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STRENGTH: Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT02104817
Collaborator
The Cleveland Clinic (Other), IQVIA RDS Inc. (Other)
13,078
Enrollment
685
Locations
2
Arms
66.9
Actual Duration (Months)
19.1
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study is a randomized, double-blind, placebo-controlled (corn oil), parallel group design that will enroll approximately 13,000 patients with hypertriglyceridemia and low HDL and high risk for CVD to be randomized 1:1 to either corn oil + statin or Epanova + statin, once daily, for approximately 3-5 years as determined when the number of MACE outcomes is reached.

Condition or Disease Intervention/Treatment Phase
  • Drug: Epanova® (omega-3 carboxylic acids)
  • Drug: corn oil control
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
13078 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Long-Term Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh Cardiovascular Risk PatienTs With Hypertriglyceridemia (STRENGTH)
Actual Study Start Date :
Oct 30, 2014
Actual Primary Completion Date :
May 27, 2020
Actual Study Completion Date :
May 27, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: EPANOVA

Epanova + statin, once daily

Drug: Epanova® (omega-3 carboxylic acids)
Adjunct to statin therapy and diet in high risk adult patients for the prevention and reduction of major adverse cardiovascular events (MACE)
Other Names:
  • omega-3 carboxylic acids

    		•
    Active Comparator: Corn oil

    Corn oil + Statin

    Drug: corn oil control
    corn oil control arm

    Outcome Measures

    Primary Outcome Measures

    1. The Composite of Major Adverse Cardiovascular Events (MACE) [From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure]

      MACE components include: cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, emergent/elective coronary revascularization, or hospitalization for unstable angina. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).

    Secondary Outcome Measures

    1. The Composite of MACE in the Subgroup of Participants With Established CV Disease(CVD) at Baseline [From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure]

      MACE components include: cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, emergent/elective coronary revascularization, or hospitalization for unstable angina. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).

    2. The Composite of CV Events [From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure]

      CV events include: cardiovascular (CV) death, non-fatal myocardial infarction (MI) and non-fatal stroke. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).

    3. The Composite of CV Events in the Subgroup of Participants With Established CV Disease (CVD) at Baseline [From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure]

      CV events include: cardiovascular (CV) death, non-fatal myocardial infarction (MI) and non-fatal stroke. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).

    4. The Composite of Coronary Events [From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure]

      Coronary events include: cardiac death (including death due to acute myocardial infarction, sudden cardiac death and death due to cardiovascular procedures), non-fatal myocardial infarction (MI), emergent/elective coronary revascularization and hospitalization for unstable angina. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).

    5. The Composite of Coronary Events in the Subgroup of Participants With Established CVD at Baseline [From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure]

      Coronary events include: cardiac death (including death due to acute myocardial infarction, sudden cardiac death and death due to cardiovascular procedures), non-fatal myocardial infarction (MI), emergent/elective coronary revascularization and hospitalization for unstable angina. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed) in the subgroup of participants with established CVD at baseline

    6. CV Death [From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure]

      Participants with no observed events are censored at the latest of the date of last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed), last date known to be alive, and date of non-cardiovascular death.

    7. CV Death in the Subgroup of Participants With Established CVD at Baseline [From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure]

      Participants with no observed events are censored at the latest of the date of last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed), last date known to be alive, and date of non-cardiovascular death in the subgroup of participants with established CVD at baseline

    8. All-cause Death [From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure]

      Participants with no observed events are censored at the latest of the date of last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed) and last date known to be alive.

    9. All-cause Death in the Subgroup of Participants With Established CVD at Baseline [From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure]

      Participants with no observed events are censored at the latest of the date of last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed) and last date known to be alive in the subgroup of participants with established CVD at baseline

    Other Outcome Measures

    1. Emergent/Elective Coronary Revascularization [From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure]

      Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).

    2. Hospitalization for Unstable Angina [From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure]

      Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).

    3. Non-fatal Myocardial Infarction [From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure]

      Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).

    4. Non-fatal Stroke [From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure]

      Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 99 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Men or women, ≥18 years of age.

    2. Patient must be on a stable diet and statin* therapy at least 4 weeks prior to randomization (Visit 2) and meet the following criteria:

    3. LDL-C <100 mg/dL

    4. TG level ≥180 and <500 mg/dL and HDL-C <42 mg/dL for men or HDL-C <47 mg/dL for women

    5. Patient is at high risk for a future cardiovascular event if at least one of the following criteria (3a, 3b or 3c)* is present via patient history, physical exam, or medical records at the time of screening:

    6. Any atherosclerotic CVD as defined in protocol.

    7. History of diabetes mellitus (type 1 or 2) and ≥40 years of age for men and ≥50 years of age for women, plus one of the risk factors defined in protocol.

    8. Male patients >50 years of age or females >60 years of age, with at least one of the risk factors defined in protocol.

    Key Exclusion Criteria:
    1. Allergy or intolerance to omega-3 carboxylic acids, omega-3 fatty acids, omega-3-acid ethyl esters, or corn oil. 2.Use of fibrates, bile acid sequestrants, or niacin or its analogues (>250 mg/day) within 4 weeks prior to Visit 2. 3.Statin naïve at Visit 1.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Birmingham Alabama United States 35205
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    605 Research Site Krugersdorp South Africa 1739
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    610 Research Site Paarl South Africa 7646
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    632 Research Site Taipei Taiwan 11101
    633 Research Site Taipei Taiwan 11217
    634 Research Site Cherkasy Ukraine 18009
    635 Research Site Ivano-Frankivsk Ukraine 76005
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    652 Research Site Lviv Ukraine 79034
    653 Research Site Lviv Ukraine 79059
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    655 Research Site Odesa Ukraine 65114
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    661 Research Site Zaporizhzhia Ukraine 69001
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    664 Research Site Airdrie United Kingdom ML6 0JS
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    Sponsors and Collaborators

    • AstraZeneca
    • The Cleveland Clinic
    • IQVIA RDS Inc.

    Investigators

    • Principal Investigator: Steven Nissen, MD, The Cleveland Clinic
    • Principal Investigator: Michael Lincoff, MD, The Cleveland Clinic
    • Principal Investigator: Stephen Nicholls, MD, MonashHeart

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT02104817
    Other Study ID Numbers:
    • D5881C00004
    • 2014-001069-28
    First Posted:
    Apr 4, 2014
    Last Update Posted:
    Aug 17, 2021
    Last Verified:
    Aug 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by AstraZeneca
    omega-3 carboxylic acid
    Additional relevant MeSH terms:
    Cardiovascular Diseases
    Atherosclerosis
    Hypertriglyceridemia

    Study Results

    Participant Flow

    Recruitment Details 686 study sites in 22 countries randomized subjects. The first patient was enrolled on 30 October 2014 and randomized on 11 November 2014. The last patient was randomized on 12 July 2017.
    Pre-assignment Detail
    Arm/Group Title Epanova Placebo
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule
    Period Title: Overall Study
    STARTED 6539 6539
    COMPLETED 80 92
    NOT COMPLETED 6459 6447

    Baseline Characteristics

    Arm/Group Title Epanova Placebo Total
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule Total of all reporting groups
    Overall Participants 6539 6539 13078
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    62.5
    (8.98)
    62.5
    (8.98)
    62.5
    (8.98)
    Sex: Female, Male (Count of Participants)
    Female
    2289
    35%
    2279
    34.9%
    4568
    34.9%
    Male
    4250
    65%
    4260
    65.1%
    8510
    65.1%
    Race/Ethnicity, Customized (Number) [Number]
    WHITE
    5341
    81.7%
    5382
    82.3%
    10723
    82%
    BLACK OR AFRICAN AMERICAN
    180
    2.8%
    166
    2.5%
    346
    2.6%
    ASIAN
    698
    10.7%
    657
    10%
    1355
    10.4%
    NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER
    10
    0.2%
    11
    0.2%
    21
    0.2%
    AMERICAN INDIAN OR ALASKA NATIVE
    114
    1.7%
    112
    1.7%
    226
    1.7%
    OTHER
    159
    2.4%
    154
    2.4%
    313
    2.4%
    MULTIPLE
    33
    0.5%
    47
    0.7%
    80
    0.6%
    UNKNOWN
    4
    0.1%
    10
    0.2%
    14
    0.1%
    NOT REPORTED
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Number) [Number]
    Australia
    58
    0.9%
    54
    0.8%
    112
    0.9%
    Belgium
    53
    0.8%
    51
    0.8%
    104
    0.8%
    Canada
    187
    2.9%
    177
    2.7%
    364
    2.8%
    China
    357
    5.5%
    356
    5.4%
    713
    5.5%
    Czech Republic
    120
    1.8%
    108
    1.7%
    228
    1.7%
    Denmark
    48
    0.7%
    73
    1.1%
    121
    0.9%
    Estonia
    57
    0.9%
    53
    0.8%
    110
    0.8%
    Hungary
    561
    8.6%
    562
    8.6%
    1123
    8.6%
    Italy
    33
    0.5%
    34
    0.5%
    67
    0.5%
    Japan
    166
    2.5%
    139
    2.1%
    305
    2.3%
    Korea, Republic Of
    68
    1%
    65
    1%
    133
    1%
    Lithuania
    170
    2.6%
    193
    3%
    363
    2.8%
    Mexico
    152
    2.3%
    155
    2.4%
    307
    2.3%
    Netherlands
    206
    3.2%
    215
    3.3%
    421
    3.2%
    New Zealand
    74
    1.1%
    77
    1.2%
    151
    1.2%
    Poland
    501
    7.7%
    492
    7.5%
    993
    7.6%
    Russia
    307
    4.7%
    326
    5%
    633
    4.8%
    South Africa
    471
    7.2%
    490
    7.5%
    961
    7.3%
    Taiwan, Province Of China
    28
    0.4%
    31
    0.5%
    59
    0.5%
    Ukraine
    1009
    15.4%
    955
    14.6%
    1964
    15%
    United Kingdom
    377
    5.8%
    382
    5.8%
    759
    5.8%
    USA
    1536
    23.5%
    1551
    23.7%
    3087
    23.6%

