Xarelto, BAY59-7939)
Rivaroxaban 5.0 mg twice daily, tablet
Drug: Aspirin placebo
Placebo(1), matching Aspirin tablets
Drug: Pantoprazole
Subjects who are not on a proton pump inhibitor (PPI) will also be randomized to pantoprazole or pantoprazole placebo
|
| Active Comparator: Aspirin + Placebo(2) Rivaroxaban Placebo twice daily and Aspirin 100 mg once daily |
Drug: Aspirin
Aspirin 100 mg once daily, tablet
Drug: Rivaroxaban placebo
Placebo(2), matching Rivaroxaban tablets
Drug: Pantoprazole
Subjects who are not on a proton pump inhibitor (PPI) will also be randomized to pantoprazole or pantoprazole placebo
|
Outcome Measures
Primary Outcome Measures
- The First Occurrence of the Composite Primary Efficacy Outcome, Myocardial Infarction (MI), Stroke, or Cardiovascular (CV) Death [For each participant, the first occurrence of the composite primary efficacy outcome after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days.]
Count of participants and time from randomization to the first occurrence of the composite primary efficacy outcome, MI, stroke, or CV death were evaluated. Hazard ratios were calculated and reported as statistical analysis.
- The First Occurrence of the Primary Safety Outcome Major Bleeding Based on a Modification of the International Society on Thrombosis and Haemostasis (ISTH) Criteria [For each participant, the first occurrence of modified ISTH major bleeding after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days.]
Modified ISTH major bleeding is defined as: i) Fatal bleeding, or ii) Symptomatic bleeding in a critical area or organ, such as intraarticular, intracranial, intramuscular with compartment syndrome, intraocular, intraspinal, liver, pancreas, pericardial, respiratory, retroperitoneal, adrenal gland or kidney; or bleeding into the surgical site requiring reoperation, or iii) Bleeding leading to hospitalization (major bleeding also includes presentation to an acute care facility with discharge on the same day). Count of participants and time from randomization to the first occurrence of the primary safety outcome major bleeding were evaluated. Hazard ratios were calculated and reported as statistical analysis.
Secondary Outcome Measures
- The First Occurrence of Myocardial Infarction (MI), Ischemic Stroke, Acute Limb Ischemia (ALI), or Coronary Heart Disease (CHD) Death [For each participant, the first occurrence of MI, ALI, or CHD death after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days.]
Count of participants and time from randomization to the first occurrence of MI, ischemic stroke, ALI, or CHD death were evaluated. Hazard ratios were calculated and reported as statistical analysis.
- The First Occurrence of MI, Ischemic Stroke, ALI, or Cardiovascular (CV) Death [For each participant, the first occurrence of MI, ischemic stroke, ALI, or CV death after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days.]
Count of participants and time from randomization to the first occurrence of MI, ischemic stroke, ALI, or CV death were evaluated. Hazard ratios were calculated and reported as statistical analysis.
- All-cause Mortality [For each participants, death by any cause after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days.]
Count of participants and time from randomization to death by all cause were evaluated. Hazard ratios were calculated and reported as statistical analysis.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-- Coronary or peripheral artery disease
Patients with coronary artery disease must also meet at least one of the following:
-
Age ≥65, or
-
Age <65 and documented atherosclerosis or revascularization involving at least 2 vascular beds, or at least 2 additional risk factors
Exclusion Criteria:
-
Need for dual antiplatelet therapy, other non-aspirin antiplatelet therapy or oral anticoagulant therapy
-
Stroke within 1 month or any history of hemorrhagic or lacunar stroke
-
Severe heart failure with known ejection fraction <30% or New York Heart Association (NYHA) class III or IV symptoms
-
Estimated glomerular filtration rate (eGFR)<15 mL/min
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Birmingham | Alabama | United States | 35294 | |
| 2 | Mobile | Alabama | United States | 36608 | |
| 3 | Anaheim | California | United States | 92801 | |
| 4 | Laguna Hills | California | United States | 92653 | |
| 5 | Northridge | California | United States | 91324 | |
| 6 | Palo Alto | California | United States | 94304-1207 | |
| 7 | Santa Rosa | California | United States | 95494 | |
| 8 | Sylmar | California | United States | 91342 | |
| 9 | Torrance | California | United States | 90502-2004 | |
| 10 | Norwalk | Connecticut | United States | 06851 | |
| 11 | Stamford | Connecticut | United States | 06905 | |
| 12 | Trumbull | Connecticut | United States | 06611 | |
| 13 | Atlantis | Florida | United States | 33462 | |
| 14 | Clearwater | Florida | United States | 33756 | |
| 15 | Coral Springs | Florida | United States | 33065 | |
| 16 | Jacksonville Beach | Florida | United States | 32250 | |
| 17 | Largo | Florida | United States | 33770 | |
| 18 | New Port Richey | Florida | United States | 34653 | |
| 19 | Safety Harbor | Florida | United States | 34695 | |
| 20 | Sarasota | Florida | United States | 34239 | |
| 21 | Meridian | Idaho | United States | 83716 | |
| 22 | Arlington Heights | Illinois | United States | 60005 | |
| 23 | Hazel Crest | Illinois | United States | 60429 | |
| 24 | Davenport | Iowa | United States | 52803 | |
| 25 | West Des Moines | Iowa | United States | 50266 | |
| 26 | Crestview Hills | Kentucky | United States | 41017-5460 | |
| 27 | Baltimore | Maryland | United States | 21215 | |
| 28 | Haverhill | Massachusetts | United States | 01830 | |
| 29 | Alpena | Michigan | United States | 49707 | |
| 30 | Jackson | Michigan | United States | 49201 | |
| 31 | Saint Louis | Missouri | United States | 63136 | |
| 32 | Kalispell | Montana | United States | 59901 | |
| 33 | New Brunswick | New Jersey | United States | 08901 | |
| 34 | Cortlandt Manor | New York | United States | 10567 | |
| 35 | Kingston | New York | United States | 12401 | |
| 36 | Saratoga Springs | New York | United States | 12866 | |
| 37 | Durham | North Carolina | United States | 27713 | |
| 38 | Pinehurst | North Carolina | United States | 28374 | |
| 39 | Elyria | Ohio | United States | 44035 | |
| 40 | Sandusky | Ohio | United States | 44870 | |
| 41 | Toledo | Ohio | United States | 43606 | |
| 42 | Doylestown | Pennsylvania | United States | 18901 | |
| 43 | Langhorne | Pennsylvania | United States | 19047 | |
| 44 | Yardley | Pennsylvania | United States | 19067 | |
| 45 | Sioux Falls | South Dakota | United States | 57108 | |
| 46 | Dallas | Texas | United States | 75216-7167 | |
| 47 | Houston | Texas | United States | 77030-4298 | |
| 48 | Houston | Texas | United States | 77030 | |
| 49 | San Antonio | Texas | United States | 78229 | |
| 50 | Bellevue | Washington | United States | 98004-4623 | |
| 51 | Puyallup | Washington | United States | 98372 | |
| 52 | Seattle | Washington | United States | 98195 | |
| 53 | Spokane | Washington | United States | 99204 | |
| 54 | Adrogue | Buenos Aires | Argentina | 1846 | |
| 55 | Bahía Blanca | Buenos Aires | Argentina | 8000 | |
| 56 | Coronel Suarez | Buenos Aires | Argentina | B7540GHD | |
| 57 | Junín | Buenos Aires | Argentina | B6000BHA | |
| 58 | La Plata | Buenos Aires | Argentina | 1900 | |
| 59 | La Plata | Buenos Aires | Argentina | B1902AGY | |
| 60 | La Plata | Buenos Aires | Argentina | B1902CNF | |
| 61 | La Plata | Buenos Aires | Argentina | B1902COS | |
| 62 | Mar del Plata | Buenos Aires | Argentina | B7600FZN | |
| 63 | Merlo | Buenos Aires | Argentina | B1722COV | |
| 64 | Munro | Buenos Aires | Argentina | B1605DSX | |
| 65 | Quilmes | Buenos Aires | Argentina | 1878 | |
| 66 | Ramos Mejía | Buenos Aires | Argentina | B1740ETD | |
| 67 | San Martín | Buenos Aires | Argentina | 1650 | |
| 68 | San Nicolás | Buenos Aires | Argentina | B2900DMH | |
| 69 | Vicente López | Buenos Aires | Argentina | B1602ABQ | |
| 70 | Zárate | Buenos Aires | Argentina | B2800DGH | |
| 71 | Buenos Aires | Ciudad Auton. De Buenos Aires | Argentina | C1119ACN | |
| 72 | Buenos Aires | Ciudad Auton. De Buenos Aires | Argentina | C1428ART | |
| 73 | Buenos Aires | Ciudad Auton. De Buenos Aires | Argentina | C1440AAD | |
| 74 | Ciudad Autón. de Buenos Aires | Ciudad Auton. De Buenos Aires | Argentina | C1425AGC | |
| 75 | Villa Allende | Córdoba | Argentina | ||
| 76 | Villa María | Córdoba | Argentina | X5900JKA | |
| 77 | Santa Rosa | La Pampa | Argentina | 6300 | |
| 78 | Rafaela | Santa Fe | Argentina | S2300MMA | |
| 79 | Rosario | Santa Fe | Argentina | 2000 | |
| 80 | Rosario | Santa Fe | Argentina | S2005PAF | |
| 81 | Rosario | Santa Fe | Argentina | ||
| 82 | Venado Tuerto | Santa Fe | Argentina | S2600KUE | |
| 83 | San Miguel de Tucumán | Tucuman | Argentina | 4000 | |
| 84 | San Miguel de Tucumán | Tucuman | Argentina | T4000IFL | |
| 85 | Ciudad Auton. de Buenos Aires | Argentina | C1023AAB | ||
| 86 | Ciudad Auton. de Buenos Aires | Argentina | C1181ACL | ||
| 87 | Ciudad Auton. de Buenos Aires | Argentina | C1405BUB | ||
| 88 | Corrientes | Argentina | 3400 | ||
| 89 | Córdoba | Argentina | X5000AAW Córdoba | ||
| 90 | Córdoba | Argentina | X5000AAX | ||
| 91 | Córdoba | Argentina | X5003DCE | ||
| 92 | Córdoba | Argentina | X5003DCP | ||
| 93 | Córdoba | Argentina | X5004CDT | ||
| 94 | Córdoba | Argentina | X5006IKK | ||
| 95 | Salta | Argentina | A4406CLA | ||
| 96 | San Juan | Argentina | 5400 | ||
| 97 | San luis | Argentina | 5700 | ||
| 98 | Santa Fe | Argentina | S3000FWO | ||
| 99 | Bruce | Australian Capital Territory | Australia | 2617 | |
| 100 | Gosford | New South Wales | Australia | 2250 | |
| 101 | New Lambton Heights | New South Wales | Australia | 2305 | |
| 102 | Birtinya | Queensland | Australia | 4575 | |
| 103 | Brisbane | Queensland | Australia | 4029 | |
| 104 | Brisbane | Queensland | Australia | 4064 | |
| 105 | Redcliffe | Queensland | Australia | 4020 | |
| 106 | Woolloongabba | Queensland | Australia | 4102 | |
| 107 | Adelaide | South Australia | Australia | 5042 | |
| 108 | Hobart | Tasmania | Australia | 7000 | |
| 109 | Launceston | Tasmania | Australia | 7250 | |
| 110 | Geelong | Victoria | Australia | 3220 | |
| 111 | Melbourne | Victoria | Australia | 3052 | |
| 112 | Melbourne | Victoria | Australia | 3181 | |
| 113 | Prahran | Victoria | Australia | 3181 | |
| 114 | Murdoch | Western Australia | Australia | 6150 | |
| 115 | Nedlands | Western Australia | Australia | 6009 | |
| 116 | Taree | Australia | 2430 | ||
| 117 | Antwerpen | Belgium | 2020 | ||
| 118 | Bonheiden | Belgium | 2820 | ||
| 119 | Brugge | Belgium | 8000 | ||
| 120 | Bruxelles - Brussel | Belgium | 1070 | ||
| 121 | Charleroi | Belgium | 6000 | ||
| 122 | Genk | Belgium | 3600 | ||
| 123 | Hasselt | Belgium | 3500 | ||
| 124 | Kortrijk | Belgium | 8500 | ||
| 125 | Leuven | Belgium | 3000 | ||
| 126 | Liege | Belgium | 4000 | ||
| 127 | Roeselare | Belgium | 8800 | ||
| 128 | Goiania | Goiás | Brazil | 74223 130 | |
| 129 | Belo Horizonte | Minas Gerais | Brazil | 30150-240 | |
| 130 | Uberaba | Minas Gerais | Brazil | 38025-260 | |
| 131 | Uberlândia | Minas Gerais | Brazil | 38411-186 | |
| 132 | Campina Grande do Sul | Parana | Brazil | 83430 000 | |
| 133 | Curitiba | Parana | Brazil | 80730-150 | |
| 134 | Canoas | Rio Grande Do Sul | Brazil | 92425-900 | |
| 135 | Pelotas | Rio Grande Do Sul | Brazil | 96015-290 | |
| 136 | Porto Alegre | Rio Grande Do Sul | Brazil | 90.620-001 | |
| 137 | Porto Alegre | Rio Grande Do Sul | Brazil | 90020-090 | |
| 138 | Porto Alegre | Rio Grande Do Sul | Brazil | 90840-440 | |
| 139 | Porto Alegre | Rio Grande Do Sul | Brazil | ||
| 140 | Blumenau | Santa Catarina | Brazil | 89010 500 | |
| 141 | Campinas | Sao Paulo | Brazil | 13010-001 | |
| 142 | Campinas | Sao Paulo | Brazil | 13020-421 | |
| 143 | Campinas | Sao Paulo | Brazil | 13060904 | |
| 144 | Matão | Sao Paulo | Brazil | 15990-060 | |
| 145 | São José do Rio Preto | Sao Paulo | Brazil | 15015-750 | |
| 146 | São José do Rio Preto | Sao Paulo | Brazil | 15090 | |
| 147 | São Paulo | Sao Paulo | Brazil | 01506-001 | |
| 148 | São Paulo | Sao Paulo | Brazil | 04012-909 | |
| 149 | Votuporanga | Sao Paulo | Brazil | ||
| 150 | Sao Paulo | Brazil | 05403-000 | ||
| 151 | Calgary | Alberta | Canada | T2N 4Z6 | |
| 152 | Edmonton | Alberta | Canada | T6G 2B7 | |
| 153 | New Westminster | British Columbia | Canada | V3L 3W4 | |
| 154 | Victoria | British Columbia | Canada | V8R 4R2 | |
| 155 | Winnipeg | Manitoba | Canada | R2H 0R8 | |
| 156 | Winnipeg | Manitoba | Canada | R2H 2A6 | |
| 157 | Winnipeg | Manitoba | Canada | R2V 4W3 | |
| 158 | Winnipeg | Manitoba | Canada | R3T 2E8 | |
| 159 | Moncton | New Brunswick | Canada | E1G 1A7 | |
| 160 | Saint John | New Brunswick | Canada | E2L 4L2 | |
| 161 | Halifax | Nova Scotia | Canada | B3H 3A7 | |
| 162 | Brampton | Ontario | Canada | L6W 2X7 | |
| 163 | Burlington | Ontario | Canada | L7M 4Y1 | |
| 164 | Burlington | Ontario | Canada | L7R 1E2 | |
| 165 | Cambridge | Ontario | Canada | N1R 6V6 | |
| 166 | Cambridge | Ontario | Canada | N1R 7R1 | |
| 167 | Grimsby | Ontario | Canada | L3M 1P3 | |
| 168 | Hamilton | Ontario | Canada | L8L 2X2 | |
| 169 | Hamilton | Ontario | Canada | L8M 1K7 | |
| 170 | London | Ontario | Canada | N6A 5A5 | |
| 171 | London | Ontario | Canada | N6G 2M1 | |
| 172 | Mississauga | Ontario | Canada | L5K 2L3 | |
| 173 | Newmarket | Ontario | Canada | L3Y 2P6 | |
| 174 | Newmarket | Ontario | Canada | L3Y 8C3 | |
| 175 | Oakville | Ontario | Canada | L6K 3W7 | |
