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SAVOR- TIMI 53: Does Saxagliptin Reduce the Risk of Cardiovascular Events When Used Alone or Added to Other Diabetes Medications

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT01107886
Collaborator
Bristol-Myers Squibb (Industry)
18,206
Enrollment
551
Locations
2
Arms
36
Duration (Months)
33
Patients Per Site
0.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether saxagliptin can reduce the risk of cardiovascular events when used alone or added to other diabetes medications

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

A Multicentre, Randomised, Double-Blind, Placebo-Controlled Phase IV Trial to Evaluate the Effect of Saxagliptin on the Incidence of Cardiovascular Death, Myocardial Infarction or Ischaemic Stroke in Patients with Type 2 Diabetes

Study Design

Study Type:
Interventional
Actual Enrollment :
18206 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicentre, Randomised, Double-Blind, Placebo-Controlled Phase IV Trial to Evaluate the Effect of Saxagliptin on the Incidence of Cardiovascular Death, Myocardial Infarction or Ischaemic Stroke in Patients With Type 2 Diabetes
Study Start Date :
May 1, 2010
Actual Primary Completion Date :
May 1, 2013
Actual Study Completion Date :
May 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Saxagliptin

Drug: Saxagliptin
5 mg or 2.5 mg once daily
Other Names:
  • Onglyza

    		•
    Placebo Comparator: Placebo

    Placebo

    Drug: Placebo

    Outcome Measures

    Primary Outcome Measures

    1. Participants With Any Event From the Composite of Cardiovascular Death (CV Death), Non-fatal Myocardial Infarction (MI), or Non-fatal Ischaemic Stroke [Randomization (day 0) up to 2.9 years]

      Participants with CV death, non-fatal MI or non-fatal ischaemic stroke. If no event, censoring occurs at the patient withdrawal of consent, last contact, or death (when applicable)-whichever was later.

    Secondary Outcome Measures

    1. Participants With Any Event From the Composite of CV Death, Non-fatal MI, Non-fatal Ischaemic Stroke, Hospitalisation for Heart Failure, Hospitalisation for Unstable Angina Pectoris, or Hospitalisation for Coronary Revascularisation [Randomization (day 0) up to 2.9 years]

      Participants with CV death, non-fatal MI, non-fatal ischaemic stroke, hospitalisation for heart failure, hospitalisation for unstable angina pectoris, or hospitalisation for coronary revascularisation. If no event, censoring occurs at the patient withdrawal of consent, last contact, or death (when applicable)-whichever was later.

    2. Participants With Event of Death [Randomization (day 0) up to 2.9 years]

      Participants with event of death. If no event, censoring occurs at the patient withdrawal of consent, or last contact -whichever was later.

    Eligibility Criteria

    Criteria

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

    • Patients with type 2 diabetes mellitus

    • HbA1c ≥6.5%. (based on the last measured and documented laboratory measurement within 6 months)

    • High risk for CV events -Established cardiovascular disease and/or multiple risk factors

    Exclusion Criteria:

    • Current or previous (within 6 months) treatment with DPP4 inhibitors and/or GLP-1 mimetics

    • Acute vascular event <2months prior to randomisation

    Contacts and Locations

    Locations

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    Sponsors and Collaborators

    • AstraZeneca
    • Bristol-Myers Squibb

    Investigators

    • Study Chair: Eugene Braunwald, TIMI
    • Principal Investigator: Itamar Raz, Hadassah Medical Organization
    • Principal Investigator: Deepak Bhatt, TIMI

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT01107886
    Other Study ID Numbers:
    • D1680C00003
    • EudraCT No 2009-017358-10
    First Posted:
    Apr 21, 2010
    Last Update Posted:
    Jul 17, 2014
    Last Verified:
    Jul 1, 2014
    Keywords provided by AstraZeneca
    Risk of cardiovascular disease and death in patients with type 2 diabetes mellitus
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Saxagliptin

    Study Results

    Participant Flow

    Recruitment Details The first participant was enrolled on 10 May 2010 and the last participant completed the study on 16 May 2013. A total of 18206 subjects were enrolled in the study of which 16492 were randomised. Study participants were randomized from 790 centers in 26 countries.
    Pre-assignment Detail Subjects meeting all inclusion criteria and with no exclusion criteria were randomised in a 1:1 ratio to receive either saxagliptin or matching placebo (Day 0).
    Arm/Group Title Saxagliptin Placebo
    Arm/Group Description 5 mg once daily in subjects with normal renal function or mild impaired renal function (eGFR >50 mL/min); 2.5 mg once daily in subjects with moderate to severe renal impairment (eGFR ≤50 mL/min). Matching Placebo
    Period Title: Overall Study
    STARTED 8280 8212
    COMPLETED 8078 7998
    NOT COMPLETED 202 214

    Baseline Characteristics

    Arm/Group Title Saxagliptin Placebo Total
    Arm/Group Description 5 mg once daily in subjects with normal renal function or mild impaired renal function (eGFR >50 mL/min); 2.5 mg once daily in subjects with moderate to severe renal impairment (eGFR ≤50 mL/min). Matching Placebo Total of all reporting groups
    Overall Participants 8280 8212 16492
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    65.1
    (8.52)
    65.0
    (8.58)
    65.0
    (8.55)
    Sex: Female, Male (Count of Participants)
    Female
    2768
    33.4%
    2687
    32.7%
    5455
    33.1%
    Male
    5512
    66.6%
    5525
    67.3%
    11037
    66.9%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1778
    21.5%
    1763
    21.5%
    3541
    21.5%
    Not Hispanic or Latino
    6502
    78.5%
    6449
    78.5%
    12951
    78.5%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    18
    0.2%
    33
    0.4%
    51
    0.3%
    Asian
    896
    10.8%
    884
    10.8%
    1780
    10.8%
    Native Hawaiian or Other Pacific Islander
    11
    0.1%
    11
    0.1%
    22
    0.1%
    Black or African American
    278
    3.4%
    290
    3.5%
    568
    3.4%
    White
    6241
    75.4%
    6166
    75.1%
    12407
    75.2%
    More than one race
    768
    9.3%
    758
    9.2%
    1526
    9.3%
    Unknown or Not Reported
    68
    0.8%
    70
    0.9%
    138
    0.8%
    Cardiovascular Risk Category: Cardiovascular disease/Multiple risk factors (CVD/MRF) (Number) [Number]
    CVD
    6494
    78.4%
    6465
    78.7%
    12959
    78.6%
    MRF
    1786
    21.6%
    1747
    21.3%
    3533
    21.4%
    Renal Functione Categor: Normal or Mild impairment/Moderate impairment/Severe impairment (Number) [Number]
    Normal or Mild impairment
    6986
    84.4%
    6930
    84.4%
    13916
    84.4%
    Moderate impairment
    1122
    13.6%
    1118
    13.6%
    2240
    13.6%
    Severe impairment
    172
    2.1%
    164
    2%
    336
    2%

    Outcome Measures

    1. Primary Outcome
    Title Participants With Any Event From the Composite of Cardiovascular Death (CV Death), Non-fatal Myocardial Infarction (MI), or Non-fatal Ischaemic Stroke
    Description Participants with CV death, non-fatal MI or non-fatal ischaemic stroke. If no event, censoring occurs at the patient withdrawal of consent, last contact, or death (when applicable)-whichever was later.
    Time Frame Randomization (day 0) up to 2.9 years

    Outcome Measure Data

    Analysis Population Description
    Intention To Treat (ITT) analysis of randomized population. Events were adjudicated by the Clinical Event Adjudication Committee.
    Arm/Group Title Saxagliptin Placebo
    Arm/Group Description 5 mg once daily in subjects with normal renal function or mild impaired renal function (eGFR >50 mL/min); 2.5 mg once daily in subjects with moderate to severe renal impairment (eGFR ≤50 mL/min). Matching Placebo
    Measure Participants 8280 8212
    Number [participants]
    613
    7.4%
    609
    7.4%
    2. Secondary Outcome
    Title Participants With Any Event From the Composite of CV Death, Non-fatal MI, Non-fatal Ischaemic Stroke, Hospitalisation for Heart Failure, Hospitalisation for Unstable Angina Pectoris, or Hospitalisation for Coronary Revascularisation
    Description Participants with CV death, non-fatal MI, non-fatal ischaemic stroke, hospitalisation for heart failure, hospitalisation for unstable angina pectoris, or hospitalisation for coronary revascularisation. If no event, censoring occurs at the patient withdrawal of consent, last contact, or death (when applicable)-whichever was later.
    Time Frame Randomization (day 0) up to 2.9 years