    Outcome Measures

    1. Primary Outcome
    Title The Composite of Major Adverse Cardiovascular Events (MACE)
    Description MACE components include: cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, emergent/elective coronary revascularization, or hospitalization for unstable angina. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
    Time Frame From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Epanova Placebo
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule
    Measure Participants 6539 6539
    Number [Number of Participants]
    785
    12%
    795
    12.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Epanova, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.837
    Comments The hypothesis is tested at the 5% level. A hierarchical test sequence is used to address the issue of multiple testing.
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.99
    Confidence Interval (2-Sided) 95%
    0.90 to 1.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title The Composite of MACE in the Subgroup of Participants With Established CV Disease(CVD) at Baseline
    Description MACE components include: cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, emergent/elective coronary revascularization, or hospitalization for unstable angina. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
    Time Frame From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Epanova Placebo
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule
    Measure Participants 6539 6539
    Overall number of participants
    785
    12%
    795
    12.2%
    Number of participants with established cardiovascular disease (CVD) at baseline
    569
    8.7%
    610
    9.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Epanova, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.269
    Comments The hypothesis is tested at the 5% level. A hierarchical test sequence is used to address the issue of multiple testing.
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.94
    Confidence Interval (2-Sided) 95%
    0.84 to 1.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title The Composite of CV Events
    Description CV events include: cardiovascular (CV) death, non-fatal myocardial infarction (MI) and non-fatal stroke. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
    Time Frame From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Epanova Placebo
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule
    Measure Participants 6539 6539
    Number [Number of Participants]
    541
    8.3%
    517
    7.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Epanova, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.402
    Comments The hypothesis is tested at the 5% level. A hierarchical test sequence is used to address the issue of multiple testing
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.05
    Confidence Interval (2-Sided) 95%
    0.93 to 1.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title The Composite of CV Events in the Subgroup of Participants With Established CV Disease (CVD) at Baseline
    Description CV events include: cardiovascular (CV) death, non-fatal myocardial infarction (MI) and non-fatal stroke. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
    Time Frame From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Epanova Placebo
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule
    Measure Participants 6539 6539
    Overall number of participants
    541
    8.3%
    517
    7.9%
    Number of participants with established CVD at baseline
    383
    5.9%
    385
    5.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Epanova, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.940
    Comments The hypothesis is tested at the 5% level. A hierarchical test sequence is used to address the issue of multiple testing
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.01
    Confidence Interval (2-Sided) 95%
    0.87 to 1.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title The Composite of Coronary Events
    Description Coronary events include: cardiac death (including death due to acute myocardial infarction, sudden cardiac death and death due to cardiovascular procedures), non-fatal myocardial infarction (MI), emergent/elective coronary revascularization and hospitalization for unstable angina. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
    Time Frame From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Epanova Placebo
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule
    Measure Participants 6539 6539
    Number [Number of Participants]
    556
    8.5%
    616
    9.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Epanova, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.092
    Comments The hypothesis is tested at the 5% level. A hierarchical test sequence is used to address the issue of multiple testing
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.91
    Confidence Interval (2-Sided) 95%
    0.81 to 1.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title The Composite of Coronary Events in the Subgroup of Participants With Established CVD at Baseline
    Description Coronary events include: cardiac death (including death due to acute myocardial infarction, sudden cardiac death and death due to cardiovascular procedures), non-fatal myocardial infarction (MI), emergent/elective coronary revascularization and hospitalization for unstable angina. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed) in the subgroup of participants with established CVD at baseline
    Time Frame From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Epanova Placebo
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule
    Measure Participants 6539 6539
    Overall number of participants
    556
    8.5%
    616
    9.4%
    Number of participants with established CVD at baseline
    417
    6.4%
    493
    7.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Epanova, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.016
    Comments The hypothesis is tested at the 5% level. A hierarchical test sequence is used to address the issue of multiple testing.
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.85
    Confidence Interval (2-Sided) 95%
    0.75 to 0.97
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title CV Death
    Description Participants with no observed events are censored at the latest of the date of last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed), last date known to be alive, and date of non-cardiovascular death.
    Time Frame From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Epanova Placebo
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule
    Measure Participants 6539 6539
    Number [Number of Participants]
    228
    3.5%
    211
    3.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Epanova, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.372
    Comments The hypothesis is tested at the 5% level. A hierarchical test sequence is used to address the issue of multiple testing
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.09
    Confidence Interval (2-Sided) 95%
    0.90 to 1.31
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title CV Death in the Subgroup of Participants With Established CVD at Baseline
    Description Participants with no observed events are censored at the latest of the date of last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed), last date known to be alive, and date of non-cardiovascular death in the subgroup of participants with established CVD at baseline
    Time Frame From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Epanova Placebo
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule
    Measure Participants 6539 6539
    Overall number of participants
    228
    3.5%
    211
    3.2%
    Number of participants with established CVD at baseline
    152
    2.3%
    138
    2.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Epanova, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.336
    Comments The hypothesis is tested at the 5% level. A hierarchical test sequence is used to address the issue of multiple testing.
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.12
    Confidence Interval (2-Sided) 95%
    0.89 to 1.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title All-cause Death
    Description Participants with no observed events are censored at the latest of the date of last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed) and last date known to be alive.
    Time Frame From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Epanova Placebo
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule
    Measure Participants 6539 6539
    Number [Number of Participants]
    373
    5.7%
    333
    5.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Epanova, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.112
    Comments The hypothesis is tested at the 5% level. A hierarchical test sequence is used to address the issue of multiple testing.
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.13
    Confidence Interval (2-Sided) 95%
    0.97 to 1.31
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title All-cause Death in the Subgroup of Participants With Established CVD at Baseline
    Description Participants with no observed events are censored at the latest of the date of last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed) and last date known to be alive in the subgroup of participants with established CVD at baseline
    Time Frame From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Epanova Placebo
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule
    Measure Participants 6539 6539
    Overall number of participants
    373
    5.7%
    333
    5.1%
    Number of participants with established CVD at baselne
    234
    3.6%
    202
    3.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Epanova, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.091
    Comments The hypothesis is tested at the 5% level. A hierarchical test sequence is used to address the issue of multiple testing.
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.18
    Confidence Interval (2-Sided) 95%
    0.97 to 1.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Other Pre-specified Outcome
    Title Emergent/Elective Coronary Revascularization
    Description Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
    Time Frame From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Epanova Placebo
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule
    Measure Participants 6539 6539
    Number [Number of Participants]
    414
    6.3%
    441
    6.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Epanova, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.408
    Comments This endpoint was not in the testing sequence and therefore not under type I error control.
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.94
    Confidence Interval (2-Sided) 95%
    0.83 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    12. Other Pre-specified Outcome
    Title Hospitalization for Unstable Angina
    Description Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
    Time Frame From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Epanova Placebo
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule
    Measure Participants 6539 6539
    Number [Number of Participants]
    87
    1.3%
    104
    1.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Epanova, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.233
    Comments This endpoint was not in the testing sequence and therefore not under type I error control.
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.84
    Confidence Interval (2-Sided) 95%
    0.63 to 1.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    13. Other Pre-specified Outcome
    Title Non-fatal Myocardial Infarction
    Description Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
    Time Frame From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Epanova Placebo
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule
    Measure Participants 6539 6539
    Number [Number of Participants]
    218
    3.3%
    226
    3.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Epanova, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.770
    Comments This endpoint was not in the testing sequence and therefore not under type I error control.
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.97
    Confidence Interval (2-Sided) 95%
    0.81 to 1.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    14. Other Pre-specified Outcome
    Title Non-fatal Stroke
    Description Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
    Time Frame From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Epanova Placebo
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule
    Measure Participants 6539 6539
    Number [Number of Participants]
    142
    2.2%
    125
    1.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Epanova, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.278