| 176 | Oshawa | Ontario | Canada | L1J 2J9 | |
| 177 | Oshawa | Ontario | Canada | L1J 2K1 | |
| 178 | Ottawa | Ontario | Canada | K2H 8T5 | |
| 179 | Peterborough | Ontario | Canada | K9J 0B2 | |
| 180 | Scarborough | Ontario | Canada | M1E 5E9 | |
| 181 | Sudbury | Ontario | Canada | P3E 1H5 | |
| 182 | Sudbury | Ontario | Canada | P3E 6C3 | |
| 183 | Toronto | Ontario | Canada | M4N 3M5 | |
| 184 | Waterloo | Ontario | Canada | ON N2T 0C1 | |
| 185 | Windsor | Ontario | Canada | N8X 5A6 | |
| 186 | Chicoutimi | Quebec | Canada | G7H 5H6 | |
| 187 | Laval | Quebec | Canada | H7M 3L9 | |
| 188 | Levis | Quebec | Canada | G6V 4Z5 | |
| 189 | Montreal | Quebec | Canada | H2W 1T8 | |
| 190 | Montreal | Quebec | Canada | H3G 1A4 | |
| 191 | Sherbrooke | Quebec | Canada | J1H 5N4 | |
| 192 | Terrebonne | Quebec | Canada | J6V 2H2 | |
| 193 | Thetford Mines | Quebec | Canada | G6G 2V4 | |
| 194 | Trois-Rivieres | Quebec | Canada | G8Z 4K4 | |
| 195 | Ontario | Canada | P3E 5M4 | ||
| 196 | Quebec | Canada | G1V 4G5 | ||
| 197 | Temuco | Araucanía | Chile | 2170000 | |
| 198 | Temuco | Araucanía | Chile | 4781156 | |
| 199 | Temuco | Araucanía | Chile | 4791348 | |
| 200 | Concepción | Bío-Bío | Chile | 4070038 | |
| 201 | Osorno | Los Lagos | Chile | 5311092 | |
| 202 | Valdivia | Los Lagos | Chile | ||
| 203 | Providencia | Santiago | Chile | 7500520 | |
| 204 | San Miguel | Santiago | Chile | 8910108 | |
| 205 | Viña del Mar | Valparaíso | Chile | 2570017 | |
| 206 | Santiago | Chile | 7500739 | ||
| 207 | Santiago | Chile | |||
| 208 | Guangzhou | Guangdong | China | 510080 | |
| 209 | Guangzhou | Guangdong | China | 510100 | |
| 210 | Wudan | Hubei | China | 430022 | |
| 211 | Wuhan | Hubei | China | ||
| 212 | Changsha | Hunan | China | 410011 | |
| 213 | Nanjing | Jiangsu | China | 210006 | |
| 214 | Nanjing | Jiangsu | China | 210029 | |
| 215 | Changchun | Jilin | China | 130000 | |
| 216 | Changchun | Jilin | China | 130033 | |
| 217 | Shenyang | Liaoning | China | 110004 | |
| 218 | Xi'an | Shanxi | China | 710061 | |
| 219 | Chengdu | Sichuan | China | 610041 | |
| 220 | Hangzhou | Zhejiang | China | 310003 | |
| 221 | Hangzhou | Zhejiang | China | 310016 | |
| 222 | Wenzhou | Zhejiang | China | 325000 | |
| 223 | Beijing | China | 100029 | ||
| 224 | Beijing | China | 100034 | ||
| 225 | Beijing | China | 100038 | ||
| 226 | Beijing | China | 100088 | ||
| 227 | Beijing | China | 100730 | ||
| 228 | Beijing | China | |||
| 229 | Shanghai | China | 200001 | ||
| 230 | Shanghai | China | 200003 | ||
| 231 | Shanghai | China | 200025 | ||
| 232 | Shanghai | China | 200030 | ||
| 233 | Shanghai | China | 200032 | ||
| 234 | Shanghai | China | 200080 | ||
| 235 | Barranquilla | Atlántico | Colombia | ||
| 236 | Cartagena | Bolívar | Colombia | ||
| 237 | Manizales | Caldas | Colombia | ||
| 238 | Montería | Córdoba | Colombia | 230002 | |
| 239 | Pasto | Nariño | Colombia | ||
| 240 | Armenia | Quindío | Colombia | ||
| 241 | Pereira | Risaralda | Colombia | ||
| 242 | Bucaramanga | Santander | Colombia | ||
| 243 | Floridablanca | Santander | Colombia | 681004 | |
| 244 | Espinal | Tolima | Colombia | ||
| 245 | Cali | Valle Del Cauca | Colombia | 760032 | |
| 246 | Barranquilla | Colombia | |||
| 247 | Santafe de Bogotá | Colombia | |||
| 248 | Brno | Czechia | 62500 | ||
| 249 | Brno | Czechia | 656 91 | ||
| 250 | Ceske Budejovice | Czechia | 370 01 | ||
| 251 | Cesky Krumlov | Czechia | 381 27 | ||
| 252 | Hodonin | Czechia | 695 01 | ||
| 253 | Hradec Kralove | Czechia | 500 05 | ||
| 254 | Jablonec nad Nisou | Czechia | 466 60 | ||
| 255 | Kolin | Czechia | 280 02 | ||
| 256 | Liberec | Czechia | 46063 | ||
| 257 | Olomouc | Czechia | 775 20 | ||
| 258 | Ostrava | Czechia | 708 52 | ||
| 259 | Ostrava | Czechia | 728 80 | ||
| 260 | Pardubice | Czechia | 530 03 | ||
| 261 | Praha 10 | Czechia | 100 34 | ||
| 262 | Praha 13 | Czechia | 158 00 | ||
| 263 | Praha 2 | Czechia | 12808 | ||
| 264 | Praha 4 | Czechia | 140 21 | ||
| 265 | Praha 5 | Czechia | 150 06 | ||
| 266 | Praha 5 | Czechia | 150 30 | ||
| 267 | Praha 6 | Czechia | 169 02 | ||
| 268 | Slany | Czechia | 274 01 | ||
| 269 | Susice | Czechia | 342 01 | ||
| 270 | Trebic | Czechia | 674 01 | ||
| 271 | Trinec | Czechia | 739 61 | ||
| 272 | Uherske Hradiste | Czechia | 686 68 | ||
| 273 | Zlin | Czechia | 762 75 | ||
| 274 | Aalborg | Denmark | DK-9000 | ||
| 275 | Aarhus N | Denmark | 8200 | ||
| 276 | Hellerup | Denmark | 2900 | ||
| 277 | Holbaek | Denmark | 4300 | ||
| 278 | Hvidovre | Denmark | 2650 | ||
| 279 | Kolding | Denmark | 6000 | ||
| 280 | København Ø | Denmark | 2100 | ||
| 281 | København | Denmark | DK-2400 | ||
| 282 | Viborg | Denmark | 8800 | ||
| 283 | Guayaquil | Guayas | Ecuador | ||
| 284 | Quito | Pichincha | Ecuador | 0 | |
| 285 | Quito | Ecuador | |||
| 286 | Kuopio | Finland | 70100 | ||
| 287 | Kuusankoski | Finland | 45700 | ||
| 288 | Tampere | Finland | 33200 | ||
| 289 | Turku | Finland | FIN-20520 | ||
| 290 | Vantaa | Finland | 01600 | ||
| 291 | Amiens | France | 80000 | ||
| 292 | Clermont Ferrand | France | 63000 | ||
| 293 | Limoges Cedex | France | 87042 | ||
| 294 | Montpellier | France | 34059 | ||
| 295 | Nice | France | 06280 | ||
| 296 | NIMES cedex 9 | France | 30029 | ||
| 297 | Paris Cedex 15 | France | 75908 | ||
| 298 | Paris | France | 75012 | ||
| 299 | Paris | France | 75018 | ||
| 300 | Saint-priest-en-jarez | France | 42270 | ||
| 301 | Nürnberg | Bayern | Germany | 90402 | |
| 302 | Würzburg | Bayern | Germany | 97078 | |
| 303 | Bad Homburg | Hessen | Germany | 61348 | |
| 304 | Frankfurt | Hessen | Germany | 60596 | |
| 305 | Kassel | Hessen | Germany | 34128 | |
| 306 | Bielefeld | Nordrhein-Westfalen | Germany | 33604 | |
| 307 | Dortmund | Nordrhein-Westfalen | Germany | 44137 | |
| 308 | Wuppertal | Nordrhein-Westfalen | Germany | 42117 | |
| 309 | Magdeburg | Sachsen-Anhalt | Germany | 39120 | |
| 310 | Dresden | Sachsen | Germany | 01067 | |
| 311 | Leipzig | Sachsen | Germany | 04289 | |
| 312 | Berlin | Germany | 12351 | ||
| 313 | Berlin | Germany | 12559 | ||
| 314 | Berlin | Germany | 13353 | ||
| 315 | Bottrop | Germany | 46242 | ||
| 316 | Frankfurt | Germany | 65929 | ||
| 317 | Hamburg | Germany | 20099 | ||
| 318 | Warendorf | Germany | 48231 | ||
| 319 | Balatonfured | Hungary | 8230 | ||
| 320 | Budapest | Hungary | 1085 | ||
| 321 | Budapest | Hungary | 1115 | ||
| 322 | Budapest | Hungary | H-1096 | ||
| 323 | Budapest | Hungary | H-1125 | ||
| 324 | Debrecen | Hungary | 4032 | ||
| 325 | Mosonmagyarovar | Hungary | 9200 | ||
| 326 | Pecs | Hungary | 7624 | ||
| 327 | Sopron | Hungary | 9400 | ||
| 328 | Szekesfehervar | Hungary | 8000 | ||
| 329 | Szekszard | Hungary | 7100 | ||
| 330 | Ballinasloe | Co. Galway | Ireland | ||
| 331 | Cork | Ireland | |||
| 332 | Dublin | Ireland | 9 | ||
| 333 | Dublin | Ireland | D07 R2WY | ||
| 334 | Dublin | Ireland | D08 NHY1 | ||
| 335 | Galway | Ireland | |||
| 336 | Afula | Israel | 1834111 | ||
| 337 | Ashkelon | Israel | 7830604 | ||
| 338 | Bnei Brak | Israel | |||
| 339 | Haifa | Israel | 3109601 | ||
| 340 | Haifa | Israel | 3436212 | ||
| 341 | Holon | Israel | 5822012 | ||
| 342 | Nahariya | Israel | 2210001 | ||
| 343 | Tel Aviv | Israel | 64239 | ||
| 344 | Tel Aviv | Israel | |||
| 345 | Zefat | Israel | 1311001 | ||
| 346 | Caserta | Campania | Italy | 81027 | |
| 347 | Bologna | Emilia-Romagna | Italy | 40133 | |
| 348 | Forlì Cesena | Emilia-Romagna | Italy | 47100 | |
| 349 | Ravenna | Emilia-Romagna | Italy | 48010 | |
| 350 | Trieste | Friuli-Venezia Giulia | Italy | 34149 | |
| 351 | Udine | Friuli-Venezia Giulia | Italy | 33038 | |
| 352 | Udine | Friuli-Venezia Giulia | Italy | 33057 | |
| 353 | Udine | Friuli-Venezia Giulia | Italy | ||
| 354 | Brescia | Lombardia | Italy | 25123 | |
| 355 | Cremona | Lombardia | Italy | 26100 | |
| 356 | Pavia | Lombardia | Italy | 27100 | |
| 357 | Ancona | Marche | Italy | 60126 | |
| 358 | Isernia | Molise | Italy | 86170 | |
| 359 | Foggia | Puglia | Italy | 71100 | |
| 360 | Lecce | Puglia | Italy | 73042 | |
| 361 | Catania | Sicilia | Italy | 95126 | |
| 362 | Palermo | Sicilia | Italy | 90146 | |
| 363 | Arezzo | Toscana | Italy | 52040 | |
| 364 | Firenze | Toscana | Italy | 50053 | |
| 365 | Perugia | Umbria | Italy | 06024 | |
| 366 | Terni | Umbria | Italy | 05100 | |
| 367 | Nagoya | Aichi | Japan | 453-8511 | |
| 368 | Toyoake | Aichi | Japan | 470-1192 | |
| 369 | Kisarazu | Chiba | Japan | 292-8535 | |
| 370 | Matsudo | Chiba | Japan | 270-2251 | |
| 371 | Imabari | Ehime | Japan | 794-0006 | |
| 372 | Matsuyama | Ehime | Japan | 790-0062 | |
| 373 | Kasuga | Fukuoka | Japan | 816-0864 | |
| 374 | Kitakyushu | Fukuoka | Japan | 802-8555 | |
| 375 | Miyako-gun | Fukuoka | Japan | 800-0344 | |
| 376 | Onga-gun | Fukuoka | Japan | 811-4342 | |
| 377 | Maebashi | Gunma | Japan | 371-0821 | |
| 378 | Onomichi | Hiroshima | Japan | 722-8503 | |
| 379 | Asahikawa | Hokkaido | Japan | 070-0038 | |
| 380 | Asahikawa | Hokkaido | Japan | 070-8610 | |
| 381 | Sapporo | Hokkaido | Japan | 006-8555 | |
| 382 | Sapporo | Hokkaido | Japan | 060-0004 | |
| 383 | Spporo | Hokkaido | Japan | 006-0852 | |
| 384 | Tomakomai | Hokkaido | Japan | 053-8567 | |
| 385 | Kobe | Hyogo | Japan | 654-0026 | |
| 386 | Takarazuka | Hyogo | Japan | 665-0873 | |
| 387 | Kaga | Ishikawa | Japan | 922-8522 | |
| 388 | Miura-gun | Kanagawa | Japan | 240-0116 | |
| 389 | Sagamihara | Kanagawa | Japan | 252-0375 | |
| 390 | Yokohama | Kanagawa | Japan | 232-0024 | |
| 391 | Naha | Okinawa | Japan | 902-8511 | |
| 392 | Kishiwada | Osaka | Japan | 596-0042 | |
| 393 | Takatsuki | Osaka | Japan | 569-1096 | |
| 394 | Tokorozawa | Saitama | Japan | 359-1141 | |
| 395 | Komatsushima | Tokushima | Japan | 773-8502 | |
| 396 | Akishima | Tokyo | Japan | 196-0003 | |
| 397 | Bunkyo-ku | Tokyo | Japan | 113-8431 | |
| 398 | Itabashi-ku | Tokyo | Japan | 173-8610 | |
| 399 | Shimonoseki | Yamaguchi | Japan | 750-0061 | |
| 400 | Chiba | Japan | 263-0043 | ||
| 401 | Fukuoka | Japan | 812-0033 | ||
| 402 | Fukuoka | Japan | 814-0180 | ||
| 403 | Gifu | Japan | 500-8384 | ||
| 404 | Gifu | Japan | 500-8717 | ||
| 405 | Kumamoto | Japan | 861-4193 | ||
| 406 | Kyoto | Japan | 600-8558 | ||
| 407 | Kyoto | Japan | 601-1495 | ||
| 408 | Kyoto | Japan | 615-8256 | ||
| 409 | Osaka | Japan | 530-0001 | ||
| 410 | Osaka | Japan | 530-8480 | ||
| 411 | Osaka | Japan | 540-0006 | ||
| 412 | Osaka | Japan | 543-0035 | ||
| 413 | Osaka | Japan | 558-8558 | ||
| 414 | Osaka | Japan | 559-0012 | ||
| 415 | Wonju | Gang''weondo | Korea, Republic of | 26426 | |
| 416 | Goyang-si | Gyeonggido | Korea, Republic of | 10326 | |
| 417 | Seongnam-si | Gyeonggido | Korea, Republic of | 463-707 | |
| 418 | Jeju | Jejudo | Korea, Republic of | 690767 | |
| 419 | Seoul | Seoul Teugbyeolsi | Korea, Republic of | 150-713 | |
| 420 | Busan | Korea, Republic of | 614-735 | ||
| 421 | Daejeon | Korea, Republic of | 302-718 | ||
| 422 | Seoul | Korea, Republic of | 03722 | ||
| 423 | Seoul | Korea, Republic of | 110-744 | ||
| 424 | Seoul | Korea, Republic of | 134-727 | ||
| 425 | Batu Caves, Selangor | Malaysia | 68100 | ||
| 426 | Kedah | Malaysia | 05460 | ||
| 427 | Kuala Lumpur | Malaysia | 50400 | ||
| 428 | Kuala Lumpur | Malaysia | 59100 | ||
| 429 | Selangor | Malaysia | 47000 | ||
| 430 | Sungai Buloh Selangor | Malaysia | 47000 | ||
| 431 | Amsterdam | Netherlands | 1091 AC | ||
| 432 | Apeldoorn | Netherlands | 7334 DZ | ||
| 433 | Arnhem | Netherlands | 6815 AD | ||
| 434 | Breda | Netherlands | 4818 CK | ||
| 435 | Delft | Netherlands | 2625 AD | ||
| 436 | Den Bosch | Netherlands | 5223 GZ | ||
| 437 | Deventer | Netherlands | 7416 SE | ||
| 438 | Doetinchem | Netherlands | 7009 BL | ||
| 439 | Drachten | Netherlands | 9205 NN | ||
| 440 | EDE | Netherlands | 6716 RP | ||
| 441 | Gorinchem | Netherlands | 4204 AA | ||
| 442 | Gouda | Netherlands | 2803 HH | ||
| 443 | Groningen | Netherlands | 9721 SW | ||
| 444 | Heerlen | Netherlands | 6401 CX | ||
| 445 | Helmond | Netherlands | 5707 HA | ||
| 446 | Hoogeveen | Netherlands | 7909 AA | ||
| 447 | Hoorn | Netherlands | 1624 NP | ||
| 448 | Leeuwarden | Netherlands | 8901 BR | ||
| 449 | Meppel | Netherlands | 7943 KA | ||
| 450 | Nijmegen | Netherlands | 6532 SZ | ||
| 451 | Roermond | Netherlands | 6043 CV | ||
| 452 | Roosendaal | Netherlands | 4708 AE | ||
| 453 | Rotterdam | Netherlands | 3045 PM | ||
| 454 | Rotterdam | Netherlands | 3083 AN | ||
| 455 | Sneek | Netherlands | 8601 ZK | ||
| 456 | Tiel | Netherlands | 4002 WP | ||
| 457 | Zwolle | Netherlands | 8011 JW | ||
| 458 | Batangas | Philippines | |||
| 459 | Cebu City | Philippines | 6000 | ||
| 460 | Dagupan City | Philippines | 2400 | ||
| 461 | Dasmarinas | Philippines | 4114 | ||
| 462 | Iloilo City | Philippines | 5000 | ||
| 463 | Laoag City | Philippines | 2900 | ||
| 464 | Manila | Philippines | 1000 | ||
| 465 | Manila | Philippines | |||
| 466 | Metro Manila | Philippines | 1502 | ||
| 467 | Muntinlupa City | Philippines | 1780 | ||
| 468 | Palawan | Philippines | 5300 | ||
| 469 | Pasig city | Philippines | 1605 | ||
| 470 | Quezon City | Philippines | 1102 | ||
| 471 | Quezon City | Philippines | 1109 | ||
| 472 | Quezon City | Philippines | NCR 1100 | ||
| 473 | Tacloban City | Philippines | 6500 | ||
| 474 | Gdansk | Poland | 80 -126 | ||
| 475 | Kielce | Poland | 25-315 | ||
| 476 | Krakow | Poland | 30-002 | ||
| 477 | Krakow | Poland | 31-271 | ||
| 478 | Krakow | Poland | 31-501 | ||
| 479 | Krakow | Poland | 31-534 | ||
| 480 | Lodz | Poland | 91-347 | ||
| 481 | Tarnow | Poland | 33-100 | ||