    Outcome Measure Data

    Analysis Population Description
    Intention To Treat (ITT) analysis of randomized population. Events were adjudicated by the Clinical Event Adjudication Committee.
    Arm/Group Title Saxagliptin Placebo
    Arm/Group Description 5 mg once daily in subjects with normal renal function or mild impaired renal function (eGFR >50 mL/min); 2.5 mg once daily in subjects with moderate to severe renal impairment (eGFR ≤50 mL/min). Matching Placebo
    Measure Participants 8280 8212
    Number [participants]
    1059
    12.8%
    1034
    12.6%
    3. Secondary Outcome
    Title Participants With Event of Death
    Description Participants with event of death. If no event, censoring occurs at the patient withdrawal of consent, or last contact -whichever was later.
    Time Frame Randomization (day 0) up to 2.9 years

    Outcome Measure Data

    Analysis Population Description
    Intention To Treat (ITT) analysis of randomized population. Events were adjudicated by the Clinical Event Adjudication Committee.
    Arm/Group Title Saxagliptin Placebo
    Arm/Group Description 5 mg once daily in subjects with normal renal function or mild impaired renal function (eGFR >50 mL/min); 2.5 mg once daily in subjects with moderate to severe renal impairment (eGFR ≤50 mL/min). Matching Placebo
    Measure Participants 8280 8212
    Number [participants]
    420
    5.1%
    378
    4.6%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Placebo Saxagliptin
    Arm/Group Description Matching Placebo 5 mg once daily in subjects with normal renal function or mild impaired renal function (eGFR >50 mL/min); 2.5 mg once daily in subjects with moderate to severe renal impairment (eGFR ≤50 mL/min).
    All Cause Mortality
    Placebo Saxagliptin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Placebo Saxagliptin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2075/8212 (25.3%) 2114/8280 (25.5%)
    Blood and lymphatic system disorders
    Anaemia 26/8212 (0.3%) 27 17/8280 (0.2%) 19
    Anaemia megaloblastic 0/8212 (0%) 0 1/8280 (0%) 1
    Anaemia of chronic disease 1/8212 (0%) 1 0/8280 (0%) 0
    Coagulopathy 1/8212 (0%) 1 0/8280 (0%) 0
    Disseminated intravascular coagulation 0/8212 (0%) 0 1/8280 (0%) 1
    Febrile neutropenia 0/8212 (0%) 0 1/8280 (0%) 1
    Haemorrhagic anaemia 1/8212 (0%) 1 1/8280 (0%) 1
    Haemorrhagic diathesis 1/8212 (0%) 1 0/8280 (0%) 0
    Hypereosinophilic syndrome 1/8212 (0%) 1 0/8280 (0%) 0
    Hypochromic anaemia 2/8212 (0%) 2 1/8280 (0%) 1
    Iron deficiency anaemia 7/8212 (0.1%) 7 5/8280 (0.1%) 5
    Leukocytosis 1/8212 (0%) 1 1/8280 (0%) 1
    Leukopenia 1/8212 (0%) 1 0/8280 (0%) 0
    Lymphopenia 1/8212 (0%) 1 3/8280 (0%) 3
    Microcytic anaemia 1/8212 (0%) 1 1/8280 (0%) 1
    Nephrogenic anaemia 0/8212 (0%) 0 2/8280 (0%) 2
    Neutropenia 1/8212 (0%) 1 1/8280 (0%) 1
    Normochromic normocytic anaemia 0/8212 (0%) 0 4/8280 (0%) 4
    Pancytopenia 1/8212 (0%) 1 1/8280 (0%) 1
    Pernicious anaemia 0/8212 (0%) 0 1/8280 (0%) 1
    Thrombocytopenia 3/8212 (0%) 3 5/8280 (0.1%) 5
    Cardiac disorders
    Acute coronary syndrome 7/8212 (0.1%) 7 5/8280 (0.1%) 5
    Acute left ventricular failure 1/8212 (0%) 1 0/8280 (0%) 0
    Acute myocardial infarction 2/8212 (0%) 2 6/8280 (0.1%) 6
    Adams-Stokes syndrome 0/8212 (0%) 0 2/8280 (0%) 2
    Angina pectoris 106/8212 (1.3%) 116 89/8280 (1.1%) 98
    Angina unstable 63/8212 (0.8%) 79 44/8280 (0.5%) 48
    Aortic valve stenosis 5/8212 (0.1%) 5 6/8280 (0.1%) 6
    Arrhythmia 4/8212 (0%) 4 3/8280 (0%) 3
    Arteriosclerosis coronary artery 2/8212 (0%) 2 2/8280 (0%) 2
    Arteriospasm coronary 1/8212 (0%) 1 0/8280 (0%) 0
    Atrial fibrillation 76/8212 (0.9%) 90 78/8280 (0.9%) 85
    Atrial flutter 11/8212 (0.1%) 13 22/8280 (0.3%) 25
    Atrial septal defect acquired 1/8212 (0%) 1 0/8280 (0%) 0
    Atrial tachycardia 1/8212 (0%) 1 1/8280 (0%) 1
    Atrial thrombosis 1/8212 (0%) 1 0/8280 (0%) 0
    Atrioventricular block 3/8212 (0%) 3 3/8280 (0%) 3
    Atrioventricular block complete 13/8212 (0.2%) 13 6/8280 (0.1%) 6
    Atrioventricular block first degree 0/8212 (0%) 0 1/8280 (0%) 1
    Atrioventricular block second degree 5/8212 (0.1%) 6 2/8280 (0%) 2
    Bifascicular block 0/8212 (0%) 0 1/8280 (0%) 1
    Bradyarrhythmia 4/8212 (0%) 4 0/8280 (0%) 0
    Bradycardia 11/8212 (0.1%) 11 14/8280 (0.2%) 15
    Bundle branch block 0/8212 (0%) 0 1/8280 (0%) 1
    Bundle branch block left 1/8212 (0%) 1 0/8280 (0%) 0
    Cardiac aneurysm 0/8212 (0%) 0 1/8280 (0%) 1
    Cardiac arrest 4/8212 (0%) 4 5/8280 (0.1%) 5
    Cardiac failure 24/8212 (0.3%) 24 21/8280 (0.3%) 22
    Cardiac failure acute 0/8212 (0%) 0 3/8280 (0%) 3
    Cardiac failure chronic 2/8212 (0%) 2 1/8280 (0%) 1
    Cardiac failure congestive 21/8212 (0.3%) 22 30/8280 (0.4%) 30
    Cardiac fibrillation 1/8212 (0%) 1 0/8280 (0%) 0
    Cardiac tamponade 1/8212 (0%) 1 2/8280 (0%) 2
    Cardiac valve disease 1/8212 (0%) 1 0/8280 (0%) 0
    Cardio-respiratory arrest 2/8212 (0%) 2 1/8280 (0%) 1
    Cardiogenic shock 1/8212 (0%) 1 1/8280 (0%) 1
    Cardiomyopathy 3/8212 (0%) 3 2/8280 (0%) 2
    Cardiopulmonary failure 2/8212 (0%) 2 0/8280 (0%) 0
    Cardiovascular disorder 0/8212 (0%) 0 1/8280 (0%) 1
    Cardiovascular insufficiency 0/8212 (0%) 0 1/8280 (0%) 1
    Congestive cardiomyopathy 2/8212 (0%) 2 2/8280 (0%) 2
    Cor pulmonale 1/8212 (0%) 1 0/8280 (0%) 0
    Coronary artery disease 18/8212 (0.2%) 19 17/8280 (0.2%) 17