    Comments This endpoint was not in the testing sequence and therefore not under type I error control.
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.14
    Confidence Interval (2-Sided) 95%
    0.90 to 1.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Predefined non-SAEs were collected from date of first IP dose until final visit/up to Month 60; if study treatment was discontinued prematurely, non-SAEs were recorded for ≤ 30 days after last IP dose. For AEs that are considered serious, lead to discontinuation, or result in dose modification, overdose, new onset diabetes mellitus, TIA, PHL cases or bleeding- related events were captured from date of first IP dose until final visit/up to Month 60, whether or not the participant discontinued IP.
    Adverse Event Reporting Description
    Arm/Group Title Epanova Placebo
    Arm/Group Description Omega-3 carboxylic acid 4 x 1 gram capsule Corn oil 4 x 1 gram capsule
    All Cause Mortality
    Epanova Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 373/6539 (5.7%) 333/6539 (5.1%)
    Serious Adverse Events
    Epanova Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2259/6532 (34.6%) 2195/6535 (33.6%)
    Blood and lymphatic system disorders
    Agranulocytosis 1/6532 (0%) 1 0/6535 (0%) 0
    Anaemia 15/6532 (0.2%) 17 19/6535 (0.3%) 25
    Anaemia macrocytic 0/6532 (0%) 0 1/6535 (0%) 1
    Antiphospholipid syndrome 1/6532 (0%) 1 0/6535 (0%) 0
    Blood loss anaemia 9/6532 (0.1%) 9 6/6535 (0.1%) 6
    Coagulopathy 3/6532 (0%) 3 0/6535 (0%) 0
    Disseminated intravascular coagulation 1/6532 (0%) 1 0/6535 (0%) 0
    Immune thrombocytopenic purpura 0/6532 (0%) 0 1/6535 (0%) 1
    Iron deficiency anaemia 9/6532 (0.1%) 10 6/6535 (0.1%) 6
    Leukocytosis 1/6532 (0%) 1 0/6535 (0%) 0
    Lymphadenopathy 1/6532 (0%) 1 2/6535 (0%) 2
    Microcytic anaemia 2/6532 (0%) 2 1/6535 (0%) 1
    Nephrogenic anaemia 0/6532 (0%) 0 1/6535 (0%) 1
    Normocytic anaemia 2/6532 (0%) 2 1/6535 (0%) 1
    Pancytopenia 0/6532 (0%) 0 1/6535 (0%) 1
    Polycythaemia 1/6532 (0%) 1 0/6535 (0%) 0
    Splenic infarction 0/6532 (0%) 0 1/6535 (0%) 1
    Splenic thrombosis 1/6532 (0%) 1 0/6535 (0%) 0
    Splenomegaly 1/6532 (0%) 1 0/6535 (0%) 0
    Thrombocytopenia 3/6532 (0%) 3 3/6535 (0%) 6
    Cardiac disorders
    Acute coronary syndrome 13/6532 (0.2%) 13 8/6535 (0.1%) 8
    Acute left ventricular failure 16/6532 (0.2%) 16 8/6535 (0.1%) 9
    Acute myocardial infarction 40/6532 (0.6%) 53 45/6535 (0.7%) 47
    Adams-stokes syndrome 0/6532 (0%) 0 2/6535 (0%) 2
    Angina pectoris 92/6532 (1.4%) 110 102/6535 (1.6%) 113
    Angina unstable 112/6532 (1.7%) 125 141/6535 (2.2%) 162
    Anginal equivalent 1/6532 (0%) 1 0/6535 (0%) 0
    Aortic valve disease 0/6532 (0%) 0 2/6535 (0%) 3
    Aortic valve incompetence 1/6532 (0%) 1 2/6535 (0%) 2
    Aortic valve stenosis 6/6532 (0.1%) 8 3/6535 (0%) 3
    Arrhythmia 12/6532 (0.2%) 12 5/6535 (0.1%) 5
    Arteriosclerosis coronary artery 19/6532 (0.3%) 23 15/6535 (0.2%) 20
    Arteriospasm coronary 0/6532 (0%) 0 1/6535 (0%) 1
    Atrial fibrillation 150/6532 (2.3%) 188 89/6535 (1.4%) 103
    Atrial flutter 14/6532 (0.2%) 20 17/6535 (0.3%) 20
    Atrial tachycardia 2/6532 (0%) 3 3/6535 (0%) 5
    Atrioventricular block 2/6532 (0%) 2 1/6535 (0%) 1
    Atrioventricular block complete 7/6532 (0.1%) 7 7/6535 (0.1%) 7
    Atrioventricular block first degree 0/6532 (0%) 0 1/6535 (0%) 1
    Atrioventricular block second degree 4/6532 (0.1%) 4 4/6535 (0.1%) 4
    Atrioventricular dissociation 1/6532 (0%) 1 0/6535 (0%) 0
    Bradyarrhythmia 0/6532 (0%) 0 1/6535 (0%) 1
    Bradycardia 8/6532 (0.1%) 8 9/6535 (0.1%) 10
    Cardiac aneurysm 0/6532 (0%) 0 1/6535 (0%) 1
    Cardiac arrest 19/6532 (0.3%) 19 11/6535 (0.2%) 11
    Cardiac asthma 0/6532 (0%) 0 1/6535 (0%) 1
    Cardiac discomfort 0/6532 (0%) 0 1/6535 (0%) 1
    Cardiac disorder 1/6532 (0%) 1 1/6535 (0%) 1
    Cardiac failure 90/6532 (1.4%) 117 92/6535 (1.4%) 132
    Cardiac failure acute 27/6532 (0.4%) 35 21/6535 (0.3%) 25
    Cardiac failure chronic 18/6532 (0.3%) 21 21/6535 (0.3%) 26
    Cardiac failure congestive 60/6532 (0.9%) 83 59/6535 (0.9%) 77
    Cardiac tamponade 1/6532 (0%) 1 1/6535 (0%) 1
    Cardiac ventricular thrombosis 1/6532 (0%) 1 0/6535 (0%) 0
    Cardio-respiratory arrest 1/6532 (0%) 1 0/6535 (0%) 0
    Cardio-respiratory distress 0/6532 (0%) 0 1/6535 (0%) 1
    Cardiogenic shock 6/6532 (0.1%) 6 1/6535 (0%) 1
    Cardiomyopathy 9/6532 (0.1%) 9 2/6535 (0%) 2
    Cardiopulmonary failure 3/6532 (0%) 3 5/6535 (0.1%) 5
    Cardiovascular deconditioning 1/6532 (0%) 1 0/6535 (0%) 0
    Cardiovascular disorder 0/6532 (0%) 0 1/6535 (0%) 1
    Cardiovascular insufficiency 0/6532 (0%) 0 1/6535 (0%) 1
    Congestive cardiomyopathy 2/6532 (0%) 2 2/6535 (0%) 2
    Coronary artery disease 82/6532 (1.3%) 89 61/6535 (0.9%) 72
    Coronary artery insufficiency 1/6532 (0%) 1 1/6535 (0%) 1
    Coronary artery occlusion 3/6532 (0%) 3 7/6535 (0.1%) 8
    Coronary artery stenosis 3/6532 (0%) 3 8/6535 (0.1%) 8
    Coronary artery thrombosis 0/6532 (0%) 0 2/6535 (0%) 2
    Diastolic dysfunction 1/6532 (0%) 1 0/6535 (0%) 0
    Extrasystoles 1/6532 (0%) 1 1/6535 (0%) 1
    Hypertensive heart disease 1/6532 (0%) 1 0/6535 (0%) 0
    Intracardiac thrombus 1/6532 (0%) 1 0/6535 (0%) 0
    Ischaemic cardiomyopathy 4/6532 (0.1%) 5 10/6535 (0.2%) 11
    Left ventricular dysfunction 3/6532 (0%) 3 4/6535 (0.1%) 4
    Left ventricular failure 6/6532 (0.1%) 6 7/6535 (0.1%) 7
    Metabolic cardiomyopathy 0/6532 (0%) 0 1/6535 (0%) 1
    Mitral valve disease 0/6532 (0%) 0 1/6535 (0%) 2
    Mitral valve incompetence 2/6532 (0%) 2 4/6535 (0.1%) 4
    Myocardial fibrosis 0/6532 (0%) 0 1/6535 (0%) 1
    Myocardial infarction 39/6532 (0.6%) 43 51/6535 (0.8%) 51
    Myocardial ischaemia 27/6532 (0.4%) 28 16/6535 (0.2%) 17
    Myocarditis 1/6532 (0%) 1 0/6535 (0%) 0
    Nodal arrhythmia 1/6532 (0%) 1 0/6535 (0%) 0
    Nodal rhythm 1/6532 (0%) 1 0/6535 (0%) 0
    Palpitations 0/6532 (0%) 0 1/6535 (0%) 1
    Paroxysmal atrioventricular block 1/6532 (0%) 1 1/6535 (0%) 1
    Pericardial effusion 2/6532 (0%) 2 3/6535 (0%) 3
    Pericarditis 1/6532 (0%) 1 5/6535 (0.1%) 5
    Pleuropericarditis 0/6532 (0%) 0 1/6535 (0%) 1
    Postinfarction angina 1/6532 (0%) 1 0/6535 (0%) 0
    Pulmonary valve stenosis 0/6532 (0%) 0 1/6535 (0%) 2
    Pulseless electrical activity 0/6532 (0%) 0 4/6535 (0.1%) 5
    Right ventricular failure 0/6532 (0%) 0 1/6535 (0%) 1
    Silent myocardial infarction 0/6532 (0%) 0 1/6535 (0%) 1
    Sinoatrial block 0/6532 (0%) 0 1/6535 (0%) 1
    Sinus arrest 1/6532 (0%) 1 0/6535 (0%) 0
    Sinus bradycardia 3/6532 (0%) 3 0/6535 (0%) 0
    Sinus node dysfunction 6/6532 (0.1%) 6 5/6535 (0.1%) 5
    Sinus tachycardia 0/6532 (0%) 0 2/6535 (0%) 2
    Supraventricular extrasystoles 0/6532 (0%) 0 1/6535 (0%) 1
    Supraventricular tachycardia 6/6532 (0.1%) 6 5/6535 (0.1%) 5
    Tachyarrhythmia 0/6532 (0%) 0 2/6535 (0%) 2
    Tachycardia 0/6532 (0%) 0 3/6535 (0%) 3
    Ventricular arrhythmia 1/6532 (0%) 1 1/6535 (0%) 1
    Ventricular dysfunction 0/6532 (0%) 0 1/6535 (0%) 1
    Ventricular extrasystoles 5/6532 (0.1%) 5 5/6535 (0.1%) 5
    Ventricular fibrillation 7/6532 (0.1%) 8 8/6535 (0.1%) 8
    Ventricular tachycardia 13/6532 (0.2%) 14 14/6535 (0.2%) 16
    Congenital, familial and genetic disorders
    Arteriovenous malformation 0/6532 (0%) 0 1/6535 (0%) 1
    Atrial septal defect 0/6532 (0%) 0 1/6535 (0%) 1
    Cerebrovascular arteriovenous malformation 0/6532 (0%) 0 1/6535 (0%) 1
    Familial mediterranean fever 0/6532 (0%) 0 1/6535 (0%) 1
    Gastrointestinal arteriovenous malformation 0/6532 (0%) 0 1/6535 (0%) 1
    Hypertrophic cardiomyopathy 1/6532 (0%) 1 0/6535 (0%) 0
    Phimosis 4/6532 (0.1%) 4 1/6535 (0%) 1
    Porokeratosis 1/6532 (0%) 1 0/6535 (0%) 0
    Pyloric stenosis 1/6532 (0%) 2 0/6535 (0%) 0
    Ear and labyrinth disorders
    Deafness 0/6532 (0%) 0 2/6535 (0%) 2
    Deafness neurosensory 0/6532 (0%) 0 2/6535 (0%) 3
    Deafness unilateral 1/6532 (0%) 1 0/6535 (0%) 0
    Hypoacusis 1/6532 (0%) 1 1/6535 (0%) 1
    Otolithiasis 0/6532 (0%) 0 2/6535 (0%) 2
    Sudden hearing loss 0/6532 (0%) 0 1/6535 (0%) 2
    Tinnitus 1/6532 (0%) 1 1/6535 (0%) 2
    Vertigo 12/6532 (0.2%) 13 11/6535 (0.2%) 11
    Vertigo positional 1/6532 (0%) 1 2/6535 (0%) 2
    Vestibular disorder 1/6532 (0%) 1 2/6535 (0%) 2
    Endocrine disorders
    Acromegaly 0/6532 (0%) 0 1/6535 (0%) 1
    Adrenal mass 1/6532 (0%) 1 1/6535 (0%) 1
    Goitre 4/6532 (0.1%) 4 8/6535 (0.1%) 8
    Hyperparathyroidism primary 1/6532 (0%) 1 1/6535 (0%) 1
    Hyperthyroidism 2/6532 (0%) 2 1/6535 (0%) 1
    Hypothyroidism 0/6532 (0%) 0 2/6535 (0%) 2
    Parathyroid disorder 0/6532 (0%) 0 1/6535 (0%) 1
    Thyroid mass 0/6532 (0%) 0 1/6535 (0%) 1
    Eye disorders
    Cataract 29/6532 (0.4%) 35 20/6535 (0.3%) 24
    Conjunctival erosion 1/6532 (0%) 1 0/6535 (0%) 0
    Conjunctivochalasis 1/6532 (0%) 1 0/6535 (0%) 0
    Corneal erosion 1/6532 (0%) 1 0/6535 (0%) 0
    Dacryostenosis acquired 1/6532 (0%) 1 0/6535 (0%) 0
    Diabetic retinopathy 1/6532 (0%) 1 0/6535 (0%) 0
    Diplopia 0/6532 (0%) 0 1/6535 (0%) 1
    Exophthalmos 0/6532 (0%) 0 1/6535 (0%) 1
    Eyelid ptosis 0/6532 (0%) 0 2/6535 (0%) 2
    Glaucoma 4/6532 (0.1%) 5 1/6535 (0%) 1
    Iridocyclitis 1/6532 (0%) 1 0/6535 (0%) 0
    Macular hole 2/6532 (0%) 2 0/6535 (0%) 0
    Maculopathy 1/6532 (0%) 1 0/6535 (0%) 0
    Open angle glaucoma 2/6532 (0%) 2 0/6535 (0%) 0
    Optic ischaemic neuropathy 1/6532 (0%) 1 0/6535 (0%) 0
    Retinal artery embolism 2/6532 (0%) 2 0/6535 (0%) 0
    Retinal artery occlusion 2/6532 (0%) 2 1/6535 (0%) 1
    Retinal detachment 1/6532 (0%) 1 2/6535 (0%) 2
    Retinal haemorrhage 1/6532 (0%) 1 1/6535 (0%) 1
    Retinal tear 2/6532 (0%) 2 0/6535 (0%) 0
    Retinal vein occlusion 1/6532 (0%) 1 0/6535 (0%) 0
    Retinopathy 0/6532 (0%) 0 1/6535 (0%) 1
    Rhegmatogenous retinal detachment 0/6532 (0%) 0 1/6535 (0%) 3
    Tractional retinal detachment 0/6532 (0%) 0 1/6535 (0%) 2
    Vitreous detachment 1/6532 (0%) 1 0/6535 (0%) 0
    Vitreous disorder 1/6532 (0%) 1 0/6535 (0%) 0
    Vitreous haemorrhage 2/6532 (0%) 2 1/6535 (0%) 1
    Gastrointestinal disorders
    Abdominal adhesions 1/6532 (0%) 1 2/6535 (0%) 2
    Abdominal discomfort 0/6532 (0%) 0 1/6535 (0%) 1
    Abdominal distension 0/6532 (0%) 0 1/6535 (0%) 1
    Abdominal hernia 5/6532 (0.1%) 5 5/6535 (0.1%) 5
    Abdominal hernia obstructive 0/6532 (0%) 0 1/6535 (0%) 1
    Abdominal incarcerated hernia 0/6532 (0%) 0 1/6535 (0%) 1
    Abdominal pain 8/6532 (0.1%) 9 9/6535 (0.1%) 11
    Abdominal pain lower 2/6532 (0%) 2 0/6535 (0%) 0
    Abdominal pain upper 3/6532 (0%) 3 3/6535 (0%) 3
    Abdominal wall haematoma 1/6532 (0%) 1 0/6535 (0%) 0
    Alcoholic pancreatitis 0/6532 (0%) 0 1/6535 (0%) 1
    Anal fistula 2/6532 (0%) 2 0/6535 (0%) 0
    Anal haemorrhage 1/6532 (0%) 1 0/6535 (0%) 0
    Anal stenosis 0/6532 (0%) 0 1/6535 (0%) 1
    Anogenital dysplasia 1/6532 (0%) 1 0/6535 (0%) 0
    Ascites 1/6532 (0%) 1 0/6535 (0%) 0
    Barrett's oesophagus 1/6532 (0%) 1 0/6535 (0%) 0
    Chronic gastritis 3/6532 (0%) 3 7/6535 (0.1%) 8
    Coeliac artery stenosis 1/6532 (0%) 1 0/6535 (0%) 0
    Colitis 7/6532 (0.1%) 7 7/6535 (0.1%) 8
    Colitis ischaemic 3/6532 (0%) 3 2/6535 (0%) 2
    Colitis ulcerative 1/6532 (0%) 1 3/6535 (0%) 4
    Colonic fistula 1/6532 (0%) 1 0/6535 (0%) 0
    Constipation 6/6532 (0.1%) 7 5/6535 (0.1%) 5
    Crohn's disease 2/6532 (0%) 2 0/6535 (0%) 0
    Dental cyst 2/6532 (0%) 2 0/6535 (0%) 0
    Diabetic gastroparesis 1/6532 (0%) 1 0/6535 (0%) 0
    Diabetic gastropathy 1/6532 (0%) 1 1/6535 (0%) 1
    Diaphragmatic hernia 1/6532 (0%) 1 0/6535 (0%) 0
    Diarrhoea 21/6532 (0.3%) 21 10/6535 (0.2%) 11
    Dieulafoy's vascular malformation 1/6532 (0%) 1 1/6535 (0%) 1
    Diverticular perforation 0/6532 (0%) 0 1/6535 (0%) 1
    Diverticulum 3/6532 (0%) 3 4/6535 (0.1%) 4
    Diverticulum intestinal 3/6532 (0%) 3 0/6535 (0%) 0
    Diverticulum intestinal haemorrhagic 1/6532 (0%) 1 3/6535 (0%) 3
    Duodenal perforation 1/6532 (0%) 1 0/6535 (0%) 0
    Duodenal polyp 1/6532 (0%) 1 1/6535 (0%) 1
    Duodenal ulcer 5/6532 (0.1%) 5 3/6535 (0%) 3
    Duodenal ulcer haemorrhage 4/6532 (0.1%) 4 3/6535 (0%) 3
    Duodenal ulcer perforation 1/6532 (0%) 1 0/6535 (0%) 0
    Duodenitis 2/6532 (0%) 2 0/6535 (0%) 0
    Duodenogastric reflux 1/6532 (0%) 1 0/6535 (0%) 0
    Dysbiosis 0/6532 (0%) 0 1/6535 (0%) 1
    Dyspepsia 2/6532 (0%) 2 1/6535 (0%) 1
    Dysphagia 2/6532 (0%) 2 1/6535 (0%) 1
    Enteritis 1/6532 (0%) 1 1/6535 (0%) 1
    Enterocolitis 0/6532 (0%) 0 2/6535 (0%) 2
    Enterovesical fistula 0/6532 (0%) 0 1/6535 (0%) 1
    Erosive duodenitis 0/6532 (0%) 0 1/6535 (0%) 1
    Faecaloma 0/6532 (0%) 0 2/6535 (0%) 2
    Functional gastrointestinal disorder 1/6532 (0%) 1 0/6535 (0%) 0
    Gastric disorder 0/6532 (0%) 0 1/6535 (0%) 1
    Gastric haemorrhage 1/6532 (0%) 1 0/6535 (0%) 0
    Gastric polyps 3/6532 (0%) 3 2/6535 (0%) 2
    Gastric ulcer 5/6532 (0.1%) 5 1/6535 (0%) 1
    Gastric ulcer haemorrhage 4/6532 (0.1%) 4 1/6535 (0%) 1
    Gastric ulcer perforation 0/6532 (0%) 0 1/6535 (0%) 1
    Gastritis 9/6532 (0.1%) 9 8/6535 (0.1%) 8