| 482 | Wroclaw | Poland | 53-114 | ||
| 483 | Timisoara | Timis | Romania | 300254 | |
| 484 | Brasov | Romania | 500326 | ||
| 485 | Bucharest | Romania | 011461 | ||
| 486 | Bucharest | Romania | 021659 | ||
| 487 | Bucharest | Romania | 022322 | ||
| 488 | Bucharest | Romania | 041915 | ||
| 489 | Bucharest | Romania | 042122 | ||
| 490 | Bucharest | Romania | 050098 | ||
| 491 | Bucharest | Romania | 061114 | ||
| 492 | Bucuresti | Romania | 50659 | ||
| 493 | Cluj Napoca | Romania | 400001 | ||
| 494 | Iasi | Romania | 700503 | ||
| 495 | Iasi | Romania | 700732 | ||
| 496 | Targu Mures | Romania | 540124 | ||
| 497 | Targu Mures | Romania | 540136 | ||
| 498 | Timisoara | Romania | 300310 | ||
| 499 | Barnaul | Russian Federation | 656038 | ||
| 500 | Kemerovo | Russian Federation | 650002 | ||
| 501 | Moscow | Russian Federation | 101990 | ||
| 502 | Moscow | Russian Federation | 107084 | ||
| 503 | Moscow | Russian Federation | 111539 | ||
| 504 | Moscow | Russian Federation | 117556 | ||
| 505 | Moscow | Russian Federation | 119435 | ||
| 506 | Moscow | Russian Federation | 121309 | ||
| 507 | Moscow | Russian Federation | 127206 | ||
| 508 | Novosibirsk | Russian Federation | 630089 | ||
| 509 | Tomsk | Russian Federation | 634012 | ||
| 510 | Zhukovskiy | Russian Federation | 140160 | ||
| 511 | Bratislava | Slovakia | 811 04 | ||
| 512 | Bratislava | Slovakia | 813 69 | ||
| 513 | Kosice | Slovakia | 040 22 | ||
| 514 | Nitra | Slovakia | 94901 | ||
| 515 | Presov | Slovakia | 080 81 | ||
| 516 | Vrable | Slovakia | 952 01 | ||
| 517 | Pinelands | Eastern Cape | South Africa | 7503 | |
| 518 | Port Elizabeth | Eastern Cape | South Africa | 6014 | |
| 519 | Bloemfontein | Freestate | South Africa | 9300 | |
| 520 | Johannesburg | Gauteng | South Africa | 2157 | |
| 521 | Cape Town | Western Cape | South Africa | 7531 | |
| 522 | Observatory | Western Cape | South Africa | 7925 | |
| 523 | Pinelands | Western Cape | South Africa | 7405 | |
| 524 | Worcester | Western Cape | South Africa | 6850 | |
| 525 | Somerset West | South Africa | 7130 | ||
| 526 | Göteborg | Sweden | 413 45 | ||
| 527 | Helsingborg | Sweden | 251 87 | ||
| 528 | Kristianstad | Sweden | 291 85 | ||
| 529 | Skellefteå | Sweden | 931 86 | ||
| 530 | Stockholm | Sweden | 111 35 | ||
| 531 | Stockholm | Sweden | 114 46 | ||
| 532 | Stockholm | Sweden | 141 86 | ||
| 533 | Stockholm | Sweden | 171 76 | ||
| 534 | Vällingby | Sweden | 162 68 | ||
| 535 | Örebro | Sweden | 701 85 | ||
| 536 | Östersund | Sweden | 831 83 | ||
| 537 | Lugano | Ticino | Switzerland | 6900 | |
| 538 | Dnipropetrovsk | Ukraine | 49 006 | ||
| 539 | Kharkiv | Ukraine | 61002 | ||
| 540 | Kharkiv | Ukraine | 61039 | ||
| 541 | Kharkiv | Ukraine | 61176 | ||
| 542 | Kiev | Ukraine | 02 091 | ||
| 543 | Kiev | Ukraine | 02660 | ||
| 544 | Kiev | Ukraine | 03 049 | ||
| 545 | Lviv | Ukraine | 790 34 | ||
| 546 | Lviv | Ukraine | 79044 | ||
| 547 | Lviv | Ukraine | 79659 | ||
| 548 | Simferopol | Ukraine | 95006 | ||
| 549 | Vinnitsa | Ukraine | 21029 | ||
| 550 | Zaporozhye | Ukraine | 69 000 | ||
| 551 | Zaporozhye | Ukraine | 69118 | ||
| 552 | Belfast | Antrim | United Kingdom | BT16 1RH | |
| 553 | Londonderry Co. Londonderry | Derry | United Kingdom | BT47 6SB | |
| 554 | Basildon | Essex | United Kingdom | SS16 5NL | |
| 555 | Stevenage | Hertfordshire | United Kingdom | SG1 4AB | |
| 556 | Blackpool | Lancashire | United Kingdom | FY4 3AD | |
| 557 | Harrow | London | United Kingdom | HA1 3UJ | |
| 558 | Portadown | North Ireland | United Kingdom | ||
| 559 | Middlesborough | North Yorkshire | United Kingdom | TS4 3BW | |
| 560 | Northampton | Northamptonshire | United Kingdom | NN1 5BD | |
| 561 | Hardwick | Stockton-on-Tees | United Kingdom | TS29 6NH | |
| 562 | Nuneaton | Warwickshire | United Kingdom | CV10 7DJ | |
| 563 | West Bromich | West Midlands | United Kingdom | B71 4HJ | |
| 564 | Wolverhampton | West Midlands | United Kingdom | WV10 0QP | |
| 565 | Worcester | Worcestershire | United Kingdom | WR5 1DD |
Sponsors and Collaborators
- Bayer
- Population Health Research Institute
- Janssen Research & Development, LLC
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT01776424
Other Study ID Numbers:
- 15786
- 2012-004180-43
First Posted:
Jan 28, 2013
Last Update Posted:
Jul 16, 2021
Last Verified:
Jul 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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 602 centers with randomized participants in 33 countries between 28 Feb 2013 (first patient first visit) and 18 Jul 2017 (last patient last visit for antithrombotic part). |
|---|---|
| Pre-assignment Detail | Overall, 29872 participants were screened, of which 2477 participants were screen failures. A total of 27395 participants were randomized to one of the study treatment arms. |
| Arm/Group Title | Rivaroxaban 2.5mg + Aspirin 100mg | Rivaroxaban 5mg + Aspirin Placebo | Rivaroxaban Placebo + Aspirin 100mg |
|---|---|---|---|
| Arm/Group Description | Participants received Rivaroxaban 2.5 mg twice daily (bid) and Aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Participants received Rivaroxaban 5 mg bid and Aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Participants received Rivaroxaban placebo bid and Aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. |
| Period Title: Overall Study | |||
| STARTED | 9152 | 9117 | 9126 |
| Treated | 9134 | 9110 | 9107 |
| COMPLETED | 9132 | 9098 | 9102 |
| NOT COMPLETED | 20 | 19 | 24 |
Baseline Characteristics
| Arm/Group Title | Rivaroxaban 2.5mg + Aspirin 100mg | Rivaroxaban 5mg + Aspirin Placebo | Rivaroxaban Placebo + Aspirin 100mg | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants received Rivaroxaban 2.5 mg twice daily (bid) and Aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Participants received Rivaroxaban 5 mg bid and Aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Participants received Rivaroxaban placebo bid and Aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Total of all reporting groups |
| Overall Participants | 9152 | 9117 | 9126 | 27395 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
68.3
(7.9)
|
68.2
(7.9)
|
68.2
(8.0)
|
68.2
(7.9)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
2059
22.5%
|
1972
21.6%
|
1989
21.8%
|
6020
22%
|
| Male |
7093
77.5%
|
7145
78.4%
|
7137
78.2%
|
21375
78%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Chinese |
388
4.2%
|
381
4.2%
|
376
4.1%
|
1145
4.2%
|
| Hispanic |
1769
19.3%
|
1751
19.2%
|
1758
19.3%
|
5278
19.3%
|
| White/Caucasian |
5673
62%
|
5672
62.2%
|
5682
62.3%
|
17027
62.2%
|
| South Asian |
107
1.2%
|
102
1.1%
|
106
1.2%
|
315
1.1%
|
| Other Asian |
956
10.4%
|
938
10.3%
|
915
10%
|
2809
10.3%
|
| Black/African American |
76
0.8%
|
94
1%
|
92
1%
|
262
1%
|
| Other |
183
2%
|
179
2%
|
197
2.2%
|
559
2%
|
Outcome Measures
| Title | The First Occurrence of the Composite Primary Efficacy Outcome, Myocardial Infarction (MI), Stroke, or Cardiovascular (CV) Death |
|---|---|
| Description | Count of participants and time from randomization to the first occurrence of the composite primary efficacy outcome, MI, stroke, or CV death were evaluated. Hazard ratios were calculated and reported as statistical analysis. |
| Time Frame | For each participant, the first occurrence of the composite primary efficacy outcome after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Analysis Set included all randomized subjects |
| Arm/Group Title | Rivaroxaban 2.5mg + Aspirin 100mg | Rivaroxaban 5mg + Aspirin Placebo | Rivaroxaban Placebo + Aspirin 100mg |
|---|---|---|---|
| Arm/Group Description | Participants received Rivaroxaban 2.5 mg twice daily (bid) and Aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Participants received Rivaroxaban 5 mg bid and Aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Participants received Rivaroxaban placebo bid and Aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. |
| Measure Participants | 9152 | 9117 | 9126 |
| Count of Participants [Participants] |
379
4.1%
|
448
4.9%
|
496
5.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 2.5mg + Aspirin 100mg, Rivaroxaban Placebo + Aspirin 100mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.00004 |
| Comments | Independent DSMB recommended to stop rivaroxaban/aspirin arms on 06FEB2017. At first interim analysis(~50% events) the log-rank test statistic for one primary comparison had crossed the modified Haybittle-Peto boundary(z=4) consistently over 3 months | |
| Method | Log Rank | |
| Comments | Log-rank test (stratified by pantoprazole randomization) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.76 | |
| Confidence Interval |
(2-Sided) 95% 0.66 to 0.86 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Stratified Cox proportional hazards model | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 5mg + Aspirin Placebo, Rivaroxaban Placebo + Aspirin 100mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.11490 |
| Comments | ||
| Method | Log Rank | |
| Comments | Log-rank test (stratified by pantoprazole randomization) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.90 | |
| Confidence Interval |
(2-Sided) 95% 0.79 to 1.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Stratified Cox proportional hazards model | |
| Title | The First Occurrence of the Primary Safety Outcome Major Bleeding Based on a Modification of the International Society on Thrombosis and Haemostasis (ISTH) Criteria |
|---|---|
| Description | Modified ISTH major bleeding is defined as: i) Fatal bleeding, or ii) Symptomatic bleeding in a critical area or organ, such as intraarticular, intracranial, intramuscular with compartment syndrome, intraocular, intraspinal, liver, pancreas, pericardial, respiratory, retroperitoneal, adrenal gland or kidney; or bleeding into the surgical site requiring reoperation, or iii) Bleeding leading to hospitalization (major bleeding also includes presentation to an acute care facility with discharge on the same day). Count of participants and time from randomization to the first occurrence of the primary safety outcome major bleeding were evaluated. Hazard ratios were calculated and reported as statistical analysis. |
| Time Frame | For each participant, the first occurrence of modified ISTH major bleeding after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Analysis Set included all randomized subjects |
| Arm/Group Title | Rivaroxaban 2.5mg + Aspirin 100mg | Rivaroxaban 5mg + Aspirin Placebo | Rivaroxaban Placebo + Aspirin 100mg |
|---|---|---|---|
| Arm/Group Description | Participants received Rivaroxaban 2.5 mg twice daily (bid) and Aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Participants received Rivaroxaban 5 mg bid and Aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Participants received Rivaroxaban placebo bid and Aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. |
| Measure Participants | 9152 | 9117 | 9126 |
| Count of Participants [Participants] |
288
3.1%
|
255
2.8%
|
170
1.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 2.5mg + Aspirin 100mg, Rivaroxaban Placebo + Aspirin 100mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.00001 |
| Comments | ||
| Method | Log Rank | |
| Comments | Log-rank test (stratified by pantoprazole randomization) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.70 | |
| Confidence Interval |
(2-Sided) 95% 1.40 to 2.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Stratified Cox proportional hazards model | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 5mg + Aspirin Placebo, Rivaroxaban Placebo + Aspirin 100mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.00003 |
| Comments | ||
| Method | Log Rank | |
| Comments | Log-rank test (stratified by pantoprazole randomization) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.51 | |
| Confidence Interval |
(2-Sided) 95% 1.25 to 1.84 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Stratified Cox proportional hazards model | |
| Title | The First Occurrence of Myocardial Infarction (MI), Ischemic Stroke, Acute Limb Ischemia (ALI), or Coronary Heart Disease (CHD) Death |
|---|---|
| Description | Count of participants and time from randomization to the first occurrence of MI, ischemic stroke, ALI, or CHD death were evaluated. Hazard ratios were calculated and reported as statistical analysis. |
| Time Frame | For each participant, the first occurrence of MI, ALI, or CHD death after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Analysis Set included all randomized subjects |
| Arm/Group Title | Rivaroxaban 2.5mg + Aspirin 100mg | Rivaroxaban 5mg + Aspirin Placebo | Rivaroxaban Placebo + Aspirin 100mg |
|---|---|---|---|
| Arm/Group Description | Participants received Rivaroxaban 2.5 mg twice daily (bid) and Aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Participants received Rivaroxaban 5 mg bid and Aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Participants received Rivaroxaban placebo bid and Aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. |
| Measure Participants | 9152 | 9117 | 9126 |
| Count of Participants [Participants] |
329
3.6%
|
397
4.4%
|
450
4.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 2.5mg + Aspirin 100mg, Rivaroxaban Placebo + Aspirin 100mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.00001 |
| Comments | Nominal p-value | |
| Method | Log Rank | |
| Comments | Log-rank test (stratified by pantoprazole randomization) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.72 | |
| Confidence Interval |
