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REDUCE-IT: A Study of AMR101 to Evaluate Its Ability to Reduce Cardiovascular Events in High-Risk Patients With Hypertriglyceridemia and on Statin

Sponsor
Amarin Pharma Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01492361
Collaborator
(none)
8,179
Enrollment
410
Locations
2
Arms
78
Actual Duration (Months)
19.9
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

AMR101 (icosapent ethyl [ethyl-EPA]) is a highly purified ethyl ester of eicosapentaenoic acid (EPA) developed by Amarin Pharma Inc. for the treatment of cardiovascular disease in statin-treated patients with hypertriglyceridemia. The purpose of this study was to evaluate whether this drug, combined with a statin therapy, will be superior to the statin therapy alone, when used as a prevention in reducing long-term cardiovascular events in high-risk patients with mixed dyslipidemia.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
8179 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Evaluation of the Effect of AMR101 on Cardiovascular Health and Mortality in Hypertriglyceridemic Patients With Cardiovascular Disease or at High Risk for Cardiovascular Disease: REDUCE-IT (Reduction of Cardiovascular Events With EPA - Intervention Trial)
Actual Study Start Date :
Nov 1, 2011
Actual Primary Completion Date :
May 1, 2018
Actual Study Completion Date :
May 1, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: AMR101

AMR101 (icosapent ethyl) + statin therapy, daily

Drug: AMR101
Parallel Assignment
Other Names:
  • VASCEPA® (icosapent ethyl)

    • Drug: Statin therapy
    Stable statin therapy (± ezetimibe) for at least 28 days before lipid qualification measurement (LDL-C >40 mg/dL and ≤100 mg/dL)
    Placebo Comparator: Placebo

    Placebo + statin therapy, daily

    Drug: Placebo
    Parallel Assignment
    Other Names:
  • matching placebo

    • Drug: Statin therapy
    Stable statin therapy (± ezetimibe) for at least 28 days before lipid qualification measurement (LDL-C >40 mg/dL and ≤100 mg/dL)

    Outcome Measures

    Primary Outcome Measures

    1. Composite of CV Death, Nonfatal MI (Including Silent MI), Nonfatal Stroke, Coronary Revascularization, or Unstable Angina Determined to be Caused by Myocardial Ischemia by Invasive / Non-invasive Testing and Requiring Emergent Hospitalization. [Total follow-up time of up to approximately 6 years.]

      The primary outcome measure was the number of patients with a first occurrence of any component of the composite of CV death, nonfatal MI (including silent MI), nonfatal stroke, coronary revascularization, or unstable angina determined to be caused by myocardial ischemia by invasive / non-invasive testing and requiring emergent hospitalization during the follow-up period.

    Secondary Outcome Measures

    1. Composite of CV Death, Nonfatal MI (Including Silent MI), or Nonfatal Stroke. [Total follow-up time of up to approximately 6 years.]

      The key secondary outcome measure was the number of patients with a first occurrence of any component of the composite of CV death, nonfatal MI (including silent MI), or nonfatal stroke during the follow-up period.

    2. Composite of CV Death or Nonfatal MI (Including Silent MI). [Total follow-up time of up to approximately 6 years.]

      Number of patients with a first occurrence of any component of the composite of CV death or nonfatal MI (including silent MI) during the follow-up period.

    3. Fatal or Nonfatal MI (Including Silent MI). [Total follow-up time of up to approximately 6 years.]

      Number of patients with a first occurrence of fatal or nonfatal MI (including silent MI) during the follow-up period.

    4. Non-elective Coronary Revascularization Represented as the Composite of Emergent or Urgent Classifications. [Total follow-up time of up to approximately 6 years.]

      Number of patients with a first occurrence of non-elective coronary revascularization represented as the composite of emergent or urgent classifications during the follow-up period.

    5. CV Death. [Total follow-up time of up to approximately 6 years.]

      Number of patients with an occurrence of CV death during the follow-up period.

    6. Unstable Angina Determined to be Caused by Myocardial Ischemia by Invasive / Non-invasive Testing and Requiring Emergent Hospitalization. [Total follow-up time of up to approximately 6 years.]

      Number of patients with a first occurrence of unstable angina determined to be caused by myocardial ischemia by invasive / non-invasive testing and requiring emergent hospitalization during the follow-up period.

    7. Fatal or Nonfatal Stroke. [Total follow-up time of up to approximately 6 years.]

      Number of patients with a first occurrence of fatal or nonfatal stroke during the follow-up period.

    8. Total Mortality, Nonfatal MI (Including Silent MI), or Nonfatal Stroke. [Total follow-up time of up to approximately 6 years.]

      Number of patients with a first occurrence of any component of the composite of total mortality, nonfatal MI (including silent MI), or nonfatal stroke during the follow-up period.

    9. Total Mortality. [Total follow-up time of up to approximately 6 years.]

      Number of patients with an occurrence of death from any cause during the follow-up period.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    45 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Men and non-pregnant or sterile women ages 45 and older

    • Hypertriglyceridemia

    • On statin therapy for at least four weeks

    • Either having established cardiovascular disease or at high risk for cardiovascular disease

    Exclusion Criteria:

    • Severe heart failure

    • Any life-threatening disease other than cardiovascular disease

    • Active severe liver disease

    • Hemoglobin A1c >10.0%

    • Poorly controlled hypertension

    • Planned coronary intervention (such as stent placement or heart bypass) or any non-cardiac major surgical procedure

    • Known familial lipoprotein lipase deficiency (Fredrickson Type I), apolipoprotein C-II deficiency, or familial dysbetalipoproteinemia (Fredrickson Type III)

    • Known hypersensitivity to the study product, fish and/or shellfish, or placebo

    • History of acute or chronic pancreatitis

    • Patients are excluded if using the following medications:

    • PCSK9 inhibitors

    • niacin >200 mg/day or fibrates;

    • any omega-3 fatty acid medications ;

    • dietary supplements containing omega-3 fatty acids (e.g., flaxseed oil, fish oil, krill oil, or algal oil);