    Gastritis erosive 6/6532 (0.1%) 6 3/6535 (0%) 3
    Gastritis haemorrhagic 1/6532 (0%) 1 1/6535 (0%) 1
    Gastroduodenal ulcer 1/6532 (0%) 1 0/6535 (0%) 0
    Gastrointestinal disorder 2/6532 (0%) 2 0/6535 (0%) 0
    Gastrointestinal erosion 0/6532 (0%) 0 1/6535 (0%) 1
    Gastrointestinal haemorrhage 24/6532 (0.4%) 31 10/6535 (0.2%) 11
    Gastrointestinal inflammation 0/6532 (0%) 0 1/6535 (0%) 1
    Gastrointestinal pain 1/6532 (0%) 1 1/6535 (0%) 1
    Gastrointestinal polyp haemorrhage 1/6532 (0%) 1 2/6535 (0%) 2
    Gastrointestinal ulcer haemorrhage 0/6532 (0%) 0 1/6535 (0%) 1
    Gastrointestinal vascular malformation haemorrhagic 1/6532 (0%) 1 1/6535 (0%) 1
    Gastrooesophageal reflux disease 7/6532 (0.1%) 7 7/6535 (0.1%) 7
    Gingival bleeding 1/6532 (0%) 1 0/6535 (0%) 0
    Haematemesis 2/6532 (0%) 2 1/6535 (0%) 1
    Haematochezia 4/6532 (0.1%) 4 1/6535 (0%) 1
    Haemorrhagic erosive gastritis 1/6532 (0%) 1 0/6535 (0%) 0
    Haemorrhoidal haemorrhage 2/6532 (0%) 2 6/6535 (0.1%) 7
    Haemorrhoids 5/6532 (0.1%) 5 5/6535 (0.1%) 5
    Haemorrhoids thrombosed 0/6532 (0%) 0 3/6535 (0%) 4
    Hiatus hernia 4/6532 (0.1%) 4 1/6535 (0%) 1
    Ileus 3/6532 (0%) 3 1/6535 (0%) 1
    Ileus paralytic 0/6532 (0%) 0 1/6535 (0%) 1
    Incarcerated inguinal hernia 0/6532 (0%) 0 1/6535 (0%) 1
    Inguinal hernia 18/6532 (0.3%) 19 11/6535 (0.2%) 12
    Intestinal haemorrhage 1/6532 (0%) 1 0/6535 (0%) 0
    Intestinal ischaemia 1/6532 (0%) 1 1/6535 (0%) 1
    Intestinal mass 1/6532 (0%) 1 1/6535 (0%) 1
    Intestinal obstruction 7/6532 (0.1%) 7 4/6535 (0.1%) 4
    Intestinal perforation 2/6532 (0%) 3 0/6535 (0%) 0
    Intestinal polyp 1/6532 (0%) 1 3/6535 (0%) 3
    Intestinal pseudo-obstruction 0/6532 (0%) 0 1/6535 (0%) 1
    Intra-abdominal haemorrhage 1/6532 (0%) 1 0/6535 (0%) 0
    Irritable bowel syndrome 0/6532 (0%) 0 2/6535 (0%) 2
    Large intestinal obstruction 1/6532 (0%) 1 1/6535 (0%) 1
    Large intestinal stenosis 1/6532 (0%) 1 0/6535 (0%) 0
    Large intestine perforation 0/6532 (0%) 0 1/6535 (0%) 1
    Large intestine polyp 14/6532 (0.2%) 15 13/6535 (0.2%) 19
    Lower gastrointestinal haemorrhage 1/6532 (0%) 1 2/6535 (0%) 2
    Mechanical ileus 0/6532 (0%) 0 2/6535 (0%) 2
    Melaena 1/6532 (0%) 1 0/6535 (0%) 0
    Mesenteric artery stenosis 1/6532 (0%) 1 1/6535 (0%) 1
    Mesenteric haemorrhage 0/6532 (0%) 0 1/6535 (0%) 1
    Mesenteric vascular insufficiency 1/6532 (0%) 1 0/6535 (0%) 0
    Mouth haemorrhage 0/6532 (0%) 0 1/6535 (0%) 1
    Nausea 4/6532 (0.1%) 4 3/6535 (0%) 3
    Noninfective sialoadenitis 0/6532 (0%) 0 2/6535 (0%) 2
    Obstructive pancreatitis 3/6532 (0%) 3 0/6535 (0%) 0
    Oedematous pancreatitis 0/6532 (0%) 0 1/6535 (0%) 1
    Oesophageal achalasia 1/6532 (0%) 1 0/6535 (0%) 0
    Oesophageal spasm 1/6532 (0%) 1 2/6535 (0%) 2
    Oesophageal stenosis 0/6532 (0%) 0 1/6535 (0%) 1
    Oesophageal varices haemorrhage 0/6532 (0%) 0 1/6535 (0%) 1
    Oesophagitis 2/6532 (0%) 2 1/6535 (0%) 1
    Pancreatic disorder 1/6532 (0%) 1 0/6535 (0%) 0
    Pancreatitis 11/6532 (0.2%) 11 10/6535 (0.2%) 10
    Pancreatitis acute 12/6532 (0.2%) 16 11/6535 (0.2%) 11
    Pancreatitis chronic 0/6532 (0%) 0 3/6535 (0%) 3
    Peptic ulcer 0/6532 (0%) 0 3/6535 (0%) 3
    Peptic ulcer haemorrhage 0/6532 (0%) 0 1/6535 (0%) 1
    Pharyngo-oesophageal diverticulum 0/6532 (0%) 0 1/6535 (0%) 1
    Pneumatosis intestinalis 1/6532 (0%) 1 0/6535 (0%) 0
    Rectal haemorrhage 7/6532 (0.1%) 8 5/6535 (0.1%) 5
    Rectal polyp 0/6532 (0%) 0 1/6535 (0%) 2
    Rectal prolapse 1/6532 (0%) 1 0/6535 (0%) 0
    Reflux gastritis 1/6532 (0%) 1 0/6535 (0%) 0
    Retroperitoneal fibrosis 1/6532 (0%) 3 0/6535 (0%) 0
    Retroperitoneal haematoma 1/6532 (0%) 1 0/6535 (0%) 0
    Retroperitoneal haemorrhage 1/6532 (0%) 1 0/6535 (0%) 0
    Retroperitoneal mass 1/6532 (0%) 1 0/6535 (0%) 0
    Small intestinal obstruction 5/6532 (0.1%) 6 9/6535 (0.1%) 12
    Thrombosis mesenteric vessel 1/6532 (0%) 1 0/6535 (0%) 0
    Tongue cyst 0/6532 (0%) 0 1/6535 (0%) 1
    Umbilical hernia 5/6532 (0.1%) 5 2/6535 (0%) 2
    Upper gastrointestinal haemorrhage 12/6532 (0.2%) 12 3/6535 (0%) 3
    Volvulus 1/6532 (0%) 1 0/6535 (0%) 0
    Volvulus of small bowel 0/6532 (0%) 0 1/6535 (0%) 1
    Vomiting 8/6532 (0.1%) 9 1/6535 (0%) 1
    General disorders
    Adverse drug reaction 1/6532 (0%) 1 1/6535 (0%) 1
    Adverse event 0/6532 (0%) 0 1/6535 (0%) 1
    Asthenia 1/6532 (0%) 1 2/6535 (0%) 2
    Cardiac death 3/6532 (0%) 3 3/6535 (0%) 3
    Catheter site haemorrhage 1/6532 (0%) 1 0/6535 (0%) 0
    Chest discomfort 2/6532 (0%) 2 4/6535 (0.1%) 4
    Chest pain 10/6532 (0.2%) 10 23/6535 (0.4%) 23
    Complication associated with device 1/6532 (0%) 1 1/6535 (0%) 1
    Cyst 0/6532 (0%) 0 1/6535 (0%) 1
    Death 57/6532 (0.9%) 57 38/6535 (0.6%) 38
    Decreased activity 0/6532 (0%) 0 1/6535 (0%) 1
    Device related thrombosis 0/6532 (0%) 0 1/6535 (0%) 1
    Drowning 0/6532 (0%) 0 1/6535 (0%) 1
    Drug intolerance 1/6532 (0%) 1 1/6535 (0%) 1
    Exercise tolerance decreased 2/6532 (0%) 2 0/6535 (0%) 0
    Fatigue 0/6532 (0%) 0 1/6535 (0%) 1
    Gait disturbance 1/6532 (0%) 1 1/6535 (0%) 1
    General physical health deterioration 2/6532 (0%) 2 0/6535 (0%) 0
    Generalised oedema 0/6532 (0%) 0 1/6535 (0%) 1
    Hernia 0/6532 (0%) 0 1/6535 (0%) 1
    Impaired healing 0/6532 (0%) 0 2/6535 (0%) 2
    Implant site haematoma 1/6532 (0%) 1 0/6535 (0%) 0
    Implant site inflammation 1/6532 (0%) 1 0/6535 (0%) 0
    Inflammation 1/6532 (0%) 1 0/6535 (0%) 0
    Injection site phlebitis 0/6532 (0%) 0 1/6535 (0%) 1
    Malaise 0/6532 (0%) 0 2/6535 (0%) 2
    Medical device site haematoma 0/6532 (0%) 0 1/6535 (0%) 1
    Mucosal inflammation 1/6532 (0%) 1 0/6535 (0%) 0
    Multi-organ disorder 1/6532 (0%) 1 0/6535 (0%) 0
    Multiple organ dysfunction syndrome 5/6532 (0.1%) 5 2/6535 (0%) 2
    No adverse event 1/6532 (0%) 1 0/6535 (0%) 0
    Nodule 0/6532 (0%) 0 1/6535 (0%) 1
    Non-cardiac chest pain 51/6532 (0.8%) 69 51/6535 (0.8%) 53
    Oedema peripheral 0/6532 (0%) 0 3/6535 (0%) 4
    Organ failure 1/6532 (0%) 1 0/6535 (0%) 0
    Pelvic mass 0/6532 (0%) 0 1/6535 (0%) 1
    Perforation 0/6532 (0%) 0 1/6535 (0%) 1
    Peripheral swelling 2/6532 (0%) 2 3/6535 (0%) 3
    Pyrexia 3/6532 (0%) 3 4/6535 (0.1%) 4
    Retention cyst 1/6532 (0%) 1 0/6535 (0%) 0
    Stent-graft endoleak 1/6532 (0%) 1 1/6535 (0%) 1
    Sudden cardiac death 5/6532 (0.1%) 5 4/6535 (0.1%) 4
    Sudden death 4/6532 (0.1%) 4 3/6535 (0%) 3
    Surgical failure 1/6532 (0%) 1 1/6535 (0%) 1
    Systemic inflammatory response syndrome 0/6532 (0%) 0 1/6535 (0%) 1
    Ulcer haemorrhage 1/6532 (0%) 1 0/6535 (0%) 0
    Unevaluable event 1/6532 (0%) 1 0/6535 (0%) 0
    Vascular stent occlusion 1/6532 (0%) 1 0/6535 (0%) 0
    Vascular stent stenosis 3/6532 (0%) 3 2/6535 (0%) 2
    Vascular stent thrombosis 1/6532 (0%) 1 5/6535 (0.1%) 5
    Hepatobiliary disorders
    Bile duct stenosis 1/6532 (0%) 2 0/6535 (0%) 0
    Bile duct stone 4/6532 (0.1%) 6 3/6535 (0%) 3
    Biliary colic 0/6532 (0%) 0 1/6535 (0%) 1
    Biliary tract disorder 1/6532 (0%) 1 0/6535 (0%) 0
    Cholangitis 6/6532 (0.1%) 6 5/6535 (0.1%) 5
    Cholangitis acute 2/6532 (0%) 2 2/6535 (0%) 2
    Cholecystitis 13/6532 (0.2%) 13 17/6535 (0.3%) 18
    Cholecystitis acute 20/6532 (0.3%) 20 12/6535 (0.2%) 13
    Cholecystitis chronic 4/6532 (0.1%) 4 4/6535 (0.1%) 5
    Cholelithiasis 27/6532 (0.4%) 28 15/6535 (0.2%) 16
    Chronic hepatitis 1/6532 (0%) 1 0/6535 (0%) 0
    Hepatic cirrhosis 3/6532 (0%) 3 2/6535 (0%) 2
    Hepatic failure 0/6532 (0%) 0 2/6535 (0%) 2
    Hepatic steatosis 1/6532 (0%) 1 2/6535 (0%) 2
    Hepatitis 1/6532 (0%) 1 1/6535 (0%) 1
    Hyperbilirubinaemia 1/6532 (0%) 1 0/6535 (0%) 0
    Ischaemic hepatitis 1/6532 (0%) 1 0/6535 (0%) 0
    Jaundice 0/6532 (0%) 0 1/6535 (0%) 1
    Jaundice cholestatic 0/6532 (0%) 0 1/6535 (0%) 1
    Liver disorder 0/6532 (0%) 0 1/6535 (0%) 1
    Non-alcoholic steatohepatitis 2/6532 (0%) 2 1/6535 (0%) 1
    Nonalcoholic fatty liver disease 2/6532 (0%) 2 1/6535 (0%) 1
    Portal vein thrombosis 0/6532 (0%) 0 1/6535 (0%) 1
    Post cholecystectomy syndrome 0/6532 (0%) 0 1/6535 (0%) 1
    Immune system disorders
    Anaphylactic reaction 1/6532 (0%) 1 3/6535 (0%) 3
    Anaphylactic shock 1/6532 (0%) 1 1/6535 (0%) 1
    Contrast media allergy 0/6532 (0%) 0 1/6535 (0%) 1
    Drug hypersensitivity 2/6532 (0%) 2 1/6535 (0%) 1
    Heart transplant rejection 0/6532 (0%) 0 1/6535 (0%) 2
    Hypersensitivity 0/6532 (0%) 0 1/6535 (0%) 1
    Kidney transplant rejection 1/6532 (0%) 1 0/6535 (0%) 0
    Sarcoidosis 0/6532 (0%) 0 1/6535 (0%) 1
    Infections and infestations
    Abdominal abscess 2/6532 (0%) 2 1/6535 (0%) 1
    Abdominal wall abscess 2/6532 (0%) 2 2/6535 (0%) 3
    Abdominal wall infection 0/6532 (0%) 0 1/6535 (0%) 1
    Abscess 1/6532 (0%) 1 0/6535 (0%) 0
    Abscess limb 4/6532 (0.1%) 4 6/6535 (0.1%) 6
    Acarodermatitis 0/6532 (0%) 0 1/6535 (0%) 1
    Acquired immunodeficiency syndrome 0/6532 (0%) 0 1/6535 (0%) 1
    Acute hepatitis b 1/6532 (0%) 1 0/6535 (0%) 0
    Acute sinusitis 1/6532 (0%) 1 3/6535 (0%) 4
    Adenovirus infection 1/6532 (0%) 1 1/6535 (0%) 1
    Anal abscess 1/6532 (0%) 1 3/6535 (0%) 3
    Appendicitis 9/6532 (0.1%) 9 14/6535 (0.2%) 14
    Appendicitis perforated 5/6532 (0.1%) 5 1/6535 (0%) 1
    Arthritis bacterial 0/6532 (0%) 0 4/6535 (0.1%) 4
    Arthritis infective 2/6532 (0%) 2 1/6535 (0%) 1
    Atypical pneumonia 1/6532 (0%) 1 1/6535 (0%) 1
    Bacteraemia 4/6532 (0.1%) 4 4/6535 (0.1%) 4
    Bacterial colitis 0/6532 (0%) 0 1/6535 (0%) 1
    Bacterial infection 1/6532 (0%) 1 0/6535 (0%) 0
    Bacterial prostatitis 0/6532 (0%) 0 1/6535 (0%) 1
    Beta haemolytic streptococcal infection 1/6532 (0%) 1 0/6535 (0%) 0
    Biliary sepsis 1/6532 (0%) 1 2/6535 (0%) 2
    Borrelia infection 0/6532 (0%) 0 1/6535 (0%) 1
    Breast abscess 2/6532 (0%) 2 1/6535 (0%) 1
    Bronchitis 10/6532 (0.2%) 11 23/6535 (0.4%) 23
    Bronchitis viral 1/6532 (0%) 1 3/6535 (0%) 3
    Bursitis infective 0/6532 (0%) 0 1/6535 (0%) 1
    Campylobacter colitis 1/6532 (0%) 1 1/6535 (0%) 1
    Campylobacter gastroenteritis 2/6532 (0%) 2 0/6535 (0%) 0
    Candida pneumonia 1/6532 (0%) 1 0/6535 (0%) 0
    Carbuncle 1/6532 (0%) 1 0/6535 (0%) 0
    Cellulitis 39/6532 (0.6%) 46 46/6535 (0.7%) 52
    Cellulitis of male external genital organ 2/6532 (0%) 2 0/6535 (0%) 0
    Cellulitis staphylococcal 1/6532 (0%) 1 1/6535 (0%) 1
    Chest wall abscess 1/6532 (0%) 1 1/6535 (0%) 1
    Cholangitis infective 1/6532 (0%) 1 0/6535 (0%) 0
    Cholecystitis infective 1/6532 (0%) 1 3/6535 (0%) 4
    Chronic sinusitis 1/6532 (0%) 1 0/6535 (0%) 0
    Clostridium difficile colitis 2/6532 (0%) 2 1/6535 (0%) 1
    Clostridium difficile infection 1/6532 (0%) 1 0/6535 (0%) 0
    Cystitis 4/6532 (0.1%) 5 1/6535 (0%) 1
    Dermatitis infected 0/6532 (0%) 0 1/6535 (0%) 1
    Device related infection 2/6532 (0%) 4 2/6535 (0%) 2
    Diabetic foot infection 1/6532 (0%) 1 3/6535 (0%) 4
    Diabetic gangrene 1/6532 (0%) 1 0/6535 (0%) 0
    Diarrhoea infectious 1/6532 (0%) 1 0/6535 (0%) 0
    Diverticulitis 13/6532 (0.2%) 16 9/6535 (0.1%) 12
    Diverticulitis intestinal haemorrhagic 1/6532 (0%) 1 0/6535 (0%) 0
    Dysentery 1/6532 (0%) 1 0/6535 (0%) 0
    Emphysematous pyelonephritis 1/6532 (0%) 1 1/6535 (0%) 1
    Empyema 0/6532 (0%) 0 1/6535 (0%) 1
    Endocarditis 1/6532 (0%) 1 2/6535 (0%) 2
    Endocarditis bacterial 1/6532 (0%) 1 0/6535 (0%) 0
    Enterococcal sepsis 1/6532 (0%) 1 0/6535 (0%) 0
    Epidemic pleurodynia 1/6532 (0%) 1 0/6535 (0%) 0
    Epididymitis 1/6532 (0%) 2 0/6535 (0%) 0
    Erysipelas 6/6532 (0.1%) 10 6/6535 (0.1%) 7
    Escherichia bacteraemia 1/6532 (0%) 1 0/6535 (0%) 0
    Escherichia infection 0/6532 (0%) 0 1/6535 (0%) 1
    Escherichia pyelonephritis 1/6532 (0%) 1 0/6535 (0%) 0
    Escherichia sepsis 2/6532 (0%) 2 0/6535 (0%) 0
    Escherichia urinary tract infection 0/6532 (0%) 0 2/6535 (0%) 2
    External ear cellulitis 1/6532 (0%) 1 0/6535 (0%) 0
    Extradural abscess 1/6532 (0%) 1 0/6535 (0%) 0
    Folliculitis 0/6532 (0%) 0 1/6535 (0%) 1
    Fournier's gangrene 1/6532 (0%) 1 0/6535 (0%) 0
    Fungal infection 1/6532 (0%) 1 0/6535 (0%) 0
    Gallbladder abscess 1/6532 (0%) 1 0/6535 (0%) 0
    Gallbladder empyema 1/6532 (0%) 1 0/6535 (0%) 0
    Gangrene 7/6532 (0.1%) 7 9/6535 (0.1%) 11
    Gastroenteritis 15/6532 (0.2%) 16 20/6535 (0.3%) 20
    Gastroenteritis clostridial 1/6532 (0%) 1 1/6535 (0%) 1
    Gastroenteritis viral 4/6532 (0.1%) 5 4/6535 (0.1%) 4
    Gastrointestinal infection 0/6532 (0%) 0 1/6535 (0%) 1
    Gastrointestinal viral infection 1/6532 (0%) 1 1/6535 (0%) 1
    Genitourinary tract infection 1/6532 (0%) 1 0/6535 (0%) 0
    Graft infection 1/6532 (0%) 1 0/6535 (0%) 0
    Groin abscess 3/6532 (0%) 3 0/6535 (0%) 0
    Hiv infection 1/6532 (0%) 1 0/6535 (0%) 0
    Haematoma infection 1/6532 (0%) 1 0/6535 (0%) 0
    Helicobacter gastritis 1/6532 (0%) 1 0/6535 (0%) 0
    Hepatic cyst infection 0/6532 (0%) 0 1/6535 (0%) 1
    Hepatitis c 0/6532 (0%) 0 3/6535 (0%) 3
    Herpes zoster 4/6532 (0.1%) 4 4/6535 (0.1%) 4
    Implant site infection 0/6532 (0%) 0 2/6535 (0%) 2
    Incision site cellulitis 0/6532 (0%) 0 1/6535 (0%) 1