(2-Sided) 95% 0.63 to 0.83 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Stratified Cox proportional hazards model | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 5mg + Aspirin Placebo, Rivaroxaban Placebo + Aspirin 100mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.06437 |
| Comments | Nominal p-value | |
| Method | Log Rank | |
| Comments | Log-rank test (stratified by pantoprazole randomization) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.88 | |
| Confidence Interval |
(2-Sided) 95% 0.77 to 1.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Stratified Cox proportional hazards model | |
| Title | The First Occurrence of MI, Ischemic Stroke, ALI, or Cardiovascular (CV) Death |
|---|---|
| Description | Count of participants and time from randomization to the first occurrence of MI, ischemic stroke, ALI, or CV death were evaluated. Hazard ratios were calculated and reported as statistical analysis. |
| Time Frame | For each participant, the first occurrence of MI, ischemic stroke, ALI, or CV death after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Analysis Set included all randomized subjects |
| Arm/Group Title | Rivaroxaban 2.5mg + Aspirin 100mg | Rivaroxaban 5mg + Aspirin Placebo | Rivaroxaban Placebo + Aspirin 100mg |
|---|---|---|---|
| Arm/Group Description | Participants received Rivaroxaban 2.5 mg twice daily (bid) and Aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Participants received Rivaroxaban 5 mg bid and Aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Participants received Rivaroxaban placebo bid and Aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. |
| Measure Participants | 9152 | 9117 | 9126 |
| Count of Participants [Participants] |
389
4.3%
|
453
5%
|
516
5.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 2.5mg + Aspirin 100mg, Rivaroxaban Placebo + Aspirin 100mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.00001 |
| Comments | Nominal p-value | |
| Method | Log Rank | |
| Comments | Log-rank test (stratified by pantoprazole randomization) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.74 | |
| Confidence Interval |
(2-Sided) 95% 0.65 to 0.85 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Stratified Cox proportional hazards model | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 5mg + Aspirin Placebo, Rivaroxaban Placebo + Aspirin 100mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.03995 |
| Comments | Nominal p-value | |
| Method | Log Rank | |
| Comments | Log-rank test (stratified by pantoprazole randomization) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.88 | |
| Confidence Interval |
() 95% 0.77 to 0.99 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Stratified Cox proportional hazards model | |
| Title | All-cause Mortality |
|---|---|
| Description | Count of participants and time from randomization to death by all cause were evaluated. Hazard ratios were calculated and reported as statistical analysis. |
| Time Frame | For each participants, death by any cause after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Analysis Set included all randomized subjects |
| Arm/Group Title | Rivaroxaban 2.5mg + Aspirin 100mg | Rivaroxaban 5mg + Aspirin Placebo | Rivaroxaban Placebo + Aspirin 100mg |
|---|---|---|---|
| Arm/Group Description | Participants received Rivaroxaban 2.5 mg twice daily (bid) and Aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Participants received Rivaroxaban 5 mg bid and Aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Participants received Rivaroxaban placebo bid and Aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. |
| Measure Participants | 9152 | 9117 | 9126 |
| Count of Participants [Participants] |
313
3.4%
|
366
4%
|
378
4.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 2.5mg + Aspirin 100mg, Rivaroxaban Placebo + Aspirin 100mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.01062 |
| Comments | Nominal p-value | |
| Method | Log Rank | |
| Comments | Log-rank test (stratified by pantoprazole randomization) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.82 | |
| Confidence Interval |
(2-Sided) 95% 0.71 to 0.96 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Stratified Cox proportional hazards model | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban 5mg + Aspirin Placebo, Rivaroxaban Placebo + Aspirin 100mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.66418 |
| Comments | Nominal p-value | |
| Method | Log Rank | |
| Comments | Log-rank test (stratified by pantoprazole randomization) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.97 | |
| Confidence Interval |
(2-Sided) 95% 0.84 to 1.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Stratified Cox proportional hazards model | |
Adverse Events
| Time Frame | From randomization up until 2 days following permanent discontinuation of any antithrombotic study treatment | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All-Cause Mortality reporting in the adverse event (AE) section encompasses all death cases in the safety analysis set before database closure in July 2017. Analysis of serious AEs in the specified time frame encompasses all subjects in the safety analysis set. | |||||
| Arm/Group Title | Rivaroxaban 2.5mg + Aspirin 100mg | Rivaroxaban 5mg + Aspirin Placebo | Rivaroxaban Placebo + Aspirin 100mg | |||
| Arm/Group Description | Participants received Rivaroxaban 2.5 mg twice daily (bid) and Aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Participants received Rivaroxaban 5 mg bid and Aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | Participants received Rivaroxaban placebo bid and Aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. | |||
All Cause Mortality |
||||||
| Rivaroxaban 2.5mg + Aspirin 100mg | Rivaroxaban 5mg + Aspirin Placebo | Rivaroxaban Placebo + Aspirin 100mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 376/9134 (4.1%) | 422/9110 (4.6%) | 442/9107 (4.9%) | |||
Serious Adverse Events |
||||||
| Rivaroxaban 2.5mg + Aspirin 100mg | Rivaroxaban 5mg + Aspirin Placebo | Rivaroxaban Placebo + Aspirin 100mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 641/9134 (7%) | 624/9110 (6.8%) | 582/9107 (6.4%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 13/9134 (0.1%) | 14 | 10/9110 (0.1%) | 11 | 2/9107 (0%) | 2 |
| Febrile neutropenia | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Haemolytic anaemia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Hypochromic anaemia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Iron deficiency anaemia | 3/9134 (0%) | 3 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Leukopenia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Microcytic anaemia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Normochromic normocytic anaemia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Pancytopenia | 3/9134 (0%) | 3 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Pernicious anaemia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Thrombocytopenia | 5/9134 (0.1%) | 5 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Hypereosinophilic syndrome | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Haemorrhagic diathesis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Immune thrombocytopenic purpura | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Cardiac disorders | ||||||
| Acute myocardial infarction | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Angina pectoris | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 3/9107 (0%) | 3 |
| Arrhythmia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Atrial fibrillation | 4/9134 (0%) | 4 | 5/9110 (0.1%) | 5 | 10/9107 (0.1%) | 10 |
| Atrial flutter | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Atrioventricular block complete | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 3/9107 (0%) | 3 |
| Bradycardia | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Cardiac arrest | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Cardiac failure | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Cardiac failure chronic | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Cardiac failure congestive | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Cardio-respiratory arrest | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Cor pulmonale | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Coronary artery disease | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Dressler's syndrome | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Myocardial ischaemia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Supraventricular tachycardia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Ventricular tachycardia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Cardiac ventricular thrombosis | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Coronary artery perforation | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Sinus node dysfunction | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||||
| Fabry's disease | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Hydrocele | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Ear and labyrinth disorders | ||||||
| Vertigo | 2/9134 (0%) | 2 | 5/9110 (0.1%) | 5 | 6/9107 (0.1%) | 6 |
| Vertigo positional | 1/9134 (0%) | 1 | 2/9110 (0%) | 2 | 1/9107 (0%) | 1 |
| Vestibular disorder | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Hypoacusis | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Ear discomfort | 0/9134 (0%) | 0 | 1/9110 (0%) | 3 | 0/9107 (0%) | 0 |
| Deafness bilateral | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Sudden hearing loss | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Endocrine disorders | ||||||
| Adrenal insufficiency | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Basedow's disease | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Hyperparathyroidism primary | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Hyperthyroidism | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Hypothyroidism | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Toxic nodular goitre | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Thyroid mass | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Eye disorders | ||||||
| Amaurosis fugax | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Blindness transient | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Blindness unilateral | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Cataract | 16/9134 (0.2%) | 19 | 11/9110 (0.1%) | 13 | 7/9107 (0.1%) | 9 |
| Cataract cortical | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Cataract nuclear | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 2 |
| Diplopia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Eyelid ptosis | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Glaucoma | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Macular oedema | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Optic ischaemic neuropathy | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Retinal artery occlusion | 2/9134 (0%) | 2 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Retinal degeneration | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Retinal detachment | 3/9134 (0%) | 3 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Retinal haemorrhage | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Retinal vein thrombosis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Sudden visual loss | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Vision blurred | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Visual acuity reduced | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Visual impairment | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Vitreous haemorrhage | 2/9134 (0%) | 3 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Macular hole | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Dacryostenosis acquired | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Entropion | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Retinal vascular thrombosis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Age-related macular degeneration | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Macular fibrosis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal distension | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Abdominal pain | 3/9134 (0%) | 3 | 4/9110 (0%) | 4 | 5/9107 (0.1%) | 5 |
| Abdominal pain upper | 1/9134 (0%) | 1 | 4/9110 (0%) | 4 | 4/9107 (0%) | 4 |
| Acute abdomen | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Anal fistula | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Ascites | 0/9134 (0%) | 0 | 1/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Barrett's oesophagus | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Chronic gastritis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Colitis ischaemic | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Constipation | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Diaphragmatic hernia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Diarrhoea | 3/9134 (0%) | 3 | 5/9110 (0.1%) | 5 | 3/9107 (0%) | 3 |
| Diverticulum | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Diverticulum intestinal | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Diverticulum intestinal haemorrhagic | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Duodenal perforation | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Duodenal ulcer | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Duodenal ulcer haemorrhage | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Dyspepsia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Enteritis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Flatulence | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Food poisoning | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Gallstone ileus | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Gastric ulcer | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Gastric ulcer haemorrhage | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Gastritis | 6/9134 (0.1%) | 7 | 2/9110 (0%) | 2 | 4/9107 (0%) | 4 |