    Coronary artery insufficiency 2/8212 (0%) 2 0/8280 (0%) 0
    Coronary artery occlusion 2/8212 (0%) 2 0/8280 (0%) 0
    Diastolic dysfunction 0/8212 (0%) 0 1/8280 (0%) 1
    Hypertensive heart disease 1/8212 (0%) 1 1/8280 (0%) 1
    Hypertrophic cardiomyopathy 1/8212 (0%) 1 0/8280 (0%) 0
    Intracardiac thrombus 2/8212 (0%) 2 2/8280 (0%) 2
    Ischaemic cardiomyopathy 6/8212 (0.1%) 7 3/8280 (0%) 3
    Left ventricular dysfunction 3/8212 (0%) 3 1/8280 (0%) 1
    Left ventricular failure 0/8212 (0%) 0 2/8280 (0%) 3
    Mitral valve incompetence 3/8212 (0%) 3 3/8280 (0%) 3
    Myocardial infarction 5/8212 (0.1%) 5 3/8280 (0%) 3
    Myocardial ischaemia 11/8212 (0.1%) 11 7/8280 (0.1%) 7
    Nodal arrhythmia 1/8212 (0%) 1 0/8280 (0%) 0
    Palpitations 4/8212 (0%) 4 3/8280 (0%) 3
    Pericardial effusion 1/8212 (0%) 1 2/8280 (0%) 2
    Pericarditis 3/8212 (0%) 4 0/8280 (0%) 0
    Pulseless electrical activity 1/8212 (0%) 1 0/8280 (0%) 0
    Right ventricular dysfunction 0/8212 (0%) 0 1/8280 (0%) 1
    Sick sinus syndrome 14/8212 (0.2%) 14 10/8280 (0.1%) 10
    Sinoatrial block 1/8212 (0%) 1 0/8280 (0%) 0
    Sinus arrhythmia 2/8212 (0%) 2 2/8280 (0%) 2
    Sinus bradycardia 6/8212 (0.1%) 6 3/8280 (0%) 3
    Sinus tachycardia 1/8212 (0%) 1 0/8280 (0%) 0
    Supraventricular tachycardia 4/8212 (0%) 4 9/8280 (0.1%) 10
    Systolic dysfunction 0/8212 (0%) 0 1/8280 (0%) 1
    Tachyarrhythmia 1/8212 (0%) 2 1/8280 (0%) 1
    Tachycardia 2/8212 (0%) 3 8/8280 (0.1%) 8
    Torsade de pointes 1/8212 (0%) 1 0/8280 (0%) 0
    Tricuspid valve incompetence 0/8212 (0%) 0 1/8280 (0%) 1
    Trifascicular block 1/8212 (0%) 1 0/8280 (0%) 0
    Ventricular arrhythmia 2/8212 (0%) 2 1/8280 (0%) 1
    Ventricular extrasystoles 4/8212 (0%) 4 1/8280 (0%) 1
    Ventricular fibrillation 5/8212 (0.1%) 5 3/8280 (0%) 3
    Ventricular hypokinesia 1/8212 (0%) 1 0/8280 (0%) 0
    Ventricular tachyarrhythmia 1/8212 (0%) 1 0/8280 (0%) 0
    Ventricular tachycardia 11/8212 (0.1%) 16 16/8280 (0.2%) 17
    Ear and labyrinth disorders
    Deafness 1/8212 (0%) 1 0/8280 (0%) 0
    Meniere's disease 1/8212 (0%) 1 0/8280 (0%) 0
    Sudden hearing loss 1/8212 (0%) 1 0/8280 (0%) 0
    Tinnitus 0/8212 (0%) 0 1/8280 (0%) 2
    Tympanic membrane perforation 0/8212 (0%) 0 1/8280 (0%) 2
    Vertigo 10/8212 (0.1%) 10 16/8280 (0.2%) 16
    Vertigo positional 1/8212 (0%) 1 3/8280 (0%) 3
    Vestibular disorder 1/8212 (0%) 1 0/8280 (0%) 0
    Endocrine disorders
    Adrenal insufficiency 1/8212 (0%) 1 0/8280 (0%) 0
    Goitre 1/8212 (0%) 1 2/8280 (0%) 2
    Hypercorticoidism 1/8212 (0%) 1 0/8280 (0%) 0
    Hyperparathyroidism primary 0/8212 (0%) 0 1/8280 (0%) 1
    Hyperthyroidism 2/8212 (0%) 2 6/8280 (0.1%) 6
    Hypothyroidism 0/8212 (0%) 0 1/8280 (0%) 1
    Toxic nodular goitre 0/8212 (0%) 0 1/8280 (0%) 1
    Eye disorders
    Angle closure glaucoma 1/8212 (0%) 1 0/8280 (0%) 0
    Cataract 13/8212 (0.2%) 15 7/8280 (0.1%) 9
    Cataract cortical 0/8212 (0%) 0 1/8280 (0%) 1
    Diabetic retinopathy 1/8212 (0%) 1 6/8280 (0.1%) 7
    Diplopia 1/8212 (0%) 1 1/8280 (0%) 1
    Eye haemorrhage 1/8212 (0%) 1 0/8280 (0%) 0
    Glaucoma 1/8212 (0%) 1 2/8280 (0%) 2
    Macular oedema 0/8212 (0%) 0 1/8280 (0%) 1
    Optic ischaemic neuropathy 3/8212 (0%) 3 0/8280 (0%) 0
    Retinal artery occlusion 1/8212 (0%) 1 1/8280 (0%) 1
    Retinal detachment 2/8212 (0%) 2 1/8280 (0%) 1
    Retinal haemorrhage 0/8212 (0%) 0 1/8280 (0%) 1
    Retinal ischaemia 0/8212 (0%) 0 1/8280 (0%) 1
    Ulcerative keratitis 0/8212 (0%) 0 1/8280 (0%) 1
    Vision blurred 0/8212 (0%) 0 2/8280 (0%) 2
    Vitreous haemorrhage 3/8212 (0%) 3 2/8280 (0%) 2
    Gastrointestinal disorders
    Abdominal adhesions 1/8212 (0%) 1 1/8280 (0%) 1
    Abdominal discomfort 0/8212 (0%) 0 1/8280 (0%) 1
    Abdominal hernia 5/8212 (0.1%) 5 3/8280 (0%) 3
    Abdominal hernia obstructive 1/8212 (0%) 1 2/8280 (0%) 2
    Abdominal pain 13/8212 (0.2%) 14 17/8280 (0.2%) 17
    Abdominal pain lower 1/8212 (0%) 1 1/8280 (0%) 1
    Abdominal pain upper 2/8212 (0%) 2 4/8280 (0%) 4
    Abdominal strangulated hernia 0/8212 (0%) 0 1/8280 (0%) 1
    Abdominal wall haematoma 3/8212 (0%) 3 0/8280 (0%) 0
    Anal fistula 2/8212 (0%) 3 0/8280 (0%) 0
    Anal polyp 0/8212 (0%) 0 1/8280 (0%) 1
    Ascites 4/8212 (0%) 4 3/8280 (0%) 3
    Colitis 5/8212 (0.1%) 5 4/8280 (0%) 4
    Colitis ischaemic 1/8212 (0%) 1 6/8280 (0.1%) 6
    Colitis ulcerative 0/8212 (0%) 0 1/8280 (0%) 1
    Colonic polyp 4/8212 (0%) 4 6/8280 (0.1%) 6
    Colonic pseudo-obstruction 0/8212 (0%) 0 1/8280 (0%) 1
    Constipation 5/8212 (0.1%) 5 4/8280 (0%) 4
    Crohn's disease 1/8212 (0%) 1 1/8280 (0%) 1
    Diabetic gastroparesis 2/8212 (0%) 5 1/8280 (0%) 1
    Diaphragmatic hernia 1/8212 (0%) 1 1/8280 (0%) 1
    Diarrhoea 15/8212 (0.2%) 15 12/8280 (0.1%) 13
    Diverticular perforation 0/8212 (0%) 0 1/8280 (0%) 1
    Diverticulitis intestinal haemorrhagic 0/8212 (0%) 0 1/8280 (0%) 1
    Diverticulum 2/8212 (0%) 2 1/8280 (0%) 1
    Diverticulum intestinal 1/8212 (0%) 1 0/8280 (0%) 0
    Diverticulum oesophageal 1/8212 (0%) 1 0/8280 (0%) 0
    Duodenal perforation 1/8212 (0%) 1 0/8280 (0%) 0
    Duodenal ulcer 7/8212 (0.1%) 7 4/8280 (0%) 4
    Duodenal ulcer haemorrhage 2/8212 (0%) 2 2/8280 (0%) 2
    Duodenal ulcer perforation 3/8212 (0%) 3 0/8280 (0%) 0
    Dyskinesia oesophageal 1/8212 (0%) 3 0/8280 (0%) 0
    Dyspepsia 1/8212 (0%) 1 2/8280 (0%) 2
    Dysphagia 1/8212 (0%) 1 3/8280 (0%) 3