    • bile acid sequestrants

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Amarin Investigational Site Birmingham Alabama United States 35205
    2 Amarin Investigational Site Birmingham Alabama United States 35235
    3 Amarin Investigational Site Huntsville Alabama United States 35801
    4 Amarin Investigational Site Mobile Alabama United States 36608
    5 Amarin Investigational Site Muscle Shoals Alabama United States 35662
    6 Amarin Investigational Site Mesa Arizona United States 85206
    7 Amarin Investigational Site Phoenix Arizona United States 85251
    8 Amarin Investigational Site Tucson Arizona United States 85745
    9 Amarin Investigational Site Little Rock Arkansas United States 72204
    10 Amarin Investigational Site Beverly Hills California United States 90211
    11 Amarin Investigational Site Chino California United States 91710
    12 Amarin Investigational Site Concord California United States 94520
    13 Amarin Investigational Site El Cajon California United States 92020
    14 Amarin Investigational Site Encino California United States 91436
    15 Amarin Investigational Site Fair Oaks California United States 95628
    16 Amarin Investigational Site Hawaiian Gardens California United States 90716
    17 Amarin Investigational Site Lancaster California United States 93534
    18 Amarin Investigational Site Lincoln California United States 95648
    19 Amarin Investigational Site Los Angeles California United States 90015
    20 Amarin Investigational Site Los Angeles California United States 90017
    21 Amarin Investigational Site Los Angeles California United States 90033
    22 Amarin Investigational Site National City California United States 91950
    23 Amarin Investigational Site Orange California United States 92868
    24 Amarin Investigational Site Paramount California United States 90723
    25 Amarin Investigational Site Roseville California United States 95661
    26 Amarin Investigational Site San Diego California United States 92123
    27 Amarin Investigational Site Torrance California United States 90502
    28 Amarin Investigational Site Ventura California United States 93003
    29 Amarin Investigational Site Walnut Creek California United States 94598
    30 Amarin Investigational Site Aurora Colorado United States 80012
    31 Amarin Investigational Site Colorado Springs Colorado United States 80909
    32 Amarin Investigational Site Golden Colorado United States 80401
    33 Amarin Investigational Site Guilford Connecticut United States 06437
    34 Amarin Investigational Site Hartford Connecticut United States 06102
    35 Amarin Investigational Site Newark Delaware United States 19718
    36 Amarin Investigational Site Wilmington Delaware United States 19803
    37 Amarin Investigational Site Washington District of Columbia United States 20037
    38 Amarin Investigational Site Boynton Beach Florida United States 33437
    39 Amarin Investigational Site Bradenton Florida United States 34209
    40 Amarin Investigational Site Clearwater Florida United States 33756
    41 Amarin Investigational Site Edgewater Florida United States 32132
    42 Amarin Investigational Site Fleming Island Florida United States 32003
    43 Amarin Investigational Site Fort Lauderdale Florida United States 33308
    44 Amarin Investigational Site Fort Lauderdale Florida United States 33312
    45 Amarin Investigational Site Inverness Florida United States 34429
    46 Amarin Investigational Site Jacksonville Florida United States 32204
    47 Amarin Investigational Site Jacksonville Florida United States 32205
    48 Amarin Investigational Site Jacksonville Florida United States 32207
    49 Amarin Investigational Site Jacksonville Florida United States 32216
    50 Amarin Investigational Site Miami Beach Florida United States 33140
    51 Amarin Investigational Site Miami Lakes Florida United States 33014
    52 Amarin Investigational Site Miami Florida United States 33144
    53 Amarin Investigational Site Miami Florida United States 33175
    54 Amarin Investigational Site Ocala Florida United States 34471
    55 Amarin Investigational Site Orlando Florida United States 32803
    56 Amarin Investigational Site Pembroke Pines Florida United States 33026
    57 Amarin Investigational Site Plantation Florida United States 33324
    58 Amarin Investigational Site Safety Harbor Florida United States 34695
    59 Amarin Investigational Site Saint Petersburg Florida United States 33713
    60 Amarin Investigational Site Sarasota Florida United States 34233
    61 Amarin Investigational Site Vero Beach Florida United States 32960
    62 Amarin Investigational Site West Palm Beach Florida United States 33401
    63 Amarin Investigational Site Conyers Georgia United States 30094
    64 Amarin Investigational Site Covington Georgia United States 30014
    65 Amarin Investigational Site Cumming Georgia United States 30041
    66 Amarin Investigational Site Roswell Georgia United States 30076
    67 Amarin Investigational Site Honolulu Hawaii United States 96818
    68 Amarin Investigational Site Addison Illinois United States 60101
    69 Amarin Investigational Site Chicago Illinois United States 60611
    70 Amarin Investigational Site Norman Illinois United States 61761
    71 Amarin Investigational Site North Chicago Illinois United States 60064
    72 Amarin Investigational Site Peoria Illinois United States 61636
    73 Amarin Investigational Site Winfield Illinois United States 60190
    74 Amarin Investigational Site Evansville Indiana United States 47713
    75 Amarin Investigational Site Iowa City Iowa United States 52242
    76 Amarin Investigational Site Wichita Kansas United States 67203
    77 Amarin Investigational Site Wichita Kansas United States 67207
    78 Amarin Investigational Site Louisville Kentucky United States 40213
    79 Amarin Investigational Site Alexandria Louisiana United States 71301
    80 Amarin Investigational Site Eunice Louisiana United States 70535
    81 Amarin Investigational Site Marrero Louisiana United States 70072
    82 Amarin Investigational Site Auburn Maine United States 04210
    83 Amarin Investigational Site Baltimore Maryland United States 21236
    84 Amarin Investigational Site Lutherville Maryland United States 21093
    85 Amarin Investigational Site Takoma Park Maryland United States 20912
    86 Amarin Investigational Site Boston Massachusetts United States 02118
    87 Amarin Investigational Site Boston Massachusetts United States 02215
    88 Amarin Investigational Site Fall River Massachusetts United States 02721
    89 Amarin Investigational Site Lansing Michigan United States 48910
    90 Amarin Investigational Site Marquette Michigan United States 49855
    91 Amarin Investigational Site Troy Michigan United States 48098
    92 Amarin Investigational Site Saint Cloud Minnesota United States 56303
    93 Amarin Investigational Site Biloxi Mississippi United States 39531
    94 Amarin Investigational Site Tupelo Mississippi United States 38801
    95 Amarin Investigational Site Chesterfield Missouri United States 63141
    96 Amarin Investigational Site Florissant Missouri United States 63031
    97 Amarin Investigational Site Jefferson City Missouri United States 65109
    98 Amarin Investigational Site Kansas City Missouri United States 64114
    99 Amarin Investigational Site Saint Louis Missouri United States 63110
    100 Amarin Investigational Site Saint Peters Missouri United States 63303
    101 Amarin Investigational Site Hastings Nebraska United States 68901
    102 Amarin Investigational Site Omaha Nebraska United States 68114
    103 Amarin Investigational Site Omaha Nebraska United States 68154
    104 Amarin Investigational Site Henderson Nevada United States 89052
    105 Amarin Investigational Site Las Vegas Nevada United States 89101
    106 Amarin Investigational Site Ocean City New Jersey United States 07712
    107 Amarin Investigational Site Albuquerque New Mexico United States 87102
    108 Amarin Investigational Site Albany New York United States 12206
    109 Amarin Investigational Site Brooklyn New York United States 11206
    110 Amarin Investigational Site Great Neck New York United States 11023
    111 Amarin Investigational Site Liverpool New York United States 13088
    112 Amarin Investigational Site New York New York United States 10001
    113 Amarin Investigational Site New York New York United States 10016
    114 Amarin Investigational Site North Massapequa New York United States 11758
    115 Amarin Investigational Site Smithtown New York United States 11787
    116 Amarin Investigational Site Vestal New York United States 13850
    117 Amarin Investigational Site West Seneca New York United States 14224
    118 Amarin Investigational Site Charlotte North Carolina United States 28204
    119 Amarin Investigational Site Durham North Carolina United States 27710
    120 Amarin Investigational Site Gastonia North Carolina United States 28054
    121 Amarin Investigational Site Kernersville North Carolina United States 27284
    122 Amarin Investigational Site Raleigh North Carolina United States 27609
    123 Amarin Investigational Site Winston-Salem North Carolina United States 27157
    124 Amarin Investigational Site Fargo North Dakota United States 58103
    125 Amarin Investigational Site Cincinnati Ohio United States 45219
    126 Amarin Investigational Site Dayton Ohio United States 45419
    127 Amarin Investigational Site Lorain Ohio United States 44053
    128 Amarin Investigational Site Sandusky Ohio United States 44870
    129 Amarin Investigational Site Tulsa Oklahoma United States 74104
    130 Amarin Investigational Site Bend Oregon United States 97702
    131 Amarin Investigational Site Portland Oregon United States 97239
    132 Amarin Investigational Site Beaver Pennsylvania United States 15009
    133 Amarin Investigational Site Doylestown Pennsylvania United States 18901
    134 Amarin Investigational Site Jersey Shore Pennsylvania United States 17740
    135 Amarin Investigational Site Newport Pennsylvania United States 17074
    136 Amarin Investigational Site Philadelphia Pennsylvania United States 19104
    137 Amarin Investigational Site Phoenixville Pennsylvania United States 19460
    138 Amarin Investigational Site Sellersville Pennsylvania United States 18960
    139 Amarin Investigational Site Tipton Pennsylvania United States 16684
    140 Amarin Investigational Site Wyomissing Pennsylvania United States 19610
    141 Amarin Investigational Site Yardley Pennsylvania United States 19067
    142 Amarin Investigational Site Lancaster South Carolina United States 29720
    143 Amarin Investigational Site Simpsonville South Carolina United States 29681
    144 Amarin Investigational Site Rapid City South Dakota United States 57701
    145 Amarin Investigational Site Bristol Tennessee United States 37620
    146 Amarin Investigational Site Columbia Tennessee United States 38401
    147 Amarin Investigational Site Germantown Tennessee United States 38138
    148 Amarin Investigational Site Jackson Tennessee United States 38301
    149 Amarin Investigational Site Knoxville Tennessee United States 37917
    150 Amarin Investigational Site Smyrna Tennessee United States 37167
    151 Amarin Investigational Site Austin Texas United States 78756
    152 Amarin Investigational Site Beaumont Texas United States 77702
    153 Amarin Investigational Site Carrollton Texas United States 75007
    154 Amarin Investigational Site Dallas Texas United States 75231
    155 Amarin Investigational Site Houston Texas United States 77024
    156 Amarin Investigational Site Houston Texas United States 77025
    157 Amarin Investigational Site Houston Texas United States 77030
    158 Amarin Investigational Site Houston Texas United States 77053
    159 Amarin Investigational Site Houston Texas United States 77070
    160 Amarin Investigational Site Houston Texas United States 77077
    161 Amarin Investigational Site Houston Texas United States 77079
    162 Amarin Investigational Site Hurst Texas United States 76054
    163 Amarin Investigational Site New Braunfels Texas United States 78130
    164 Amarin Investigational Site Plano Texas United States 75075
    165 Amarin Investigational Site San Antonio Texas United States 78228
    166 Amarin Investigational Site San Antonio Texas United States 78238
    167 Amarin Investigational Site Splendora Texas United States 77372
    168 Amarin Investigational Site Tomball Texas United States 77375
    169 Amarin Investigational Site West Jordan Utah United States 84088
    170 Amarin Investigational Site Falls Church Virginia United States 22044
    171 Amarin Investigational Site Manassas Virginia United States 20109
    172 Amarin Investigational Site Midlothian Virginia United States 23114
    173 Amarin Investigational Site Newport News Virginia United States 23606
    174 Amarin Investigational Site Burien Washington United States 98166
    175 Amarin Investigational Site Tacoma Washington United States 98405
    176 Amarin Investigational Site Huntington West Virginia United States 25701
    177 Amarin Investigational Site Camperdown New South Wales Australia 2015
    178 Amarin Investigational Site Lismore New South Wales Australia 2480
    179 Amarin Investigational Site Brisbane Queensland Australia 4064
    180 Amarin Investigational Site Chermside Queensland Australia 4032
    181 Amarin Investigational Site Bedford Park South Australia Australia 5042
    182 Amarin Investigational Site Launceston Tasmania Australia 7250
    183 Amarin Investigational Site Fitzroy Victoria Australia 3065
    184 Amarin Investigational Site Geelong Victoria Australia 3220
    185 Amarin Investigational Site Heidelberg Heights Victoria Australia 3081
    186 Amarin Investigational Site Melbourne Victoria Australia 3004
    187 Amarin Investigational Site Fremantle Western Australia Australia 6160
    188 Amarin Investigational Site Joondalup Western Australia Australia 6027
    189 Amarin Investigational Site Murdoch Western Australia Australia 6150
    190 Amarin Investigational Site Nedlands Western Australia Australia 6009
    191 Amarin Investigational Site Perth Western Australia Australia 6000
    192 Amarin Investigational Site Edmonton Alberta Canada T5A 4L8
    193 Amarin Investigational Site Coquitlam British Columbia Canada V3K 3V9
    194 Amarin Investigational Site Vancouver British Columbia Canada V5Z 1M9
    195 Amarin Investigational Site Vancouver British Columbia Canada V6Z1Y6
    196 Amarin Investigational Site Brampton Ontario Canada L6Z 4N5
    197 Amarin Investigational Site Collingwood Ontario Canada L9Y 1W3
    198 Amarin Investigational Site Corunna Ontario Canada N0N 1G0
    199 Amarin Investigational Site Newmarket Ontario Canada L3Y 5G8
    200 Amarin Investigational Site Sarnia Ontario Canada N7T 4X3
    201 Amarin Investigational Site Strathroy Ontario Canada N7G 1Y7
    202 Amarin Investigational Site Laval Quebec Canada H7T 2P5
    203 Amarin Investigational Site Montreal Quebec Canada H1T 1C8
    204 Amarin Investigational Site Montreal Quebec Canada H3H 1A1
    205 Amarin Investigational Site Sherbrooke Quebec Canada J1J 2E3
    206 Amarin Investigational Site St. Charles-Borromée Quebec Canada J6E 6J2
    207 Amarin Investigational Site Québec Canada G1V 4G5
    208 Amarin Investigational Site Québec Canada G1V 4M6
    209 Amarin Investigational Site Hyderabad Andhra Pradesh India 500001
    210 Amarin Investigational Site Hyderabad Andhra Pradesh India 500004
    211 Amarin Investigational Site Secunderabad Andhra Pradesh India 500003
    212 Amarin Investigational Site Visakhapatnam Andhra Pradesh India 530013
    213 Amarin Investigational Site New Delhi Delhi India 110025
    214 Amarin Investigational Site New Delhi Delhi India 110060
    215 Amarin Investigational Site Bangalore Karnataka India 560034
    216 Amarin Investigational Site Bangalore Karnataka India 560038
    217 Amarin Investigational Site Bangalore Karnataka India 560052
    218 Amarin Investigational Site Mysore Karnataka India 570015
    219 Amarin Investigational Site Mysore Karnataka India 570020
    220 Amarin Investigational Site Kottayam Kerala India 686016
    221 Amarin Investigational Site Mumbai Maharashtra India 422055
    222 Amarin Investigational Site Nashik Maharashtra India 422005
    223 Amarin Investigational Site Pune Maharashtra India 411004
    224 Amarin Investigational Site Chennai Tamil Nadu India 600086
    225 Amarin Investigational Site Coimbatore Tamil Nadu India 641037
    226 Amarin Investigational Site Almelo Netherlands 7600 SZ
    227 Amarin Investigational Site Amersfoort Netherlands 3813 TZ
    228 Amarin Investigational Site Blaricum Netherlands 1261 AN
    229 Amarin Investigational Site Capelle aan den Ijssel Netherlands 2906 ZC
    230 Amarin Investigational Site Den Haag Netherlands 2597 AX
    231 Amarin Investigational Site Den Helder Netherlands 1782 GZ
    232 Amarin Investigational Site Deventer Netherlands 7416 SE
    233 Amarin Investigational Site Ede Netherlands 6716 RP
    234 Amarin Investigational Site Eindhoven Netherlands 5611 NV
    235 Amarin Investigational Site Enschede Netherlands 7513 ER
    236 Amarin Investigational Site Goes Netherlands 4462 RA
    237 Amarin Investigational Site Gorinchem Netherlands 4204 AA
    238 Amarin Investigational Site Gouda Netherlands 2803 HH
    239 Amarin Investigational Site Groningen Netherlands 9728 NT
    240 Amarin Investigational Site Haarlem Netherlands 2035 RC
    241 Amarin Investigational Site Harderwijk Netherlands 3844 DG
    242 Amarin Investigational Site Heerenveen Netherlands 8441 PW
    243 Amarin Investigational Site Heerlen Netherlands 6419 PC
    244 Amarin Investigational Site Hoofddorp Netherlands 2134 TM
    245 Amarin Investigational Site Leeuwarden Netherlands 8934 AD
    246 Amarin Investigational Site Leiderdorp Netherlands 2353 GA
    247 Amarin Investigational Site Nijmegen Netherlands 6532 SZ
    248 Amarin Investigational Site Roosendaal Netherlands 4708 AE
    249 Amarin Investigational Site Rotterdam Netherlands 3021 HC
    250 Amarin Investigational Site Rotterdam Netherlands 3045 PM
    251 Amarin Investigational Site Rotterdam Netherlands 3083 AN
    252 Amarin Investigational Site s'Hertogenbosch Netherlands 5223 GV
    253 Amarin Investigational Site Schiedam Netherlands 3118 JH
    254 Amarin Investigational Site Sneek Netherlands 8601 ZK
    255 Amarin Investigational Site Tilburg Netherlands 5022 GC
    256 Amarin Investigational Site Tilburg Netherlands 5042 AD
    257 Amarin Investigational Site Uden Netherlands 5406 PT
    258 Amarin Investigational Site Veldhoven Netherlands 5504 DB
    259 Amarin Investigational Site Zoetermeer Netherlands 2725 NA
    260 Amarin Investigational Site Zutphen Netherlands 7207 AE
    261 Amarin Investigational Site Takapuna Auckland New Zealand 0622
    262 Amarin Investigational Site Christchurch New Zealand 8011
    263 Amarin Investigational Site Dunedin New Zealand 9016
    264 Amarin Investigational Site Hamilton New Zealand 3240
    265 Amarin Investigational Site Hastings New Zealand 4120
    266 Amarin Investigational Site Nelson New Zealand 7010
    267 Amarin Investigational Site New Plymouth New Zealand 4342
    268 Amarin Investigational Site Takapuna Auckland New Zealand 0622
    269 Amarin Investigational Site Tauranga New Zealand 3112
    270 Amarin Investigational Site Whangarei New Zealand 0110
    271 Amarin Investigational Site Bialystok Poland 15-351
    272 Amarin Investigational Site Bialystok Poland 15-875
    273 Amarin Investigational Site Katowice Poland 40-748
    274 Amarin Investigational Site Katowice Poland 40-772
    275 Amarin Investigational Site Kraków Poland 31-011
    276 Amarin Investigational Site Mikolów Poland 43-190
    277 Amarin Investigational Site Skierniewice Poland 96-100
    278 Amarin Investigational Site Tarnów Poland 33-100
    279 Amarin Investigational Site Warszawa Poland 01-231
    280 Amarin Investigational Site Warszawa Poland 04-628
    281 Amarin Investigational Site Warszawska Poland 01-192
    282 Amarin Investigational Site Wroclaw Poland 50-088
    283 Amarin Investigational Site Wroclaw Poland 50-315
    284 Amarin Investigational Site Zgierz Poland 95-100
    285 Amarin Investigational Site Argeş Romania 110084
    286 Amarin Investigational Site Brăila Romania 810249
    287 Amarin Investigational Site Bucharest Romania 010628
    288 Amarin Investigational Site Bucharest Romania 050098
    289 Amarin Investigational Site Bucharest Romania 050524
    290 Amarin Investigational Site Bucuresti Romania 011234
    291 Amarin Investigational Site Bucuresti Romania 0200054
    292 Amarin Investigational Site Bucuresti Romania 061098
    293 Amarin Investigational Site Cluj-Napoca Romania 400006
    294 Amarin Investigational Site Constanţa Romania 900203
    295 Amarin Investigational Site Craiova, Dolj Romania 200030
    296 Amarin Investigational Site Iaşi Romania 700661
    297 Amarin Investigational Site Maramureş Romania 430123
    298 Amarin Investigational Site Mureş Romania 540098
    299 Amarin Investigational Site Sibiu Romania 550245
    300 Amarin Investigational Site Timişoara Romania 300359
    301 Amarin Investigational Site Târgu Mureş Romania 540136
    302 Amarin Investigational Site Arkhangelsk Russian Federation 163000
    303 Amarin Investigational Site Arkhangelsk Russian Federation 163001
    304 Amarin Investigational Site Arkhangelsk Russian Federation 163045
    305 Amarin Investigational Site Ekaterinburg Russian Federation 620102
    306 Amarin Investigational Site Ekaterinburg Russian Federation 620109
    307 Amarin Investigational Site Kazan Russian Federation 420012
    308 Amarin Investigational Site Kazan Russian Federation 420097
    309 Amarin Investigational Site Kemerovo Russian Federation 650000
    310 Amarin Investigational Site Kemerovo Russian Federation 650002
    311 Amarin Investigational Site Kirovsk, Leningradskaya Region Russian Federation 187342
    312 Amarin Investigational Site Krasnodar Russian Federation 350086
    313 Amarin Investigational Site Moscow Russian Federation 109240
    314 Amarin Investigational Site Moscow Russian Federation 111020
    315 Amarin Investigational Site Moscow Russian Federation 111539
    316 Amarin Investigational Site Moscow Russian Federation 115093
    317 Amarin Investigational Site Moscow Russian Federation 117292
    318 Amarin Investigational Site Moscow Russian Federation 117593
    319 Amarin Investigational Site Moscow Russian Federation 117630
    320 Amarin Investigational Site Moscow Russian Federation 117997
    321 Amarin Investigational Site Moscow Russian Federation 121374
    322 Amarin Investigational Site Moscow Russian Federation 121552
    323 Amarin Investigational Site Moscow Russian Federation 124489
    324 Amarin Investigational Site Nizhny Novgorod Russian Federation 603126
    325 Amarin Investigational Site Novosibirsk Russian Federation 630008
    326 Amarin Investigational Site Novosibirsk Russian Federation 630047
    327 Amarin Investigational Site Novosibirsk Russian Federation 630089
    328 Amarin Investigational Site Petrozavodsk Russian Federation 185000
    329 Amarin Investigational Site Saint-Petersburg Russian Federation 190000
    330 Amarin Investigational Site Saint-Petersburg Russian Federation 190107
    331 Amarin Investigational Site Saint-Petersburg Russian Federation 192283
    332 Amarin Investigational Site Saint-Petersburg Russian Federation 194044
    333 Amarin Investigational Site Saint-Petersburg Russian Federation 194156
    334 Amarin Investigational Site Saint-Petersburg Russian Federation 194291
    335 Amarin Investigational Site Saint-Petersburg Russian Federation 194354
    336 Amarin Investigational Site Saint-Petersburg Russian Federation 196601
    337 Amarin Investigational Site Saint-Petersburg Russian Federation 197022
    338 Amarin Investigational Site Saint-Petersburg Russian Federation 197110
    339 Amarin Investigational Site Saint-Petersburg Russian Federation 197227
    340 Amarin Investigational Site Saint-Petersburg Russian Federation 197341
    341 Amarin Investigational Site Saint-Petersburg Russian Federation 197729
    342 Amarin Investigational Site Saint-Petersburg Russian Federation 198205
    343 Amarin Investigational Site Saint-Petersburg Russian Federation 199106
    344 Amarin Investigational Site Saratov Russian Federation 410002
    345 Amarin Investigational Site Saratov Russian Federation 410028
    346 Amarin Investigational Site Sestroretsk, Saint-Petersburg Russian Federation 197706
    347 Amarin Investigational Site Tomsk Russian Federation 634050
    348 Amarin Investigational Site Tomsk Russian Federation 643012
    349 Amarin Investigational Site Volgograd Russian Federation 400001
    350 Amarin Investigational Site Voronezh Russian Federation 394018
    351 Amarin Investigational Site Voronezh Russian Federation 394065
    352 Amarin Investigational Site Yaroslavl Russian Federation 150030
    353 Amarin Investigational Site Yaroslavl Russian Federation 150062
    354 Amarin Investigational Site Bloemfontein Freestate South Africa 9301
    355 Amarin Investigational Site Benoni Gauteng South Africa 1500
    356 Amarin Investigational Site Pretoria Gauteng South Africa 0157
    357 Amarin Investigational Site Soweto Gauteng South Africa 2013
    358 Amarin Investigational Site Witbank Gauteng South Africa 1035
    359 Amarin Investigational Site Durban KwaZulu-Natal South Africa 4001
    360 Amarin Investigational Site Newlands KwaZulu-Natal South Africa 4037
    361 Amarin Investigational Site Bellville Western Cape South Africa 7530
    362 Amarin Investigational Site Cape Town Western Cape South Africa 7925
    363 Amarin Investigational Site Durbanville Western Cape South Africa 7550
    364 Amarin Investigational Site Goodwood Western Cape South Africa 7460
    365 Amarin Investigational Site Kraaifontein Western Cape South Africa 7570
    366 Amarin Investigational Site Paarl Western Cape South Africa 7646
    367 Amarin Investigational Site Panorama Western Cape South Africa 7500
    368 Amarin Investigational Site Parow Western Cape South Africa 7500
    369 Amarin Investigational Site Pinelands Western Cape South Africa 7405
    370 Amarin Investigational Site Somerset West Western Cape South Africa 7130
    371 Amarin Investigational Site Worcester Western Cape South Africa 6850
    372 Amarin Investigational Site Lutsk Volyn Region Ukraine 43000
    373 Amarin Investigational Site Cherkasy Ukraine 18009
    374 Amarin Investigational Site Chernivtsi Ukraine 58002
    375 Amarin Investigational Site Dnipropetrovsk Ukraine 49006
    376 Amarin Investigational Site Dnipropetrovsk Ukraine 49023
    377 Amarin Investigational Site Dnipropetrovsk Ukraine 49027
    378 Amarin Investigational Site Donetsk Ukraine 83001
    379 Amarin Investigational Site Donetsk Ukraine 83045
    380 Amarin Investigational Site Ivano-Frankivsk Ukraine 76005
    381 Amarin Investigational Site Ivano-Frankivsk Ukraine 76018
    382 Amarin Investigational Site Kharkiv Ukraine 61002
    383 Amarin Investigational Site Kharkiv Ukraine 61018
    384 Amarin Investigational Site Kharkiv Ukraine 61039
    385 Amarin Investigational Site Kharkiv Ukraine 61176
    386 Amarin Investigational Site Kyiv Ukraine 01032
    387 Amarin Investigational Site Kyiv Ukraine 01103
    388 Amarin Investigational Site Kyiv Ukraine 01151
    389 Amarin Investigational Site Kyiv Ukraine 01601
    390 Amarin Investigational Site Kyiv Ukraine 02091
    391 Amarin Investigational Site Kyiv Ukraine 02660
    392 Amarin Investigational Site Kyiv Ukraine 03151
    393 Amarin Investigational Site Kyiv Ukraine 04050
    394 Amarin Investigational Site Kyiv Ukraine 04114
    395 Amarin Investigational Site Luhansk Ukraine 91016
    396 Amarin Investigational Site Lutsk Ukraine 43024
    397 Amarin Investigational Site Lviv Ukraine 79034
    398 Amarin Investigational Site Odesa Ukraine 65009
    399 Amarin Investigational Site Odesa Ukraine 65025
    400 Amarin Investigational Site Odesa Ukraine 65082
    401 Amarin Investigational Site Poltava Ukraine 36011
    402 Amarin Investigational Site Ternopil Ukraine 46003
    403 Amarin Investigational Site Uzhgorod Ukraine 88000
    404 Amarin Investigational Site Uzhgorod Ukraine 88014
    405 Amarin Investigational Site Vinnytsya Ukraine 21018
    406 Amarin Investigational Site Vinnytsya Ukraine 21029
    407 Amarin Investigational Site Zaporizhzhia Ukraine 69035
    408 Amarin Investigational Site Zaporizhzhia Ukraine 69065
    409 Amarin Investigational Site Zaporizhzhia Ukraine 69106
    410 Amarin Investigational Site Zaporizhzhia Ukraine 69600

    Sponsors and Collaborators

    • Amarin Pharma Inc.