    Infected cyst 1/6532 (0%) 1 0/6535 (0%) 0
    Infected dermal cyst 1/6532 (0%) 1 0/6535 (0%) 0
    Infected skin ulcer 1/6532 (0%) 1 1/6535 (0%) 1
    Infection 0/6532 (0%) 0 1/6535 (0%) 1
    Infectious pleural effusion 1/6532 (0%) 1 0/6535 (0%) 0
    Infective aneurysm 0/6532 (0%) 0 1/6535 (0%) 1
    Infective exacerbation of chronic obstructive airways disease 2/6532 (0%) 2 3/6535 (0%) 3
    Infective tenosynovitis 1/6532 (0%) 1 0/6535 (0%) 0
    Influenza 12/6532 (0.2%) 13 15/6535 (0.2%) 15
    Intervertebral discitis 1/6532 (0%) 1 0/6535 (0%) 0
    Intestinal gangrene 0/6532 (0%) 0 1/6535 (0%) 1
    Kidney infection 0/6532 (0%) 0 1/6535 (0%) 1
    Klebsiella infection 0/6532 (0%) 0 1/6535 (0%) 1
    Large intestine infection 0/6532 (0%) 0 1/6535 (0%) 1
    Laryngitis 0/6532 (0%) 0 1/6535 (0%) 1
    Liver abscess 3/6532 (0%) 6 2/6535 (0%) 2
    Localised infection 1/6532 (0%) 1 5/6535 (0.1%) 9
    Lower respiratory tract infection 8/6532 (0.1%) 8 12/6535 (0.2%) 13
    Lower respiratory tract infection bacterial 1/6532 (0%) 1 0/6535 (0%) 0
    Lyme disease 2/6532 (0%) 2 0/6535 (0%) 0
    Lymphangitis 0/6532 (0%) 0 1/6535 (0%) 1
    Mastitis 0/6532 (0%) 0 1/6535 (0%) 1
    Mediastinitis 2/6532 (0%) 2 0/6535 (0%) 0
    Medical device site abscess 0/6532 (0%) 0 1/6535 (0%) 1
    Medical device site infection 1/6532 (0%) 1 1/6535 (0%) 1
    Medical device site joint infection 1/6532 (0%) 1 0/6535 (0%) 0
    Meningitis 0/6532 (0%) 0 1/6535 (0%) 1
    Meningitis bacterial 0/6532 (0%) 0 2/6535 (0%) 3
    Meningoencephalitis herpetic 1/6532 (0%) 1 0/6535 (0%) 0
    Moraxella infection 0/6532 (0%) 0 1/6535 (0%) 1
    Mycetoma mycotic 1/6532 (0%) 1 0/6535 (0%) 0
    Nasopharyngitis 1/6532 (0%) 1 0/6535 (0%) 0
    Necrotising fasciitis 2/6532 (0%) 2 0/6535 (0%) 0
    Oesophageal candidiasis 2/6532 (0%) 2 1/6535 (0%) 1
    Orchitis 1/6532 (0%) 1 1/6535 (0%) 1
    Osteomyelitis 9/6532 (0.1%) 11 12/6535 (0.2%) 16
    Osteomyelitis acute 0/6532 (0%) 0 1/6535 (0%) 1
    Osteomyelitis chronic 0/6532 (0%) 0 1/6535 (0%) 1
    Otitis externa 0/6532 (0%) 0 1/6535 (0%) 1
    Otitis media 1/6532 (0%) 1 1/6535 (0%) 1
    Otitis media acute 2/6532 (0%) 2 0/6535 (0%) 0
    Otitis media bacterial 0/6532 (0%) 0 1/6535 (0%) 1
    Otitis media chronic 0/6532 (0%) 0 1/6535 (0%) 1
    Parainfluenzae virus infection 0/6532 (0%) 0 1/6535 (0%) 1
    Parotitis 0/6532 (0%) 0 2/6535 (0%) 2
    Pelvic infection 0/6532 (0%) 0 1/6535 (0%) 1
    Perineal abscess 0/6532 (0%) 0 1/6535 (0%) 1
    Periodontitis 0/6532 (0%) 0 1/6535 (0%) 1
    Perirectal abscess 2/6532 (0%) 2 0/6535 (0%) 0
    Peritonitis 1/6532 (0%) 1 3/6535 (0%) 3
    Peritonsillitis 1/6532 (0%) 1 0/6535 (0%) 0
    Pilonidal cyst 1/6532 (0%) 1 1/6535 (0%) 1
    Pneumonia 113/6532 (1.7%) 130 126/6535 (1.9%) 135
    Pneumonia bacterial 1/6532 (0%) 1 2/6535 (0%) 2
    Pneumonia haemophilus 1/6532 (0%) 1 1/6535 (0%) 1
    Pneumonia legionella 1/6532 (0%) 1 1/6535 (0%) 1
    Pneumonia pseudomonal 0/6532 (0%) 0 1/6535 (0%) 1
    Pneumonia staphylococcal 0/6532 (0%) 0 1/6535 (0%) 1
    Pneumonia streptococcal 2/6532 (0%) 2 0/6535 (0%) 0
    Pneumonia viral 2/6532 (0%) 2 0/6535 (0%) 0
    Post procedural cellulitis 0/6532 (0%) 0 1/6535 (0%) 1
    Post procedural sepsis 4/6532 (0.1%) 4 1/6535 (0%) 1
    Postoperative abscess 2/6532 (0%) 2 0/6535 (0%) 0
    Postoperative wound infection 8/6532 (0.1%) 8 2/6535 (0%) 2
    Pseudomonas infection 1/6532 (0%) 1 0/6535 (0%) 0
    Psoas abscess 1/6532 (0%) 1 0/6535 (0%) 0
    Pulmonary nocardiosis 0/6532 (0%) 0 1/6535 (0%) 1
    Pulmonary sepsis 1/6532 (0%) 1 1/6535 (0%) 1
    Pyelonephritis 9/6532 (0.1%) 9 12/6535 (0.2%) 12
    Pyelonephritis acute 7/6532 (0.1%) 9 3/6535 (0%) 3
    Pyelonephritis chronic 5/6532 (0.1%) 5 1/6535 (0%) 1
    Rectal abscess 1/6532 (0%) 1 0/6535 (0%) 0
    Renal abscess 1/6532 (0%) 1 0/6535 (0%) 0
    Renal cyst infection 0/6532 (0%) 0 1/6535 (0%) 1
    Respiratory tract infection 0/6532 (0%) 0 2/6535 (0%) 2
    Respiratory tract infection viral 0/6532 (0%) 0 1/6535 (0%) 1
    Rotavirus infection 0/6532 (0%) 0 1/6535 (0%) 1
    Salmonellosis 1/6532 (0%) 1 0/6535 (0%) 0
    Scrotal abscess 0/6532 (0%) 0 2/6535 (0%) 2
    Sepsis 49/6532 (0.8%) 51 43/6535 (0.7%) 47
    Septic necrosis 0/6532 (0%) 0 1/6535 (0%) 1
    Septic shock 8/6532 (0.1%) 8 7/6535 (0.1%) 10
    Sinobronchitis 1/6532 (0%) 1 0/6535 (0%) 0
    Sinusitis 2/6532 (0%) 2 2/6535 (0%) 2
    Skin infection 1/6532 (0%) 1 0/6535 (0%) 0
    Staphylococcal abscess 0/6532 (0%) 0 2/6535 (0%) 2
    Staphylococcal bacteraemia 2/6532 (0%) 2 3/6535 (0%) 3
    Staphylococcal infection 1/6532 (0%) 1 3/6535 (0%) 3
    Staphylococcal sepsis 1/6532 (0%) 1 4/6535 (0.1%) 4
    Streptococcal abscess 1/6532 (0%) 1 0/6535 (0%) 0
    Streptococcal sepsis 2/6532 (0%) 2 0/6535 (0%) 0
    Subcutaneous abscess 0/6532 (0%) 0 2/6535 (0%) 2
    Tonsillitis 0/6532 (0%) 0 1/6535 (0%) 1
    Tooth abscess 1/6532 (0%) 1 1/6535 (0%) 1
    Tracheitis 0/6532 (0%) 0 1/6535 (0%) 1
    Tracheobronchitis 0/6532 (0%) 0 1/6535 (0%) 1
    Upper respiratory tract infection 1/6532 (0%) 1 3/6535 (0%) 3
    Urinary tract infection 24/6532 (0.4%) 26 36/6535 (0.6%) 40
    Urosepsis 9/6532 (0.1%) 9 9/6535 (0.1%) 9
    Vestibular neuronitis 3/6532 (0%) 4 2/6535 (0%) 2
    Viral infection 1/6532 (0%) 1 2/6535 (0%) 2
    Wound infection 1/6532 (0%) 1 7/6535 (0.1%) 7
    Wound infection bacterial 1/6532 (0%) 1 0/6535 (0%) 0
    Wound sepsis 2/6532 (0%) 2 1/6535 (0%) 1
    Injury, poisoning and procedural complications
    Abdominal injury 0/6532 (0%) 0 1/6535 (0%) 1
    Accidental overdose 3/6532 (0%) 3 1/6535 (0%) 1
    Acetabulum fracture 1/6532 (0%) 1 0/6535 (0%) 0
    Airway complication of anaesthesia 0/6532 (0%) 0 1/6535 (0%) 1
    Alcohol poisoning 0/6532 (0%) 0 1/6535 (0%) 1
    Animal bite 1/6532 (0%) 1 0/6535 (0%) 0
    Ankle fracture 5/6532 (0.1%) 5 9/6535 (0.1%) 10
    Arterial bypass occlusion 1/6532 (0%) 1 1/6535 (0%) 1
    Arterial bypass stenosis 1/6532 (0%) 1 0/6535 (0%) 0
    Back injury 0/6532 (0%) 0 1/6535 (0%) 1
    Bone contusion 1/6532 (0%) 1 0/6535 (0%) 0
    Brain contusion 1/6532 (0%) 1 0/6535 (0%) 0
    Burns second degree 1/6532 (0%) 1 0/6535 (0%) 0
    Carbon monoxide poisoning 1/6532 (0%) 1 0/6535 (0%) 0
    Carotid artery restenosis 1/6532 (0%) 1 0/6535 (0%) 0
    Cervical vertebral fracture 2/6532 (0%) 2 1/6535 (0%) 1
    Chest injury 0/6532 (0%) 0 5/6535 (0.1%) 5
    Clavicle fracture 1/6532 (0%) 1 3/6535 (0%) 3
    Concussion 1/6532 (0%) 1 2/6535 (0%) 2
    Contusion 1/6532 (0%) 3 0/6535 (0%) 0
    Coronary artery restenosis 1/6532 (0%) 1 0/6535 (0%) 0
    Craniocerebral injury 3/6532 (0%) 3 2/6535 (0%) 2
    Cystitis radiation 1/6532 (0%) 1 0/6535 (0%) 0
    Epicondylitis 1/6532 (0%) 1 0/6535 (0%) 0
    Eyelid injury 1/6532 (0%) 1 1/6535 (0%) 1
    Facial bones fracture 1/6532 (0%) 1 1/6535 (0%) 1
    Fall 15/6532 (0.2%) 19 10/6535 (0.2%) 10
    Femoral neck fracture 9/6532 (0.1%) 9 7/6535 (0.1%) 7
    Femur fracture 8/6532 (0.1%) 8 9/6535 (0.1%) 9
    Fibula fracture 1/6532 (0%) 1 3/6535 (0%) 3
    Foot fracture 3/6532 (0%) 3 1/6535 (0%) 1
    Forearm fracture 2/6532 (0%) 2 0/6535 (0%) 0
    Foreign body aspiration 1/6532 (0%) 1 0/6535 (0%) 0
    Foreign body in gastrointestinal tract 0/6532 (0%) 0 2/6535 (0%) 2
    Fracture displacement 1/6532 (0%) 1 1/6535 (0%) 1
    Frostbite 0/6532 (0%) 0 1/6535 (0%) 1
    Hand fracture 1/6532 (0%) 1 0/6535 (0%) 0
    Head injury 5/6532 (0.1%) 5 8/6535 (0.1%) 8
    Hip fracture 4/6532 (0.1%) 4 11/6535 (0.2%) 11
    Humerus fracture 5/6532 (0.1%) 5 6/6535 (0.1%) 6
    Hyphaema 0/6532 (0%) 0 1/6535 (0%) 1
    Incisional hernia 5/6532 (0.1%) 5 4/6535 (0.1%) 5
    Inflammation of wound 1/6532 (0%) 1 0/6535 (0%) 0
    Injury 1/6532 (0%) 1 2/6535 (0%) 2
    Intentional overdose 0/6532 (0%) 0 1/6535 (0%) 1
    Joint dislocation 0/6532 (0%) 0 4/6535 (0.1%) 4
    Joint injury 1/6532 (0%) 2 3/6535 (0%) 3
    Ligament rupture 2/6532 (0%) 2 1/6535 (0%) 1
    Ligament sprain 0/6532 (0%) 0 2/6535 (0%) 2
    Limb injury 2/6532 (0%) 2 3/6535 (0%) 4
    Limb traumatic amputation 1/6532 (0%) 1 0/6535 (0%) 0
    Lower limb fracture 3/6532 (0%) 4 3/6535 (0%) 3
    Lumbar vertebral fracture 2/6532 (0%) 2 2/6535 (0%) 2
    Mallet finger 1/6532 (0%) 1 0/6535 (0%) 0
    Meniscus injury 4/6532 (0.1%) 4 3/6535 (0%) 3
    Multiple fractures 1/6532 (0%) 1 3/6535 (0%) 3
    Multiple injuries 3/6532 (0%) 3 1/6535 (0%) 1
    Muscle injury 1/6532 (0%) 1 0/6535 (0%) 0
    Muscle rupture 2/6532 (0%) 2 1/6535 (0%) 1
    Muscle strain 1/6532 (0%) 1 1/6535 (0%) 1
    Neck injury 0/6532 (0%) 0 1/6535 (0%) 1
    Overdose 1/6532 (0%) 1 2/6535 (0%) 2
    Patella fracture 3/6532 (0%) 3 0/6535 (0%) 0
    Pelvic organ injury 1/6532 (0%) 1 0/6535 (0%) 0
    Peripheral artery restenosis 0/6532 (0%) 0 1/6535 (0%) 1
    Peripheral nerve injury 1/6532 (0%) 1 0/6535 (0%) 0
    Periprosthetic fracture 0/6532 (0%) 0 1/6535 (0%) 1
    Pharyngeal contusion 0/6532 (0%) 0 1/6535 (0%) 1
    Poisoning 1/6532 (0%) 1 0/6535 (0%) 0
    Post concussion syndrome 1/6532 (0%) 1 0/6535 (0%) 0
    Post laminectomy syndrome 0/6532 (0%) 0 1/6535 (0%) 1
    Post procedural complication 2/6532 (0%) 2 2/6535 (0%) 3
    Post procedural fever 2/6532 (0%) 2 1/6535 (0%) 1
    Post procedural haematoma 1/6532 (0%) 1 4/6535 (0.1%) 4
    Post procedural haematuria 0/6532 (0%) 0 1/6535 (0%) 1
    Post procedural haemorrhage 7/6532 (0.1%) 8 7/6535 (0.1%) 7
    Post procedural swelling 1/6532 (0%) 1 0/6535 (0%) 0
    Postoperative delirium 1/6532 (0%) 1 0/6535 (0%) 0
    Postoperative hypotension 0/6532 (0%) 0 1/6535 (0%) 1
    Postoperative ileus 2/6532 (0%) 2 2/6535 (0%) 5
    Postoperative respiratory failure 1/6532 (0%) 1 0/6535 (0%) 0
    Postoperative thoracic procedure complication 1/6532 (0%) 1 0/6535 (0%) 0
    Procedural haemorrhage 1/6532 (0%) 1 0/6535 (0%) 0
    Procedural hypotension 1/6532 (0%) 1 0/6535 (0%) 0
    Procedural nausea 1/6532 (0%) 1 0/6535 (0%) 0
    Procedural pain 1/6532 (0%) 1 7/6535 (0.1%) 7
    Pseudomeningocele 0/6532 (0%) 0 1/6535 (0%) 1
    Pubis fracture 1/6532 (0%) 1 0/6535 (0%) 0
    Pulmonary contusion 1/6532 (0%) 1 0/6535 (0%) 0
    Radiation dysphagia 0/6532 (0%) 0 1/6535 (0%) 1
    Radiation injury 0/6532 (0%) 0 1/6535 (0%) 1
    Radius fracture 0/6532 (0%) 0 6/6535 (0.1%) 6
    Rib fracture 7/6532 (0.1%) 7 5/6535 (0.1%) 5
    Road traffic accident 6/6532 (0.1%) 6 5/6535 (0.1%) 5
    Scapula fracture 1/6532 (0%) 1 0/6535 (0%) 0
    Shunt thrombosis 1/6532 (0%) 1 1/6535 (0%) 1
    Skeletal injury 0/6532 (0%) 0 2/6535 (0%) 2
    Skin abrasion 0/6532 (0%) 0 2/6535 (0%) 2
    Skin laceration 2/6532 (0%) 2 6/6535 (0.1%) 6
    Skull fracture 1/6532 (0%) 1 0/6535 (0%) 0
    Skull fractured base 1/6532 (0%) 1 1/6535 (0%) 1
    Soft tissue injury 0/6532 (0%) 0 2/6535 (0%) 2
    Spinal compression fracture 9/6532 (0.1%) 10 5/6535 (0.1%) 5
    Spinal cord injury 1/6532 (0%) 1 0/6535 (0%) 0
    Spinal fracture 2/6532 (0%) 2 2/6535 (0%) 2
    Splenic injury 1/6532 (0%) 1 0/6535 (0%) 0
    Splenic rupture 1/6532 (0%) 1 0/6535 (0%) 0
    Stress fracture 1/6532 (0%) 1 0/6535 (0%) 0
    Subcutaneous haematoma 1/6532 (0%) 1 0/6535 (0%) 0
    Subdural haematoma 11/6532 (0.2%) 14 9/6535 (0.1%) 10
    Subdural haemorrhage 1/6532 (0%) 1 0/6535 (0%) 0
    Suture related complication 1/6532 (0%) 1 0/6535 (0%) 0
    Tendon injury 0/6532 (0%) 0 1/6535 (0%) 1
    Tendon rupture 6/6532 (0.1%) 6 5/6535 (0.1%) 5
    Thermal burn 2/6532 (0%) 2 1/6535 (0%) 1
    Thoracic vertebral fracture 3/6532 (0%) 3 0/6535 (0%) 0
    Tibia fracture 1/6532 (0%) 1 3/6535 (0%) 3
    Toxicity to various agents 2/6532 (0%) 2 5/6535 (0.1%) 5
    Traumatic arthrosis 0/6532 (0%) 0 1/6535 (0%) 1
    Traumatic haematoma 1/6532 (0%) 1 0/6535 (0%) 0
    Traumatic haemothorax 1/6532 (0%) 1 0/6535 (0%) 0
    Traumatic ulcer 1/6532 (0%) 1 0/6535 (0%) 0
    Ulna fracture 0/6532 (0%) 0 1/6535 (0%) 1
    Upper limb fracture 2/6532 (0%) 2 0/6535 (0%) 0
    Urethral injury 1/6532 (0%) 1 0/6535 (0%) 0
    Vascular graft occlusion 1/6532 (0%) 1 1/6535 (0%) 1
    Vascular procedure complication 0/6532 (0%) 0 1/6535 (0%) 1
    Vascular pseudoaneurysm 2/6532 (0%) 2 2/6535 (0%) 2
    Wound 2/6532 (0%) 2 0/6535 (0%) 0
    Wrist fracture 0/6532 (0%) 0 3/6535 (0%) 3
    Investigations
    Activated partial thromboplastin time prolonged 0/6532 (0%) 0 1/6535 (0%) 1
    Alanine aminotransferase increased 0/6532 (0%) 0 1/6535 (0%) 1
    Anticoagulation drug level above therapeutic 2/6532 (0%) 2 0/6535 (0%) 0
    Anticoagulation drug level increased 1/6532 (0%) 1 0/6535 (0%) 0
    Aspartate aminotransferase increased 0/6532 (0%) 0 1/6535 (0%) 1
    Blood calcium decreased 1/6532 (0%) 1 0/6535 (0%) 0
    Blood creatinine increased 1/6532 (0%) 1 0/6535 (0%) 0
    Blood glucose abnormal 3/6532 (0%) 3 0/6535 (0%) 0
    Blood glucose decreased 1/6532 (0%) 1 1/6535 (0%) 1
    Blood glucose fluctuation 0/6532 (0%) 0 1/6535 (0%) 2
    Blood glucose increased 1/6532 (0%) 1 2/6535 (0%) 2
    Blood lactic acid increased 0/6532 (0%) 0 1/6535 (0%) 1
    Blood pressure increased 0/6532 (0%) 0 3/6535 (0%) 3
    C-reactive protein increased 1/6532 (0%) 1 0/6535 (0%) 0