    Enteritis 0/8212 (0%) 0 3/8280 (0%) 3
    Enterovesical fistula 1/8212 (0%) 1 0/8280 (0%) 0
    Epigastric discomfort 1/8212 (0%) 1 0/8280 (0%) 0
    Faecaloma 0/8212 (0%) 0 1/8280 (0%) 1
    Femoral hernia 0/8212 (0%) 0 1/8280 (0%) 1
    Food poisoning 2/8212 (0%) 2 1/8280 (0%) 1
    Gastric antral vascular ectasia 0/8212 (0%) 0 1/8280 (0%) 1
    Gastric haemorrhage 4/8212 (0%) 4 0/8280 (0%) 0
    Gastric ulcer 7/8212 (0.1%) 7 3/8280 (0%) 3
    Gastric ulcer haemorrhage 4/8212 (0%) 4 3/8280 (0%) 3
    Gastritis 11/8212 (0.1%) 12 15/8280 (0.2%) 15
    Gastritis atrophic 0/8212 (0%) 0 1/8280 (0%) 1
    Gastritis erosive 3/8212 (0%) 3 1/8280 (0%) 1
    Gastritis haemorrhagic 1/8212 (0%) 1 1/8280 (0%) 1
    Gastrointestinal angiodysplasia 1/8212 (0%) 1 0/8280 (0%) 0
    Gastrointestinal haemorrhage 18/8212 (0.2%) 25 15/8280 (0.2%) 15
    Gastrointestinal hypomotility 1/8212 (0%) 1 0/8280 (0%) 0
    Gastrointestinal inflammation 0/8212 (0%) 0 2/8280 (0%) 2
    Gastrointestinal telangiectasia 3/8212 (0%) 3 0/8280 (0%) 0
    Gastrointestinal ulcer haemorrhage 1/8212 (0%) 1 1/8280 (0%) 1
    Gastrointestinal vascular malformation 1/8212 (0%) 1 2/8280 (0%) 2
    Gastrooesophageal reflux disease 8/8212 (0.1%) 8 7/8280 (0.1%) 7
    Gingival bleeding 0/8212 (0%) 0 1/8280 (0%) 1
    Haematemesis 0/8212 (0%) 0 2/8280 (0%) 2
    Haematochezia 2/8212 (0%) 2 0/8280 (0%) 0
    Haemorrhagic erosive gastritis 1/8212 (0%) 1 0/8280 (0%) 0
    Haemorrhoidal haemorrhage 4/8212 (0%) 4 0/8280 (0%) 0
    Haemorrhoids 3/8212 (0%) 3 5/8280 (0.1%) 5
    Hiatus hernia 0/8212 (0%) 0 2/8280 (0%) 2
    Ileus 1/8212 (0%) 1 1/8280 (0%) 1
    Impaired gastric emptying 1/8212 (0%) 1 0/8280 (0%) 0
    Inflammatory bowel disease 1/8212 (0%) 1 0/8280 (0%) 0
    Inguinal hernia 4/8212 (0%) 4 6/8280 (0.1%) 6
    Inguinal hernia, obstructive 2/8212 (0%) 2 0/8280 (0%) 0
    Intestinal ischaemia 2/8212 (0%) 3 1/8280 (0%) 1
    Intestinal obstruction 3/8212 (0%) 3 5/8280 (0.1%) 5
    Intestinal perforation 2/8212 (0%) 2 0/8280 (0%) 0
    Intestinal polyp haemorrhage 3/8212 (0%) 3 0/8280 (0%) 0
    Irritable bowel syndrome 1/8212 (0%) 1 1/8280 (0%) 1
    Large intestinal haemorrhage 0/8212 (0%) 0 1/8280 (0%) 1
    Large intestine perforation 1/8212 (0%) 1 1/8280 (0%) 1
    Lower gastrointestinal haemorrhage 4/8212 (0%) 4 0/8280 (0%) 0
    Mallory-Weiss syndrome 0/8212 (0%) 0 2/8280 (0%) 2
    Megacolon 1/8212 (0%) 1 1/8280 (0%) 1
    Mesenteric artery stenosis 1/8212 (0%) 1 0/8280 (0%) 0
    Mesenteric artery thrombosis 0/8212 (0%) 0 1/8280 (0%) 1
    Mesenteric vascular insufficiency 0/8212 (0%) 0 1/8280 (0%) 1
    Nausea 0/8212 (0%) 0 4/8280 (0%) 4
    Oesophageal fibrosis 1/8212 (0%) 1 0/8280 (0%) 0
    Oesophageal obstruction 0/8212 (0%) 0 1/8280 (0%) 1
    Oesophageal spasm 0/8212 (0%) 0 1/8280 (0%) 1
    Oesophageal stenosis 0/8212 (0%) 0 1/8280 (0%) 1
    Oesophageal varices haemorrhage 1/8212 (0%) 1 0/8280 (0%) 0
    Oesophagitis 0/8212 (0%) 0 4/8280 (0%) 4
    Oesophagitis ulcerative 0/8212 (0%) 0 1/8280 (0%) 1
    Omental infarction 1/8212 (0%) 1 0/8280 (0%) 0
    Pancreatic duct dilatation 1/8212 (0%) 1 0/8280 (0%) 0
    Pancreatic mass 0/8212 (0%) 0 1/8280 (0%) 1
    Pancreatitis 12/8212 (0.1%) 14 18/8280 (0.2%) 19
    Pancreatitis acute 6/8212 (0.1%) 6 4/8280 (0%) 5
    Pancreatitis chronic 2/8212 (0%) 2 2/8280 (0%) 2
    Pancreatolithiasis 1/8212 (0%) 1 0/8280 (0%) 0
    Peptic ulcer 1/8212 (0%) 1 1/8280 (0%) 1
    Rectal haemorrhage 2/8212 (0%) 2 0/8280 (0%) 0
    Rectal polyp 2/8212 (0%) 2 2/8280 (0%) 2
    Rectal prolapse 0/8212 (0%) 0 3/8280 (0%) 3
    Reflux gastritis 1/8212 (0%) 1 1/8280 (0%) 1
    Retroperitoneal fibrosis 0/8212 (0%) 0 1/8280 (0%) 1
    Small intestinal haemorrhage 1/8212 (0%) 1 0/8280 (0%) 0
    Small intestinal obstruction 4/8212 (0%) 6 4/8280 (0%) 4
    Small intestinal perforation 0/8212 (0%) 0 3/8280 (0%) 3
    Tongue disorder 0/8212 (0%) 0 1/8280 (0%) 1
    Umbilical hernia 4/8212 (0%) 4 5/8280 (0.1%) 5
    Umbilical hernia, obstructive 2/8212 (0%) 2 3/8280 (0%) 3
    Upper gastrointestinal haemorrhage 9/8212 (0.1%) 10 5/8280 (0.1%) 5
    Varices oesophageal 2/8212 (0%) 2 0/8280 (0%) 0
    Vomiting 1/8212 (0%) 1 6/8280 (0.1%) 6
    General disorders
    Adverse drug reaction 2/8212 (0%) 2 1/8280 (0%) 1
    Application site pain 0/8212 (0%) 0 1/8280 (0%) 1
    Asthenia 1/8212 (0%) 1 4/8280 (0%) 4
    Catheter site haemorrhage 0/8212 (0%) 0 1/8280 (0%) 1
    Chest discomfort 2/8212 (0%) 3 0/8280 (0%) 0
    Chest pain 10/8212 (0.1%) 10 14/8280 (0.2%) 14
    Cyst 1/8212 (0%) 1 0/8280 (0%) 0
    Death 1/8212 (0%) 1 5/8280 (0.1%) 5
    Device battery issue 1/8212 (0%) 1 0/8280 (0%) 0
    Device breakage 0/8212 (0%) 0 3/8280 (0%) 3
    Device damage 0/8212 (0%) 0 1/8280 (0%) 1
    Device dislocation 1/8212 (0%) 1 1/8280 (0%) 1
    Device failure 1/8212 (0%) 1 1/8280 (0%) 1
    Device lead damage 1/8212 (0%) 1 1/8280 (0%) 1
    Device malfunction 0/8212 (0%) 0 4/8280 (0%) 4
    Exercise tolerance decreased 0/8212 (0%) 0 1/8280 (0%) 1
    Fatigue 1/8212 (0%) 1 3/8280 (0%) 3
    Feeling cold 0/8212 (0%) 0 1/8280 (0%) 1
    Foaming at mouth 1/8212 (0%) 1 0/8280 (0%) 0
    Gait disturbance 2/8212 (0%) 2 1/8280 (0%) 1
    General physical health deterioration 1/8212 (0%) 1 1/8280 (0%) 1
    General symptom 0/8212 (0%) 0 1/8280 (0%) 1
    Generalised oedema 2/8212 (0%) 2 1/8280 (0%) 1
    Hernia 0/8212 (0%) 0 1/8280 (0%) 1