    Investigators

    • Principal Investigator: Deepak L. Bhatt, MD, MPH, Brigham and Women's Hospital, 75 Francis Street, Boston

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Amarin Pharma Inc.
    ClinicalTrials.gov Identifier:
    NCT01492361
    Other Study ID Numbers:
    • AMR-01-01-0019
    First Posted:
    Dec 15, 2011
    Last Update Posted:
    Apr 14, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Amarin Pharma Inc.
    Coronary Artery Disease
    Myocardial Ischemia
    Coronary Disease
    Heart Diseases
    Acute Coronary Syndrome
    Cardiovascular Diseases
    Arteriosclerosis
    Arterial Occlusive Diseases
    Vascular Diseases
    Angina Pectoris
    Chest Pain
    Anticholesteremic Agents
    Hypolipidemic Agents
    Lipid Regulating Agents
    Hypertriglyceridemia
    Omega-3 Fatty Acids
    Statin
    Triglycerides
    EPA
    Docosahexaenoic Acid
    Fish
    Fatty acids
    Fibrates
    Niacin
    Lipids
    Lipoprotein
    Atorvastatin
    Lovaza
    Simvastatin
    Lovastatin
    Pravastatin
    Fluvastatin
    Rosuvastatin
    Trilipix
    Vytorin
    Simcor
    Ezetimibe
    Zetia
    Ethyl-EPA
    Ethyl Icosapentate
    Crestor
    Zocor
    Lipitor
    LDL
    HDL
    Cholesterol
    Dyslipidemia
    AMR101
    Cardiovascular Disease, Unspecified
    VASCEPA
    Icosapent Ethyl
    Additional relevant MeSH terms:
    Cardiovascular Diseases
    Hypertriglyceridemia
    Eicosapentaenoic acid ethyl ester

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title AMR101 Placebo
    Arm/Group Description AMR101: Parallel Assignment Placebo: Parallel Assignment
    Period Title: Overall Study
    STARTED 4089 4090
    Completed Final Visit 3419 3335
    Death Before Final Visit 265 295
    COMPLETED 3684 3630
    NOT COMPLETED 405 460

    Baseline Characteristics

    Arm/Group Title AMR101 Placebo Total
    Arm/Group Description AMR101: Parallel Assignment Placebo: Parallel Assignment Total of all reporting groups
    Overall Participants 4089 4090 8179
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    64.0
    64.0
    64.0
    Sex: Female, Male (Count of Participants)
    Female
    1162
    28.4%
    1195
    29.2%
    2357
    28.8%
    Male
    2927
    71.6%
    2895
    70.8%
    5822
    71.2%
    Race/Ethnicity, Customized (Count of Participants)
    White
    3691
    90.3%
    3688
    90.2%
    7379
    90.2%
    Other than white
    398
    9.7%
    401
    9.8%
    799
    9.8%
    Missing
    0
    0%
    1
    0%
    1
    0%
    Region of Enrollment (participants) [Number]
    New Zealand
    73
    1.8%
    61
    1.5%
    134
    1.6%
    Canada
    123
    3%
    127
    3.1%
    250
    3.1%
    Netherlands
    847
    20.7%
    831
    20.3%
    1678
    20.5%
    Romania
    109
    2.7%
    93
    2.3%
    202
    2.5%
    United States
    1548
    37.9%
    1598
    39.1%
    3146
    38.5%
    Ukraine
    397
    9.7%
    439
    10.7%
    836
    10.2%
    Poland
    195
    4.8%
    164
    4%
    359
    4.4%
    South Africa
    213
    5.2%
    201
    4.9%
    414
    5.1%
    Australia
    102
    2.5%
    87
    2.1%
    189
    2.3%
    India
    130
    3.2%
    132
    3.2%
    262
    3.2%
    Russia
    352
    8.6%
    357
    8.7%
    709
    8.7%
    Cardiovascular Risk Stratum (Count of Participants)
    Secondary-prevention cohort
    2892
    70.7%
    2893
    70.7%
    5785
    70.7%
    Primary-prevention cohort
    1197
    29.3%
    1197
    29.3%
    2394
    29.3%