| Gastritis erosive | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Gastrooesophageal reflux disease | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Gastrointestinal disorder | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Gastrointestinal haemorrhage | 5/9134 (0.1%) | 7 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Haemorrhoids | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Ileus | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 3/9107 (0%) | 3 |
| Ileus paralytic | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Incarcerated inguinal hernia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Inguinal hernia | 5/9134 (0.1%) | 5 | 2/9110 (0%) | 2 | 5/9107 (0.1%) | 5 |
| Intestinal ischaemia | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Intestinal obstruction | 2/9134 (0%) | 2 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Intestinal perforation | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Large intestine perforation | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Melaena | 4/9134 (0%) | 4 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Oesophageal achalasia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Oesophageal stenosis | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Oesophagitis | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Pancreatitis | 5/9134 (0.1%) | 5 | 10/9110 (0.1%) | 11 | 8/9107 (0.1%) | 9 |
| Pancreatitis acute | 6/9134 (0.1%) | 6 | 5/9110 (0.1%) | 5 | 10/9107 (0.1%) | 10 |
| Pancreatitis chronic | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Pancreatitis haemorrhagic | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Peptic ulcer | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Peptic ulcer haemorrhage | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Small intestinal obstruction | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Spigelian hernia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Stomatitis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Umbilical hernia | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Umbilical hernia, obstructive | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Volvulus | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Vomiting | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 2/9107 (0%) | 2 |
| Pancreatic mass | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Anal haemorrhage | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Subileus | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Lower gastrointestinal haemorrhage | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Dyschezia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Gastric antral vascular ectasia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Large intestine polyp | 7/9134 (0.1%) | 7 | 14/9110 (0.2%) | 14 | 9/9107 (0.1%) | 9 |
| Oesophageal rupture | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Haemorrhoidal haemorrhage | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Faecaloma | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Alcoholic pancreatitis | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Gastrointestinal toxicity | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Gastric mucosal lesion | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Diverticular perforation | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Inguinal hernia strangulated | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Ischaemic enteritis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Abdominal incarcerated hernia | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| General disorders | ||||||
| Asthenia | 0/9134 (0%) | 0 | 3/9110 (0%) | 3 | 1/9107 (0%) | 1 |
| Chest discomfort | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Chest pain | 7/9134 (0.1%) | 7 | 13/9110 (0.1%) | 13 | 4/9107 (0%) | 4 |
| Death | 3/9134 (0%) | 3 | 3/9110 (0%) | 3 | 7/9107 (0.1%) | 7 |
| Face oedema | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Gait disturbance | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Generalised oedema | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Impaired healing | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Malaise | 0/9134 (0%) | 0 | 3/9110 (0%) | 3 | 0/9107 (0%) | 0 |
| Oedema peripheral | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Pain | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Pyrexia | 2/9134 (0%) | 2 | 2/9110 (0%) | 2 | 2/9107 (0%) | 2 |
| Sudden death | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Peripheral swelling | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Nodule | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Microlithiasis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Unevaluable event | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Non-cardiac chest pain | 9/9134 (0.1%) | 9 | 4/9110 (0%) | 5 | 7/9107 (0.1%) | 7 |
| Accidental death | 0/9134 (0%) | 0 | 3/9110 (0%) | 3 | 0/9107 (0%) | 0 |
| Stent-graft endoleak | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Medical device site erosion | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Vascular stent stenosis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Multiple organ dysfunction syndrome | 3/9134 (0%) | 3 | 1/9110 (0%) | 1 | 2/9107 (0%) | 2 |
| Hepatobiliary disorders | ||||||
| Bile duct stone | 4/9134 (0%) | 4 | 3/9110 (0%) | 3 | 2/9107 (0%) | 2 |
| Biliary colic | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Cholangitis | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 3/9107 (0%) | 3 |
| Cholangitis acute | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Cholecystitis | 8/9134 (0.1%) | 8 | 9/9110 (0.1%) | 9 | 10/9107 (0.1%) | 10 |
| Cholecystitis acute | 5/9134 (0.1%) | 5 | 7/9110 (0.1%) | 7 | 9/9107 (0.1%) | 9 |
| Cholecystitis chronic | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Cholelithiasis | 4/9134 (0%) | 4 | 1/9110 (0%) | 1 | 6/9107 (0.1%) | 6 |
| Cholestasis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Cirrhosis alcoholic | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Hepatic failure | 1/9134 (0%) | 1 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Hepatitis | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Jaundice | 2/9134 (0%) | 2 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Jaundice cholestatic | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Liver disorder | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Bile duct stenosis | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Bile duct obstruction | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Hepatic mass | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Drug-induced liver injury | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Immune system disorders | ||||||
| Anaphylactic reaction | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Contrast media reaction | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Food allergy | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Hypersensitivity | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Infections and infestations | ||||||
| Appendicitis | 3/9134 (0%) | 3 | 6/9110 (0.1%) | 6 | 0/9107 (0%) | 0 |
| Appendicitis perforated | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Bacteraemia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 2/9107 (0%) | 2 |
| Brain abscess | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Bronchitis | 3/9134 (0%) | 3 | 3/9110 (0%) | 4 | 1/9107 (0%) | 1 |
| Cellulitis | 9/9134 (0.1%) | 9 | 11/9110 (0.1%) | 12 | 7/9107 (0.1%) | 8 |
| Clostridium difficile colitis | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Cytomegalovirus infection | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Dengue fever | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Dermatitis infected | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Diabetic gangrene | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Diarrhoea infectious | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Diverticulitis | 3/9134 (0%) | 3 | 4/9110 (0%) | 5 | 3/9107 (0%) | 3 |
| Diverticulitis intestinal haemorrhagic | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Encephalitis | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Encephalitis viral | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Erysipelas | 3/9134 (0%) | 3 | 5/9110 (0.1%) | 5 | 6/9107 (0.1%) | 7 |
| Gangrene | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Gastroenteritis | 5/9134 (0.1%) | 5 | 3/9110 (0%) | 3 | 4/9107 (0%) | 4 |
| Herpes zoster | 4/9134 (0%) | 4 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Infected skin ulcer | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Influenza | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Laryngitis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Liver abscess | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 1/9107 (0%) | 1 |
| Localised infection | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Lower respiratory tract infection | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Mediastinitis | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Orchitis | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Osteomyelitis | 2/9134 (0%) | 2 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Otitis media chronic | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Periodontitis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Peritonitis | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Pharyngitis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Pneumonia | 15/9134 (0.2%) | 16 | 21/9110 (0.2%) | 26 | 23/9107 (0.3%) | 23 |
| Pneumonia klebsiella | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Postoperative wound infection | 2/9134 (0%) | 3 | 4/9110 (0%) | 4 | 3/9107 (0%) | 3 |
| Pulmonary tuberculosis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Pyelonephritis | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 3/9107 (0%) | 4 |
| Pyelonephritis acute | 1/9134 (0%) | 2 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Renal abscess | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Sepsis | 17/9134 (0.2%) | 19 | 16/9110 (0.2%) | 16 | 15/9107 (0.2%) | 15 |
| Septic shock | 3/9134 (0%) | 3 | 7/9110 (0.1%) | 7 | 7/9107 (0.1%) | 7 |
| Skin infection | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Subcutaneous abscess | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Superinfection | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Tooth abscess | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Tracheobronchitis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Tuberculosis | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Upper respiratory tract infection | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Urinary tract infection | 15/9134 (0.2%) | 16 | 13/9110 (0.1%) | 14 | 7/9107 (0.1%) | 7 |
| Viral myocarditis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Wound infection | 1/9134 (0%) | 1 | 2/9110 (0%) | 2 | 6/9107 (0.1%) | 6 |
| Urosepsis | 8/9134 (0.1%) | 8 | 4/9110 (0%) | 4 | 6/9107 (0.1%) | 7 |
| Anal abscess | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 1/9107 (0%) | 1 |
| Rectal abscess | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Groin abscess | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Staphylococcal bacteraemia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Postoperative abscess | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Campylobacter infection | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Haematoma infection | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Pulmonary sepsis | 1/9134 (0%) | 1 | 2/9110 (0%) | 2 | 2/9107 (0%) | 2 |
| Neuroborreliosis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Escherichia urinary tract infection | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Arthritis bacterial | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 2/9107 (0%) | 2 |
| Abscess neck | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Clostridium difficile infection | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Escherichia bacteraemia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Pneumonia necrotising | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Subdiaphragmatic abscess | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Staphylococcal sepsis | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Infective exacerbation of chronic obstructive airways disease | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Periorbital cellulitis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Biliary sepsis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Cerebral toxoplasmosis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Staphylococcal infection | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Enteritis infectious | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Klebsiella bacteraemia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Intervertebral discitis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Diabetic foot infection | 1/9134 (0%) | 1 | 3/9110 (0%) | 4 | 2/9107 (0%) | 2 |
| Bacterial infection | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Arthritis infective | 0/9134 (0%) | 0 | 3/9110 (0%) | 3 | 0/9107 (0%) | 0 |