    Hernia obstructive 0/8212 (0%) 0 1/8280 (0%) 1
    Hypothermia 1/8212 (0%) 1 0/8280 (0%) 0
    Impaired healing 1/8212 (0%) 1 3/8280 (0%) 3
    Implant site haematoma 1/8212 (0%) 1 0/8280 (0%) 0
    Inflammation 1/8212 (0%) 1 2/8280 (0%) 2
    Ischaemic ulcer 1/8212 (0%) 2 0/8280 (0%) 0
    Lipogranuloma 0/8212 (0%) 0 1/8280 (0%) 1
    Malaise 1/8212 (0%) 1 0/8280 (0%) 0
    Medical device complication 0/8212 (0%) 0 1/8280 (0%) 1
    Multi-organ disorder 0/8212 (0%) 0 1/8280 (0%) 1
    Multi-organ failure 5/8212 (0.1%) 5 7/8280 (0.1%) 7
    Necrobiosis 0/8212 (0%) 0 1/8280 (0%) 1
    Necrosis 0/8212 (0%) 0 1/8280 (0%) 2
    Non-cardiac chest pain 109/8212 (1.3%) 131 108/8280 (1.3%) 125
    Oedema peripheral 1/8212 (0%) 1 4/8280 (0%) 4
    Organ failure 0/8212 (0%) 0 1/8280 (0%) 1
    Pain 0/8212 (0%) 0 2/8280 (0%) 2
    Polyp 1/8212 (0%) 1 0/8280 (0%) 0
    Pyrexia 7/8212 (0.1%) 7 7/8280 (0.1%) 7
    Spinal pain 0/8212 (0%) 0 1/8280 (0%) 1
    Systemic inflammatory response syndrome 1/8212 (0%) 1 3/8280 (0%) 3
    Hepatobiliary disorders
    Bile duct obstruction 1/8212 (0%) 1 0/8280 (0%) 0
    Bile duct stone 5/8212 (0.1%) 5 3/8280 (0%) 3
    Biliary colic 4/8212 (0%) 4 0/8280 (0%) 0
    Biliary dyskinesia 0/8212 (0%) 0 1/8280 (0%) 1
    Biliary polyp 0/8212 (0%) 0 1/8280 (0%) 1
    Cholangitis 2/8212 (0%) 2 0/8280 (0%) 0
    Cholangitis acute 1/8212 (0%) 1 1/8280 (0%) 1
    Cholecystitis 10/8212 (0.1%) 12 13/8280 (0.2%) 13
    Cholecystitis acute 14/8212 (0.2%) 14 22/8280 (0.3%) 22
    Cholecystitis chronic 4/8212 (0%) 4 1/8280 (0%) 1
    Cholelithiasis 27/8212 (0.3%) 28 26/8280 (0.3%) 27
    Drug-induced liver injury 2/8212 (0%) 2 0/8280 (0%) 0
    Gallbladder disorder 1/8212 (0%) 1 0/8280 (0%) 0
    Gallbladder perforation 1/8212 (0%) 1 0/8280 (0%) 0
    Hepatic cirrhosis 6/8212 (0.1%) 6 2/8280 (0%) 2
    Hepatic failure 2/8212 (0%) 2 3/8280 (0%) 3
    Hepatic function abnormal 1/8212 (0%) 1 1/8280 (0%) 1
    Hepatic ischaemia 0/8212 (0%) 0 1/8280 (0%) 1
    Hepatic lesion 1/8212 (0%) 1 0/8280 (0%) 0
    Hepatitis 1/8212 (0%) 1 1/8280 (0%) 1
    Hydrocholecystis 1/8212 (0%) 1 0/8280 (0%) 0
    Ischaemic hepatitis 1/8212 (0%) 1 0/8280 (0%) 0
    Jaundice 2/8212 (0%) 2 0/8280 (0%) 0
    Liver disorder 2/8212 (0%) 2 0/8280 (0%) 0
    Portal vein thrombosis 0/8212 (0%) 0 1/8280 (0%) 1
    Immune system disorders
    Allergy to venom 0/8212 (0%) 0 1/8280 (0%) 1
    Anaphylactic reaction 1/8212 (0%) 1 1/8280 (0%) 1
    Anaphylactic shock 0/8212 (0%) 0 1/8280 (0%) 1
    Autoimmune disorder 0/8212 (0%) 0 1/8280 (0%) 1
    Cryoglobulinaemia 0/8212 (0%) 0 1/8280 (0%) 1
    Drug hypersensitivity 4/8212 (0%) 4 4/8280 (0%) 4
    Hypersensitivity 0/8212 (0%) 0 3/8280 (0%) 3
    Sarcoidosis 1/8212 (0%) 1 1/8280 (0%) 1
    Infections and infestations
    Abdominal abscess 1/8212 (0%) 1 1/8280 (0%) 1
    Abdominal wall abscess 1/8212 (0%) 1 1/8280 (0%) 1
    Abscess 2/8212 (0%) 2 0/8280 (0%) 0
    Abscess limb 4/8212 (0%) 4 5/8280 (0.1%) 5
    Abscess soft tissue 1/8212 (0%) 1 0/8280 (0%) 0
    Acarodermatitis 0/8212 (0%) 0 1/8280 (0%) 1
    Acinetobacter bacteraemia 1/8212 (0%) 1 0/8280 (0%) 0
    Acute sinusitis 1/8212 (0%) 1 0/8280 (0%) 0
    Adenovirus infection 0/8212 (0%) 0 1/8280 (0%) 1
    Anal abscess 1/8212 (0%) 2 0/8280 (0%) 0
    Appendicitis 9/8212 (0.1%) 9 7/8280 (0.1%) 7
    Appendicitis perforated 1/8212 (0%) 1 0/8280 (0%) 0
    Arthritis bacterial 2/8212 (0%) 2 3/8280 (0%) 3
    Arthritis infective 1/8212 (0%) 1 0/8280 (0%) 0
    Bacteraemia 2/8212 (0%) 2 3/8280 (0%) 3
    Bacterial infection 1/8212 (0%) 1 1/8280 (0%) 1
    Bacterial sepsis 1/8212 (0%) 1 1/8280 (0%) 1
    Bone abscess 0/8212 (0%) 0 1/8280 (0%) 1
    Breast cellulitis 1/8212 (0%) 1 1/8280 (0%) 1
    Breast infection 1/8212 (0%) 1 0/8280 (0%) 0
    Bronchiolitis 0/8212 (0%) 0 1/8280 (0%) 1
    Bronchitis 35/8212 (0.4%) 35 23/8280 (0.3%) 23
    Bronchitis viral 1/8212 (0%) 1 0/8280 (0%) 0
    Bronchopneumonia 8/8212 (0.1%) 9 10/8280 (0.1%) 10
    Bursitis infective 1/8212 (0%) 1 0/8280 (0%) 0
    Campylobacter infection 0/8212 (0%) 0 1/8280 (0%) 1
    Carbuncle 1/8212 (0%) 1 0/8280 (0%) 0
    Cellulitis 65/8212 (0.8%) 70 58/8280 (0.7%) 70
    Cellulitis gangrenous 0/8212 (0%) 0 1/8280 (0%) 1
    Cellulitis of male external genital organ 1/8212 (0%) 1 1/8280 (0%) 1
    Cellulitis staphylococcal 3/8212 (0%) 3 1/8280 (0%) 1
    Cervicitis 0/8212 (0%) 0 1/8280 (0%) 1
    Chest wall abscess 1/8212 (0%) 1 0/8280 (0%) 0
    Cholangitis suppurative 0/8212 (0%) 0 1/8280 (0%) 1
    Cholecystitis infective 1/8212 (0%) 1 0/8280 (0%) 0
    Chronic sinusitis 0/8212 (0%) 0 1/8280 (0%) 1
    Clostridial infection 0/8212 (0%) 0 2/8280 (0%) 2
    Clostridium difficile colitis 6/8212 (0.1%) 6 2/8280 (0%) 2
    Clostridium difficile sepsis 1/8212 (0%) 1 0/8280 (0%) 0
    Creutzfeldt-Jakob disease 0/8212 (0%) 0 1/8280 (0%) 1
    Cystitis 2/8212 (0%) 2 2/8280 (0%) 4
    Dengue fever 0/8212 (0%) 0 1/8280 (0%) 1
    Device related infection 2/8212 (0%) 2 2/8280 (0%) 2
    Diabetic foot infection 3/8212 (0%) 3 10/8280 (0.1%) 11
    Diabetic gangrene 4/8212 (0%) 4 9/8280 (0.1%) 9
    Diarrhoea infectious 1/8212 (0%) 1 0/8280 (0%) 0
    Diverticulitis 10/8212 (0.1%) 13 10/8280 (0.1%) 11
    Ear infection 0/8212 (0%) 0 1/8280 (0%) 1
    Emphysematous cystitis 1/8212 (0%) 1 0/8280 (0%) 0
    Empyema 0/8212 (0%) 0 1/8280 (0%) 1
    Endocarditis 1/8212 (0%) 1 1/8280 (0%) 1
    Endocarditis enterococcal 0/8212 (0%) 0 1/8280 (0%) 1