    Ejection fraction decreased 1/6532 (0%) 1 0/6535 (0%) 0
    Electrocardiogram change 0/6532 (0%) 0 1/6535 (0%) 1
    Gamma-glutamyltransferase increased 0/6532 (0%) 0 1/6535 (0%) 1
    Glycosylated haemoglobin increased 0/6532 (0%) 0 1/6535 (0%) 1
    Haemoglobin decreased 1/6532 (0%) 1 0/6535 (0%) 0
    Heart rate irregular 0/6532 (0%) 0 1/6535 (0%) 1
    Hepatic enzyme increased 1/6532 (0%) 1 0/6535 (0%) 0
    International normalised ratio increased 1/6532 (0%) 1 0/6535 (0%) 0
    Intraocular pressure increased 1/6532 (0%) 1 0/6535 (0%) 0
    Liver function test abnormal 0/6532 (0%) 0 1/6535 (0%) 1
    Liver function test increased 1/6532 (0%) 1 0/6535 (0%) 0
    Platelet count decreased 0/6532 (0%) 0 1/6535 (0%) 1
    Prostatic specific antigen increased 1/6532 (0%) 1 0/6535 (0%) 0
    Sinus rhythm 1/6532 (0%) 1 0/6535 (0%) 0
    Transaminases increased 1/6532 (0%) 1 1/6535 (0%) 1
    Transplant evaluation 0/6532 (0%) 0 1/6535 (0%) 1
    Trial of void 0/6532 (0%) 0 1/6535 (0%) 1
    Troponin i increased 0/6532 (0%) 0 2/6535 (0%) 2
    Troponin increased 2/6532 (0%) 2 0/6535 (0%) 0
    Weight decreased 1/6532 (0%) 1 0/6535 (0%) 0
    Weight increased 1/6532 (0%) 1 0/6535 (0%) 0
    Metabolism and nutrition disorders
    Cardiometabolic syndrome 0/6532 (0%) 0 1/6535 (0%) 1
    Central obesity 0/6532 (0%) 0 1/6535 (0%) 1
    Decreased appetite 1/6532 (0%) 1 0/6535 (0%) 0
    Dehydration 8/6532 (0.1%) 9 12/6535 (0.2%) 13
    Diabetes mellitus 43/6532 (0.7%) 47 49/6535 (0.7%) 50
    Diabetes mellitus inadequate control 26/6532 (0.4%) 29 24/6535 (0.4%) 32
    Diabetic complication 1/6532 (0%) 1 0/6535 (0%) 0
    Diabetic ketoacidosis 6/6532 (0.1%) 6 6/6535 (0.1%) 6
    Diabetic ketosis 0/6532 (0%) 0 1/6535 (0%) 1
    Diabetic metabolic decompensation 16/6532 (0.2%) 16 13/6535 (0.2%) 14
    Electrolyte imbalance 2/6532 (0%) 2 1/6535 (0%) 1
    Failure to thrive 0/6532 (0%) 0 1/6535 (0%) 1
    Fluid overload 3/6532 (0%) 3 3/6535 (0%) 3
    Gout 6/6532 (0.1%) 6 7/6535 (0.1%) 9
    Hypercalcaemia 0/6532 (0%) 0 2/6535 (0%) 2
    Hyperglycaemia 13/6532 (0.2%) 13 12/6535 (0.2%) 14
    Hyperglycaemic hyperosmolar nonketotic syndrome 1/6532 (0%) 1 0/6535 (0%) 0
    Hyperhomocysteinaemia 0/6532 (0%) 0 1/6535 (0%) 1
    Hyperkalaemia 5/6532 (0.1%) 5 13/6535 (0.2%) 13
    Hypertriglyceridaemia 2/6532 (0%) 2 2/6535 (0%) 2
    Hypervolaemia 0/6532 (0%) 0 1/6535 (0%) 1
    Hypocalcaemia 0/6532 (0%) 0 2/6535 (0%) 3
    Hypoglycaemia 14/6532 (0.2%) 15 16/6535 (0.2%) 18
    Hypokalaemia 2/6532 (0%) 2 3/6535 (0%) 4
    Hypomagnesaemia 0/6532 (0%) 0 3/6535 (0%) 3
    Hyponatraemia 4/6532 (0.1%) 4 1/6535 (0%) 1
    Hypovolaemia 4/6532 (0.1%) 4 1/6535 (0%) 1
    Ketoacidosis 1/6532 (0%) 1 0/6535 (0%) 0
    Lactic acidosis 1/6532 (0%) 1 1/6535 (0%) 1
    Malnutrition 0/6532 (0%) 0 1/6535 (0%) 1
    Metabolic acidosis 2/6532 (0%) 2 1/6535 (0%) 1
    Obesity 6/6532 (0.1%) 6 10/6535 (0.2%) 10
    Type 2 diabetes mellitus 28/6532 (0.4%) 32 18/6535 (0.3%) 19
    Vitamin b12 deficiency 1/6532 (0%) 1 0/6535 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 10/6532 (0.2%) 11 12/6535 (0.2%) 14
    Arthritis 8/6532 (0.1%) 8 6/6535 (0.1%) 6
    Arthropathy 1/6532 (0%) 1 1/6535 (0%) 1
    Back pain 8/6532 (0.1%) 10 11/6535 (0.2%) 11
    Bone lesion 0/6532 (0%) 0 1/6535 (0%) 1
    Bursitis 2/6532 (0%) 2 1/6535 (0%) 1
    Cervical spinal stenosis 6/6532 (0.1%) 6 4/6535 (0.1%) 4
    Chondrocalcinosis pyrophosphate 2/6532 (0%) 2 1/6535 (0%) 1
    Compartment syndrome 1/6532 (0%) 1 0/6535 (0%) 0
    Costochondritis 2/6532 (0%) 2 2/6535 (0%) 2
    Crystal arthropathy 1/6532 (0%) 1 0/6535 (0%) 0
    Fibromyalgia 0/6532 (0%) 0 1/6535 (0%) 1
    Flank pain 1/6532 (0%) 1 2/6535 (0%) 2
    Foot deformity 4/6532 (0.1%) 5 0/6535 (0%) 0
    Fracture nonunion 0/6532 (0%) 0 1/6535 (0%) 1
    Gouty arthritis 1/6532 (0%) 1 0/6535 (0%) 0
    Groin pain 0/6532 (0%) 0 1/6535 (0%) 1
    Haematoma muscle 1/6532 (0%) 1 0/6535 (0%) 0
    Inguinal mass 1/6532 (0%) 1 0/6535 (0%) 0
    Intervertebral disc degeneration 4/6532 (0.1%) 4 1/6535 (0%) 1
    Intervertebral disc disorder 2/6532 (0%) 2 2/6535 (0%) 2
    Intervertebral disc displacement 0/6532 (0%) 0 1/6535 (0%) 1
    Intervertebral disc protrusion 13/6532 (0.2%) 13 17/6535 (0.3%) 17
    Joint ankylosis 1/6532 (0%) 1 0/6535 (0%) 0
    Joint effusion 0/6532 (0%) 0 1/6535 (0%) 1
    Limb deformity 0/6532 (0%) 0 1/6535 (0%) 1
    Limb discomfort 0/6532 (0%) 0 1/6535 (0%) 1
    Limb mass 1/6532 (0%) 1 0/6535 (0%) 0
    Lumbar spinal stenosis 18/6532 (0.3%) 18 11/6535 (0.2%) 11
    Mandibular mass 0/6532 (0%) 0 1/6535 (0%) 1
    Meniscal degeneration 0/6532 (0%) 0 1/6535 (0%) 1
    Mobility decreased 1/6532 (0%) 1 2/6535 (0%) 2
    Muscle spasms 1/6532 (0%) 1 0/6535 (0%) 0
    Muscular weakness 4/6532 (0.1%) 4 1/6535 (0%) 1
    Musculoskeletal chest pain 7/6532 (0.1%) 7 9/6535 (0.1%) 9
    Musculoskeletal pain 3/6532 (0%) 3 6/6535 (0.1%) 6
    Myalgia 1/6532 (0%) 1 1/6535 (0%) 1
    Myopathy 1/6532 (0%) 1 0/6535 (0%) 0
    Neck pain 0/6532 (0%) 0 1/6535 (0%) 1
    Neuropathic arthropathy 2/6532 (0%) 2 0/6535 (0%) 0
    Osteitis 1/6532 (0%) 1 1/6535 (0%) 1
    Osteoarthritis 66/6532 (1%) 69 58/6535 (0.9%) 67
    Osteochondrosis 1/6532 (0%) 1 1/6535 (0%) 1
    Osteonecrosis 3/6532 (0%) 3 2/6535 (0%) 2
    Osteonecrosis of jaw 1/6532 (0%) 1 1/6535 (0%) 1
    Osteoporosis 2/6532 (0%) 2 1/6535 (0%) 1
    Pain in extremity 6/6532 (0.1%) 6 4/6535 (0.1%) 4
    Periarthritis 1/6532 (0%) 3 2/6535 (0%) 2
    Polymyalgia rheumatica 1/6532 (0%) 1 2/6535 (0%) 2
    Psoriatic arthropathy 1/6532 (0%) 1 1/6535 (0%) 1
    Rhabdomyolysis 1/6532 (0%) 1 1/6535 (0%) 1
    Rheumatic disorder 0/6532 (0%) 0 1/6535 (0%) 1
    Rheumatoid arthritis 0/6532 (0%) 0 4/6535 (0.1%) 4
    Rotator cuff syndrome 6/6532 (0.1%) 6 10/6535 (0.2%) 10
    Spinal instability 1/6532 (0%) 1 1/6535 (0%) 1
    Spinal osteoarthritis 17/6532 (0.3%) 17 8/6535 (0.1%) 8
    Spinal pain 4/6532 (0.1%) 4 1/6535 (0%) 1
    Spinal stenosis 4/6532 (0.1%) 4 11/6535 (0.2%) 11
    Spondylolisthesis 4/6532 (0.1%) 4 3/6535 (0%) 3
    Spondylolysis 0/6532 (0%) 0 1/6535 (0%) 1
    Synovial cyst 0/6532 (0%) 0 1/6535 (0%) 1
    Tendon disorder 1/6532 (0%) 1 1/6535 (0%) 1
    Tendonitis 0/6532 (0%) 0 2/6535 (0%) 2
    Tenosynovitis 1/6532 (0%) 1 0/6535 (0%) 0
    Thoracic spinal stenosis 1/6532 (0%) 1 0/6535 (0%) 0
    Vertebral foraminal stenosis 2/6532 (0%) 2 0/6535 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acoustic neuroma 0/6532 (0%) 0 1/6535 (0%) 1
    Acute lymphocytic leukaemia 1/6532 (0%) 2 0/6535 (0%) 0
    Acute myeloid leukaemia 0/6532 (0%) 0 2/6535 (0%) 2
    Acute promyelocytic leukaemia 1/6532 (0%) 1 0/6535 (0%) 0
    Adenocarcinoma gastric 3/6532 (0%) 5 1/6535 (0%) 1
    Adenocarcinoma of colon 4/6532 (0.1%) 5 6/6535 (0.1%) 6
    Adenocarcinoma pancreas 4/6532 (0.1%) 4 0/6535 (0%) 0
    Adrenal adenoma 2/6532 (0%) 2 1/6535 (0%) 1
    Anal cancer 0/6532 (0%) 0 1/6535 (0%) 1
    Angiomyolipoma 1/6532 (0%) 1 0/6535 (0%) 0
    Anogenital warts 0/6532 (0%) 0 1/6535 (0%) 1
    B-cell prolymphocytic leukaemia 0/6532 (0%) 0 1/6535 (0%) 1
    B-cell small lymphocytic lymphoma 0/6532 (0%) 0 1/6535 (0%) 1
    Basal cell carcinoma 15/6532 (0.2%) 15 17/6535 (0.3%) 22
    Benign bone neoplasm 1/6532 (0%) 1 0/6535 (0%) 0
    Benign neoplasm 0/6532 (0%) 0 1/6535 (0%) 1
    Benign neoplasm of adrenal gland 1/6532 (0%) 1 0/6535 (0%) 0
    Benign neoplasm of bladder 1/6532 (0%) 1 0/6535 (0%) 0
    Benign neoplasm of eyelid 1/6532 (0%) 1 0/6535 (0%) 0
    Benign neoplasm of thyroid gland 0/6532 (0%) 0 1/6535 (0%) 1
    Benign ovarian tumour 0/6532 (0%) 0 1/6535 (0%) 1
    Benign pancreatic neoplasm 0/6532 (0%) 0 1/6535 (0%) 1
    Bile duct cancer 0/6532 (0%) 0 1/6535 (0%) 1
    Bladder cancer 9/6532 (0.1%) 9 9/6535 (0.1%) 10
    Bladder cancer recurrent 0/6532 (0%) 0 2/6535 (0%) 2
    Bladder cancer stage i, with cancer in situ 1/6532 (0%) 1 0/6535 (0%) 0
    Bladder neoplasm 3/6532 (0%) 3 6/6535 (0.1%) 7
    Bladder squamous cell carcinoma stage unspecified 1/6532 (0%) 1 0/6535 (0%) 0
    Bladder transitional cell carcinoma 3/6532 (0%) 3 5/6535 (0.1%) 5
    Bladder transitional cell carcinoma recurrent 1/6532 (0%) 1 1/6535 (0%) 1
    Bone cancer 1/6532 (0%) 1 1/6535 (0%) 1
    Bowen's disease 0/6532 (0%) 0 3/6535 (0%) 3
    Brain cancer metastatic 0/6532 (0%) 0 1/6535 (0%) 1
    Brain neoplasm malignant 2/6532 (0%) 2 0/6535 (0%) 0
    Breast cancer 8/6532 (0.1%) 9 17/6535 (0.3%) 17
    Breast cancer female 3/6532 (0%) 3 3/6535 (0%) 3
    Breast cancer metastatic 1/6532 (0%) 1 1/6535 (0%) 1
    Breast cancer stage i 1/6532 (0%) 1 0/6535 (0%) 0
    Breast cancer stage ii 1/6532 (0%) 1 0/6535 (0%) 0
    Breast neoplasm 1/6532 (0%) 1 3/6535 (0%) 4
    Bronchial carcinoma 2/6532 (0%) 2 1/6535 (0%) 1
    Bronchioloalveolar carcinoma 1/6532 (0%) 1 0/6535 (0%) 0
    Carcinoid tumour pulmonary 0/6532 (0%) 0 2/6535 (0%) 2
    Cardiac neoplasm malignant 0/6532 (0%) 0 1/6535 (0%) 1
    Castleman's disease 1/6532 (0%) 1 0/6535 (0%) 0
    Cervix carcinoma 1/6532 (0%) 1 1/6535 (0%) 1
    Cholangiocarcinoma 2/6532 (0%) 2 1/6535 (0%) 1
    Chronic lymphocytic leukaemia 1/6532 (0%) 1 0/6535 (0%) 0
    Chronic myeloid leukaemia 0/6532 (0%) 0 1/6535 (0%) 1
    Clear cell renal cell carcinoma 3/6532 (0%) 3 2/6535 (0%) 2
    Colon adenoma 3/6532 (0%) 4 4/6535 (0.1%) 4
    Colon cancer 10/6532 (0.2%) 11 20/6535 (0.3%) 21
    Colon cancer metastatic 2/6532 (0%) 2 1/6535 (0%) 1
    Colon cancer stage 0 1/6532 (0%) 1 0/6535 (0%) 0
    Colon cancer stage iv 1/6532 (0%) 1 1/6535 (0%) 1
    Colon neoplasm 5/6532 (0.1%) 5 0/6535 (0%) 0
    Colorectal adenocarcinoma 0/6532 (0%) 0 1/6535 (0%) 1
    Colorectal cancer 1/6532 (0%) 1 2/6535 (0%) 2
    Colorectal cancer metastatic 0/6532 (0%) 0 1/6535 (0%) 2
    Craniopharyngioma 1/6532 (0%) 1 0/6535 (0%) 0
    Diffuse large b-cell lymphoma 0/6532 (0%) 0 1/6535 (0%) 1
    Ear neoplasm 1/6532 (0%) 1 0/6535 (0%) 0
    Endometrial adenocarcinoma 1/6532 (0%) 1 1/6535 (0%) 1
    Endometrial cancer 0/6532 (0%) 0 2/6535 (0%) 2
    Essential thrombocythaemia 1/6532 (0%) 1 0/6535 (0%) 0
    Female reproductive neoplasm 1/6532 (0%) 1 0/6535 (0%) 0
    Gallbladder cancer 1/6532 (0%) 1 0/6535 (0%) 0
    Gastric adenoma 1/6532 (0%) 1 0/6535 (0%) 0
    Gastric cancer 3/6532 (0%) 3 4/6535 (0.1%) 4
    Gastrointestinal carcinoma 2/6532 (0%) 2 1/6535 (0%) 1
    Gastrointestinal stromal tumour 0/6532 (0%) 0 1/6535 (0%) 1
    Glioblastoma multiforme 1/6532 (0%) 1 0/6535 (0%) 0
    Haemangioma of bone 1/6532 (0%) 1 0/6535 (0%) 0
    Head and neck cancer metastatic 0/6532 (0%) 0 1/6535 (0%) 1
    Hepatic cancer 3/6532 (0%) 3 5/6535 (0.1%) 5
    Hepatic neoplasm 0/6532 (0%) 0 1/6535 (0%) 1
    Hepatocellular carcinoma 4/6532 (0.1%) 4 3/6535 (0%) 3
    Immune reconstitution inflammatory syndrome associated kaposi's sarcoma 1/6532 (0%) 1 0/6535 (0%) 0
    Intestinal adenocarcinoma 0/6532 (0%) 0 1/6535 (0%) 1
    Intraductal papillary mucinous neoplasm 1/6532 (0%) 1 0/6535 (0%) 0
    Intraductal papilloma of breast 1/6532 (0%) 1 0/6535 (0%) 0
    Intraductal proliferative breast lesion 0/6532 (0%) 0 1/6535 (0%) 1
    Invasive breast carcinoma 1/6532 (0%) 1 0/6535 (0%) 0
    Invasive ductal breast carcinoma 4/6532 (0.1%) 4 5/6535 (0.1%) 5
    Keratinising squamous cell carcinoma of nasopharynx 1/6532 (0%) 1 0/6535 (0%) 0
    Large intestine benign neoplasm 1/6532 (0%) 1 0/6535 (0%) 0
    Laryngeal cancer 2/6532 (0%) 2 3/6535 (0%) 4
    Laryngeal neoplasm 0/6532 (0%) 0 1/6535 (0%) 1
    Laryngeal squamous cell carcinoma 1/6532 (0%) 1 1/6535 (0%) 1
    Lentigo maligna 0/6532 (0%) 0 1/6535 (0%) 1
    Leukaemia 0/6532 (0%) 0 1/6535 (0%) 1
    Lipoma 0/6532 (0%) 0 2/6535 (0%) 2
    Lung adenocarcinoma 7/6532 (0.1%) 9 9/6535 (0.1%) 11
    Lung adenocarcinoma recurrent 0/6532 (0%) 0 1/6535 (0%) 1
    Lung cancer metastatic 3/6532 (0%) 4 2/6535 (0%) 2
    Lung carcinoma cell type unspecified stage ii 1/6532 (0%) 1 0/6535 (0%) 0
    Lung carcinoma cell type unspecified stage iv 3/6532 (0%) 3 0/6535 (0%) 0
    Lung neoplasm 3/6532 (0%) 3 3/6535 (0%) 3
    Lung neoplasm malignant 8/6532 (0.1%) 8 12/6535 (0.2%) 12
    Lymphoma 4/6532 (0.1%) 4 1/6535 (0%) 1
    Malignant melanoma 11/6532 (0.2%) 12 7/6535 (0.1%) 7
    Malignant melanoma stage iv 1/6532 (0%) 1 0/6535 (0%) 0
    Malignant neoplasm of eye 1/6532 (0%) 1 0/6535 (0%) 0
    Malignant neoplasm of renal pelvis 0/6532 (0%) 0 1/6535 (0%) 1
    Malignant neoplasm of spinal cord 0/6532 (0%) 0 1/6535 (0%) 1
    Malignant pleural effusion 0/6532 (0%) 0 1/6535 (0%) 1
    Malignant polyp 0/6532 (0%) 0 1/6535 (0%) 1
    Mantle cell lymphoma 1/6532 (0%) 1 1/6535 (0%) 1
    Meningioma 2/6532 (0%) 3 2/6535 (0%) 2
    Meningioma benign 1/6532 (0%) 1 0/6535 (0%) 0
    Metastases to bone 2/6532 (0%) 2 2/6535 (0%) 2
    Metastases to central nervous system 2/6532 (0%) 2 1/6535 (0%) 1
    Metastases to liver 3/6532 (0%) 3 1/6535 (0%) 1
    Metastases to lung 4/6532 (0.1%) 4 0/6535 (0%) 0
    Metastases to lymph nodes 2/6532 (0%) 2 0/6535 (0%) 0
    Metastases to peritoneum 2/6532 (0%) 2 1/6535 (0%) 1
    Metastases to pleura 0/6532 (0%) 0 1/6535 (0%) 1
    Metastases to rectum 1/6532 (0%) 1 0/6535 (0%) 0