| Gastroenteritis bacterial | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Klebsiella infection | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Borrelia infection | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Atypical mycobacterial infection | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Biliary tract infection | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Peritonitis bacterial | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Mycobacterial infection | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Soft tissue infection | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Cholecystitis infective | 1/9134 (0%) | 1 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Device related infection | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Post procedural sepsis | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Post procedural infection | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Gastroenteritis norovirus | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Infectious pleural effusion | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Colonic abscess | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Cholangitis infective | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Varicella zoster virus infection | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Infected bite | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Bacterial abdominal infection | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| Blindness traumatic | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Carbon monoxide poisoning | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Chemical poisoning | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Clavicle fracture | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Concussion | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Extradural haematoma | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Fall | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Fat embolism | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Femoral neck fracture | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Femur fracture | 3/9134 (0%) | 4 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Foreign body in eye | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Gun shot wound | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Hand fracture | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Head injury | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Hip fracture | 4/9134 (0%) | 4 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Incisional hernia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Incisional hernia, obstructive | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Injury | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Ligament sprain | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Multiple injuries | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Overdose | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Poisoning deliberate | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Radius fracture | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Rib fracture | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Road traffic accident | 4/9134 (0%) | 4 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Spinal compression fracture | 2/9134 (0%) | 2 | 2/9110 (0%) | 2 | 2/9107 (0%) | 2 |
| Spinal cord injury cervical | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Spinal fracture | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Subarachnoid haemorrhage | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Subdural haematoma | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Tendon rupture | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Tibia fracture | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Ulna fracture | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Vascular injury | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Wound secretion | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Cervical vertebral fracture | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Muscle strain | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Contusion | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Post procedural haemorrhage | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Brain contusion | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Thermal burn | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Wound necrosis | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Postoperative ileus | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Wound evisceration | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Postoperative renal failure | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Vascular procedure complication | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Pelvic fracture | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Limb injury | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Skull fracture | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Chest injury | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Bladder injury | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Vascular bypass dysfunction | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Limb crushing injury | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Post procedural swelling | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Craniocerebral injury | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Procedural intestinal perforation | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Traumatic haemothorax | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Investigations | ||||||
| Amylase increased | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 2 |
| Arteriogram coronary | 9/9134 (0.1%) | 11 | 9/9110 (0.1%) | 9 | 12/9107 (0.1%) | 14 |
| Aspartate aminotransferase increased | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Biopsy prostate | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Blood glucose increased | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Blood pressure increased | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Bronchoscopy | 1/9134 (0%) | 2 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Catheterisation cardiac | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Colonoscopy | 0/9134 (0%) | 0 | 2/9110 (0%) | 3 | 1/9107 (0%) | 1 |
| Haemoglobin decreased | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Lipase increased | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Liver function test abnormal | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Prostatic specific antigen increased | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Weight decreased | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Urological examination | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Computerised tomogram thorax | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Angiogram peripheral | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Anticoagulation drug level above therapeutic | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Hepatic enzyme increased | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Blood electrolytes abnormal | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Investigation | 0/9134 (0%) | 0 | 1/9110 (0%) | 2 | 1/9107 (0%) | 1 |
| Stenotrophomonas test positive | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Influenza A virus test positive | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Hepatitis B core antibody positive | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Cachexia | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Dehydration | 4/9134 (0%) | 4 | 2/9110 (0%) | 2 | 1/9107 (0%) | 1 |
| Diabetes mellitus | 4/9134 (0%) | 5 | 5/9110 (0.1%) | 5 | 6/9107 (0.1%) | 6 |
| Diabetes mellitus inadequate control | 1/9134 (0%) | 1 | 3/9110 (0%) | 4 | 4/9107 (0%) | 4 |
| Diabetic ketoacidosis | 1/9134 (0%) | 1 | 2/9110 (0%) | 2 | 1/9107 (0%) | 1 |
| Fluid overload | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Gout | 1/9134 (0%) | 1 | 4/9110 (0%) | 4 | 1/9107 (0%) | 1 |
| Hyperammonaemia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Hyperglycaemia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Hyperkalaemia | 2/9134 (0%) | 2 | 2/9110 (0%) | 3 | 1/9107 (0%) | 1 |
| Hypoglycaemia | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Hypokalaemia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Hypomagnesaemia | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Hyponatraemia | 0/9134 (0%) | 0 | 3/9110 (0%) | 3 | 2/9107 (0%) | 2 |
| Lactic acidosis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Marasmus | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Hyperglycaemic hyperosmolar nonketotic syndrome | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Type 2 diabetes mellitus | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Diabetic metabolic decompensation | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 3/9134 (0%) | 3 | 3/9110 (0%) | 3 | 1/9107 (0%) | 1 |
| Arthritis | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 2/9107 (0%) | 2 |
| Arthropathy | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Back pain | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Bursitis | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Haemarthrosis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Joint swelling | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Lumbar spinal stenosis | 3/9134 (0%) | 3 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Muscle atrophy | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Musculoskeletal pain | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Myalgia | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Myopathy | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Neck pain | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Osteitis | 3/9134 (0%) | 3 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Osteoarthritis | 5/9134 (0.1%) | 6 | 6/9110 (0.1%) | 7 | 8/9107 (0.1%) | 8 |
| Pain in extremity | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 4/9107 (0%) | 4 |
| Polymyalgia rheumatica | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Rhabdomyolysis | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Rotator cuff syndrome | 0/9134 (0%) | 0 | 4/9110 (0%) | 4 | 1/9107 (0%) | 1 |
| Scoliosis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Spinal column stenosis | 1/9134 (0%) | 3 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Spinal osteoarthritis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Synovial cyst | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Intervertebral disc protrusion | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Musculoskeletal chest pain | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Spondyloarthropathy | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Facet joint syndrome | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Seronegative arthritis | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Acute leukaemia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Acute myeloid leukaemia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Adenocarcinoma | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Adenocarcinoma gastric | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Adenocarcinoma of colon | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Adenoma benign | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| B-cell lymphoma | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 2/9107 (0%) | 2 |
| Basal cell carcinoma | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Bile duct cancer | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Bladder cancer | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 6/9107 (0.1%) | 6 |
| Bladder cancer recurrent | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Bladder neoplasm | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 1/9107 (0%) | 1 |
| Bone cancer | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Bowen's disease | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Breast cancer | 5/9134 (0.1%) | 5 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Bronchial carcinoma | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Cervix carcinoma | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Cholangiocarcinoma | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 1/9107 (0%) | 1 |
| Cholesteatoma | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 2/9107 (0%) | 3 |
| Colon cancer | 9/9134 (0.1%) | 9 | 7/9110 (0.1%) | 7 | 4/9107 (0%) | 4 |
| Colon cancer stage IV | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Fibroma | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Gastric cancer | 8/9134 (0.1%) | 8 | 8/9110 (0.1%) | 9 | 5/9107 (0.1%) | 5 |
| Gastrointestinal carcinoma | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Haemangioma of skin | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Hodgkin's disease | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Hypopharyngeal cancer | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Intracranial tumour haemorrhage | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Laryngeal neoplasm | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Leukaemia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Lipoma | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Lung adenocarcinoma | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Lung carcinoma cell type unspecified stage IV | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Lymphoma | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Malignant neoplasm of renal pelvis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Malignant neoplasm of spermatic cord | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Meningioma | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Meningioma benign | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Mesothelioma | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Mesothelioma malignant | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Metastases to bone | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Metastases to liver | 1/9134 (0%) | 1 | 2/9110 (0%) | 2 | 1/9107 (0%) | 1 |