    Endophthalmitis 1/8212 (0%) 1 0/8280 (0%) 0
    Enterobacter bacteraemia 1/8212 (0%) 1 0/8280 (0%) 0
    Enterobacter infection 1/8212 (0%) 1 0/8280 (0%) 0
    Enterobacter pneumonia 0/8212 (0%) 0 1/8280 (0%) 1
    Enterococcal bacteraemia 0/8212 (0%) 0 1/8280 (0%) 1
    Enterococcal sepsis 1/8212 (0%) 1 0/8280 (0%) 0
    Enterocolitis infectious 0/8212 (0%) 0 2/8280 (0%) 2
    Erysipelas 6/8212 (0.1%) 6 6/8280 (0.1%) 6
    Escherichia bacteraemia 1/8212 (0%) 1 1/8280 (0%) 1
    Escherichia infection 1/8212 (0%) 1 0/8280 (0%) 0
    Escherichia sepsis 0/8212 (0%) 0 1/8280 (0%) 1
    Escherichia urinary tract infection 0/8212 (0%) 0 1/8280 (0%) 1
    Febrile infection 1/8212 (0%) 1 0/8280 (0%) 0
    Furuncle 1/8212 (0%) 1 0/8280 (0%) 0
    Gallbladder abscess 0/8212 (0%) 0 1/8280 (0%) 1
    Gangrene 16/8212 (0.2%) 17 22/8280 (0.3%) 23
    Gastric ulcer helicobacter 1/8212 (0%) 1 0/8280 (0%) 0
    Gastroenteritis 17/8212 (0.2%) 17 28/8280 (0.3%) 29
    Gastroenteritis clostridial 1/8212 (0%) 1 0/8280 (0%) 0
    Gastroenteritis norovirus 1/8212 (0%) 1 0/8280 (0%) 0
    Gastroenteritis shigella 1/8212 (0%) 1 0/8280 (0%) 0
    Gastroenteritis viral 1/8212 (0%) 1 3/8280 (0%) 3
    Graft infection 3/8212 (0%) 3 0/8280 (0%) 0
    Groin abscess 1/8212 (0%) 1 0/8280 (0%) 0
    Groin infection 1/8212 (0%) 1 0/8280 (0%) 0
    H1N1 influenza 1/8212 (0%) 1 1/8280 (0%) 1
    HIV infection 0/8212 (0%) 0 1/8280 (0%) 1
    Helicobacter infection 3/8212 (0%) 3 1/8280 (0%) 1
    Hepatitis B 0/8212 (0%) 0 1/8280 (0%) 1
    Herpes zoster 1/8212 (0%) 1 1/8280 (0%) 1
    Herpes zoster ophthalmic 1/8212 (0%) 1 0/8280 (0%) 0
    Implant site cellulitis 1/8212 (0%) 1 0/8280 (0%) 0
    Incision site infection 1/8212 (0%) 1 0/8280 (0%) 0
    Infected dermal cyst 1/8212 (0%) 1 0/8280 (0%) 0
    Infected fistula 1/8212 (0%) 1 0/8280 (0%) 0
    Infected skin ulcer 8/8212 (0.1%) 9 4/8280 (0%) 4
    Infection 1/8212 (0%) 1 3/8280 (0%) 3
    Infectious peritonitis 2/8212 (0%) 2 0/8280 (0%) 0
    Infectious thyroiditis 1/8212 (0%) 1 0/8280 (0%) 0
    Infective exacerbation of chronic obstructive airways disease 0/8212 (0%) 0 2/8280 (0%) 2
    Influenza 2/8212 (0%) 2 6/8280 (0.1%) 6
    Intestinal gangrene 0/8212 (0%) 0 1/8280 (0%) 1
    Klebsiella infection 0/8212 (0%) 0 1/8280 (0%) 1
    Labyrinthitis 1/8212 (0%) 1 1/8280 (0%) 1
    Liver abscess 2/8212 (0%) 2 1/8280 (0%) 1
    Lobar pneumonia 8/8212 (0.1%) 8 16/8280 (0.2%) 16
    Localised infection 11/8212 (0.1%) 11 8/8280 (0.1%) 8
    Lower respiratory tract infection 2/8212 (0%) 2 4/8280 (0%) 6
    Ludwig angina 1/8212 (0%) 1 0/8280 (0%) 0
    Lung infection pseudomonal 1/8212 (0%) 1 0/8280 (0%) 0
    Lyme disease 0/8212 (0%) 0 1/8280 (0%) 1
    Mastoiditis 1/8212 (0%) 1 0/8280 (0%) 0
    Mediastinitis 1/8212 (0%) 1 0/8280 (0%) 0
    Meningitis 0/8212 (0%) 0 1/8280 (0%) 1
    Necrotising fasciitis 4/8212 (0%) 4 0/8280 (0%) 0
    Oesophageal candidiasis 0/8212 (0%) 0 1/8280 (0%) 1
    Orchitis 1/8212 (0%) 1 0/8280 (0%) 0
    Osteomyelitis 24/8212 (0.3%) 25 18/8280 (0.2%) 23
    Osteomyelitis chronic 3/8212 (0%) 3 0/8280 (0%) 0
    Otitis externa 1/8212 (0%) 1 2/8280 (0%) 2
    Parametritis 0/8212 (0%) 0 1/8280 (0%) 1
    Pelvic abscess 1/8212 (0%) 1 0/8280 (0%) 0
    Peridiverticular abscess 1/8212 (0%) 1 0/8280 (0%) 0
    Perihepatic abscess 0/8212 (0%) 0 1/8280 (0%) 1
    Perineal abscess 1/8212 (0%) 1 1/8280 (0%) 1
    Perinephric abscess 0/8212 (0%) 0 1/8280 (0%) 1
    Periorbital cellulitis 0/8212 (0%) 0 1/8280 (0%) 1
    Perirectal abscess 1/8212 (0%) 1 0/8280 (0%) 0
    Peritoneal abscess 0/8212 (0%) 0 1/8280 (0%) 1
    Peritonitis 4/8212 (0%) 4 5/8280 (0.1%) 5
    Peritonitis bacterial 0/8212 (0%) 0 1/8280 (0%) 1
    Pilonidal cyst 2/8212 (0%) 2 0/8280 (0%) 0
    Pneumococcal bacteraemia 0/8212 (0%) 0 1/8280 (0%) 1
    Pneumococcal sepsis 0/8212 (0%) 0 1/8280 (0%) 1
    Pneumocystis jiroveci infection 0/8212 (0%) 0 1/8280 (0%) 1
    Pneumonia 118/8212 (1.4%) 127 151/8280 (1.8%) 168
    Pneumonia bacterial 2/8212 (0%) 2 0/8280 (0%) 0
    Pneumonia chlamydial 0/8212 (0%) 0 1/8280 (0%) 1
    Pneumonia fungal 1/8212 (0%) 1 0/8280 (0%) 0
    Pneumonia legionella 1/8212 (0%) 1 1/8280 (0%) 1
    Pneumonia mycoplasmal 1/8212 (0%) 1 0/8280 (0%) 0
    Pneumonia pneumococcal 0/8212 (0%) 0 1/8280 (0%) 1
    Pneumonia staphylococcal 2/8212 (0%) 2 0/8280 (0%) 0
    Pneumonia viral 1/8212 (0%) 1 0/8280 (0%) 0
    Post procedural infection 2/8212 (0%) 2 3/8280 (0%) 3
    Post procedural sepsis 0/8212 (0%) 0 1/8280 (0%) 1
    Postoperative abscess 2/8212 (0%) 2 2/8280 (0%) 2
    Postoperative wound infection 9/8212 (0.1%) 10 8/8280 (0.1%) 9
    Prostatic abscess 0/8212 (0%) 0 1/8280 (0%) 1
    Pseudomonal sepsis 0/8212 (0%) 0 1/8280 (0%) 1
    Pulmonary sepsis 4/8212 (0%) 4 6/8280 (0.1%) 6
    Pyelonephritis 7/8212 (0.1%) 7 11/8280 (0.1%) 11
    Pyelonephritis acute 1/8212 (0%) 1 5/8280 (0.1%) 6
    Rectal abscess 1/8212 (0%) 1 0/8280 (0%) 0
    Renal abscess 0/8212 (0%) 0 3/8280 (0%) 3
    Respiratory tract infection 3/8212 (0%) 3 2/8280 (0%) 2
    Respiratory tract infection viral 1/8212 (0%) 1 1/8280 (0%) 1
    Retroperitoneal abscess 1/8212 (0%) 1 0/8280 (0%) 0
    Rhinitis 0/8212 (0%) 0 1/8280 (0%) 1
    Sepsis 20/8212 (0.2%) 22 21/8280 (0.3%) 21
    Sepsis syndrome 0/8212 (0%) 0 1/8280 (0%) 1
    Septic shock 9/8212 (0.1%) 9 11/8280 (0.1%) 11
    Sinusitis 1/8212 (0%) 1 0/8280 (0%) 0