    Metastases to soft tissue 1/6532 (0%) 1 0/6535 (0%) 0
    Metastasis 1/6532 (0%) 1 0/6535 (0%) 0
    Metastatic gastric cancer 0/6532 (0%) 0 1/6535 (0%) 1
    Metastatic malignant melanoma 3/6532 (0%) 3 0/6535 (0%) 0
    Metastatic neoplasm 0/6532 (0%) 0 2/6535 (0%) 2
    Metastatic squamous cell carcinoma 2/6532 (0%) 2 1/6535 (0%) 1
    Metastatic uterine cancer 1/6532 (0%) 1 0/6535 (0%) 0
    Mucoepidermoid carcinoma 0/6532 (0%) 0 1/6535 (0%) 1
    Myelodysplastic syndrome 2/6532 (0%) 2 1/6535 (0%) 1
    Myelofibrosis 0/6532 (0%) 0 1/6535 (0%) 1
    Neoplasm 1/6532 (0%) 1 1/6535 (0%) 1
    Neoplasm malignant 4/6532 (0.1%) 4 4/6535 (0.1%) 4
    Neoplasm of appendix 0/6532 (0%) 0 1/6535 (0%) 1
    Neoplasm prostate 0/6532 (0%) 0 1/6535 (0%) 1
    Neoplasm skin 1/6532 (0%) 1 1/6535 (0%) 1
    Neuroendocrine carcinoma 2/6532 (0%) 2 0/6535 (0%) 0
    Neuroendocrine carcinoma metastatic 2/6532 (0%) 2 0/6535 (0%) 0
    Neuroendocrine carcinoma of the skin 2/6532 (0%) 2 0/6535 (0%) 0
    Neuroendocrine tumour 3/6532 (0%) 3 0/6535 (0%) 0
    Nodular melanoma 0/6532 (0%) 0 1/6535 (0%) 1
    Non-hodgkin's lymphoma 2/6532 (0%) 2 3/6535 (0%) 3
    Non-hodgkin's lymphoma stage i 0/6532 (0%) 0 1/6535 (0%) 1
    Non-small cell lung cancer 0/6532 (0%) 0 4/6535 (0.1%) 4
    Non-small cell lung cancer metastatic 1/6532 (0%) 1 0/6535 (0%) 0
    Non-small cell lung cancer stage iiia 1/6532 (0%) 1 0/6535 (0%) 0
    Non-small cell lung cancer stage iv 1/6532 (0%) 1 0/6535 (0%) 0
    Oesophageal adenocarcinoma 3/6532 (0%) 3 1/6535 (0%) 1
    Oesophageal cancer metastatic 1/6532 (0%) 1 0/6535 (0%) 0
    Oesophageal carcinoma 6/6532 (0.1%) 6 2/6535 (0%) 2
    Oesophageal papilloma 0/6532 (0%) 0 1/6535 (0%) 1
    Oesophageal squamous cell carcinoma 1/6532 (0%) 1 3/6535 (0%) 3
    Oral neoplasm 1/6532 (0%) 1 0/6535 (0%) 0
    Oropharyngeal cancer 1/6532 (0%) 1 0/6535 (0%) 0
    Oropharyngeal squamous cell carcinoma 1/6532 (0%) 1 0/6535 (0%) 0
    Ovarian adenoma 0/6532 (0%) 0 2/6535 (0%) 2
    Ovarian cancer 0/6532 (0%) 0 1/6535 (0%) 1
    Ovarian endometrioid carcinoma 1/6532 (0%) 1 0/6535 (0%) 0
    Ovarian granulosa cell tumour 0/6532 (0%) 0 1/6535 (0%) 1
    Paget's disease of the vulva 1/6532 (0%) 1 0/6535 (0%) 0
    Pancreatic carcinoma 12/6532 (0.2%) 12 4/6535 (0.1%) 6
    Pancreatic carcinoma metastatic 4/6532 (0.1%) 4 2/6535 (0%) 2
    Pancreatic carcinoma stage iv 1/6532 (0%) 1 0/6535 (0%) 0
    Papillary renal cell carcinoma 1/6532 (0%) 1 2/6535 (0%) 2
    Papillary thyroid cancer 1/6532 (0%) 1 2/6535 (0%) 2
    Parathyroid tumour benign 0/6532 (0%) 0 3/6535 (0%) 3
    Pituitary tumour benign 0/6532 (0%) 0 4/6535 (0.1%) 6
    Plasma cell myeloma 2/6532 (0%) 2 4/6535 (0.1%) 5
    Plasmacytoma 1/6532 (0%) 1 1/6535 (0%) 1
    Prostate cancer 34/6532 (0.5%) 34 33/6535 (0.5%) 34
    Prostate cancer metastatic 2/6532 (0%) 2 3/6535 (0%) 4
    Prostate cancer recurrent 0/6532 (0%) 0 1/6535 (0%) 1
    Prostate cancer stage iv 1/6532 (0%) 1 0/6535 (0%) 0
    Prostatic adenoma 1/6532 (0%) 1 0/6535 (0%) 0
    Queyrat erythroplasia 1/6532 (0%) 1 0/6535 (0%) 0
    Rectal adenocarcinoma 0/6532 (0%) 0 4/6535 (0.1%) 4
    Rectal cancer 2/6532 (0%) 2 4/6535 (0.1%) 4
    Rectal cancer metastatic 1/6532 (0%) 1 1/6535 (0%) 1
    Rectal cancer stage iv 1/6532 (0%) 1 0/6535 (0%) 0
    Rectal neoplasm 1/6532 (0%) 1 0/6535 (0%) 0
    Rectosigmoid cancer 2/6532 (0%) 2 1/6535 (0%) 1
    Renal cancer 2/6532 (0%) 2 1/6535 (0%) 1
    Renal cancer metastatic 1/6532 (0%) 1 0/6535 (0%) 0
    Renal cancer stage i 1/6532 (0%) 1 0/6535 (0%) 0
    Renal cell carcinoma 6/6532 (0.1%) 7 0/6535 (0%) 0
    Renal cell carcinoma stage iv 1/6532 (0%) 1 0/6535 (0%) 0
    Renal neoplasm 1/6532 (0%) 1 1/6535 (0%) 1
    Retroperitoneal neoplasm 1/6532 (0%) 1 0/6535 (0%) 0
    Salivary gland adenoma 0/6532 (0%) 0 1/6535 (0%) 1
    Salivary gland neoplasm 1/6532 (0%) 1 0/6535 (0%) 0
    Schwannoma 0/6532 (0%) 0 1/6535 (0%) 1
    Secretory adenoma of pituitary 1/6532 (0%) 1 0/6535 (0%) 0
    Sinonasal papilloma 0/6532 (0%) 0 1/6535 (0%) 1
    Skin cancer 3/6532 (0%) 3 2/6535 (0%) 2
    Small cell lung cancer 2/6532 (0%) 2 1/6535 (0%) 1
    Small cell lung cancer metastatic 1/6532 (0%) 1 1/6535 (0%) 1
    Small intestine carcinoma 0/6532 (0%) 0 1/6535 (0%) 1
    Soft tissue neoplasm 1/6532 (0%) 1 0/6535 (0%) 0
    Spindle cell sarcoma 1/6532 (0%) 1 0/6535 (0%) 0
    Squamous cell carcinoma 3/6532 (0%) 4 4/6535 (0.1%) 5
    Squamous cell carcinoma of lung 6/6532 (0.1%) 6 5/6535 (0.1%) 5
    Squamous cell carcinoma of skin 4/6532 (0.1%) 4 8/6535 (0.1%) 10
    Squamous cell carcinoma of the oral cavity 2/6532 (0%) 2 0/6535 (0%) 0
    Squamous cell carcinoma of the tongue 2/6532 (0%) 2 3/6535 (0%) 3
    Superficial spreading melanoma stage unspecified 1/6532 (0%) 1 0/6535 (0%) 0
    T-cell lymphoma 1/6532 (0%) 1 0/6535 (0%) 0
    Thyroid adenoma 1/6532 (0%) 1 0/6535 (0%) 0
    Thyroid cancer 0/6532 (0%) 0 3/6535 (0%) 3
    Thyroid cancer metastatic 0/6532 (0%) 0 1/6535 (0%) 1
    Tongue neoplasm 0/6532 (0%) 0 2/6535 (0%) 2
    Tongue neoplasm malignant stage unspecified 0/6532 (0%) 0 2/6535 (0%) 2
    Transitional cell carcinoma 4/6532 (0.1%) 4 4/6535 (0.1%) 4
    Ureteric cancer 1/6532 (0%) 1 0/6535 (0%) 0
    Urinary tract neoplasm 1/6532 (0%) 1 0/6535 (0%) 0
    Uterine cancer 4/6532 (0.1%) 4 0/6535 (0%) 0
    Uterine leiomyoma 1/6532 (0%) 1 5/6535 (0.1%) 5
    Vaginal adenocarcinoma 0/6532 (0%) 0 1/6535 (0%) 1
    Nervous system disorders
    Altered state of consciousness 2/6532 (0%) 2 1/6535 (0%) 1
    Amnesia 1/6532 (0%) 1 1/6535 (0%) 1
    Amyotrophic lateral sclerosis 1/6532 (0%) 2 0/6535 (0%) 0
    Aphasia 0/6532 (0%) 0 2/6535 (0%) 2
    Autonomic nervous system imbalance 1/6532 (0%) 1 0/6535 (0%) 0
    Balance disorder 0/6532 (0%) 0 1/6535 (0%) 1
    Basal ganglia infarction 1/6532 (0%) 1 0/6535 (0%) 0
    Basilar artery aneurysm 1/6532 (0%) 1 0/6535 (0%) 0
    Basilar artery stenosis 1/6532 (0%) 1 0/6535 (0%) 0
    Brain stem ischaemia 1/6532 (0%) 1 0/6535 (0%) 0
    Brain stem stroke 0/6532 (0%) 0 1/6535 (0%) 1
    Carotid arteriosclerosis 1/6532 (0%) 1 2/6535 (0%) 2
    Carotid artery disease 2/6532 (0%) 2 0/6535 (0%) 0
    Carotid artery occlusion 1/6532 (0%) 1 2/6535 (0%) 2
    Carotid artery stenosis 17/6532 (0.3%) 18 14/6535 (0.2%) 15
    Carpal tunnel syndrome 3/6532 (0%) 3 4/6535 (0.1%) 4
    Cerebellar infarction 0/6532 (0%) 0 2/6535 (0%) 2
    Cerebellar stroke 0/6532 (0%) 0 1/6535 (0%) 1
    Cerebral artery stenosis 1/6532 (0%) 1 0/6535 (0%) 0
    Cerebral haematoma 0/6532 (0%) 0 1/6535 (0%) 1
    Cerebral haemorrhage 2/6532 (0%) 2 2/6535 (0%) 2
    Cerebral infarction 12/6532 (0.2%) 12 17/6535 (0.3%) 18
    Cerebral ischaemia 6/6532 (0.1%) 6 12/6535 (0.2%) 15
    Cerebral small vessel ischaemic disease 0/6532 (0%) 0 1/6535 (0%) 1
    Cerebral venous sinus thrombosis 0/6532 (0%) 0 1/6535 (0%) 1
    Cerebrovascular accident 45/6532 (0.7%) 46 42/6535 (0.6%) 43
    Cerebrovascular insufficiency 4/6532 (0.1%) 4 4/6535 (0.1%) 4
    Cerebrovascular stenosis 1/6532 (0%) 1 0/6535 (0%) 0
    Cervical radiculopathy 1/6532 (0%) 1 2/6535 (0%) 2
    Cervicobrachial syndrome 1/6532 (0%) 1 0/6535 (0%) 0
    Cluster headache 1/6532 (0%) 1 0/6535 (0%) 0
    Cognitive disorder 0/6532 (0%) 0 1/6535 (0%) 1
    Dementia 4/6532 (0.1%) 4 3/6535 (0%) 4
    Dementia alzheimer's type 0/6532 (0%) 0 1/6535 (0%) 1
    Demyelination 1/6532 (0%) 1 0/6535 (0%) 0
    Diabetic autonomic neuropathy 0/6532 (0%) 0 1/6535 (0%) 1
    Diabetic coma 0/6532 (0%) 0 1/6535 (0%) 1
    Diabetic neuropathy 6/6532 (0.1%) 7 6/6535 (0.1%) 6
    Dizziness 6/6532 (0.1%) 6 6/6535 (0.1%) 6
    Dizziness postural 0/6532 (0%) 0 1/6535 (0%) 1
    Embolic stroke 0/6532 (0%) 0 1/6535 (0%) 1
    Encephalopathy 3/6532 (0%) 3 4/6535 (0.1%) 4
    Epilepsy 4/6532 (0.1%) 4 3/6535 (0%) 3
    Essential tremor 1/6532 (0%) 1 0/6535 (0%) 0
    Facial paralysis 10/6532 (0.2%) 10 6/6535 (0.1%) 6
    Facial paresis 1/6532 (0%) 1 0/6535 (0%) 0
    Generalised tonic-clonic seizure 0/6532 (0%) 0 1/6535 (0%) 1
    Haemorrhage intracranial 2/6532 (0%) 2 2/6535 (0%) 2
    Haemorrhagic stroke 4/6532 (0.1%) 4 4/6535 (0.1%) 4
    Haemorrhagic transformation stroke 0/6532 (0%) 0 1/6535 (0%) 1
    Headache 2/6532 (0%) 2 1/6535 (0%) 1
    Hemiparesis 1/6532 (0%) 1 3/6535 (0%) 4
    Hepatic encephalopathy 1/6532 (0%) 2 0/6535 (0%) 0
    Hypertensive encephalopathy 3/6532 (0%) 3 3/6535 (0%) 3
    Hypoaesthesia 2/6532 (0%) 2 1/6535 (0%) 1
    Hypotonia 0/6532 (0%) 0 1/6535 (0%) 1
    Iiird nerve paralysis 1/6532 (0%) 1 1/6535 (0%) 1
    Intracranial aneurysm 0/6532 (0%) 0 2/6535 (0%) 2
    Intracranial mass 1/6532 (0%) 1 0/6535 (0%) 0
    Ischaemic cerebral infarction 0/6532 (0%) 0 2/6535 (0%) 2
    Ischaemic stroke 30/6532 (0.5%) 33 24/6535 (0.4%) 24
    Lacunar infarction 3/6532 (0%) 3 7/6535 (0.1%) 8
    Lacunar stroke 1/6532 (0%) 1 0/6535 (0%) 0
    Loss of consciousness 3/6532 (0%) 3 4/6535 (0.1%) 4
    Lumbar radiculopathy 3/6532 (0%) 3 2/6535 (0%) 2
    Lumbosacral plexus lesion 1/6532 (0%) 1 0/6535 (0%) 0
    Lumbosacral radiculopathy 1/6532 (0%) 1 2/6535 (0%) 2
    Memory impairment 0/6532 (0%) 0 1/6535 (0%) 1
    Mental impairment 1/6532 (0%) 1 0/6535 (0%) 0
    Metabolic encephalopathy 4/6532 (0.1%) 4 1/6535 (0%) 1
    Migraine 2/6532 (0%) 3 1/6535 (0%) 1
    Monoplegia 0/6532 (0%) 0 1/6535 (0%) 1
    Motor neurone disease 2/6532 (0%) 2 0/6535 (0%) 0
    Multiple sclerosis 2/6532 (0%) 2 0/6535 (0%) 0
    Multiple sclerosis relapse 2/6532 (0%) 4 0/6535 (0%) 0
    Myasthenia gravis 2/6532 (0%) 6 0/6535 (0%) 0
    Myelopathy 1/6532 (0%) 1 0/6535 (0%) 0
    Myoclonus 1/6532 (0%) 1 0/6535 (0%) 0
    Nerve compression 0/6532 (0%) 0 1/6535 (0%) 1
    Nervous system disorder 1/6532 (0%) 1 1/6535 (0%) 1
    Neuralgia 0/6532 (0%) 0 1/6535 (0%) 2
    Neurological symptom 1/6532 (0%) 1 0/6535 (0%) 0
    Neuropathy peripheral 1/6532 (0%) 1 4/6535 (0.1%) 4
    Normal pressure hydrocephalus 0/6532 (0%) 0 2/6535 (0%) 2
    Paraesthesia 0/6532 (0%) 0 2/6535 (0%) 2
    Paraparesis 0/6532 (0%) 0 1/6535 (0%) 1
    Paraplegia 1/6532 (0%) 1 0/6535 (0%) 0
    Parkinson's disease 0/6532 (0%) 0 2/6535 (0%) 2
    Parkinsonism 1/6532 (0%) 1 1/6535 (0%) 1
    Polyneuropathy 0/6532 (0%) 0 1/6535 (0%) 1
    Posterior reversible encephalopathy syndrome 1/6532 (0%) 1 1/6535 (0%) 1
    Presyncope 8/6532 (0.1%) 8 5/6535 (0.1%) 5
    Radial nerve palsy 1/6532 (0%) 1 0/6535 (0%) 0
    Radicular pain 1/6532 (0%) 1 0/6535 (0%) 0
    Radiculopathy 6/6532 (0.1%) 6 2/6535 (0%) 2
    Sciatica 4/6532 (0.1%) 4 3/6535 (0%) 3
    Seizure 4/6532 (0.1%) 4 5/6535 (0.1%) 5
    Somnolence 1/6532 (0%) 1 0/6535 (0%) 0
    Spinal cord compression 0/6532 (0%) 0 1/6535 (0%) 1
    Spinal cord haematoma 1/6532 (0%) 1 0/6535 (0%) 0
    Spinal cord herniation 0/6532 (0%) 0 1/6535 (0%) 1
    Spinal cord infarction 0/6532 (0%) 0 1/6535 (0%) 1
    Spinal cord ischaemia 1/6532 (0%) 1 0/6535 (0%) 0
    Spinal vascular disorder 0/6532 (0%) 0 1/6535 (0%) 1
    Spondylitic myelopathy 1/6532 (0%) 1 0/6535 (0%) 0
    Subarachnoid haemorrhage 5/6532 (0.1%) 5 3/6535 (0%) 3
    Syncope 32/6532 (0.5%) 33 15/6535 (0.2%) 16
    Thalamic infarction 2/6532 (0%) 2 1/6535 (0%) 1
    Transient aphasia 0/6532 (0%) 0 1/6535 (0%) 1
    Transient global amnesia 1/6532 (0%) 1 0/6535 (0%) 0
    Transient ischaemic attack 41/6532 (0.6%) 46 41/6535 (0.6%) 45
    Tremor 1/6532 (0%) 2 0/6535 (0%) 0
    Vascular dementia 3/6532 (0%) 3 0/6535 (0%) 0
    Vascular encephalopathy 9/6532 (0.1%) 9 1/6535 (0%) 1
    Vascular headache 1/6532 (0%) 1 0/6535 (0%) 0
    Vertebrobasilar insufficiency 4/6532 (0.1%) 4 2/6535 (0%) 2
    Vertebrobasilar stroke 0/6532 (0%) 0 1/6535 (0%) 1
    Vocal cord paralysis 0/6532 (0%) 0 1/6535 (0%) 1
    Product Issues
    Device dislocation 1/6532 (0%) 1 0/6535 (0%) 0
    Device failure 0/6532 (0%) 0 1/6535 (0%) 1
    Device lead damage 0/6532 (0%) 0 1/6535 (0%) 1
    Device malfunction 0/6532 (0%) 0 1/6535 (0%) 1
    Device occlusion 2/6532 (0%) 2 0/6535 (0%) 0
    Device power source issue 1/6532 (0%) 1 0/6535 (0%) 0
    Thrombosis in device 0/6532 (0%) 0 1/6535 (0%) 1
    Psychiatric disorders
    Acute psychosis 1/6532 (0%) 1 0/6535 (0%) 0
    Anxiety 2/6532 (0%) 4 2/6535 (0%) 2
    Anxiety disorder 0/6532 (0%) 0 2/6535 (0%) 3
    Bipolar disorder 0/6532 (0%) 0 4/6535 (0.1%) 5
    Borderline personality disorder 1/6532 (0%) 1 0/6535 (0%) 0
    Completed suicide 2/6532 (0%) 2 2/6535 (0%) 2
    Confusional state 1/6532 (0%) 1 2/6535 (0%) 2
    Conversion disorder 1/6532 (0%) 1 0/6535 (0%) 0
    Delirium 1/6532 (0%) 1 3/6535 (0%) 3
    Depressed mood 0/6532 (0%) 0 1/6535 (0%) 1
    Depression 10/6532 (0.2%) 14 9/6535 (0.1%) 11
    Depression suicidal 1/6532 (0%) 1 0/6535 (0%) 0
    Insomnia 1/6532 (0%) 1 0/6535 (0%) 0
    Major depression 6/6532 (0.1%) 7 3/6535 (0%) 3
    Mania 0/6532 (0%) 0 1/6535 (0%) 1
    Mental disorder 1/6532 (0%) 1 0/6535 (0%) 0
    Mental status changes 4/6532 (0.1%) 4 5/6535 (0.1%) 5
    Mood disorder due to a general medical condition 1/6532 (0%) 1 0/6535 (0%) 0
    Organic brain syndrome 0/6532 (0%) 0 1/6535 (0%) 1
    Post-traumatic stress disorder 1/6532 (0%) 2 0/6535 (0%) 0
    Psychotic disorder 0/6532 (0%) 0 1/6535 (0%) 1