| Metastases to lung | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Metastases to neck | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Metastatic malignant melanoma | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Myelodysplastic syndrome | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Neoplasm malignant | 0/9134 (0%) | 0 | 5/9110 (0.1%) | 5 | 7/9107 (0.1%) | 7 |
| Oesophageal carcinoma | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 3/9107 (0%) | 4 |
| Pancreatic carcinoma | 4/9134 (0%) | 4 | 5/9110 (0.1%) | 5 | 1/9107 (0%) | 1 |
| Pancreatic carcinoma metastatic | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Papillary thyroid cancer | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Plasma cell myeloma | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Prostate cancer metastatic | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Prostate cancer recurrent | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Prostate cancer stage IV | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Rectal adenocarcinoma | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Rectal cancer | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Rectal cancer stage IV | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Renal cancer | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Retroperitoneal cancer | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Skin cancer | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Small cell lung cancer | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Small intestine carcinoma metastatic | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Squamous cell carcinoma of lung | 2/9134 (0%) | 2 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Squamous cell carcinoma of the cervix | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Tongue neoplasm malignant stage unspecified | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Tonsil cancer | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Tracheal cancer | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Transitional cell carcinoma | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Uterine leiomyoma | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Colon adenoma | 3/9134 (0%) | 3 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Tumour haemorrhage | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Lung cancer metastatic | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 2/9107 (0%) | 2 |
| Renal cancer metastatic | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Metastases to peritoneum | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Small intestine carcinoma | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Brain cancer metastatic | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Hepatic cancer metastatic | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Neuroendocrine carcinoma | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Cancer pain | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Lung neoplasm malignant | 17/9134 (0.2%) | 18 | 13/9110 (0.1%) | 13 | 11/9107 (0.1%) | 12 |
| Extradural neoplasm | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Prostate cancer | 12/9134 (0.1%) | 12 | 10/9110 (0.1%) | 10 | 4/9107 (0%) | 4 |
| Brain neoplasm | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Nervous system neoplasm benign | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Metastatic neoplasm | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Colorectal cancer | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Renal neoplasm | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Malignant mesenchymoma | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Pituitary tumour benign | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Adrenal neoplasm | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Pancreatic neoplasm | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Lung neoplasm | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Splenic marginal zone lymphoma | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Tonsillar neoplasm | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Metastasis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Gastrooesophageal cancer | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Colon cancer stage 0 | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Ameloblastoma | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Gallbladder cancer metastatic | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Renal cell carcinoma | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Intraductal papillary mucinous neoplasm | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Hepatic cancer | 2/9134 (0%) | 2 | 2/9110 (0%) | 2 | 3/9107 (0%) | 3 |
| Hepatocellular carcinoma | 4/9134 (0%) | 4 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Central nervous system neuroblastoma | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Adrenal gland cancer | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Nervous system disorders | ||||||
| Altered state of consciousness | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Amnesia | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Amyotrophic lateral sclerosis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Carotid artery stenosis | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 2/9107 (0%) | 2 |
| Carpal tunnel syndrome | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Cerebral haemorrhage | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Cerebral infarction | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Cerebral ischaemia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Cerebral venous thrombosis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Cerebrospinal fluid leakage | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Cerebrovascular accident | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Cervicobrachial syndrome | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Dementia | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Dementia Alzheimer's type | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Demyelination | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Depressed level of consciousness | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Dizziness | 2/9134 (0%) | 2 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Encephalopathy | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Epilepsy | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 2/9107 (0%) | 2 |
| Facial paralysis | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Generalised tonic-clonic seizure | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Headache | 3/9134 (0%) | 3 | 3/9110 (0%) | 3 | 0/9107 (0%) | 0 |
| Hemianopia | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Hepatic encephalopathy | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Hypoglycaemic coma | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Loss of consciousness | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 2/9107 (0%) | 2 |
| Migraine | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Monoplegia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Myasthenia gravis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Nerve compression | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Nervous system disorder | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Paraesthesia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Peroneal nerve palsy | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Polyneuropathy | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Post herpetic neuralgia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Presyncope | 1/9134 (0%) | 2 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Sciatica | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Seizure | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 2/9107 (0%) | 2 |
| Status epilepticus | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Syncope | 5/9134 (0.1%) | 5 | 7/9110 (0.1%) | 8 | 3/9107 (0%) | 3 |
| Temporal lobe epilepsy | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Transient global amnesia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Transient ischaemic attack | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Uraemic encephalopathy | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Cerebral haematoma | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Cubital tunnel syndrome | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Chronic inflammatory demyelinating polyradiculoneuropathy | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Vascular dementia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Thalamus haemorrhage | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Putamen haemorrhage | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Neuromuscular pain | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Psychiatric disorders | ||||||
| Alcohol abuse | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Completed suicide | 2/9134 (0%) | 2 | 3/9110 (0%) | 3 | 0/9107 (0%) | 0 |
| Confusional state | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 1/9107 (0%) | 2 |
| Delirium | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Depression | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Insomnia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Mania | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Panic attack | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Stereotypy | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Suicide attempt | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Mental status changes | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Acute prerenal failure | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Azotaemia | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Calculus bladder | 3/9134 (0%) | 3 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Calculus urinary | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Dysuria | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Haematuria | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Nephrolithiasis | 6/9134 (0.1%) | 6 | 2/9110 (0%) | 2 | 3/9107 (0%) | 3 |
| Nephrotic syndrome | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Renal failure | 8/9134 (0.1%) | 8 | 6/9110 (0.1%) | 6 | 5/9107 (0.1%) | 6 |
| Urinary incontinence | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Urinary retention | 3/9134 (0%) | 3 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Tubulointerstitial nephritis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Bladder mass | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Diabetic nephropathy | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Renal impairment | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Chronic kidney disease | 4/9134 (0%) | 4 | 2/9110 (0%) | 2 | 3/9107 (0%) | 3 |
| Urethral stenosis | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Stress urinary incontinence | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Acute kidney injury | 25/9134 (0.3%) | 26 | 22/9110 (0.2%) | 22 | 16/9107 (0.2%) | 16 |
| Prerenal failure | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| End stage renal disease | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Ureterolithiasis | 0/9134 (0%) | 0 | 2/9110 (0%) | 2 | 0/9107 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Benign prostatic hyperplasia | 6/9134 (0.1%) | 6 | 1/9110 (0%) | 1 | 2/9107 (0%) | 2 |
| Pelvic prolapse | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Prostatic haemorrhage | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Uterine polyp | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Uterine prolapse | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute pulmonary oedema | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Acute respiratory distress syndrome | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Acute respiratory failure | 4/9134 (0%) | 4 | 4/9110 (0%) | 4 | 8/9107 (0.1%) | 9 |
| Asphyxia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Asthma | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Chronic obstructive pulmonary disease | 4/9134 (0%) | 4 | 11/9110 (0.1%) | 11 | 5/9107 (0.1%) | 5 |
| Dyspnoea | 1/9134 (0%) | 1 | 5/9110 (0.1%) | 5 | 4/9107 (0%) | 4 |
| Dyspnoea exertional | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Emphysema | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Epistaxis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Hypoxia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Interstitial lung disease | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Laryngeal oedema | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Lung disorder | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Non-cardiogenic pulmonary oedema | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Pleural effusion | 4/9134 (0%) | 4 | 5/9110 (0.1%) | 5 | 4/9107 (0%) | 4 |