    Outcome Measures

    1. Primary Outcome
    Title Composite of CV Death, Nonfatal MI (Including Silent MI), Nonfatal Stroke, Coronary Revascularization, or Unstable Angina Determined to be Caused by Myocardial Ischemia by Invasive / Non-invasive Testing and Requiring Emergent Hospitalization.
    Description The primary outcome measure was the number of patients with a first occurrence of any component of the composite of CV death, nonfatal MI (including silent MI), nonfatal stroke, coronary revascularization, or unstable angina determined to be caused by myocardial ischemia by invasive / non-invasive testing and requiring emergent hospitalization during the follow-up period.
    Time Frame Total follow-up time of up to approximately 6 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title AMR101 Placebo
    Arm/Group Description AMR101: Parallel Assignment Placebo: Parallel Assignment
    Measure Participants 4089 4090
    Count of Participants [Participants]
    705
    17.2%
    901
    22%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection AMR101, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.00000001
    Comments The 2-sided alpha level for the primary analysis was adjusted to 0.0437 from 0.05 to account for the two interim analyses based on a group sequential design with O'Brien-Fleming boundaries generated using the Lan-DeMets alpha-spending function.
    Method Log Rank
    Comments Stratified by CV risk category, use of ezetimibe, and geographical region
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.75
    Confidence Interval (2-Sided) 95%
    0.68 to 0.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Composite of CV Death, Nonfatal MI (Including Silent MI), or Nonfatal Stroke.
    Description The key secondary outcome measure was the number of patients with a first occurrence of any component of the composite of CV death, nonfatal MI (including silent MI), or nonfatal stroke during the follow-up period.
    Time Frame Total follow-up time of up to approximately 6 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title AMR101 Placebo
    Arm/Group Description AMR101: Parallel Assignment Placebo: Parallel Assignment
    Measure Participants 4089 4090
    Count of Participants [Participants]
    459
    11.2%
    606
    14.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection AMR101, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0000006
    Comments Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
    Method Log Rank
    Comments Stratified by CV risk category, use of ezetimibe, and geographical region.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.74
    Confidence Interval (2-Sided) 95%
    0.65 to 0.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Composite of CV Death or Nonfatal MI (Including Silent MI).
    Description Number of patients with a first occurrence of any component of the composite of CV death or nonfatal MI (including silent MI) during the follow-up period.
    Time Frame Total follow-up time of up to approximately 6 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title AMR101 Placebo
    Arm/Group Description AMR101: Parallel Assignment Placebo: Parallel Assignment
    Measure Participants 4089 4090
    Count of Participants [Participants]
    392
    9.6%
    507
    12.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection AMR101, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
    Method Log Rank
    Comments Stratified by CV risk category, use of ezetimibe, and geographical region.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.75
    Confidence Interval (2-Sided) 95%
    0.66 to 0.86
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Fatal or Nonfatal MI (Including Silent MI).
    Description Number of patients with a first occurrence of fatal or nonfatal MI (including silent MI) during the follow-up period.
    Time Frame Total follow-up time of up to approximately 6 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title AMR101 Placebo
    Arm/Group Description AMR101: Parallel Assignment Placebo: Parallel Assignment
    Measure Participants 4089 4090
    Count of Participants [Participants]
    250
    6.1%
    355
    8.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection AMR101, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
    Method Log Rank
    Comments Stratified by CV risk category, use of ezetimibe, and geographical region.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.69
    Confidence Interval (2-Sided) 95%
    0.58 to 0.81
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Non-elective Coronary Revascularization Represented as the Composite of Emergent or Urgent Classifications.
    Description Number of patients with a first occurrence of non-elective coronary revascularization represented as the composite of emergent or urgent classifications during the follow-up period.
    Time Frame Total follow-up time of up to approximately 6 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title AMR101 Placebo
    Arm/Group Description AMR101: Parallel Assignment Placebo: Parallel Assignment
    Measure Participants 4089 4090
    Count of Participants [Participants]
    216
    5.3%
    321
    7.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection AMR101, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
    Method Log Rank
    Comments Stratified by CV risk category, use of ezetimibe, and geographical region.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.65
    Confidence Interval (2-Sided) 95%
    0.55 to 0.78
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title CV Death.
    Description Number of patients with an occurrence of CV death during the follow-up period.
    Time Frame Total follow-up time of up to approximately 6 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title AMR101 Placebo
    Arm/Group Description AMR101: Parallel Assignment Placebo: Parallel Assignment
    Measure Participants 4089 4090
    Count of Participants [Participants]
    174
    4.3%
    213
    5.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection AMR101, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0315
    Comments Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
    Method Log Rank
    Comments Stratified by CV risk category, use of ezetimibe, and geographical region.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.80
    Confidence Interval (2-Sided) 95%
    0.66 to 0.98
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Unstable Angina Determined to be Caused by Myocardial Ischemia by Invasive / Non-invasive Testing and Requiring Emergent Hospitalization.
    Description Number of patients with a first occurrence of unstable angina determined to be caused by myocardial ischemia by invasive / non-invasive testing and requiring emergent hospitalization during the follow-up period.
    Time Frame Total follow-up time of up to approximately 6 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title AMR101 Placebo
    Arm/Group Description AMR101: Parallel Assignment Placebo: Parallel Assignment
    Measure Participants 4089 4090
    Count of Participants [Participants]
    108
    2.6%
    157
    3.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection AMR101, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0018
    Comments Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
    Method Log Rank
    Comments Stratified by CV risk category, use of ezetimibe, and geographical region.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.68
    Confidence Interval (2-Sided) 95%
    0.53 to 0.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Fatal or Nonfatal Stroke.
    Description Number of patients with a first occurrence of fatal or nonfatal stroke during the follow-up period.
    Time Frame Total follow-up time of up to approximately 6 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title AMR101 Placebo
    Arm/Group Description AMR101: Parallel Assignment Placebo: Parallel Assignment
    Measure Participants 4089 4090
    Count of Participants [Participants]
    98
    2.4%
    134
    3.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection AMR101, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0129
    Comments Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
    Method Log Rank
    Comments Stratified by CV risk category, use of ezetimibe, and geographical region.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.72
    Confidence Interval (2-Sided) 95%
    0.55 to 0.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Total Mortality, Nonfatal MI (Including Silent MI), or Nonfatal Stroke.
    Description Number of patients with a first occurrence of any component of the composite of total mortality, nonfatal MI (including silent MI), or nonfatal stroke during the follow-up period.
    Time Frame Total follow-up time of up to approximately 6 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title AMR101 Placebo
    Arm/Group Description AMR101: Parallel Assignment Placebo: Parallel Assignment
    Measure Participants 4089 4090
    Count of Participants [Participants]
    549
    13.4%
    690
    16.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection AMR101, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
    Method Log Rank
    Comments Stratified by CV risk category, use of ezetimibe, and geographical region.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.77
    Confidence Interval (2-Sided) 95%
    0.69 to 0.86
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Total Mortality.
    Description Number of patients with an occurrence of death from any cause during the follow-up period.
    Time Frame Total follow-up time of up to approximately 6 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title AMR101 Placebo
    Arm/Group Description AMR101: Parallel Assignment Placebo: Parallel Assignment
    Measure Participants 4089 4090
    Count of Participants [Participants]
    274
    6.7%
    310
    7.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection AMR101, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0915
    Comments Prespecified secondary end points were tested in a hierarchical fashion, in the order listed here, at the final alpha level of 0.0437.
    Method Log Rank
    Comments Stratified by CV risk category, use of ezetimibe, and geographical region.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.87
    Confidence Interval (2-Sided) 95%
    0.74 to 1.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Up to maximum duration of approximate 6 years from first dose of study treatment until end of study treatment plus 30 days post treatment.
    Adverse Event Reporting Description Adverse events were collected from first dose of study treatment until the completion or withdrawal from study plus 30 days post treatment.
    Arm/Group Title AMR101 Placebo
    Arm/Group Description AMR101: Parallel Assignment Placebo: Parallel Assignment
    All Cause Mortality
    AMR101 Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 274/4089 (6.7%) 310/4090 (7.6%)
    Serious Adverse Events
    AMR101 Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1252/4089 (30.6%) 1254/4090 (30.7%)
    Blood and lymphatic system disorders
    Anaemia 22/4089 (0.5%) 20/4090 (0.5%)
    Iron deficiency anaemia 4/4089 (0.1%) 3/4090 (0.1%)
    Haemorrhagic anaemia 4/4089 (0.1%) 1/4090 (0%)
    Thrombocytopenia 3/4089 (0.1%) 0/4090 (0%)
    Febrile neutropenia 2/4089 (0%) 0/4090 (0%)
    Lymphadenopathy 1/4089 (0%) 1/4090 (0%)
    Coagulopathy 1/4089 (0%) 0/4090 (0%)
    Lymphoid tissue hyperplasia 1/4089 (0%) 0/4090 (0%)
    Neutropenia 1/4089 (0%) 0/4090 (0%)
    Normocytic anaemia 1/4089 (0%) 0/4090 (0%)
    Thrombotic microangiopathy 1/4089 (0%) 0/4090 (0%)
    Autoimmune haemolytic anaemia 0/4089 (0%) 2/4090 (0%)
    Pancytopenia 0/4089 (0%) 2/4090 (0%)
    Splenic infarction 0/4089 (0%) 2/4090 (0%)
    Immune thrombocytopenic purpura 0/4089 (0%) 1/4090 (0%)
    Microcytic anaemia 0/4089 (0%) 1/4090 (0%)
    Pernicious anaemia 0/4089 (0%) 1/4090 (0%)
    Splenomegaly 0/4089 (0%) 1/4090 (0%)
    Cardiac disorders
    Angina pectoris 48/4089 (1.2%) 48/4090 (1.2%)
    Angina unstable 41/4089 (1%) 53/4090 (1.3%)
    Atrial fibrillation 21/4089 (0.5%) 17/4090 (0.4%)
    Cardiac failure congestive 19/4089 (0.5%) 13/4090 (0.3%)
    Aortic valve stenosis 10/4089 (0.2%) 7/4090 (0.2%)
    Coronary artery disease 9/4089 (0.2%) 16/4090 (0.4%)
    Cardiac failure 7/4089 (0.2%) 8/4090 (0.2%)
    Acute coronary syndrome 6/4089 (0.1%) 4/4090 (0.1%)
    Myocardial infarction 4/4089 (0.1%) 12/4090 (0.3%)
    Cardiac arrest 4/4089 (0.1%) 9/4090 (0.2%)
    Myocardial ischaemia 4/4089 (0.1%) 4/4090 (0.1%)
    Cardiomyopathy 4/4089 (0.1%) 2/4090 (0%)
    Mitral valve incompetence 4/4089 (0.1%) 2/4090 (0%)
    Ischaemic cardiomyopathy 3/4089 (0.1%) 3/4090 (0.1%)
    Arrhythmia 3/4089 (0.1%) 2/4090 (0%)
    Palpitations 3/4089 (0.1%) 1/4090 (0%)
    Cardiac failure acute 3/4089 (0.1%) 0/4090 (0%)
    Ventricular arrhythmia 3/4089 (0.1%) 0/4090 (0%)