    Schizophrenia 1/6532 (0%) 1 0/6535 (0%) 0
    Stress 0/6532 (0%) 0 1/6535 (0%) 1
    Suicidal ideation 0/6532 (0%) 0 3/6535 (0%) 4
    Renal and urinary disorders
    Acute kidney injury 46/6532 (0.7%) 54 53/6535 (0.8%) 59
    Azotaemia 0/6532 (0%) 0 3/6535 (0%) 3
    Bladder mass 1/6532 (0%) 1 0/6535 (0%) 0
    Bladder outlet obstruction 1/6532 (0%) 1 0/6535 (0%) 0
    Bladder prolapse 1/6532 (0%) 1 0/6535 (0%) 0
    Calculus bladder 2/6532 (0%) 2 0/6535 (0%) 0
    Calculus urinary 3/6532 (0%) 3 5/6535 (0.1%) 5
    Chronic kidney disease 15/6532 (0.2%) 16 7/6535 (0.1%) 8
    Cystitis haemorrhagic 0/6532 (0%) 0 1/6535 (0%) 1
    Diabetic nephropathy 3/6532 (0%) 3 2/6535 (0%) 2
    Dysuria 1/6532 (0%) 1 0/6535 (0%) 0
    End stage renal disease 4/6532 (0.1%) 6 9/6535 (0.1%) 10
    Genitourinary symptom 0/6532 (0%) 0 1/6535 (0%) 1
    Haematuria 8/6532 (0.1%) 8 6/6535 (0.1%) 9
    Hydronephrosis 6/6532 (0.1%) 6 2/6535 (0%) 2
    Hypertensive nephropathy 1/6532 (0%) 1 0/6535 (0%) 0
    Hypertonic bladder 1/6532 (0%) 1 0/6535 (0%) 0
    Ketonuria 0/6532 (0%) 0 1/6535 (0%) 1
    Lower urinary tract symptoms 0/6532 (0%) 0 2/6535 (0%) 2
    Nephrolithiasis 15/6532 (0.2%) 18 20/6535 (0.3%) 24
    Nephropathy 0/6532 (0%) 0 1/6535 (0%) 1
    Nephrotic syndrome 2/6532 (0%) 2 1/6535 (0%) 1
    Renal artery arteriosclerosis 0/6532 (0%) 0 1/6535 (0%) 1
    Renal artery stenosis 1/6532 (0%) 1 1/6535 (0%) 1
    Renal artery thrombosis 1/6532 (0%) 1 0/6535 (0%) 0
    Renal colic 3/6532 (0%) 4 3/6535 (0%) 3
    Renal cyst 1/6532 (0%) 1 2/6535 (0%) 2
    Renal embolism 0/6532 (0%) 0 1/6535 (0%) 1
    Renal failure 17/6532 (0.3%) 18 16/6535 (0.2%) 17
    Renal haematoma 0/6532 (0%) 0 1/6535 (0%) 1
    Renal haemorrhage 1/6532 (0%) 1 0/6535 (0%) 0
    Renal impairment 6/6532 (0.1%) 6 2/6535 (0%) 2
    Renal injury 1/6532 (0%) 1 0/6535 (0%) 0
    Renal ischaemia 0/6532 (0%) 0 1/6535 (0%) 1
    Renal mass 2/6532 (0%) 2 1/6535 (0%) 1
    Stag horn calculus 0/6532 (0%) 0 1/6535 (0%) 1
    Stress urinary incontinence 0/6532 (0%) 0 1/6535 (0%) 1
    Tubulointerstitial nephritis 1/6532 (0%) 1 0/6535 (0%) 0
    Ureteric stenosis 2/6532 (0%) 2 0/6535 (0%) 0
    Ureterolithiasis 8/6532 (0.1%) 9 8/6535 (0.1%) 9
    Urethral haemorrhage 0/6532 (0%) 0 1/6535 (0%) 1
    Urethral stenosis 2/6532 (0%) 2 0/6535 (0%) 0
    Urinary bladder haemorrhage 0/6532 (0%) 0 1/6535 (0%) 1
    Urinary fistula 0/6532 (0%) 0 1/6535 (0%) 1
    Urinary incontinence 0/6532 (0%) 0 2/6535 (0%) 2
    Urinary retention 6/6532 (0.1%) 7 5/6535 (0.1%) 5
    Reproductive system and breast disorders
    Acquired hydrocele 1/6532 (0%) 1 0/6535 (0%) 0
    Adenomyosis 0/6532 (0%) 0 1/6535 (0%) 1
    Adnexal torsion 0/6532 (0%) 0 1/6535 (0%) 1
    Balanoposthitis 0/6532 (0%) 0 1/6535 (0%) 1
    Benign prostatic hyperplasia 11/6532 (0.2%) 13 18/6535 (0.3%) 18
    Breast discharge 1/6532 (0%) 1 0/6535 (0%) 0
    Breast disorder 0/6532 (0%) 0 1/6535 (0%) 1
    Breast hyperplasia 0/6532 (0%) 0 1/6535 (0%) 1
    Breast mass 1/6532 (0%) 1 0/6535 (0%) 0
    Breast pain 0/6532 (0%) 0 1/6535 (0%) 1
    Endometrial hyperplasia 4/6532 (0.1%) 4 0/6535 (0%) 0
    Endometrial thickening 0/6532 (0%) 0 1/6535 (0%) 1
    Endometriosis 0/6532 (0%) 0 1/6535 (0%) 1
    Epididymal cyst 0/6532 (0%) 0 1/6535 (0%) 1
    Female genital tract fistula 1/6532 (0%) 1 0/6535 (0%) 0
    Genital leukoplakia 1/6532 (0%) 1 0/6535 (0%) 0
    Haemorrhagic ovarian cyst 1/6532 (0%) 1 0/6535 (0%) 0
    Ovarian cyst 2/6532 (0%) 2 0/6535 (0%) 0
    Pelvic congestion 0/6532 (0%) 0 1/6535 (0%) 1
    Pelvic fluid collection 1/6532 (0%) 1 0/6535 (0%) 0
    Pelvic prolapse 3/6532 (0%) 3 0/6535 (0%) 0
    Perineal cyst 1/6532 (0%) 2 0/6535 (0%) 0
    Peyronie's disease 1/6532 (0%) 1 0/6535 (0%) 0
    Postmenopausal haemorrhage 4/6532 (0.1%) 4 1/6535 (0%) 1
    Prostatic disorder 0/6532 (0%) 0 1/6535 (0%) 1
    Prostatitis 1/6532 (0%) 1 0/6535 (0%) 0
    Prostatomegaly 0/6532 (0%) 0 2/6535 (0%) 3
    Seminal vesiculitis 0/6532 (0%) 0 1/6535 (0%) 1
    Spermatocele 0/6532 (0%) 0 1/6535 (0%) 1
    Testicular cyst 0/6532 (0%) 0 1/6535 (0%) 1
    Testicular mass 0/6532 (0%) 0 1/6535 (0%) 1
    Uterine polyp 1/6532 (0%) 1 2/6535 (0%) 2
    Uterine prolapse 2/6532 (0%) 2 3/6535 (0%) 3
    Vaginal fistula 0/6532 (0%) 0 1/6535 (0%) 1
    Vaginal haemorrhage 1/6532 (0%) 1 0/6535 (0%) 0
    Vaginal prolapse 2/6532 (0%) 2 1/6535 (0%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 4/6532 (0.1%) 4 1/6535 (0%) 1
    Acute respiratory distress syndrome 3/6532 (0%) 3 0/6535 (0%) 0
    Acute respiratory failure 23/6532 (0.4%) 29 15/6535 (0.2%) 16
    Asphyxia 2/6532 (0%) 2 0/6535 (0%) 0
    Aspiration 1/6532 (0%) 1 1/6535 (0%) 1
    Asthma 8/6532 (0.1%) 8 11/6535 (0.2%) 11
    Atelectasis 0/6532 (0%) 0 1/6535 (0%) 1
    Bronchial hyperreactivity 1/6532 (0%) 1 0/6535 (0%) 0
    Bronchiectasis 1/6532 (0%) 1 3/6535 (0%) 3
    Bronchitis chronic 0/6532 (0%) 0 2/6535 (0%) 2
    Bronchospasm 2/6532 (0%) 2 0/6535 (0%) 0
    Chronic obstructive pulmonary disease 31/6532 (0.5%) 35 38/6535 (0.6%) 42
    Chronic respiratory failure 1/6532 (0%) 1 0/6535 (0%) 0
    Chylothorax 2/6532 (0%) 2 0/6535 (0%) 0
    Cough 0/6532 (0%) 0 2/6535 (0%) 2
    Dysphonia 1/6532 (0%) 1 0/6535 (0%) 0
    Dyspnoea 11/6532 (0.2%) 11 15/6535 (0.2%) 17
    Dyspnoea exertional 3/6532 (0%) 3 2/6535 (0%) 2
    Emphysema 1/6532 (0%) 1 1/6535 (0%) 1
    Epiglottic cyst 1/6532 (0%) 1 0/6535 (0%) 0
    Epistaxis 13/6532 (0.2%) 13 7/6535 (0.1%) 7
    Haemoptysis 3/6532 (0%) 3 4/6535 (0.1%) 4
    Haemothorax 3/6532 (0%) 3 0/6535 (0%) 0
    Hypercapnia 1/6532 (0%) 1 0/6535 (0%) 0
    Hypersensitivity pneumonitis 0/6532 (0%) 0 1/6535 (0%) 1
    Hypoxia 2/6532 (0%) 2 3/6535 (0%) 3
    Interstitial lung disease 2/6532 (0%) 3 0/6535 (0%) 0
    Laryngeal oedema 0/6532 (0%) 0 1/6535 (0%) 1
    Laryngospasm 1/6532 (0%) 1 0/6535 (0%) 0
    Nasal congestion 0/6532 (0%) 0 1/6535 (0%) 1
    Nasal septum deviation 1/6532 (0%) 1 3/6535 (0%) 3
    Organising pneumonia 1/6532 (0%) 1 1/6535 (0%) 1
    Pharyngeal stenosis 0/6532 (0%) 0 1/6535 (0%) 1
    Pickwickian syndrome 1/6532 (0%) 1 1/6535 (0%) 1
    Pleural effusion 4/6532 (0.1%) 4 3/6535 (0%) 3
    Pleuritic pain 1/6532 (0%) 1 1/6535 (0%) 1
    Pneumonia aspiration 6/6532 (0.1%) 8 7/6535 (0.1%) 7
    Pneumonitis 0/6532 (0%) 0 2/6535 (0%) 2
    Pneumothorax 2/6532 (0%) 2 3/6535 (0%) 3
    Pneumothorax spontaneous 3/6532 (0%) 3 0/6535 (0%) 0
    Pulmonary arterial hypertension 1/6532 (0%) 1 1/6535 (0%) 1
    Pulmonary congestion 0/6532 (0%) 0 1/6535 (0%) 1
    Pulmonary embolism 23/6532 (0.4%) 23 20/6535 (0.3%) 20
    Pulmonary haemorrhage 0/6532 (0%) 0 1/6535 (0%) 1
    Pulmonary hypertension 0/6532 (0%) 0 3/6535 (0%) 5
    Pulmonary infarction 0/6532 (0%) 0 1/6535 (0%) 1
    Pulmonary mass 1/6532 (0%) 1 0/6535 (0%) 0
    Pulmonary oedema 7/6532 (0.1%) 7 4/6535 (0.1%) 6
    Respiratory arrest 2/6532 (0%) 2 0/6535 (0%) 0
    Respiratory distress 2/6532 (0%) 3 2/6535 (0%) 2
    Respiratory failure 6/6532 (0.1%) 7 12/6535 (0.2%) 17
    Sleep apnoea syndrome 7/6532 (0.1%) 7 7/6535 (0.1%) 7
    Tonsillar disorder 1/6532 (0%) 1 0/6535 (0%) 0
    Vocal cord polyp 1/6532 (0%) 1 0/6535 (0%) 0
    Skin and subcutaneous tissue disorders
    Acanthosis 1/6532 (0%) 1 0/6535 (0%) 0
    Alopecia scarring 1/6532 (0%) 1 0/6535 (0%) 0
    Angioedema 2/6532 (0%) 2 1/6535 (0%) 1
    Decubitus ulcer 2/6532 (0%) 2 0/6535 (0%) 0
    Dermal cyst 0/6532 (0%) 0 1/6535 (0%) 1
    Dermatitis 1/6532 (0%) 1 0/6535 (0%) 0
    Dermatitis allergic 2/6532 (0%) 2 0/6535 (0%) 0
    Dermatitis contact 0/6532 (0%) 0 2/6535 (0%) 2
    Dermatomyositis 1/6532 (0%) 1 0/6535 (0%) 0
    Diabetic foot 6/6532 (0.1%) 7 14/6535 (0.2%) 16
    Eczema 0/6532 (0%) 0 1/6535 (0%) 1
    Erythema multiforme 1/6532 (0%) 1 0/6535 (0%) 0
    Granuloma annulare 1/6532 (0%) 1 0/6535 (0%) 0
    Henoch-schonlein purpura 0/6532 (0%) 0 1/6535 (0%) 1
    Hidradenitis 0/6532 (0%) 0 1/6535 (0%) 1
    Hypersensitivity vasculitis 0/6532 (0%) 0 1/6535 (0%) 1
    Ischaemic skin ulcer 1/6532 (0%) 1 2/6535 (0%) 2
    Panniculitis 0/6532 (0%) 0 1/6535 (0%) 1
    Pruritus 1/6532 (0%) 1 0/6535 (0%) 0
    Skin necrosis 1/6532 (0%) 1 0/6535 (0%) 0
    Skin ulcer 8/6532 (0.1%) 9 12/6535 (0.2%) 14
    Urticaria 2/6532 (0%) 2 0/6535 (0%) 0
    Social circumstances
    Aborted pregnancy 1/6532 (0%) 1 0/6535 (0%) 0
    Surgical and medical procedures
    Hospitalisation 1/6532 (0%) 1 0/6535 (0%) 0
    Vascular disorders
    Accelerated hypertension 1/6532 (0%) 1 1/6535 (0%) 1
    Aneurysm 0/6532 (0%) 0 2/6535 (0%) 2
    Aortic aneurysm 16/6532 (0.2%) 16 11/6535 (0.2%) 12
    Aortic aneurysm rupture 2/6532 (0%) 2 0/6535 (0%) 0
    Aortic dissection 5/6532 (0.1%) 5 2/6535 (0%) 2
    Aortic embolus 1/6532 (0%) 1 0/6535 (0%) 0
    Aortic stenosis 8/6532 (0.1%) 8 4/6535 (0.1%) 5
    Arterial occlusive disease 1/6532 (0%) 1 0/6535 (0%) 0
    Arterial stenosis 1/6532 (0%) 1 0/6535 (0%) 0
    Arteriosclerosis 3/6532 (0%) 3 2/6535 (0%) 2
    Blood pressure inadequately controlled 0/6532 (0%) 0 1/6535 (0%) 1
    Circulatory collapse 3/6532 (0%) 3 3/6535 (0%) 4
    Deep vein thrombosis 14/6532 (0.2%) 15 15/6535 (0.2%) 16
    Diabetic vascular disorder 2/6532 (0%) 3 1/6535 (0%) 1
    Dry gangrene 0/6532 (0%) 0 2/6535 (0%) 2
    Embolism 0/6532 (0%) 0 1/6535 (0%) 1
    Embolism venous 1/6532 (0%) 1 1/6535 (0%) 1
    Essential hypertension 1/6532 (0%) 1 1/6535 (0%) 2
    Extremity necrosis 2/6532 (0%) 2 5/6535 (0.1%) 6
    Femoral artery perforation 1/6532 (0%) 1 0/6535 (0%) 0
    Haematoma 5/6532 (0.1%) 5 0/6535 (0%) 0
    Haemodynamic instability 0/6532 (0%) 0 1/6535 (0%) 1
    Hypertension 30/6532 (0.5%) 33 31/6535 (0.5%) 35
    Hypertensive crisis 15/6532 (0.2%) 19 9/6535 (0.1%) 12
    Hypertensive emergency 1/6532 (0%) 1 4/6535 (0.1%) 4
    Hypertensive urgency 6/6532 (0.1%) 6 4/6535 (0.1%) 4
    Hypotension 11/6532 (0.2%) 11 10/6535 (0.2%) 12
    Hypovolaemic shock 1/6532 (0%) 1 4/6535 (0.1%) 4
    Iliac artery occlusion 0/6532 (0%) 0 3/6535 (0%) 3
    Iliac artery stenosis 3/6532 (0%) 3 2/6535 (0%) 2
    Inferior vena cava perforation 1/6532 (0%) 1 0/6535 (0%) 0
    Intermittent claudication 4/6532 (0.1%) 4 4/6535 (0.1%) 7
    Jugular vein thrombosis 0/6532 (0%) 0 1/6535 (0%) 1
    Leriche syndrome 1/6532 (0%) 1 0/6535 (0%) 0
    Lymphoedema 2/6532 (0%) 2 3/6535 (0%) 3
    Malignant hypertension 0/6532 (0%) 0 1/6535 (0%) 1
    Neurogenic shock 0/6532 (0%) 0 1/6535 (0%) 1
    Orthostatic hypotension 4/6532 (0.1%) 4 10/6535 (0.2%) 11
    Peripheral arterial occlusive disease 30/6532 (0.5%) 39 45/6535 (0.7%) 52
    Peripheral artery aneurysm 3/6532 (0%) 4 3/6535 (0%) 4
    Peripheral artery aneurysm rupture 1/6532 (0%) 1 0/6535 (0%) 0
    Peripheral artery occlusion 7/6532 (0.1%) 8 8/6535 (0.1%) 10
    Peripheral artery stenosis 7/6532 (0.1%) 8 3/6535 (0%) 5
    Peripheral artery thrombosis 4/6532 (0.1%) 4 1/6535 (0%) 2
    Peripheral coldness 1/6532 (0%) 1 0/6535 (0%) 0
    Peripheral ischaemia 16/6532 (0.2%) 21 11/6535 (0.2%) 13
    Peripheral vascular disorder 13/6532 (0.2%) 20 12/6535 (0.2%) 16
    Peripheral venous disease 0/6532 (0%) 0 1/6535 (0%) 1
    Phlebitis 1/6532 (0%) 1 1/6535 (0%) 1
    Shock 0/6532 (0%) 0 1/6535 (0%) 1
    Subclavian artery stenosis 1/6532 (0%) 1 0/6535 (0%) 0
    Subclavian steal syndrome 1/6532 (0%) 1 0/6535 (0%) 0
    Subclavian vein thrombosis 1/6532 (0%) 1 0/6535 (0%) 0
    Thrombophlebitis 1/6532 (0%) 1 3/6535 (0%) 3
    Thrombosis 0/6532 (0%) 0 1/6535 (0%) 1
    Vasculitis 1/6532 (0%) 1 1/6535 (0%) 1
    Venous thrombosis limb 1/6532 (0%) 1 0/6535 (0%) 0
    Other (Not Including Serious) Adverse Events
    Epanova Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1405/6532 (21.5%) 826/6535 (12.6%)
    Gastrointestinal disorders
    Abdominal discomfort 87/6532 (1.3%) 102 35/6535 (0.5%) 38
    Abdominal pain 90/6532 (1.4%) 104 54/6535 (0.8%) 61
    Abdominal pain upper 80/6532 (1.2%) 99 59/6535 (0.9%) 68
    Diarrhoea 765/6532 (11.7%) 1049 316/6535 (4.8%) 386
    Dyspepsia 89/6532 (1.4%) 104 41/6535 (0.6%) 53
    Nausea 204/6532 (3.1%) 229 110/6535 (1.7%) 126
    Infections and infestations
    Nasopharyngitis 97/6532 (1.5%) 193 75/6535 (1.1%) 145
    Metabolism and nutrition disorders
    Diabetes mellitus 147/6532 (2.3%) 150 121/6535 (1.9%) 122
    Type 2 diabetes mellitus 130/6532 (2%) 131 153/6535 (2.3%) 155

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The Principal Investigator shall provide AstraZeneca with copies of any materials relating to the Study, the Study Documentation, or the Developed Technologies that either Party intends to publish (or submit for publication) or make any presentations relating to, at least 60 days in advance of publication, submission or presentation.

    Results Point of Contact

    Name/Title AstraZenenca Information Center
    Organization AstraZeneca
    Phone 1-877-240-9479
    Email information.center@astrazeneca.com
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT02104817
    Other Study ID Numbers:
    • D5881C00004
    • 2014-001069-28
    First Posted:
    Apr 4, 2014
    Last Update Posted:
    Aug 17, 2021
    Last Verified:
    Aug 1, 2021