| Pleurisy | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Pneumonia aspiration | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Pneumonitis | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Pneumothorax | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Pulmonary embolism | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Pulmonary fibrosis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Pulmonary hypertension | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Pulmonary vasculitis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Respiratory disorder | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Respiratory distress | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Respiratory failure | 5/9134 (0.1%) | 5 | 7/9110 (0.1%) | 7 | 7/9107 (0.1%) | 7 |
| Sleep apnoea syndrome | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Throat irritation | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Vocal cord polyp | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Pulmonary mass | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Bronchial polyp | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Laryngeal mass | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Obstructive airways disorder | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Acute interstitial pneumonitis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Organising pneumonia | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Upper airway obstruction | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Angioedema | 1/9134 (0%) | 3 | 3/9110 (0%) | 3 | 5/9107 (0.1%) | 5 |
| Decubitus ulcer | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Dermatitis allergic | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 2/9107 (0%) | 2 |
| Dermatitis exfoliative | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Dermatomyositis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Erythema multiforme | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Hyperhidrosis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Hypersensitivity vasculitis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Ingrowing nail | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Lichen planus | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Pemphigoid | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Pruritus | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Psoriasis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Rash | 2/9134 (0%) | 3 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Rash erythematous | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Rash generalised | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Rash pruritic | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Skin ulcer | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Urticaria | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Pruritus generalised | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Diabetic foot | 2/9134 (0%) | 3 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Leukoplakia | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Capillaritis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Drug reaction with eosinophilia and systemic symptoms | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Surgical and medical procedures | ||||||
| Appendicectomy | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Cardiac pacemaker battery replacement | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Carotid endarterectomy | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Cholecystectomy | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Coronary artery bypass | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Foot amputation | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Gastric polypectomy | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Hernia hiatus repair | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Inguinal hernia repair | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Knee arthroplasty | 2/9134 (0%) | 3 | 2/9110 (0%) | 3 | 0/9107 (0%) | 0 |
| Mole excision | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Nasal polypectomy | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Ptosis repair | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 2 |
| Transurethral prostatectomy | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Umbilical hernia repair | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Cardiac pacemaker replacement | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Glaucoma surgery | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Coronary angioplasty | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Diabetes mellitus management | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Transurethral bladder resection | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Sigmoidectomy | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Peripheral artery angioplasty | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Joint arthroplasty | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Arteriovenous shunt operation | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Skin neoplasm excision | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Hernia repair | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Tooth extraction | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Shoulder operation | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Cataract operation | 2/9134 (0%) | 3 | 3/9110 (0%) | 4 | 6/9107 (0.1%) | 8 |
| Bladder neoplasm surgery | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Gastrointestinal endoscopic therapy | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Vascular graft | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Stoma closure | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Catheter management | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Large intestinal polypectomy | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Vascular disorders | ||||||
| Aortic aneurysm | 2/9134 (0%) | 3 | 2/9110 (0%) | 2 | 2/9107 (0%) | 2 |
| Aortic thrombosis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Arteriosclerosis | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Circulatory collapse | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Embolism arterial | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Hypertension | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 2/9107 (0%) | 2 |
| Hypertensive crisis | 2/9134 (0%) | 2 | 1/9110 (0%) | 1 | 2/9107 (0%) | 2 |
| Hypotension | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Orthostatic hypotension | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Peripheral ischaemia | 1/9134 (0%) | 1 | 1/9110 (0%) | 1 | 1/9107 (0%) | 1 |
| Renovascular hypertension | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Varicose vein | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Aneurysm ruptured | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Dry gangrene | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Haemodynamic instability | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Peripheral artery aneurysm | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Peripheral artery occlusion | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
| Hypertensive emergency | 0/9134 (0%) | 0 | 0/9110 (0%) | 0 | 1/9107 (0%) | 1 |
| Aortic rupture | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Peripheral arterial occlusive disease | 2/9134 (0%) | 2 | 0/9110 (0%) | 0 | 2/9107 (0%) | 2 |
| Peripheral artery stenosis | 1/9134 (0%) | 1 | 0/9110 (0%) | 0 | 0/9107 (0%) | 0 |
| Peripheral venous disease | 0/9134 (0%) | 0 | 1/9110 (0%) | 1 | 0/9107 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Rivaroxaban 2.5mg + Aspirin 100mg | Rivaroxaban 5mg + Aspirin Placebo | Rivaroxaban Placebo + Aspirin 100mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 553/9134 (6.1%) | 526/9110 (5.8%) | 500/9107 (5.5%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 14/9134 (0.2%) | 24 | 11/9110 (0.1%) | 13 | 9/9107 (0.1%) | 11 |
| Iron deficiency anaemia | 9/9134 (0.1%) | 12 | 12/9110 (0.1%) | 16 | 1/9107 (0%) | 1 |
| Cardiac disorders | ||||||
| Atrial fibrillation | 23/9134 (0.3%) | 40 | 18/9110 (0.2%) | 32 | 19/9107 (0.2%) | 28 |
| Ear and labyrinth disorders | ||||||
| Vertigo | 10/9134 (0.1%) | 13 | 12/9110 (0.1%) | 18 | 15/9107 (0.2%) | 19 |
| Eye disorders | ||||||
| Cataract | 12/9134 (0.1%) | 12 | 15/9110 (0.2%) | 16 | 12/9107 (0.1%) | 13 |
| Conjunctival haemorrhage | 10/9134 (0.1%) | 13 | 11/9110 (0.1%) | 14 | 3/9107 (0%) | 3 |
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 19/9134 (0.2%) | 37 | 13/9110 (0.1%) | 26 | 11/9107 (0.1%) | 18 |
| Abdominal pain | 7/9134 (0.1%) | 10 | 12/9110 (0.1%) | 22 | 3/9107 (0%) | 3 |
| Abdominal pain upper | 28/9134 (0.3%) | 42 | 17/9110 (0.2%) | 29 | 21/9107 (0.2%) | 27 |
| Constipation | 25/9134 (0.3%) | 32 | 18/9110 (0.2%) | 20 | 24/9107 (0.3%) | 37 |
| Dental caries | 15/9134 (0.2%) | 15 | 12/9110 (0.1%) | 13 | 9/9107 (0.1%) | 9 |
| Diarrhoea | 47/9134 (0.5%) | 64 | 58/9110 (0.6%) | 79 | 26/9107 (0.3%) | 32 |
| Dyspepsia | 14/9134 (0.2%) | 19 | 12/9110 (0.1%) | 20 | 13/9107 (0.1%) | 22 |
| Gastritis | 18/9134 (0.2%) | 27 | 7/9110 (0.1%) | 7 | 12/9107 (0.1%) | 20 |
| Gingival bleeding | 11/9134 (0.1%) | 13 | 11/9110 (0.1%) | 13 | 6/9107 (0.1%) | 7 |
| Nausea | 21/9134 (0.2%) | 30 | 17/9110 (0.2%) | 26 | 14/9107 (0.2%) | 21 |
| Stomatitis | 12/9134 (0.1%) | 12 | 12/9110 (0.1%) | 12 | 4/9107 (0%) | 4 |
| Vomiting | 8/9134 (0.1%) | 9 | 8/9110 (0.1%) | 9 | 11/9107 (0.1%) | 14 |
| Large intestine polyp | 16/9134 (0.2%) | 17 | 12/9110 (0.1%) | 14 | 8/9107 (0.1%) | 8 |
| General disorders | ||||||
| Chest discomfort | 5/9134 (0.1%) | 5 | 3/9110 (0%) | 4 | 10/9107 (0.1%) | 10 |
| Chest pain | 7/9134 (0.1%) | 11 | 8/9110 (0.1%) | 11 | 10/9107 (0.1%) | 10 |
| Oedema peripheral | 3/9134 (0%) | 7 | 7/9110 (0.1%) | 8 | 12/9107 (0.1%) | 15 |
| Pyrexia | 6/9134 (0.1%) | 6 | 10/9110 (0.1%) | 10 | 8/9107 (0.1%) | 9 |
| Infections and infestations | ||||||
| Bronchitis | 14/9134 (0.2%) | 15 | 7/9110 (0.1%) | 7 | 13/9107 (0.1%) | 13 |
| Cystitis | 6/9134 (0.1%) | 6 | 10/9110 (0.1%) | 13 | 7/9107 (0.1%) | 7 |
| Gastroenteritis | 16/9134 (0.2%) | 21 | 10/9110 (0.1%) | 10 | 10/9107 (0.1%) | 11 |
| Herpes zoster | 9/9134 (0.1%) | 9 | 15/9110 (0.2%) | 15 | 19/9107 (0.2%) | 21 |
| Influenza | 18/9134 (0.2%) | 18 | 14/9110 (0.2%) | 16 | 24/9107 (0.3%) | 25 |
| Periodontitis | 12/9134 (0.1%) | 13 | 11/9110 (0.1%) | 11 | 12/9107 (0.1%) | 12 |
| Pharyngitis | 8/9134 (0.1%) | 8 | 7/9110 (0.1%) | 7 | 12/9107 (0.1%) | 13 |
| Viral upper respiratory tract infection | 187/9134 (2%) | 283 | 181/9110 (2%) | 283 | 193/9107 (2.1%) | 286 |
| Injury, poisoning and procedural complications | ||||||
| Contusion | 36/9134 (0.4%) | 41 | 22/9110 (0.2%) | 26 | 27/9107 (0.3%) | 41 |
| Investigations | ||||||
| Occult blood positive | 12/9134 (0.1%) | 12 | 7/9110 (0.1%) | 7 | 3/9107 (0%) | 4 |
| Metabolism and nutrition disorders | ||||||
| Diabetes mellitus | 26/9134 (0.3%) | 27 | 16/9110 (0.2%) | 16 | 28/9107 (0.3%) | 28 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 19/9134 (0.2%) | 23 | 19/9110 (0.2%) | 23 | 21/9107 (0.2%) | 27 |
| Back pain | 25/9134 (0.3%) | 27 | 37/9110 (0.4%) | 39 | 25/9107 (0.3%) | 27 |
| Lumbar spinal stenosis | 10/9134 (0.1%) | 10 | 5/9110 (0.1%) | 5 | 6/9107 (0.1%) | 6 |
| Muscle spasms | 9/9134 (0.1%) | 10 | 10/9110 (0.1%) | 12 | 6/9107 (0.1%) | 9 |
| Musculoskeletal pain | 10/9134 (0.1%) | 10 | 8/9110 (0.1%) | 8 | 11/9107 (0.1%) | 11 |
| Myalgia | 5/9134 (0.1%) | 6 | 14/9110 (0.2%) | 18 | 13/9107 (0.1%) | 14 |
| Osteoarthritis | 5/9134 (0.1%) | 7 | 10/9110 (0.1%) | 10 | 8/9107 (0.1%) | 10 |
| Pain in extremity | 14/9134 (0.2%) | 19 | 8/9110 (0.1%) | 10 | 9/9107 (0.1%) | 12 |
| Spinal osteoarthritis | 10/9134 (0.1%) | 10 | 7/9110 (0.1%) | 7 | 8/9107 (0.1%) | 8 |
| Nervous system disorders | ||||||
| Dizziness | 25/9134 (0.3%) | 41 | 25/9110 (0.3%) | 36 | 35/9107 (0.4%) | 42 |
| Headache | 20/9134 (0.2%) | 31 | 21/9110 (0.2%) | 32 | 22/9107 (0.2%) | 32 |
| Hypoaesthesia | 6/9134 (0.1%) | 6 | 8/9110 (0.1%) | 9 | 12/9107 (0.1%) | 15 |
| Psychiatric disorders | ||||||
| Insomnia | 6/9134 (0.1%) | 6 | 12/9110 (0.1%) | 14 | 4/9107 (0%) | 4 |
| Renal and urinary disorders | ||||||
| Haematuria | 23/9134 (0.3%) | 31 | 15/9110 (0.2%) | 25 | 7/9107 (0.1%) | 8 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 7/9134 (0.1%) | 9 | 12/9110 (0.1%) | 18 | 11/9107 (0.1%) | 13 |
| Epistaxis | 38/9134 (0.4%) | 73 | 29/9110 (0.3%) | 45 | 24/9107 (0.3%) | 29 |
| Haemoptysis | 10/9134 (0.1%) | 25 | 5/9110 (0.1%) | 6 | 5/9107 (0.1%) | 5 |
| Upper respiratory tract inflammation | 10/9134 (0.1%) | 11 | 8/9110 (0.1%) | 8 | 4/9107 (0%) | 4 |
| Skin and subcutaneous tissue disorders | ||||||
| Eczema | 18/9134 (0.2%) | 24 | 19/9110 (0.2%) | 25 | 22/9107 (0.2%) | 25 |
| Haemorrhage subcutaneous | 48/9134 (0.5%) | 85 | 18/9110 (0.2%) | 23 | 17/9107 (0.2%) | 29 |
| Pruritus | 19/9134 (0.2%) | 27 | 22/9110 (0.2%) | 34 | 16/9107 (0.2%) | 20 |
| Rash | 11/9134 (0.1%) | 20 | 14/9110 (0.2%) | 27 | 18/9107 (0.2%) | 30 |
| Urticaria | 11/9134 (0.1%) | 13 | 11/9110 (0.1%) | 11 | 5/9107 (0.1%) | 5 |
| Vascular disorders | ||||||
| Hypertension | 25/9134 (0.3%) | 25 | 16/9110 (0.2%) | 18 | 11/9107 (0.1%) | 11 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Global principal investigator (PI) to provide to Bayer for review any proposed Publication/oral presentation relating to Study/Study Drug/Results at least 45 days prior to submission or presentation of the Publication. Abstracts to be provided to Bayer 5 working days before Publication. 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:
NCT01776424
Other Study ID Numbers:
- 15786
- 2012-004180-43
First Posted:
Jan 28, 2013
Last Update Posted:
Jul 16, 2021
Last Verified:
Jul 1, 2021