    Cardiogenic shock 2/4089 (0%) 3/4090 (0.1%)
    Pericarditis 2/4089 (0%) 3/4090 (0.1%)
    Ventricular tachycardia 2/4089 (0%) 1/4090 (0%)
    Left ventricular failure 2/4089 (0%) 0/4090 (0%)
    Supraventricular extrasystoles 2/4089 (0%) 0/4090 (0%)
    Acute myocardial infarction 1/4089 (0%) 4/4090 (0.1%)
    Atrial flutter 1/4089 (0%) 3/4090 (0.1%)
    Aortic valve incompetence 1/4089 (0%) 2/4090 (0%)
    Arteriosclerosis coronary artery 1/4089 (0%) 2/4090 (0%)
    Coronary artery stenosis 1/4089 (0%) 2/4090 (0%)
    Left ventricular dysfunction 1/4089 (0%) 2/4090 (0%)
    Bradycardia 1/4089 (0%) 1/4090 (0%)
    Cardiac failure chronic 1/4089 (0%) 1/4090 (0%)
    Atrioventricular block complete 1/4089 (0%) 0/4090 (0%)
    Atrioventricular block second degree 1/4089 (0%) 0/4090 (0%)
    Bundle branch block left 1/4089 (0%) 0/4090 (0%)
    Cardiac valve disease 1/4089 (0%) 0/4090 (0%)
    Cor pulmonale chronic 1/4089 (0%) 0/4090 (0%)
    Hypertensive heart disease 1/4089 (0%) 0/4090 (0%)
    Pleuropericarditis 1/4089 (0%) 0/4090 (0%)
    Sinus node dysfunction 1/4089 (0%) 0/4090 (0%)
    Ventricular parasystole 1/4089 (0%) 0/4090 (0%)
    Cardio-respiratory arrest 0/4089 (0%) 4/4090 (0.1%)
    Cardiac tamponade 0/4089 (0%) 3/4090 (0.1%)
    Arteriospasm coronary 0/4089 (0%) 2/4090 (0%)
    Pericardial effusion 0/4089 (0%) 2/4090 (0%)
    Silent myocardial infarction 0/4089 (0%) 2/4090 (0%)
    Ventricular fibrillation 0/4089 (0%) 2/4090 (0%)
    Aortic valve disease 0/4089 (0%) 1/4090 (0%)
    Aortic valve disease mixed 0/4089 (0%) 1/4090 (0%)
    Cardiac ventricular thrombosis 0/4089 (0%) 1/4090 (0%)
    Congestive cardiomyopathy 0/4089 (0%) 1/4090 (0%)
    Coronary artery dissection 0/4089 (0%) 1/4090 (0%)
    Coronary artery occlusion 0/4089 (0%) 1/4090 (0%)
    Microvascular coronary artery disease 0/4089 (0%) 1/4090 (0%)
    Pericardial haemorrhage 0/4089 (0%) 1/4090 (0%)
    Stress cardiomyopathy 0/4089 (0%) 1/4090 (0%)
    Tachycardia paroxysmal 0/4089 (0%) 1/4090 (0%)
    Congenital, familial and genetic disorders
    Hypertrophic cardiomyopathy 2/4089 (0%) 0/4090 (0%)
    Pancreas divisum 1/4089 (0%) 0/4090 (0%)
    Ear and labyrinth disorders
    Vertigo 5/4089 (0.1%) 8/4090 (0.2%)
    Vertigo positional 2/4089 (0%) 5/4090 (0.1%)
    Vestibular disorder 0/4089 (0%) 2/4090 (0%)
    Ear pain 0/4089 (0%) 1/4090 (0%)
    Inner ear disorder 0/4089 (0%) 1/4090 (0%)
    Sudden hearing loss 0/4089 (0%) 1/4090 (0%)
    Endocrine disorders
    Thyroid mass 2/4089 (0%) 0/4090 (0%)
    Hyperthyroidism 1/4089 (0%) 0/4090 (0%)
    Goitre 0/4089 (0%) 4/4090 (0.1%)
    Addison's disease 0/4089 (0%) 1/4090 (0%)
    Hypothyroidism 0/4089 (0%) 1/4090 (0%)
    Inappropriate antidiuretic hormone secretion 0/4089 (0%) 1/4090 (0%)
    Toxic nodular goitre 0/4089 (0%) 1/4090 (0%)
    Eye disorders
    Cataract 4/4089 (0.1%) 5/4090 (0.1%)
    Retinal detachment 3/4089 (0.1%) 0/4090 (0%)
    Eyelid ptosis 1/4089 (0%) 1/4090 (0%)
    Retinal haemorrhage 1/4089 (0%) 1/4090 (0%)
    Diplopia 1/4089 (0%) 0/4090 (0%)
    Eye swelling 1/4089 (0%) 0/4090 (0%)
    Retinal vein thrombosis 1/4089 (0%) 0/4090 (0%)
    Retinal artery occlusion 0/4089 (0%) 2/4090 (0%)
    Chalazion 0/4089 (0%) 1/4090 (0%)
    Visual impairment 0/4089 (0%) 1/4090 (0%)
    Gastrointestinal disorders
    Gastrointestinal haemorrhage 26/4089 (0.6%) 20/4090 (0.5%)
    Small intestinal obstruction 16/4089 (0.4%) 12/4090 (0.3%)
    Inguinal hernia 11/4089 (0.3%) 8/4090 (0.2%)
    Rectal haemorrhage 10/4089 (0.2%) 6/4090 (0.1%)
    Abdominal pain 7/4089 (0.2%) 4/4090 (0.1%)
    Vomiting 7/4089 (0.2%) 4/4090 (0.1%)
    Constipation 6/4089 (0.1%) 8/4090 (0.2%)
    Colitis 6/4089 (0.1%) 6/4090 (0.1%)
    Abdominal pain upper 5/4089 (0.1%) 6/4090 (0.1%)
    Diarrhoea 5/4089 (0.1%) 6/4090 (0.1%)
    Lower gastrointestinal haemorrhage 5/4089 (0.1%) 4/4090 (0.1%)
    Colitis ischaemic 5/4089 (0.1%) 1/4090 (0%)
    Gastric ulcer 5/4089 (0.1%) 1/4090 (0%)
    Ileus 4/4089 (0.1%) 5/4090 (0.1%)
    Large intestine polyp 4/4089 (0.1%) 5/4090 (0.1%)
    Pancreatitis acute 4/4089 (0.1%) 5/4090 (0.1%)
    Gastrooesophageal reflux disease 4/4089 (0.1%) 2/4090 (0%)
    Nausea 4/4089 (0.1%) 0/4090 (0%)
    Pancreatitis 3/4089 (0.1%) 7/4090 (0.2%)
    Abdominal hernia 3/4089 (0.1%) 6/4090 (0.1%)
    Melaena 3/4089 (0.1%) 4/4090 (0.1%)
    Diverticulum intestinal haemorrhagic 3/4089 (0.1%) 3/4090 (0.1%)
    Upper gastrointestinal haemorrhage 3/4089 (0.1%) 3/4090 (0.1%)
    Haemorrhoids 3/4089 (0.1%) 2/4090 (0%)
    Ascites 3/4089 (0.1%) 1/4090 (0%)
    Diverticulum 3/4089 (0.1%) 1/4090 (0%)
    Gastric ulcer haemorrhage 3/4089 (0.1%) 1/4090 (0%)
    Haemorrhoidal haemorrhage 3/4089 (0.1%) 1/4090 (0%)
    Haematemesis 3/4089 (0.1%) 0/4090 (0%)
    Hiatus hernia 2/4089 (0%) 5/4090 (0.1%)
    Obstructive pancreatitis 2/4089 (0%) 4/4090 (0.1%)
    Intestinal ischaemia 2/4089 (0%) 3/4090 (0.1%)
    Duodenal ulcer 2/4089 (0%) 2/4090 (0%)
    Anal fistula 2/4089 (0%) 1/4090 (0%)
    Large intestine perforation 2/4089 (0%) 1/4090 (0%)
    Peptic ulcer 2/4089 (0%) 1/4090 (0%)
    Duodenal ulcer haemorrhage 2/4089 (0%) 0/4090 (0%)
    Enteritis 2/4089 (0%) 0/4090 (0%)
    Gastritis erosive 2/4089 (0%) 0/4090 (0%)
    Pancreatitis chronic 2/4089 (0%) 0/4090 (0%)
    Retroperitoneal fibrosis 2/4089 (0%) 0/4090 (0%)
    Umbilical hernia 1/4089 (0%) 10/4090 (0.2%)
    Gastric haemorrhage 1/4089 (0%) 3/4090 (0.1%)
    Haematochezia 1/4089 (0%) 2/4090 (0%)
    Diverticular perforation 1/4089 (0%) 1/4090 (0%)
    Diverticulum intestinal 1/4089 (0%) 1/4090 (0%)
    Faeces discoloured 1/4089 (0%) 1/4090 (0%)
    Gastric polyps 1/4089 (0%) 1/4090 (0%)
    Intestinal obstruction 1/4089 (0%) 1/4090 (0%)
    Large intestinal haemorrhage 1/4089 (0%) 1/4090 (0%)
    Peritoneal disorder 1/4089 (0%) 1/4090 (0%)
    Appendix disorder 1/4089 (0%) 0/4090 (0%)
    Chronic gastritis 1/4089 (0%) 0/4090 (0%)
    Duodenogastric reflux 1/4089 (0%) 0/4090 (0%)
    Dyspepsia 1/4089 (0%) 0/4090 (0%)
    Gastric antral vascular ectasia 1/4089 (0%) 0/4090 (0%)
    Gastrointestinal angiodysplasia haemorrhagic 1/4089 (0%) 0/4090 (0%)
    Gastrointestinal pain 1/4089 (0%) 0/4090 (0%)
    Intestinal perforation 1/4089 (0%) 0/4090 (0%)
    Intra-abdominal haemorrhage 1/4089 (0%) 0/4090 (0%)
    Mallory-Weiss syndrome 1/4089 (0%) 0/4090 (0%)
    Pancreatic cyst 1/4089 (0%) 0/4090 (0%)
    Pancreatitis haemorrhagic 1/4089 (0%) 0/4090 (0%)
    Peptic ulcer haemorrhage 1/4089 (0%) 0/4090 (0%)
    Peritoneal adhesions 1/4089 (0%) 0/4090 (0%)
    Pharyngo-oesophageal diverticulum 1/4089 (0%) 0/4090 (0%)
    Proctitis ulcerative 1/4089 (0%) 0/4090 (0%)
    Rectal prolapse 1/4089 (0%) 0/4090 (0%)
    Retroperitoneal haemorrhage 1/4089 (0%) 0/4090 (0%)
    Subileus 1/4089 (0%) 0/4090 (0%)
    Thrombosis mesenteric vessel 1/4089 (0%) 0/4090 (0%)
    Volvulus 1/4089 (0%) 0/4090 (0%)
    Gastritis 0/4089 (0%) 6/4090 (0.1%)
    Dysphagia 0/4089 (0%) 2/4090 (0%)
    Food poisoning 0/4089 (0%) 2/4090 (0%)
    Gastrointestinal obstruction 0/4089 (0%) 2/4090 (0%)
    Impaired gastric emptying 0/4089 (0%) 2/4090 (0%)
    Oesophagitis 0/4089 (0%) 2/4090 (0%)
    Abdominal adhesions 0/4089 (0%) 1/4090 (0%)
    Abdominal hernia obstructive 0/4089 (0%) 1/4090 (0%)
    Colitis ulcerative 0/4089 (0%) 1/4090 (0%)
    Crohn's disease 0/4089 (0%) 1/4090 (0%)
    Duodenal perforation 0/4089 (0%) 1/4090 (0%)
    Duodenitis haemorrhagic 0/4089 (0%) 1/4090 (0%)
    Enterovesical fistula 0/4089 (0%) 1/4090 (0%)
    Epigastric discomfort 0/4089 (0%) 1/4090 (0%)
    Gastric perforation 0/4089 (0%) 1/4090 (0%)
    Gastric ulcer perforation 0/4089 (0%) 1/4090 (0%)
    Gastroduodenitis 0/4089 (0%) 1/4090 (0%)
    Gastrointestinal angiodysplasia 0/4089 (0%) 1/4090 (0%)
    Gastrointestinal inflammation 0/4089 (0%) 1/4090 (0%)
    Irritable bowel syndrome 0/4089 (0%) 1/4090 (0%)
    Mesenteric arterial occlusion 0/4089 (0%) 1/4090 (0%)
    Mouth haemorrhage 0/4089 (0%) 1/4090 (0%)
    Oesophageal food impaction 0/4089 (0%) 1/4090 (0%)
    Oesophageal haemorrhage 0/4089 (0%) 1/4090 (0%)
    Oesophageal pain 0/4089 (0%) 1/4090 (0%)
    Pancreatic mass 0/4089 (0%) 1/4090 (0%)
    Portal hypertensive gastropathy 0/4089 (0%) 1/4090 (0%)
    Rectal polyp 0/4089 (0%) 1/4090 (0%)
    Retroperitoneal haematoma 0/4089 (0%) 1/4090 (0%)
    Strangulated umbilical hernia 0/4089 (0%) 1/4090 (0%)
    General disorders
    Chest pain 66/4089 (1.6%) 66/4090 (1.6%)
    Non-cardiac chest pain 49/4089 (1.2%) 52/4090 (1.3%)
    Asthenia 6/4089 (0.1%) 8/4090 (0.2%)
    Malaise 5/4089 (0.1%) 3/4090 (0.1%)
    Pyrexia 4/4089 (0.1%) 5/4090 (0.1%)
    Oedema peripheral 3/4089 (0.1%) 2/4090 (0%)
    Multiple organ dysfunction syndrome 2/4089 (0%) 1/4090 (0%)
    General physical health deterioration 2/4089 (0%) 0/4090 (0%)
    Systemic inflammatory response syndrome 1/4089 (0%) 7/4090 (0.2%)
    Chest discomfort 1/4089 (0%) 4/4090 (0.1%)
    Fatigue 1/4089 (0%) 2/4090 (0%)
    Cyst 1/4089 (0%) 1/4090 (0%)
    Impaired healing 1/4089 (0%) 1/4090 (0%)
    Adverse drug reaction 1/4089 (0%) 0/4090 (0%)
    Chills 1/4089 (0%) 0/4090 (0%)
    Complication associated with device 1/4089 (0%) 0/4090 (0%)
    Drowning 1/4089 (0%) 0/4090 (0%)
    Gait disturbance 1/4089 (0%) 0/4090 (0%)
    Generalised oedema 1/4089 (0%) 0/4090 (0%)
    Peripheral swelling 1/4089 (0%) 0/4090 (0%)
    Swelling 1/4089 (0%) 0/4090 (0%)
    Ulcer 1/4089 (0%) 0/4090 (0%)
    Ulcer haemorrhage 1/4089 (0%) 0/4090 (0%)
    Vascular stent restenosis 1/4089 (0%) 0/4090 (0%)
    Exercise tolerance decreased 0/4089 (0%) 3/4090 (0.1%)
    Incarcerated hernia 0/4089 (0%) 2/4090 (0%)
    Polyp 0/4089 (0%) 2/4090 (0%)
    Catheter site haemorrhage 0/4089 (0%) 1/4090 (0%)
    Death 0/4089 (0%) 1/4090 (0%)
    Pain 0/4089 (0%) 1/4090 (0%)
    Pelvic mass 0/4089 (0%) 1/4090 (0%)
    Suprapubic pain 0/4089 (0%) 1/4090 (0%)
    Hepatobiliary disorders
    Cholelithiasis 15/4089 (0.4%) 18/4090 (0.4%)
    Cholecystitis acute 15/4089 (0.4%) 7/4090 (0.2%)
    Cholecystitis 9/4089 (0.2%) 7/4090 (0.2%)
    Cholangitis 4/4089 (0.1%) 1/4090 (0%)
    Bile duct stone 3/4089 (0.1%) 2/4090 (0%)
    Jaundice cholestatic 3/4089 (0.1%) 0/4090 (0%)
    Cholecystitis chronic 1/4089 (0%) 1/4090 (0%)
    Ischaemic hepatitis 1/4089 (0%) 1/4090 (0%)
    Alcoholic liver disease 1/4089 (0%) 0/4090 (0%)
    Cryptogenic cirrhosis 1/4089 (0%) 0/4090 (0%)
    Gallbladder polyp 1/4089 (0%) 0/4090 (0%)
    Hepatic steatosis 1/4089 (0%) 0/4090 (0%)
    Gallbladder disorder 0/4089 (0%) 2/4090 (0%)
    Gallbladder enlargement 0/4089 (0%) 2/4090 (0%)
    Hepatic cirrhosis 0/4089 (0%) 2/4090 (0%)
    Biliary colic 0/4089 (0%) 1/4090 (0%)
    Biliary dilatation 0/4089 (0%) 1/4090 (0%)
    Cholestasis 0/4089 (0%) 1/4090 (0%)
    Liver disorder 0/4089 (0%) 1/4090 (0%)
    Non-alcoholic steatohepatitis 0/4089 (0%) 1/4090 (0%)
    Immune system disorders
    Anaphylactic shock 1/4089 (0%) 2/4090 (0%)
    Hypersensitivity 1/4089 (0%) 1/4090 (0%)
    Allergy to arthropod sting 1/4089 (0%) 0/4090 (0%)
    Anaphylactic reaction 0/4089 (0%) 1/4090 (0%)
    Sarcoidosis 0/4089 (0%) 1/4090 (0%)
    Infections and infestations
    Pneumonia 105/4089 (2.6%) 118/4090 (2.9%)
    Cellulitis 36/4089 (0.9%) 28/4090 (0.7%)
    Sepsis 25/4089 (0.6%) 31/4090 (0.8%)
    Urinary tract infection 25/4089 (0.6%) 22/4090 (0.5%)
    Gastroenteritis 16/4089 (0.4%) 16/4090 (0.4%)
    Erysipelas 13/4089 (0.3%) 3/4090 (0.1%)
    Osteomyelitis 12/4089 (0.3%) 7/4090 (0.2%)
    Septic shock 12/4089 (0.3%) 3/4090 (0.1%)
    Bronchitis 11/4089 (0.3%) 10/4090 (0.2%)
    Diverticulitis 11/4089 (0.3%) 9/4090 (0.2%)
    Urosepsis 11/4089 (0.3%) 9/4090 (0.2%)
    Appendicitis 9/4089 (0.2%) 6/4090 (0.1%)
    Postoperative wound infection 8/4089 (0.2%) 4/4090 (0.1%)
    Pyelonephritis 7/4089 (0.2%) 4/4090 (0.1%)
    Gastroenteritis viral 5/4089 (0.1%) 1/4090 (0%)
    Arthritis bacterial 4/4089 (0.1%) 2/4090 (0%)
    Wound infection 4/4089 (0.1%) 2/4090 (0%)
    Bacteraemia 3/4089 (0.1%) 4/4090 (0.1%)
    Cystitis 3/4089 (0.1%) 3/4090 (0.1%)
    Localised infection 3/4089 (0.1%) 3/4090 (0.1%)
    Arthritis infective 3/4089 (0.1%) 2/4090 (0%)
    Staphylococcal infection 3/4089 (0.1%) 2/4090 (0%)
    Abscess limb 3/4089 (0.1%) 1/4090 (0%)
    Gangrene 3/4089 (0.1%) 1/4090 (0%)
    Intervertebral discitis 3/4089 (0.1%) 1/4090 (0%)
    Laryngitis 3/4089 (0.1%) 0/4090 (0%)
    Influenza 2/4089 (0%) 4/4090 (0.1%)
    Pyelonephritis acute 2/4089 (0%) 4/4090 (0.1%)
    Anal abscess 2/4089 (0%) 2/4090 (0%)
    Herpes zoster 2/4089 (0%) 1/4090 (0%)
    Infective exacerbation of chronic obstructive airways disease 2/4089 (0%) 1/4090 (0%)
    Liver abscess 2/4089 (0%) 1/4090 (0%)
    Appendicitis perforated 2/4089 (0%) 0/4090 (0%)
    Meningitis bacterial 2/4089 (0%) 0/4090 (0%)
    Necrotising fasciitis 2/4089 (0%) 0/4090 (0%)
    Parainfluenzae virus infection 2/4089 (0%) 0/4090 (0%)
    Perirectal abscess 2/4089 (0%) 0/4090 (0%)
    Pneumococcal sepsis 2/4089 (0%) 0/4090 (0%)
    Pneumonia streptococcal 2/4089 (0%) 0/4090 (0%)
    Pulmonary tuberculosis 2/4089 (0%) 0/4090 (0%)
    Lower respiratory tract infection 1/4089 (0%) 5/4090 (0.1%)