    Skin bacterial infection 2/8212 (0%) 2 0/8280 (0%) 0
    Skin infection 1/8212 (0%) 2 1/8280 (0%) 1
    Staphylococcal bacteraemia 1/8212 (0%) 1 0/8280 (0%) 0
    Staphylococcal infection 4/8212 (0%) 4 3/8280 (0%) 5
    Staphylococcal sepsis 0/8212 (0%) 0 1/8280 (0%) 1
    Staphylococcal skin infection 1/8212 (0%) 1 0/8280 (0%) 0
    Streptococcal bacteraemia 1/8212 (0%) 1 1/8280 (0%) 1
    Streptococcal urinary tract infection 0/8212 (0%) 0 1/8280 (0%) 1
    Subcutaneous abscess 3/8212 (0%) 3 4/8280 (0%) 4
    Subdiaphragmatic abscess 0/8212 (0%) 0 1/8280 (0%) 1
    Syphilis 1/8212 (0%) 1 0/8280 (0%) 0
    Testicular abscess 0/8212 (0%) 0 1/8280 (0%) 1
    Thrombophlebitis septic 0/8212 (0%) 0 1/8280 (0%) 1
    Tracheobronchitis 1/8212 (0%) 1 1/8280 (0%) 1
    Typhoid fever 1/8212 (0%) 1 0/8280 (0%) 0
    Upper respiratory tract infection 7/8212 (0.1%) 7 7/8280 (0.1%) 8
    Urinary tract infection 49/8212 (0.6%) 50 40/8280 (0.5%) 42
    Urinary tract infection bacterial 0/8212 (0%) 0 1/8280 (0%) 1
    Urinary tract infection staphylococcal 0/8212 (0%) 0 1/8280 (0%) 1
    Urosepsis 8/8212 (0.1%) 8 10/8280 (0.1%) 10
    Vaginal abscess 1/8212 (0%) 1 0/8280 (0%) 0
    Viral infection 4/8212 (0%) 4 1/8280 (0%) 1
    Viral upper respiratory tract infection 2/8212 (0%) 2 0/8280 (0%) 0
    Vulval abscess 0/8212 (0%) 0 1/8280 (0%) 1
    Wound infection 7/8212 (0.1%) 7 7/8280 (0.1%) 7
    Wound infection staphylococcal 1/8212 (0%) 1 0/8280 (0%) 0
    Wound sepsis 2/8212 (0%) 2 1/8280 (0%) 1
    Injury, poisoning and procedural complications
    Accident 0/8212 (0%) 0 1/8280 (0%) 1
    Acetabulum fracture 1/8212 (0%) 1 1/8280 (0%) 1
    Allergic transfusion reaction 1/8212 (0%) 1 0/8280 (0%) 0
    Anaemia postoperative 1/8212 (0%) 1 1/8280 (0%) 1
    Anastomotic ulcer haemorrhage 0/8212 (0%) 0 1/8280 (0%) 1
    Ankle fracture 8/8212 (0.1%) 8 3/8280 (0%) 3
    Arteriovenous fistula site complication 0/8212 (0%) 0 2/8280 (0%) 2
    Arteriovenous graft site haematoma 0/8212 (0%) 0 1/8280 (0%) 1
    Bone fissure 0/8212 (0%) 0 1/8280 (0%) 1
    Brachial plexus injury 0/8212 (0%) 0 1/8280 (0%) 1
    Burns second degree 2/8212 (0%) 2 0/8280 (0%) 0
    Burns third degree 0/8212 (0%) 0 1/8280 (0%) 1
    Carbon monoxide poisoning 1/8212 (0%) 1 0/8280 (0%) 0
    Cartilage injury 0/8212 (0%) 0 1/8280 (0%) 1
    Cervical vertebral fracture 1/8212 (0%) 1 0/8280 (0%) 0
    Chest injury 1/8212 (0%) 1 0/8280 (0%) 0
    Clavicle fracture 0/8212 (0%) 0 1/8280 (0%) 1
    Concussion 2/8212 (0%) 2 5/8280 (0.1%) 5
    Contrast media reaction 1/8212 (0%) 1 0/8280 (0%) 0
    Contusion 1/8212 (0%) 1 4/8280 (0%) 4
    Craniocerebral injury 2/8212 (0%) 2 3/8280 (0%) 3
    Cystitis radiation 1/8212 (0%) 1 0/8280 (0%) 0
    Face injury 0/8212 (0%) 0 1/8280 (0%) 1
    Facial bones fracture 2/8212 (0%) 2 3/8280 (0%) 3
    Fall 8/8212 (0.1%) 8 6/8280 (0.1%) 6
    Feeding tube complication 1/8212 (0%) 1 0/8280 (0%) 0
    Femoral neck fracture 5/8212 (0.1%) 5 10/8280 (0.1%) 10
    Femur fracture 10/8212 (0.1%) 10 13/8280 (0.2%) 15
    Fibula fracture 4/8212 (0%) 4 1/8280 (0%) 1
    Foot fracture 2/8212 (0%) 2 3/8280 (0%) 3
    Forearm fracture 1/8212 (0%) 1 1/8280 (0%) 1
    Foreign body 0/8212 (0%) 0 1/8280 (0%) 1
    Fracture 0/8212 (0%) 0 1/8280 (0%) 1
    Fractured coccyx 1/8212 (0%) 1 0/8280 (0%) 0
    Graft complication 1/8212 (0%) 1 0/8280 (0%) 0
    Graft dysfunction 1/8212 (0%) 1 0/8280 (0%) 0
    Graft thrombosis 1/8212 (0%) 1 1/8280 (0%) 2
    Hand fracture 1/8212 (0%) 1 2/8280 (0%) 2
    Head injury 4/8212 (0%) 4 5/8280 (0.1%) 5
    Heart injury 0/8212 (0%) 0 1/8280 (0%) 1
    Hip fracture 10/8212 (0.1%) 10 8/8280 (0.1%) 9
    Humerus fracture 5/8212 (0.1%) 5 9/8280 (0.1%) 9
    Incisional hernia 5/8212 (0.1%) 5 6/8280 (0.1%) 6
    Joint dislocation 1/8212 (0%) 1 4/8280 (0%) 4
    Laceration 3/8212 (0%) 3 0/8280 (0%) 0
    Ligament rupture 2/8212 (0%) 2 1/8280 (0%) 1
    Ligament sprain 1/8212 (0%) 1 1/8280 (0%) 1
    Limb injury 1/8212 (0%) 1 4/8280 (0%) 4
    Limb traumatic amputation 1/8212 (0%) 1 0/8280 (0%) 0
    Lower limb fracture 2/8212 (0%) 2 7/8280 (0.1%) 7
    Lumbar vertebral fracture 3/8212 (0%) 3 1/8280 (0%) 1
    Meniscus lesion 1/8212 (0%) 1 0/8280 (0%) 0
    Multiple drug overdose intentional 0/8212 (0%) 0 1/8280 (0%) 1
    Multiple fractures 4/8212 (0%) 4 3/8280 (0%) 3
    Muscle strain 1/8212 (0%) 1 0/8280 (0%) 0
    Near drowning 0/8212 (0%) 0 1/8280 (0%) 1
    Overdose 3/8212 (0%) 3 2/8280 (0%) 2
    Patella fracture 1/8212 (0%) 1 5/8280 (0.1%) 5
    Pelvic fracture 1/8212 (0%) 1 3/8280 (0%) 3
    Peripheral artery restenosis 1/8212 (0%) 1 0/8280 (0%) 0
    Periprosthetic fracture 1/8212 (0%) 1 0/8280 (0%) 0
    Pneumothorax traumatic 0/8212 (0%) 0 1/8280 (0%) 1
    Post concussion syndrome 0/8212 (0%) 0 1/8280 (0%) 1
    Post embolisation syndrome 1/8212 (0%) 1 0/8280 (0%) 0
    Post procedural bile leak 0/8212 (0%) 0 1/8280 (0%) 1
    Post procedural complication 1/8212 (0%) 1 3/8280 (0%) 3
    Post procedural discharge 0/8212 (0%) 0 1/8280 (0%) 1
    Post procedural haematoma 1/8212 (0%) 1 1/8280 (0%) 1
    Post procedural haematuria 0/8212 (0%) 0 1/8280 (0%) 1
    Post procedural haemorrhage 5/8212 (0.1%) 6 1/8280 (0%) 1
    Postoperative fever 1/8212 (0%) 2 0/8280 (0%) 0
    Postoperative hernia 1/8212 (0%) 1 0/8280 (0%) 0
    Postoperative renal failure 1/8212 (0%) 1 0/8280 (0%) 0
    Postoperative thoracic procedure complication 0/8212 (0%) 0 1/8280 (0%) 1