    Upper respiratory tract infection 1/4089 (0%) 5/4090 (0.1%)
    Endocarditis 1/4089 (0%) 4/4090 (0.1%)
    Viral infection 1/4089 (0%) 3/4090 (0.1%)
    Abscess intestinal 1/4089 (0%) 2/4090 (0%)
    Clostridium difficile infection 1/4089 (0%) 2/4090 (0%)
    Implant site infection 1/4089 (0%) 2/4090 (0%)
    Peritonitis 1/4089 (0%) 2/4090 (0%)
    Pneumonia staphylococcal 1/4089 (0%) 2/4090 (0%)
    Bronchitis viral 1/4089 (0%) 1/4090 (0%)
    Escherichia urinary tract infection 1/4089 (0%) 1/4090 (0%)
    Gastroenteritis rotavirus 1/4089 (0%) 1/4090 (0%)
    Pneumonia influenzal 1/4089 (0%) 1/4090 (0%)
    Pneumonia pseudomonal 1/4089 (0%) 1/4090 (0%)
    Postoperative abscess 1/4089 (0%) 1/4090 (0%)
    Respiratory syncytial virus infection 1/4089 (0%) 1/4090 (0%)
    Streptococcal sepsis 1/4089 (0%) 1/4090 (0%)
    Tracheobronchitis 1/4089 (0%) 1/4090 (0%)
    Acquired immunodeficiency syndrome 1/4089 (0%) 0/4090 (0%)
    Bronchiolitis 1/4089 (0%) 0/4090 (0%)
    Bronchitis bacterial 1/4089 (0%) 0/4090 (0%)
    Campylobacter gastroenteritis 1/4089 (0%) 0/4090 (0%)
    Catheter site cellulitis 1/4089 (0%) 0/4090 (0%)
    Cellulitis streptococcal 1/4089 (0%) 0/4090 (0%)
    Clostridium difficile colitis 1/4089 (0%) 0/4090 (0%)
    Cystitis bacterial 1/4089 (0%) 0/4090 (0%)
    Cystitis escherichia 1/4089 (0%) 0/4090 (0%)
    Cytomegalovirus infection 1/4089 (0%) 0/4090 (0%)
    Dengue fever 1/4089 (0%) 0/4090 (0%)
    Device related sepsis 1/4089 (0%) 0/4090 (0%)
    Diabetic foot infection 1/4089 (0%) 0/4090 (0%)
    Diarrhoea infectious 1/4089 (0%) 0/4090 (0%)
    Epiglottitis 1/4089 (0%) 0/4090 (0%)
    Gastrointestinal bacterial overgrowth 1/4089 (0%) 0/4090 (0%)
    Gastrointestinal infection 1/4089 (0%) 0/4090 (0%)
    Genital infection fungal 1/4089 (0%) 0/4090 (0%)
    Graft infection 1/4089 (0%) 0/4090 (0%)
    Groin abscess 1/4089 (0%) 0/4090 (0%)
    Hepatitis C 1/4089 (0%) 0/4090 (0%)
    Incision site abscess 1/4089 (0%) 0/4090 (0%)
    Infected skin ulcer 1/4089 (0%) 0/4090 (0%)
    Infectious colitis 1/4089 (0%) 0/4090 (0%)
    Infective exacerbation of bronchiectasis 1/4089 (0%) 0/4090 (0%)
    Joint abscess 1/4089 (0%) 0/4090 (0%)
    Keratitis bacterial 1/4089 (0%) 0/4090 (0%)
    Latent tuberculosis 1/4089 (0%) 0/4090 (0%)
    Lower respiratory tract infection viral 1/4089 (0%) 0/4090 (0%)
    Mastitis 1/4089 (0%) 0/4090 (0%)
    Meningitis 1/4089 (0%) 0/4090 (0%)
    Mycobacterial infection 1/4089 (0%) 0/4090 (0%)
    Parotitis 1/4089 (0%) 0/4090 (0%)
    Peritonitis bacterial 1/4089 (0%) 0/4090 (0%)
    Pharyngolaryngeal abscess 1/4089 (0%) 0/4090 (0%)
    Pilonidal cyst 1/4089 (0%) 0/4090 (0%)
    Pneumonia bacterial 1/4089 (0%) 0/4090 (0%)
    Post procedural infection 1/4089 (0%) 0/4090 (0%)
    Rectal abscess 1/4089 (0%) 0/4090 (0%)
    Respiratory tract infection 1/4089 (0%) 0/4090 (0%)
    Shunt infection 1/4089 (0%) 0/4090 (0%)
    Skin infection 1/4089 (0%) 0/4090 (0%)
    Staphylococcal bacteraemia 1/4089 (0%) 0/4090 (0%)
    Staphylococcal sepsis 1/4089 (0%) 0/4090 (0%)
    Subacute endocarditis 1/4089 (0%) 0/4090 (0%)
    Systemic candida 1/4089 (0%) 0/4090 (0%)
    Tick-borne fever 1/4089 (0%) 0/4090 (0%)
    Viral sepsis 1/4089 (0%) 0/4090 (0%)
    Viral upper respiratory tract infection 1/4089 (0%) 0/4090 (0%)
    Vulval cellulitis 1/4089 (0%) 0/4090 (0%)
    Wound sepsis 1/4089 (0%) 0/4090 (0%)
    Infection 0/4089 (0%) 2/4090 (0%)
    Orchitis 0/4089 (0%) 2/4090 (0%)
    Rotavirus infection 0/4089 (0%) 2/4090 (0%)
    Abdominal abscess 0/4089 (0%) 1/4090 (0%)
    Abdominal infection 0/4089 (0%) 1/4090 (0%)
    Abdominal wall abscess 0/4089 (0%) 1/4090 (0%)
    Bacterial sepsis 0/4089 (0%) 1/4090 (0%)
    Biliary abscess 0/4089 (0%) 1/4090 (0%)
    Breast abscess 0/4089 (0%) 1/4090 (0%)
    Bursitis infective 0/4089 (0%) 1/4090 (0%)
    Cholecystitis infective 0/4089 (0%) 1/4090 (0%)
    Device related infection 0/4089 (0%) 1/4090 (0%)
    Diverticulitis intestinal haemorrhagic 0/4089 (0%) 1/4090 (0%)
    Enterococcal bacteraemia 0/4089 (0%) 1/4090 (0%)
    Epididymitis 0/4089 (0%) 1/4090 (0%)
    Gas gangrene 0/4089 (0%) 1/4090 (0%)
    H1N1 influenza 0/4089 (0%) 1/4090 (0%)
    Helicobacter gastritis 0/4089 (0%) 1/4090 (0%)
    Hepatitis viral 0/4089 (0%) 1/4090 (0%)
    Klebsiella infection 0/4089 (0%) 1/4090 (0%)
    Listeriosis 0/4089 (0%) 1/4090 (0%)
    Neutropenic sepsis 0/4089 (0%) 1/4090 (0%)
    Oral candidiasis 0/4089 (0%) 1/4090 (0%)
    Osteomyelitis acute 0/4089 (0%) 1/4090 (0%)
    Otitis media acute 0/4089 (0%) 1/4090 (0%)
    Parasitic gastroenteritis 0/4089 (0%) 1/4090 (0%)
    Pelvic abscess 0/4089 (0%) 1/4090 (0%)
    Pharyngeal abscess 0/4089 (0%) 1/4090 (0%)
    Pneumonia respiratory syncytial viral 0/4089 (0%) 1/4090 (0%)
    Pneumonia viral 0/4089 (0%) 1/4090 (0%)
    Post procedural cellulitis 0/4089 (0%) 1/4090 (0%)
    Pseudomembranous colitis 0/4089 (0%) 1/4090 (0%)
    Pseudomonas infection 0/4089 (0%) 1/4090 (0%)
    Pyelocystitis 0/4089 (0%) 1/4090 (0%)
    Respiratory tract infection viral 0/4089 (0%) 1/4090 (0%)
    Rhinovirus infection 0/4089 (0%) 1/4090 (0%)
    Sepsis syndrome 0/4089 (0%) 1/4090 (0%)
    Sialoadenitis 0/4089 (0%) 1/4090 (0%)
    Streptococcal bacteraemia 0/4089 (0%) 1/4090 (0%)
    Streptococcal infection 0/4089 (0%) 1/4090 (0%)
    Tooth abscess 0/4089 (0%) 1/4090 (0%)
    Wound abscess 0/4089 (0%) 1/4090 (0%)
    Wound infection staphylococcal 0/4089 (0%) 1/4090 (0%)
    Injury, poisoning and procedural complications
    Fall 16/4089 (0.4%) 15/4090 (0.4%)
    Subdural haematoma 9/4089 (0.2%) 5/4090 (0.1%)
    Hip fracture 8/4089 (0.2%) 8/4090 (0.2%)
    Incisional hernia 6/4089 (0.1%) 3/4090 (0.1%)
    Post procedural haemorrhage 5/4089 (0.1%) 3/4090 (0.1%)
    Rib fracture 5/4089 (0.1%) 3/4090 (0.1%)
    Head injury 5/4089 (0.1%) 2/4090 (0%)
    Femur fracture 4/4089 (0.1%) 10/4090 (0.2%)
    Ankle fracture 4/4089 (0.1%) 5/4090 (0.1%)
    Tendon rupture 4/4089 (0.1%) 4/4090 (0.1%)
    Lumbar vertebral fracture 4/4089 (0.1%) 1/4090 (0%)
    Humerus fracture 3/4089 (0.1%) 4/4090 (0.1%)
    Road traffic accident 3/4089 (0.1%) 4/4090 (0.1%)
    Laceration 3/4089 (0.1%) 0/4090 (0%)
    Multiple injuries 3/4089 (0.1%) 0/4090 (0%)
    Joint dislocation 2/4089 (0%) 3/4090 (0.1%)
    Spinal fracture 2/4089 (0%) 2/4090 (0%)
    Tibia fracture 2/4089 (0%) 2/4090 (0%)
    Ligament injury 2/4089 (0%) 1/4090 (0%)
    Postoperative ileus 2/4089 (0%) 1/4090 (0%)
    Subarachnoid haemorrhage 2/4089 (0%) 1/4090 (0%)
    Subdural haemorrhage 2/4089 (0%) 1/4090 (0%)
    Thoracic vertebral fracture 2/4089 (0%) 1/4090 (0%)
    Traumatic haematoma 2/4089 (0%) 1/4090 (0%)
    Clavicle fracture 2/4089 (0%) 0/4090 (0%)
    Lower limb fracture 2/4089 (0%) 0/4090 (0%)
    Muscle rupture 2/4089 (0%) 0/4090 (0%)
    Muscle strain 2/4089 (0%) 0/4090 (0%)
    Postoperative fever 2/4089 (0%) 0/4090 (0%)
    Postoperative hernia 2/4089 (0%) 0/4090 (0%)
    Wound dehiscence 2/4089 (0%) 0/4090 (0%)
    Craniocerebral injury 1/4089 (0%) 3/4090 (0.1%)
    Femoral neck fracture 1/4089 (0%) 2/4090 (0%)
    Pelvic fracture 1/4089 (0%) 2/4090 (0%)
    Concussion 1/4089 (0%) 1/4090 (0%)
    Fibula fracture 1/4089 (0%) 1/4090 (0%)
    Fractured sacrum 1/4089 (0%) 1/4090 (0%)
    Limb injury 1/4089 (0%) 1/4090 (0%)
    Post procedural discharge 1/4089 (0%) 1/4090 (0%)
    Post procedural haematoma 1/4089 (0%) 1/4090 (0%)
    Post procedural swelling 1/4089 (0%) 1/4090 (0%)
    Ulna fracture 1/4089 (0%) 1/4090 (0%)
    Wound 1/4089 (0%) 1/4090 (0%)
    Accidental overdose 1/4089 (0%) 0/4090 (0%)
    Avulsion fracture 1/4089 (0%) 0/4090 (0%)
    Bone fragmentation 1/4089 (0%) 0/4090 (0%)
    Cartilage injury 1/4089 (0%) 0/4090 (0%)
    Chest injury 1/4089 (0%) 0/4090 (0%)
    Dislocation of sternum 1/4089 (0%) 0/4090 (0%)
    Foot fracture 1/4089 (0%) 0/4090 (0%)
    Foreign body in gastrointestinal tract 1/4089 (0%) 0/4090 (0%)
    Fracture 1/4089 (0%) 0/4090 (0%)
    Hand fracture 1/4089 (0%) 0/4090 (0%)
    Incarcerated incisional hernia 1/4089 (0%) 0/4090 (0%)
    Multiple fractures 1/4089 (0%) 0/4090 (0%)
    Muscle injury 1/4089 (0%) 0/4090 (0%)
    Overdose 1/4089 (0%) 0/4090 (0%)
    Patella fracture 1/4089 (0%) 0/4090 (0%)
    Periprosthetic fracture 1/4089 (0%) 0/4090 (0%)
    Post laminectomy syndrome 1/4089 (0%) 0/4090 (0%)
    Post procedural pulmonary embolism 1/4089 (0%) 0/4090 (0%)
    Postoperative adhesion 1/4089 (0%) 0/4090 (0%)
    Postoperative renal failure 1/4089 (0%) 0/4090 (0%)
    Postoperative thrombosis 1/4089 (0%) 0/4090 (0%)
    Radiation oesophagitis 1/4089 (0%) 0/4090 (0%)
    Spinal cord injury 1/4089 (0%) 0/4090 (0%)
    Toxicity to various agents 1/4089 (0%) 0/4090 (0%)
    Traumatic liver injury 1/4089 (0%) 0/4090 (0%)
    Procedural pain 0/4089 (0%) 3/4090 (0.1%)
    Alcohol poisoning 0/4089 (0%) 2/4090 (0%)
    Brain contusion 0/4089 (0%) 2/4090 (0%)
    Jaw fracture 0/4089 (0%) 2/4090 (0%)
    Meniscus injury 0/4089 (0%) 2/4090 (0%)
    Spinal compression fracture 0/4089 (0%) 2/4090 (0%)
    Stomal hernia 0/4089 (0%) 2/4090 (0%)
    Anaemia postoperative 0/4089 (0%) 1/4090 (0%)
    Axillary nerve injury 0/4089 (0%) 1/4090 (0%)
    Back injury 0/4089 (0%) 1/4090 (0%)
    Carbon monoxide poisoning 0/4089 (0%) 1/4090 (0%)
    Cervical vertebral fracture 0/4089 (0%) 1/4090 (0%)
    Compression fracture 0/4089 (0%) 1/4090 (0%)
    Facial bones fracture 0/4089 (0%) 1/4090 (0%)
    Forearm fracture 0/4089 (0%) 1/4090 (0%)
    Gastrointestinal stoma complication 0/4089 (0%) 1/4090 (0%)
    Heat stroke 0/4089 (0%) 1/4090 (0%)
    Oesophageal injury 0/4089 (0%) 1/4090 (0%)
    Poisoning deliberate 0/4089 (0%) 1/4090 (0%)
    Post procedural complication 0/4089 (0%) 1/4090 (0%)
    Post procedural haematuria 0/4089 (0%) 1/4090 (0%)
    Procedural hypertension 0/4089 (0%) 1/4090 (0%)
    Pubis fracture 0/4089 (0%) 1/4090 (0%)
    Radiation injury 0/4089 (0%) 1/4090 (0%)
    Sciatic nerve injury 0/4089 (0%) 1/4090 (0%)
    Skull fractured base 0/4089 (0%) 1/4090 (0%)
    Spinal column injury 0/4089 (0%) 1/4090 (0%)
    Stress fracture 0/4089 (0%) 1/4090 (0%)
    Thermal burn 0/4089 (0%) 1/4090 (0%)
    Traumatic intracranial haemorrhage 0/4089 (0%) 1/4090 (0%)
    Traumatic renal injury 0/4089 (0%) 1/4090 (0%)
    Upper limb fracture 0/4089 (0%) 1/4090 (0%)
    Ureteric anastomosis complication 0/4089 (0%) 1/4090 (0%)
    Urethral injury 0/4089 (0%) 1/4090 (0%)
    Vascular pseudoaneurysm 0/4089 (0%) 1/4090 (0%)
    Investigations
    Troponin increased 2/4089 (0%) 3/4090 (0.1%)
    Arteriogram coronary 2/4089 (0%) 1/4090 (0%)
    Ejection fraction decreased 2/4089 (0%) 1/4090 (0%)
    Blood pressure increased 1/4089 (0%) 2/4090 (0%)
    Blood glucose increased 1/4089 (0%) 1/4090 (0%)
    Weight decreased 1/4089 (0%) 1/4090 (0%)
    Biopsy pleura 1/4089 (0%) 0/4090 (0%)
    Prostatic specific antigen increased 1/4089 (0%) 0/4090 (0%)
    Transaminases increased 1/4089 (0%) 0/4090 (0%)
    Influenza A virus test positive 0/4089 (0%) 3/4090 (0.1%)
    Alanine aminotransferase increased 0/4089 (0%) 2/4090 (0%)
    Anticoagulation drug level above therapeutic 0/4089 (0%) 1/4090 (0%)
    Blood pressure difference of extremities 0/4089 (0%) 1/4090 (0%)
    Cardiac murmur 0/4089 (0%) 1/4090 (0%)
    Ejection fraction abnormal 0/4089 (0%) 1/4090 (0%)
    Electrocardiogram T wave abnormal 0/4089 (0%) 1/4090 (0%)
    Influenza virus test positive 0/4089 (0%) 1/4090 (0%)
    Lipase increased 0/4089 (0%) 1/4090 (0%)
    Metabolism and nutrition disorders
    Dehydration 16/4089 (0.4%) 11/4090 (0.3%)
    Hypoglycaemia 15/4089 (0.4%) 14/4090 (0.3%)
    Diabetes mellitus 11/4089 (0.3%) 8/4090 (0.2%)
    Hyperglycaemia 10/4089 (0.2%) 8/4090 (0.2%)
    Obesity 9/4089 (0.2%) 5/4090 (0.1%)
    Diabetes mellitus inadequate control 5/4089 (0.1%) 3/4090 (0.1%)
    Hypomagnesaemia 5/4089 (0.1%) 0/4090 (0%)
    Diabetic ketoacidosis 4/4089 (0.1%) 1/4090 (0%)
    Hyperkalaemia 3/4089 (0.1%) 6/4090 (0.1%)
    Hypokalaemia 3/4089 (0.1%) 3/4090 (0.1%)
    Type 2 diabetes mellitus 2/4089 (0%) 4/4090 (0.1%)
    Hyponatraemia 2/4089 (0%) 3/4090 (0.1%)
    Metabolic acidosis 2/4089 (0%) 3/4090 (0.1%)
    Hypocalcaemia 2/4089 (0%) 1/4090 (0%)
    Hypovolaemia 2/4089 (0%) 1/4090 (0%)
    Gout 2/4089 (0%) 0/4090 (0%)
    Lactic acidosis 1/4089 (0%) 1/4090 (0%)
    Acidosis 1/4089 (0%) 0/4090 (0%)
    Failure to thrive 1/4089 (0%) 0/4090 (0%)
    Hypercalcaemia 1/4089 (0%) 0/4090 (0%)
    Hyperglycaemic hyperosmolar nonketotic syndrome 1/4089 (0%) 0/4090 (0%)
    Hypophosphataemia 1/4089 (0%) 0/4090 (0%)
    Shock hypoglycaemic 1/4089 (0%) 0/4090 (0%)
    Tumour lysis syndrome 1/4089 (0%) 0/4090 (0%)
    Diabetic metabolic decompensation 0/4089 (0%) 1/4090 (0%)
    Electrolyte imbalance 0/4089 (0%) 1/4090 (0%)
    Hypernatraemia 0/4089 (0%) 1/4090 (0%)
    Hyperosmolar state 0/4089 (0%) 1/4090 (0%)
    Iron deficiency 0/4089 (0%) 1/4090 (0%)
    Musculoskeletal and connective tissue disorders
    Osteoarthritis 81/4089 (2%) 73/4090 (1.8%)
    Back pain 17/4089 (0.4%) 11/4090 (0.3%)
    Intervertebral disc protrusion 16/4089 (0.4%) 7/4090 (0.2%)
    Spinal column stenosis 11/4089 (0.3%) 5/4090 (0.1%)
    Rotator cuff syndrome 10/4089 (0.2%) 12/4090 (0.3%)
    Lumbar spinal stenosis 10/4089 (0.2%) 10/4090 (0.2%)
    Arthralgia 7/4089 (0.2%) 9/4090 (0.2%)
    Arthritis 6/4089 (0.1%) 6/4090 (0.1%)
    Musculoskeletal chest pain 6/4089 (0.1%) 1/4090 (0%)
    Musculoskeletal pain 5/4089 (0.1%) 3/4090 (0.1%)
    Pain in extremity 5/4089 (0.1%) 2/4090 (0%)
    Spinal osteoarthritis 3/4089 (0.1%) 3/4090 (0.1%)
    Spondylolisthesis 3/4089 (0.1%) 2/4090 (0%)
    Foot deformity 2/4089 (0%) 4/4090 (0.1%)
    Intervertebral disc degeneration 2/4089 (0%) 3/4090 (0.1%)
    Bursitis 2/4089 (0%) 2/4090 (0%)
    Rhabdomyolysis 2/4089 (0%) 1/4090 (0%)
    Cervical spinal stenosis 1/4089 (0%) 4/4090 (0.1%)
    Vertebral foraminal stenosis 1/4089 (0%) 2/4090 (0%)
    Flank pain 1/4089 (0%) 1/4090 (0%)
    Muscular weakness 1/4089 (0%) 1/4090 (0%)
    Osteonecrosis 1/4089 (0%) 1/4090 (0%)
    Polymyalgia rheumatica 1/4089 (0%) 1/4090 (0%)
    Pseudarthrosis 1/4089 (0%) 1/4090 (0%)
    Gouty arthritis 1/4089 (0%) 0/4090 (0%)
    Intervertebral disc compression 1/4089 (0%) 0/4090 (0%)
    Knee deformity 1/4089 (0%) 0/4090 (0%)
    Mandibular mass 1/4089 (0%) 0/4090 (0%)
    Mobility decreased 1/4089 (0%) 0/4090 (0%)
    Muscle spasms 1/4089 (0%) 0/4090 (0%)
    Neck pain 1/4089 (0%) 0/4090 (0%)
    Osteochondrosis 1/4089 (0%) 0/4090 (0%)
    Pathological fracture 1/4089 (0%) 0/4090 (0%)
    Periarthritis 1/4089 (0%) 0/4090 (0%)
    Rheumatic fever 1/4089 (0%) 0/4090 (0%)
    Soft tissue mass 1/4089 (0%) 0/4090 (0%)
    Sympathetic posterior cervical syndrome 1/4089 (0%) 0/4090 (0%)
    Synovial cyst 1/4089 (0%) 0/4090 (0%)
    Tendonitis 1/4089 (0%) 0/4090 (0%)
    Costochondritis 0/4089 (0%) 5/4090 (0.1%)
    Rheumatoid arthritis 0/4089 (0%) 3/4090 (0.1%)
    Exostosis 0/4089 (0%) 2/4090 (0%)
    Arthropathy 0/4089 (0%) 1/4090 (0%)
    Back disorder 0/4089 (0%) 1/4090 (0%)
    Coccydynia 0/4089 (0%) 1/4090 (0%)
    Gouty tophus 0/4089 (0%) 1/4090 (0%)
    Haemarthrosis 0/4089 (0%) 1/4090 (0%)
    Intervertebral disc disorder 0/4089 (0%) 1/4090 (0%)
    Joint range of motion decreased 0/4089 (0%) 1/4090 (0%)
    Myalgia 0/4089 (0%) 1/4090 (0%)
    Pain in jaw 0/4089 (0%) 1/4090 (0%)
    Systemic lupus erythematosus 0/4089 (0%) 1/4090 (0%)
    Temporomandibular joint syndrome 0/4089 (0%) 1/4090 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Prostate cancer 26/4089 (0.6%) 26/4090 (0.6%)
    Breast cancer 14/4089 (0.3%) 8/4090 (0.2%)
    Colon cancer 10/4089 (0.2%) 6/4090 (0.1%)
    Lung neoplasm malignant 8/4089 (0.2%) 14/4090 (0.3%)
    Bladder cancer 8/4089 (0.2%) 9/4090 (0.2%)
    Lung cancer metastatic 8/4089 (0.2%) 9/4090 (0.2%)
    Malignant melanoma 7/4089 (0.2%) 4/4090 (0.1%)
    Adenocarcinoma of colon 6/4089 (0.1%) 6/4090 (0.1%)
    Pancreatic carcinoma 6/4089 (0.1%) 4/4090 (0.1%)
    Renal cancer 6/4089 (0.1%) 4/4090 (0.1%)
    Prostate cancer metastatic 5/4089 (0.1%) 5/4090 (0.1%)
    Bladder transitional cell carcinoma 5/4089 (0.1%) 4/4090 (0.1%)
    Pancreatic carcinoma metastatic 5/4089 (0.1%) 2/4090 (0%)
    Lung adenocarcinoma 4/4089 (0.1%) 6/4090 (0.1%)
    Squamous cell carcinoma of lung 4/4089 (0.1%) 5/4090 (0.1%)
    Gastric cancer 4/4089 (0.1%) 3/4090 (0.1%)
    Metastases to liver 4/4089 (0.1%) 3/4090 (0.1%)
    Squamous cell carcinoma 4/4089 (0.1%) 3/4090 (0.1%)
    Basal cell carcinoma 3/4089 (0.1%) 2/4090 (0%)
    Bladder neoplasm 3/4089 (0.1%) 2/4090 (0%)
    Cancer pain 3/4089 (0.1%) 1/4090 (0%)
    Hepatic cancer 3/4089 (0.1%) 1/4090 (0%)
    Metastases to lung 3/4089 (0.1%) 0/4090 (0%)
    Non-small cell lung cancer metastatic 3/4089 (0.1%) 0/4090 (0%)
    Rectal cancer 2/4089 (0%) 6/4090 (0.1%)
    Non-small cell lung cancer 2/4089 (0%) 3/4090 (0.1%)
    Colon cancer metastatic 2/4089 (0%) 2/4090 (0%)
    Endometrial cancer 2/4089 (0%) 2/4090 (0%)
    Non-Hodgkin's lymphoma 2/4089 (0%) 2/4090 (0%)
    Prostate cancer recurrent 2/4089 (0%) 2/4090 (0%)
    Rectal adenocarcinoma 2/4089 (0%) 2/4090 (0%)
    Transitional cell carcinoma 2/4089 (0%) 2/4090 (0%)
    Breast cancer metastatic 2/4089 (0%) 1/4090 (0%)
    Cervix carcinoma 2/4089 (0%) 1/4090 (0%)
    Meningioma 2/4089 (0%) 1/4090 (0%)
    Metastases to bone 2/4089 (0%) 1/4090 (0%)
    Parathyroid tumour benign 2/4089 (0%) 1/4090 (0%)
    Renal cancer metastatic 2/4089 (0%) 1/4090 (0%)
    Bladder cancer recurrent 2/4089 (0%) 0/4090 (0%)
    Brain neoplasm 2/4089 (0%) 0/4090 (0%)
    Breast cancer recurrent 2/4089 (0%) 0/4090 (0%)
    Chronic lymphocytic leukaemia 2/4089 (0%) 0/4090 (0%)
    Invasive ductal breast carcinoma 2/4089 (0%) 0/4090 (0%)
    Malignant melanoma in situ 2/4089 (0%) 0/4090 (0%)
    Metastatic renal cell carcinoma 2/4089 (0%) 0/4090 (0%)
    Renal neoplasm 2/4089 (0%) 0/4090 (0%)
    Colon adenoma 1/4089 (0%) 4/4090 (0.1%)
    Acute myeloid leukaemia 1/4089 (0%) 3/4090 (0.1%)
    Colon neoplasm 1/4089 (0%) 3/4090 (0.1%)
    Renal cell carcinoma 1/4089 (0%) 2/4090 (0%)
    Bone cancer 1/4089 (0%) 1/4090 (0%)
    Colon cancer recurrent 1/4089 (0%) 1/4090 (0%)
    Colorectal cancer 1/4089 (0%) 1/4090 (0%)
    Endometrial adenocarcinoma 1/4089 (0%) 1/4090 (0%)
    Gastrointestinal stromal tumour 1/4089 (0%) 1/4090 (0%)
    Lipoma 1/4089 (0%) 1/4090 (0%)
    Metastases to peritoneum 1/4089 (0%) 1/4090 (0%)
    Metastatic carcinoma of the bladder 1/4089 (0%) 1/4090 (0%)
    Mucinous adenocarcinoma of appendix 1/4089 (0%) 1/4090 (0%)
    Myelodysplastic syndrome 1/4089 (0%) 1/4090 (0%)
    Oesophageal carcinoma 1/4089 (0%) 1/4090 (0%)
    Pancreatic neoplasm 1/4089 (0%) 1/4090 (0%)
    Plasma cell myeloma 1/4089 (0%) 1/4090 (0%)
    Prostatic adenoma 1/4089 (0%) 1/4090 (0%)
    Small cell lung cancer 1/4089 (0%) 1/4090 (0%)
    Thyroid cancer metastatic 1/4089 (0%) 1/4090 (0%)
    Uterine cancer 1/4089 (0%) 1/4090 (0%)
    Adenocarcinoma 1/4089 (0%) 0/4090 (0%)
    Adenocarcinoma gastric 1/4089 (0%) 0/4090 (0%)
    Anal cancer 1/4089 (0%) 0/4090 (0%)
    B-cell lymphoma 1/4089 (0%) 0/4090 (0%)
    Benign neoplasm of thyroid gland 1/4089 (0%) 0/4090 (0%)
    Breast cancer male 1/4089 (0%) 0/4090 (0%)
    Cervix neoplasm 1/4089 (0%) 0/4090 (0%)
    Cholangiocarcinoma 1/4089 (0%) 0/4090 (0%)
    Cholesteatoma 1/4089 (0%) 0/4090 (0%)
    Colorectal adenocarcinoma 1/4089 (0%) 0/4090 (0%)
    Diffuse large B-cell lymphoma 1/4089 (0%) 0/4090 (0%)
    Endometrial cancer stage I 1/4089 (0%) 0/4090 (0%)
    Extranodal marginal zone B-cell lymphoma 1/4089 (0%) 0/4090 (0%)
    Gastrointestinal stromal cancer 1/4089 (0%) 0/4090 (0%)
    Hepatocellular carcinoma 1/4089 (0%) 0/4090 (0%)
    Iris melanoma 1/4089 (0%) 0/4090 (0%)
    Large cell lung cancer metastatic 1/4089 (0%) 0/4090 (0%)
    Large intestine benign neoplasm 1/4089 (0%) 0/4090 (0%)
    Leiomyosarcoma 1/4089 (0%) 0/4090 (0%)
    Lung adenocarcinoma stage IV 1/4089 (0%) 0/4090 (0%)
    Lung carcinoma cell type unspecified recurrent 1/4089 (0%) 0/4090 (0%)
    Malignant glioma 1/4089 (0%) 0/4090 (0%)
    Metastases to abdominal cavity 1/4089 (0%) 0/4090 (0%)
    Metastases to chest wall 1/4089 (0%) 0/4090 (0%)
    Metastases to kidney 1/4089 (0%) 0/4090 (0%)
    Metastasis 1/4089 (0%) 0/4090 (0%)
    Metastatic gastric cancer 1/4089 (0%) 0/4090 (0%)
    Metastatic squamous cell carcinoma 1/4089 (0%) 0/4090 (0%)
    Nasal neoplasm 1/4089 (0%) 0/4090 (0%)
    Oesophageal neoplasm 1/4089 (0%) 0/4090 (0%)
    Oropharyngeal cancer 1/4089 (0%) 0/4090 (0%)
    Ovarian epithelial cancer 1/4089 (0%) 0/4090 (0%)
    Ovarian granulosa-theca cell tumour 1/4089 (0%) 0/4090 (0%)
    Pituitary tumour 1/4089 (0%) 0/4090 (0%)
    Pleural mesothelioma 1/4089 (0%) 0/4090 (0%)
    Salivary gland adenoma 1/4089 (0%) 0/4090 (0%)
    Small cell lung cancer metastatic 1/4089 (0%) 0/4090 (0%)
    Small intestine carcinoma 1/4089 (0%) 0/4090 (0%)
    Squamous cell carcinoma of skin 1/4089 (0%) 0/4090 (0%)
    Testis cancer 1/4089 (0%) 0/4090 (0%)
    Thyroid cancer 1/4089 (0%) 0/4090 (0%)
    Transitional cell cancer of the renal pelvis and ureter 1/4089 (0%) 0/4090 (0%)
    Tumour ulceration 1/4089 (0%) 0/4090 (0%)
    Uterine leiomyoma 1/4089 (0%) 0/4090 (0%)
    Breast cancer stage I 0/4089 (0%) 2/4090 (0%)
    Clear cell renal cell carcinoma 0/4089 (0%) 2/4090 (0%)
    Laryngeal cancer 0/4089 (0%) 2/4090 (0%)
    Lymphocytic leukaemia 0/4089 (0%) 2/4090 (0%)
    Metastases to central nervous system 0/4089 (0%) 2/4090 (0%)
    Acute lymphocytic leukaemia 0/4089 (0%) 1/4090 (0%)
    Adenoid cystic carcinoma 0/4089 (0%) 1/4090 (0%)
    Adrenal adenoma 0/4089 (0%) 1/4090 (0%)
    Adrenal neoplasm 0/4089 (0%) 1/4090 (0%)
    Anal squamous cell carcinoma 0/4089 (0%) 1/4090 (0%)
    Bladder cancer stage III 0/4089 (0%) 1/4090 (0%)
    Central nervous system neoplasm 0/4089 (0%) 1/4090 (0%)
    Colorectal cancer metastatic 0/4089 (0%) 1/4090 (0%)
    Duodenal neoplasm 0/4089 (0%) 1/4090 (0%)
    Endometrial cancer metastatic 0/4089 (0%) 1/4090 (0%)
    Gastric adenoma 0/4089 (0%) 1/4090 (0%)
    Gastric cancer recurrent 0/4089 (0%) 1/4090 (0%)
    Gastric neoplasm 0/4089 (0%) 1/4090 (0%)
    Gastrointestinal tract adenoma 0/4089 (0%) 1/4090 (0%)
    Hepatic cancer metastatic 0/4089 (0%) 1/4090 (0%)
    Intraductal proliferative breast lesion 0/4089 (0%) 1/4090 (0%)
    Lip and/or oral cavity cancer 0/4089 (0%) 1/4090 (0%)
    Lung adenocarcinoma stage II 0/4089 (0%) 1/4090 (0%)
    Malignant mesenteric neoplasm 0/4089 (0%) 1/4090 (0%)
    Metastases to lymph nodes 0/4089 (0%) 1/4090 (0%)
    Metastatic neoplasm 0/4089 (0%) 1/4090 (0%)
    Mucoepidermoid carcinoma of salivary gland 0/4089 (0%) 1/4090 (0%)
    Neoplasm malignant 0/4089 (0%) 1/4090 (0%)
    Neuroendocrine carcinoma of the skin 0/4089 (0%) 1/4090 (0%)
    Neuroma 0/4089 (0%) 1/4090 (0%)
    Nodular melanoma 0/4089 (0%) 1/4090 (0%)
    Non-small cell lung cancer stage III 0/4089 (0%) 1/4090 (0%)
    Non-small cell lung cancer stage IV 0/4089 (0%) 1/4090 (0%)
    Oesophageal cancer metastatic 0/4089 (0%) 1/4090 (0%)
    Ovarian adenoma 0/4089 (0%) 1/4090 (0%)
    Ovarian cancer metastatic 0/4089 (0%) 1/4090 (0%)
    Ovarian epithelial cancer metastatic 0/4089 (0%) 1/4090 (0%)
    Ovarian neoplasm 0/4089 (0%) 1/4090 (0%)
    Penile cancer 0/4089 (0%) 1/4090 (0%)
    Prostate cancer stage IV 0/4089 (0%) 1/4090 (0%)
    Rectal neoplasm 0/4089 (0%) 1/4090 (0%)
    Refractory anaemia with ringed sideroblasts 0/4089 (0%) 1/4090 (0%)
    Refractory cytopenia with unilineage dysplasia 0/4089 (0%) 1/4090 (0%)
    Retroperitoneal cancer 0/4089 (0%) 1/4090 (0%)
    Schwannoma 0/4089 (0%) 1/4090 (0%)
    Skin cancer 0/4089 (0%) 1/4090 (0%)
    Squamous cell carcinoma of pharynx 0/4089 (0%) 1/4090 (0%)
    Throat cancer 0/4089 (0%) 1/4090 (0%)
    Tongue cancer metastatic 0/4089 (0%) 1/4090 (0%)
    Tonsil cancer 0/4089 (0%) 1/4090 (0%)
    Transitional cell carcinoma recurrent 0/4089 (0%) 1/4090 (0%)
    Urethral cancer 0/4089 (0%) 1/4090 (0%)
    Nervous system disorders
    Syncope 28/4089 (0.7%) 31/4090 (0.8%)
    Dizziness 11/4089 (0.3%) 10/4090 (0.2%)
    Transient ischaemic attack 8/4089 (0.2%) 3/4090 (0.1%)
    Encephalopathy 7/4089 (0.2%) 2/4090 (0%)
    Presyncope 6/4089 (0.1%) 6/4090 (0.1%)
    Cerebrovascular accident 3/4089 (0.1%) 5/4090 (0.1%)
    Headache 3/4089 (0.1%) 4/4090 (0.1%)
    Seizure 3/4089 (0.1%) 4/4090 (0.1%)
    Metabolic encephalopathy 2/4089 (0%) 3/4090 (0.1%)
    Carpal tunnel syndrome 2/4089 (0%) 1/4090 (0%)
    Cervical radiculopathy 2/4089 (0%) 1/4090 (0%)
    Ataxia 2/4089 (0%) 0/4090 (0%)
    Dementia 2/4089 (0%) 0/4090 (0%)
    Epilepsy 2/4089 (0%) 0/4090 (0%)
    Intracranial aneurysm 2/4089 (0%) 0/4090 (0%)
    Lumbar radiculopathy 1/4089 (0%) 3/4090 (0.1%)
    Neuralgia 1/4089 (0%) 2/4090 (0%)
    Aphasia 1/4089 (0%) 1/4090 (0%)
    Cerebral infarction 1/4089 (0%) 1/4090 (0%)
    Dementia Alzheimer's type 1/4089 (0%) 1/4090 (0%)
    Facial paralysis 1/4089 (0%) 1/4090 (0%)
    Hydrocephalus 1/4089 (0%) 1/4090 (0%)
    Hypertensive encephalopathy 1/4089 (0%) 1/4090 (0%)
    Neuropathy peripheral 1/4089 (0%) 1/4090 (0%)
    Transient global amnesia 1/4089 (0%) 1/4090 (0%)
    Unresponsive to stimuli 1/4089 (0%) 1/4090 (0%)
    Brain injury 1/4089 (0%) 0/4090 (0%)
    Carotid artery occlusion 1/4089 (0%) 0/4090 (0%)
    Cerebrospinal fluid leakage 1/4089 (0%) 0/4090 (0%)
    Cognitive disorder 1/4089 (0%) 0/4090 (0%)
    Dural arteriovenous fistula 1/4089 (0%) 0/4090 (0%)
    Haemorrhagic transformation stroke 1/4089 (0%) 0/4090 (0%)
    Hypoaesthesia 1/4089 (0%) 0/4090 (0%)
    IIIrd nerve paralysis 1/4089 (0%) 0/4090 (0%)
    Intracranial mass 1/4089 (0%) 0/4090 (0%)
    Ischaemic stroke 1/4089 (0%) 0/4090 (0%)
    Migraine 1/4089 (0%) 0/4090 (0%)
    Nerve compression 1/4089 (0%) 0/4090 (0%)
    Neurodegenerative disorder 1/4089 (0%) 0/4090 (0%)
    Neurological symptom 1/4089 (0%) 0/4090 (0%)
    Pseudoradicular syndrome 1/4089 (0%) 0/4090 (0%)
    Quadriplegia 1/4089 (0%) 0/4090 (0%)
    Radicular syndrome 1/4089 (0%) 0/4090 (0%)
    Sensory ganglionitis 1/4089 (0%) 0/4090 (0%)
    Speech disorder 1/4089 (0%) 0/4090 (0%)
    Toxic encephalopathy 1/4089 (0%) 0/4090 (0%)
    Trigeminal nerve disorder 1/4089 (0%) 0/4090 (0%)
    Vasogenic cerebral oedema 1/4089 (0%) 0/4090 (0%)
    Vocal cord paralysis 1/4089 (0%) 0/4090 (0%)
    Hemiparesis 0/4089 (0%) 5/4090 (0.1%)
    Cerebral haemorrhage 0/4089 (0%) 2/4090 (0%)
    Hypoxic-ischaemic encephalopathy 0/4089 (0%) 2/4090 (0%)
    Loss of consciousness 0/4089 (0%) 2/4090 (0%)
    Sciatica 0/4089 (0%) 2/4090 (0%)
    Acute disseminated encephalomyelitis 0/4089 (0%) 1/4090 (0%)
    Altered state of consciousness 0/4089 (0%) 1/4090 (0%)
    Amyotrophic lateral sclerosis 0/4089 (0%) 1/4090 (0%)
    Autonomic nervous system imbalance 0/4089 (0%) 1/4090 (0%)
    Carotid artery disease 0/4089 (0%) 1/4090 (0%)
    Demyelinating polyneuropathy 0/4089 (0%) 1/4090 (0%)
    Diabetic neuropathy 0/4089 (0%) 1/4090 (0%)
    Haemorrhage intracranial 0/4089 (0%) 1/4090 (0%)
    Hypoglycaemic coma 0/4089 (0%) 1/4090 (0%)
    Hypoglycaemic encephalopathy 0/4089 (0%) 1/4090 (0%)
    Hypoglycaemic unconsciousness 0/4089 (0%) 1/4090 (0%)
    Multiple sclerosis 0/4089 (0%) 1/4090 (0%)
    Multiple sclerosis relapse 0/4089 (0%) 1/4090 (0%)
    Myelopathy 0/4089 (0%) 1/4090 (0%)
    Paraesthesia 0/4089 (0%) 1/4090 (0%)
    Polyneuropathy 0/4089 (0%) 1/4090 (0%)
    Reversible ischaemic neurological deficit 0/4089 (0%) 1/4090 (0%)
    Spinal cord herniation 0/4089 (0%) 1/4090 (0%)
    Status epilepticus 0/4089 (0%) 1/4090 (0%)
    Trigeminal neuralgia 0/4089 (0%) 1/4090 (0%)
    Vascular dementia 0/4089 (0%) 1/4090 (0%)
    Product Issues
    Device malfunction 2/4089 (0%) 2/4090 (0%)
    Device breakage 1/4089 (0%) 2/4090 (0%)
    Device dislocation 1/4089 (0%) 2/4090 (0%)
    Device failure 1/4089 (0%) 2/4090 (0%)
    Device occlusion 0/4089 (0%) 1/4090 (0%)
    Psychiatric disorders
    Delirium 5/4089 (0.1%) 2/4090 (0%)
    Suicide attempt 3/4089 (0.1%) 1/4090 (0%)
    Mental status changes 2/4089 (0%) 3/4090 (0.1%)
    Depression 2/4089 (0%) 2/4090 (0%)
    Anxiety 2/4089 (0%) 0/4090 (0%)
    Panic attack 2/4089 (0%) 0/4090 (0%)
    Alcohol abuse 1/4089 (0%) 3/4090 (0.1%)
    Completed suicide 1/4089 (0%) 2/4090 (0%)
    Suicidal ideation 1/4089 (0%) 2/4090 (0%)
    Alcohol withdrawal syndrome 1/4089 (0%) 1/4090 (0%)
    Confusional state 1/4089 (0%) 1/4090 (0%)
    Aggression 1/4089 (0%) 0/4090 (0%)
    Agitated depression 1/4089 (0%) 0/4090 (0%)
    Delirium tremens 1/4089 (0%) 0/4090 (0%)
    Major depression 1/4089 (0%) 0/4090 (0%)
    Schizoaffective disorder 1/4089 (0%) 0/4090 (0%)
    Acute psychosis 0/4089 (0%) 1/4090 (0%)
    Alcoholism 0/4089 (0%) 1/4090 (0%)
    Bipolar disorder 0/4089 (0%) 1/4090 (0%)
    Mania 0/4089 (0%) 1/4090 (0%)
    Psychotic disorder 0/4089 (0%) 1/4090 (0%)
    Schizophrenia 0/4089 (0%) 1/4090 (0%)
    Renal and urinary disorders
    Acute kidney injury 47/4089 (1.1%) 34/4090 (0.8%)
    Nephrolithiasis 13/4089 (0.3%) 12/4090 (0.3%)
    Renal failure 11/4089 (0.3%) 6/4090 (0.1%)
    Haematuria 8/4089 (0.2%) 4/4090 (0.1%)
    Ureterolithiasis 6/4089 (0.1%) 7/4090 (0.2%)
    Chronic kidney disease 6/4089 (0.1%) 4/4090 (0.1%)
    Urinary retention 5/4089 (0.1%) 4/4090 (0.1%)
    Renal impairment 5/4089 (0.1%) 1/4090 (0%)
    Renal cyst 4/4089 (0.1%) 0/4090 (0%)
    Urethral stenosis 3/4089 (0.1%) 2/4090 (0%)
    Urinary tract obstruction 3/4089 (0.1%) 1/4090 (0%)
    Calculus urinary 2/4089 (0%) 3/4090 (0.1%)
    Renal colic 2/4089 (0%) 3/4090 (0.1%)
    End stage renal disease 2/4089 (0%) 1/4090 (0%)
    Cystitis haemorrhagic 2/4089 (0%) 0/4090 (0%)
    Bladder outlet obstruction 1/4089 (0%) 2/4090 (0%)
    Stress urinary incontinence 1/4089 (0%) 2/4090 (0%)
    Bladder neck obstruction 1/4089 (0%) 1/4090 (0%)
    Nephropathy 1/4089 (0%) 1/4090 (0%)
    Urinary bladder haemorrhage 1/4089 (0%) 1/4090 (0%)
    Bladder stenosis 1/4089 (0%) 0/4090 (0%)
    Incontinence 1/4089 (0%) 0/4090 (0%)
    Renal artery fibromuscular dysplasia 1/4089 (0%) 0/4090 (0%)
    Renal disorder 1/4089 (0%) 0/4090 (0%)
    Renal injury 1/4089 (0%) 0/4090 (0%)
    Tubulointerstitial nephritis 1/4089 (0%) 0/4090 (0%)
    Ureteric dilatation 1/4089 (0%) 0/4090 (0%)
    Ureteric stenosis 1/4089 (0%) 0/4090 (0%)
    Urethral meatus stenosis 1/4089 (0%) 0/4090 (0%)
    Calculus bladder 0/4089 (0%) 4/4090 (0.1%)
    Urinary incontinence 0/4089 (0%) 4/4090 (0.1%)
    Acute prerenal failure 0/4089 (0%) 2/4090 (0%)
    Bladder dysfunction 0/4089 (0%) 1/4090 (0%)
    Bladder prolapse 0/4089 (0%) 1/4090 (0%)
    Diabetic nephropathy 0/4089 (0%) 1/4090 (0%)
    Dysuria 0/4089 (0%) 1/4090 (0%)
    Hydronephrosis 0/4089 (0%) 1/4090 (0%)
    Hypertonic bladder 0/4089 (0%) 1/4090 (0%)
    Nephropathy toxic 0/4089 (0%) 1/4090 (0%)
    Renal haemorrhage 0/4089 (0%) 1/4090 (0%)
    Stag horn calculus 0/4089 (0%) 1/4090 (0%)
    Urinary bladder polyp 0/4089 (0%) 1/4090 (0%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 18/4089 (0.4%) 11/4090 (0.3%)
    Prostatitis 6/4089 (0.1%) 3/4090 (0.1%)
    Prostatomegaly 2/4089 (0%) 2/4090 (0%)
    Adnexa uteri mass 1/4089 (0%) 0/4090 (0%)
    Genital haemorrhage 1/4089 (0%) 0/4090 (0%)
    Menorrhagia 1/4089 (0%) 0/4090 (0%)
    Pelvic prolapse 1/4089 (0%) 0/4090 (0%)
    Peyronie's disease 1/4089 (0%) 0/4090 (0%)
    Prostatism 1/4089 (0%) 0/4090 (0%)
    Vaginal prolapse 1/4089 (0%) 0/4090 (0%)
    Uterine polyp 0/4089 (0%) 2/4090 (0%)
    Endometrial hyperplasia 0/4089 (0%) 1/4090 (0%)
    Endometrial hypoplasia 0/4089 (0%) 1/4090 (0%)
    Female genital tract fistula 0/4089 (0%) 1/4090 (0%)
    Ovarian cyst 0/4089 (0%) 1/4090 (0%)
    Ovarian cyst ruptured 0/4089 (0%) 1/4090 (0%)
    Seminal vesicular cyst 0/4089 (0%) 1/4090 (0%)
    Testicular cyst 0/4089 (0%) 1/4090 (0%)
    Uterine prolapse 0/4089 (0%) 1/4090 (0%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 33/4089 (0.8%) 34/4090 (0.8%)
    Acute respiratory failure 19/4089 (0.5%) 18/4090 (0.4%)
    Respiratory failure 16/4089 (0.4%) 15/4090 (0.4%)
    Dyspnoea 16/4089 (0.4%) 13/4090 (0.3%)
    Pulmonary embolism 14/4089 (0.3%) 22/4090 (0.5%)
    Asthma 9/4089 (0.2%) 5/4090 (0.1%)
    Pleural effusion 7/4089 (0.2%) 11/4090 (0.3%)
    Epistaxis 7/4089 (0.2%) 4/4090 (0.1%)
    Pneumonia aspiration 7/4089 (0.2%) 4/4090 (0.1%)
    Dyspnoea exertional 4/4089 (0.1%) 2/4090 (0%)
    Pulmonary fibrosis 4/4089 (0.1%) 1/4090 (0%)
    Pulmonary oedema 3/4089 (0.1%) 7/4090 (0.2%)
    Hypoxia 3/4089 (0.1%) 5/4090 (0.1%)
    Pneumothorax 3/4089 (0.1%) 2/4090 (0%)
    Pleurisy 3/4089 (0.1%) 1/4090 (0%)
    Acute respiratory distress syndrome 2/4089 (0%) 2/4090 (0%)
    Sleep apnoea syndrome 2/4089 (0%) 2/4090 (0%)
    Pulmonary hypertension 2/4089 (0%) 1/4090 (0%)
    Pleuritic pain 1/4089 (0%) 4/4090 (0.1%)
    Interstitial lung disease 1/4089 (0%) 2/4090 (0%)
    Respiratory distress 1/4089 (0%) 2/4090 (0%)
    Acute pulmonary oedema 1/4089 (0%) 1/4090 (0%)
    Atelectasis 1/4089 (0%) 1/4090 (0%)
    Bronchial hyperreactivity 1/4089 (0%) 1/4090 (0%)
    Haemothorax 1/4089 (0%) 1/4090 (0%)
    Nasal polyps 1/4089 (0%) 1/4090 (0%)
    Pneumonitis 1/4089 (0%) 1/4090 (0%)
    Respiratory acidosis 1/4089 (0%) 1/4090 (0%)
    Aspiration 1/4089 (0%) 0/4090 (0%)
    Bronchitis chronic 1/4089 (0%) 0/4090 (0%)
    Emphysema 1/4089 (0%) 0/4090 (0%)
    Haemoptysis 1/4089 (0%) 0/4090 (0%)
    Hiccups 1/4089 (0%) 0/4090 (0%)
    Lung disorder 1/4089 (0%) 0/4090 (0%)
    Pharyngeal mass 1/4089 (0%) 0/4090 (0%)
    Pneumomediastinum 1/4089 (0%) 0/4090 (0%)
    Rhinitis allergic 1/4089 (0%) 0/4090 (0%)
    Status asthmaticus 1/4089 (0%) 0/4090 (0%)
    Wheezing 1/4089 (0%) 0/4090 (0%)
    Bronchiectasis 0/4089 (0%) 4/4090 (0.1%)
    Bronchial fistula 0/4089 (0%) 1/4090 (0%)
    Bronchospasm 0/4089 (0%) 1/4090 (0%)
    Hypercapnia 0/4089 (0%) 1/4090 (0%)
    Nasal septum deviation 0/4089 (0%) 1/4090 (0%)
    Nasal turbinate hypertrophy 0/4089 (0%) 1/4090 (0%)
    Pulmonary mass 0/4089 (0%) 1/4090 (0%)
    Respiratory arrest 0/4089 (0%) 1/4090 (0%)
    Tracheal mass 0/4089 (0%) 1/4090 (0%)
    Skin and subcutaneous tissue disorders
    Skin ulcer 5/4089 (0.1%) 3/4090 (0.1%)
    Diabetic foot 2/4089 (0%) 2/4090 (0%)
    Diabetic ulcer 2/4089 (0%) 1/4090 (0%)
    Angioedema 1/4089 (0%) 1/4090 (0%)
    Dermal cyst 1/4089 (0%) 0/4090 (0%)
    Ecchymosis 1/4089 (0%) 0/4090 (0%)
    Granuloma annulare 1/4089 (0%) 0/4090 (0%)
    Photosensitivity reaction 1/4089 (0%) 0/4090 (0%)
    Rash erythematous 1/4089 (0%) 0/4090 (0%)
    Hyperhidrosis 0/4089 (0%) 1/4090 (0%)
    Panniculitis 0/4089 (0%) 1/4090 (0%)
    Urticaria 0/4089 (0%) 1/4090 (0%)
    Surgical and medical procedures
    Knee arthroplasty 3/4089 (0.1%) 0/4090 (0%)
    Implantable defibrillator insertion 2/4089 (0%) 1/4090 (0%)
    Lung lobectomy 1/4089 (0%) 1/4090 (0%)
    Aortic valve replacement 1/4089 (0%) 0/4090 (0%)
    Artificial urinary sphincter implant 1/4089 (0%) 0/4090 (0%)
    Hospitalisation 1/4089 (0%) 0/4090 (0%)
    Polypectomy 1/4089 (0%) 0/4090 (0%)
    Rotator cuff repair 1/4089 (0%) 0/4090 (0%)
    Shoulder operation 1/4089 (0%) 0/4090 (0%)
    Stem cell transplant 1/4089 (0%) 0/4090 (0%)
    Transurethral prostatectomy 1/4089 (0%) 0/4090 (0%)
    Cardiac ablation 0/4089 (0%) 2/4090 (0%)
    Spinal operation 0/4089 (0%) 2/4090 (0%)
    Endotracheal intubation 0/4089 (0%) 1/4090 (0%)
    Gastric bypass 0/4089 (0%) 1/4090 (0%)
    Hip arthroplasty 0/4089 (0%) 1/4090 (0%)
    Large intestinal polypectomy 0/4089 (0%) 1/4090 (0%)
    Transurethral bladder resection 0/4089 (0%) 1/4090 (0%)
    Vascular disorders
    Hypertensive crisis 15/4089 (0.4%) 11/4090 (0.3%)
    Hypertension 12/4089 (0.3%) 16/4090 (0.4%)
    Hypotension 9/4089 (0.2%) 11/4090 (0.3%)
    Deep vein thrombosis 5/4089 (0.1%) 8/4090 (0.2%)
    Aortic stenosis 4/4089 (0.1%) 10/4090 (0.2%)
    Orthostatic hypotension 4/4089 (0.1%) 5/4090 (0.1%)
    Aortic aneurysm 3/4089 (0.1%) 1/4090 (0%)
    Peripheral arterial occlusive disease 2/4089 (0%) 3/4090 (0.1%)
    Hypovolaemic shock 2/4089 (0%) 1/4090 (0%)
    Accelerated hypertension 2/4089 (0%) 0/4090 (0%)
    Peripheral vascular disorder 2/4089 (0%) 0/4090 (0%)
    Shock haemorrhagic 2/4089 (0%) 0/4090 (0%)
    Peripheral ischaemia 1/4089 (0%) 3/4090 (0.1%)
    Peripheral artery occlusion 1/4089 (0%) 2/4090 (0%)
    Aortic aneurysm rupture 1/4089 (0%) 1/4090 (0%)
    Haematoma 1/4089 (0%) 1/4090 (0%)
    Hypertensive emergency 1/4089 (0%) 1/4090 (0%)
    Intermittent claudication 1/4089 (0%) 1/4090 (0%)
    Shock 1/4089 (0%) 1/4090 (0%)
    Angiodysplasia 1/4089 (0%) 0/4090 (0%)
    Arteriovenous fistula 1/4089 (0%) 0/4090 (0%)
    Circulatory collapse 1/4089 (0%) 0/4090 (0%)
    Embolism arterial 1/4089 (0%) 0/4090 (0%)
    Extravasation blood 1/4089 (0%) 0/4090 (0%)
    Iliac artery occlusion 1/4089 (0%) 0/4090 (0%)
    Jugular vein thrombosis 1/4089 (0%) 0/4090 (0%)
    Malignant hypertension 1/4089 (0%) 0/4090 (0%)
    Peripheral embolism 1/4089 (0%) 0/4090 (0%)
    Renovascular hypertension 1/4089 (0%) 0/4090 (0%)
    Thrombophlebitis superficial 1/4089 (0%) 0/4090 (0%)
    Vena cava thrombosis 1/4089 (0%) 0/4090 (0%)
    Blood pressure fluctuation 0/4089 (0%) 1/4090 (0%)
    Extremity necrosis 0/4089 (0%) 1/4090 (0%)
    Leriche syndrome 0/4089 (0%) 1/4090 (0%)
    Temporal arteritis 0/4089 (0%) 1/4090 (0%)
    Thrombophlebitis 0/4089 (0%) 1/4090 (0%)
    Thrombosis 0/4089 (0%) 1/4090 (0%)
    Vasculitis 0/4089 (0%) 1/4090 (0%)
    Other (Not Including Serious) Adverse Events
    AMR101 Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3268/4089 (79.9%) 3248/4090 (79.4%)
    Blood and lymphatic system disorders
    Anaemia 178/4089 (4.4%) 224/4090 (5.5%)
    Eye disorders
    Cataract 230/4089 (5.6%) 205/4090 (5%)
    Gastrointestinal disorders
    Diarrhoea 363/4089 (8.9%) 450/4090 (11%)
    Constipation 216/4089 (5.3%) 142/4090 (3.5%)
    General disorders
    Oedema peripheral 264/4089 (6.5%) 201/4090 (4.9%)
    Fatigue 227/4089 (5.6%) 195/4090 (4.8%)
    Chest pain 226/4089 (5.5%) 240/4090 (5.9%)
    Infections and infestations
    Nasopharyngitis 314/4089 (7.7%) 300/4090 (7.3%)
    Upper respiratory tract infection 311/4089 (7.6%) 315/4090 (7.7%)
    Bronchitis 295/4089 (7.2%) 292/4090 (7.1%)
    Influenza 261/4089 (6.4%) 267/4090 (6.5%)
    Urinary tract infection 240/4089 (5.9%) 246/4090 (6%)
    Musculoskeletal and connective tissue disorders
    Back pain 322/4089 (7.9%) 303/4090 (7.4%)
    Arthralgia 309/4089 (7.6%) 306/4090 (7.5%)
    Pain in extremity 232/4089 (5.7%) 239/4090 (5.8%)
    Nervous system disorders
    Dizziness 227/4089 (5.6%) 238/4090 (5.8%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 243/4089 (5.9%) 233/4090 (5.7%)
    Cough 241/4089 (5.9%) 241/4090 (5.9%)
    Vascular disorders
    Hypertension 312/4089 (7.6%) 333/4090 (8.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Alexander Giaquinto, Executive Director, Regulatory Affairs
    Organization Amarin Pharma, Inc.
    Phone 908-326-1324
    Email alex.giaquinto@amarincorp.com
    Responsible Party:
    Amarin Pharma Inc.
    ClinicalTrials.gov Identifier:
    NCT01492361
    Other Study ID Numbers:
    • AMR-01-01-0019
    First Posted:
    Dec 15, 2011
    Last Update Posted:
    Apr 14, 2022
    Last Verified:
    Mar 1, 2022