    Postoperative wound complication 1/8212 (0%) 1 5/8280 (0.1%) 5
    Procedural pain 2/8212 (0%) 2 2/8280 (0%) 2
    Pubis fracture 3/8212 (0%) 3 2/8280 (0%) 2
    Radius fracture 5/8212 (0.1%) 5 5/8280 (0.1%) 5
    Rib fracture 4/8212 (0%) 4 3/8280 (0%) 3
    Road traffic accident 7/8212 (0.1%) 7 4/8280 (0%) 4
    Scapula fracture 1/8212 (0%) 1 0/8280 (0%) 0
    Seroma 0/8212 (0%) 0 2/8280 (0%) 2
    Skeletal injury 0/8212 (0%) 0 1/8280 (0%) 1
    Skull fracture 1/8212 (0%) 1 0/8280 (0%) 0
    Skull fractured base 0/8212 (0%) 0 1/8280 (0%) 1
    Spinal compression fracture 7/8212 (0.1%) 7 2/8280 (0%) 2
    Spinal fracture 0/8212 (0%) 0 2/8280 (0%) 2
    Splenic haematoma 0/8212 (0%) 0 1/8280 (0%) 1
    Splenic rupture 1/8212 (0%) 1 0/8280 (0%) 0
    Sternal fracture 2/8212 (0%) 2 1/8280 (0%) 1
    Subdural haematoma 8/8212 (0.1%) 8 9/8280 (0.1%) 9
    Subdural haemorrhage 2/8212 (0%) 2 2/8280 (0%) 2
    Suture related complication 0/8212 (0%) 0 1/8280 (0%) 1
    Tendon injury 1/8212 (0%) 1 0/8280 (0%) 0
    Tendon rupture 3/8212 (0%) 3 3/8280 (0%) 3
    Thermal burn 1/8212 (0%) 1 1/8280 (0%) 1
    Tibia fracture 3/8212 (0%) 3 1/8280 (0%) 1
    Tooth fracture 0/8212 (0%) 0 1/8280 (0%) 1
    Toxicity to various agents 5/8212 (0.1%) 5 5/8280 (0.1%) 5
    Tracheal injury 1/8212 (0%) 1 0/8280 (0%) 0
    Traumatic haematoma 1/8212 (0%) 1 0/8280 (0%) 0
    Traumatic intracranial haemorrhage 0/8212 (0%) 0 1/8280 (0%) 1
    Traumatic ulcer 0/8212 (0%) 0 1/8280 (0%) 1
    Ulna fracture 0/8212 (0%) 0 1/8280 (0%) 1
    Upper limb fracture 2/8212 (0%) 2 4/8280 (0%) 4
    Vascular graft complication 1/8212 (0%) 1 0/8280 (0%) 0
    Vascular graft occlusion 0/8212 (0%) 0 2/8280 (0%) 2
    Vascular graft thrombosis 1/8212 (0%) 1 2/8280 (0%) 2
    Vascular pseudoaneurysm 0/8212 (0%) 0 1/8280 (0%) 1
    Wound 0/8212 (0%) 0 3/8280 (0%) 3
    Wound dehiscence 1/8212 (0%) 1 0/8280 (0%) 0
    Wound haemorrhage 0/8212 (0%) 0 1/8280 (0%) 1
    Wound necrosis 0/8212 (0%) 0 3/8280 (0%) 3
    Wound secretion 1/8212 (0%) 1 0/8280 (0%) 0
    Wrist fracture 3/8212 (0%) 3 6/8280 (0.1%) 6
    Investigations
    Alanine aminotransferase increased 0/8212 (0%) 0 1/8280 (0%) 1
    Arteriogram coronary 1/8212 (0%) 1 0/8280 (0%) 0
    Aspartate aminotransferase increased 1/8212 (0%) 1 0/8280 (0%) 0
    Blood bilirubin increased 0/8212 (0%) 0 1/8280 (0%) 1
    Blood creatine phosphokinase increased 1/8212 (0%) 1 0/8280 (0%) 0
    Blood creatinine increased 2/8212 (0%) 2 1/8280 (0%) 1
    Blood glucose increased 1/8212 (0%) 1 0/8280 (0%) 0
    Blood potassium increased 1/8212 (0%) 1 0/8280 (0%) 0
    Blood pressure abnormal 0/8212 (0%) 0 1/8280 (0%) 1
    Blood pressure increased 2/8212 (0%) 2 1/8280 (0%) 1
    C-reactive protein increased 0/8212 (0%) 0 1/8280 (0%) 1
    Cardiac stress test abnormal 1/8212 (0%) 1 1/8280 (0%) 1
    Chest X-ray abnormal 1/8212 (0%) 1 0/8280 (0%) 0
    Clostridium test positive 1/8212 (0%) 1 1/8280 (0%) 1
    Coagulation factor VIII level increased 1/8212 (0%) 1 0/8280 (0%) 0
    Coagulation test abnormal 1/8212 (0%) 1 0/8280 (0%) 0
    Ejection fraction decreased 3/8212 (0%) 3 0/8280 (0%) 0
    Electrocardiogram abnormal 0/8212 (0%) 0 1/8280 (0%) 1
    Haemoglobin decreased 0/8212 (0%) 0 1/8280 (0%) 1
    Heart rate increased 0/8212 (0%) 0 1/8280 (0%) 1
    Hepatic enzyme increased 6/8212 (0.1%) 6 5/8280 (0.1%) 5
    International normalised ratio increased 0/8212 (0%) 0 1/8280 (0%) 1
    Liver function test abnormal 3/8212 (0%) 3 2/8280 (0%) 2
    Prostatic specific antigen increased 0/8212 (0%) 0 1/8280 (0%) 1
    Transaminases increased 0/8212 (0%) 0 4/8280 (0%) 4
    Troponin increased 1/8212 (0%) 1 1/8280 (0%) 1
    Urine albumin/creatinine ratio increased 0/8212 (0%) 0 1/8280 (0%) 1
    Weight decreased 1/8212 (0%) 1 1/8280 (0%) 1
    Metabolism and nutrition disorders
    Decreased appetite 0/8212 (0%) 0 1/8280 (0%) 1
    Dehydration 17/8212 (0.2%) 18 13/8280 (0.2%) 13
    Diabetes mellitus 13/8212 (0.2%) 14 12/8280 (0.1%) 14
    Diabetes mellitus inadequate control 11/8212 (0.1%) 13 10/8280 (0.1%) 12
    Diabetic complication 0/8212 (0%) 0 1/8280 (0%) 1
    Diabetic ketoacidosis 5/8212 (0.1%) 6 8/8280 (0.1%) 10
    Electrolyte imbalance 0/8212 (0%) 0 1/8280 (0%) 1
    Failure to thrive 2/8212 (0%) 2 1/8280 (0%) 1
    Fluid overload 5/8212 (0.1%) 5 1/8280 (0%) 1
    Fluid retention 0/8212 (0%) 0 1/8280 (0%) 1
    Gout 2/8212 (0%) 2 8/8280 (0.1%) 8
    Hypercalcaemia 3/8212 (0%) 3 1/8280 (0%) 1
    Hyperglycaemia 58/8212 (0.7%) 62 51/8280 (0.6%) 55
    Hyperglycaemic hyperosmolar nonketotic syndrome 0/8212 (0%) 0 2/8280 (0%) 2
    Hyperkalaemia 13/8212 (0.2%) 15 17/8280 (0.2%) 17
    Hyperosmolar state 1/8212 (0%) 1 1/8280 (0%) 1
    Hypokalaemia 0/8212 (0%) 0 2/8280 (0%) 2
    Hyponatraemia 7/8212 (0.1%) 8 3/8280 (0%) 3
    Hypovolaemia 2/8212 (0%) 2 2/8280 (0%) 2
    Ketoacidosis 1/8212 (0%) 1 2/8280 (0%) 2
    Lactic acidosis 3/8212 (0%) 3 1/8280 (0%) 1
    Malnutrition 2/8212 (0%) 2 0/8280 (0%) 0
    Metabolic acidosis 1/8212 (0%) 1 1/8280 (0%) 1
    Obesity 2/8212 (0%) 2 1/8280 (0%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 4/8212 (0%) 4 8/8280 (0.1%) 8
    Arthritis 5/8212 (0.1%) 5 3/8280 (0%) 3
    Arthropathy 0/8212 (0%) 0 1/8280 (0%) 1
    Articular calcification 1/8212 (0%) 1 0/8280 (0%) 0
    Back pain 10/8212 (0.1%) 10 9/8280 (0.1%) 9
    Bursitis 1/8212 (0%) 1 5/8280 (0.1%) 5
    Carpal collapse 0/8212 (0%) 0 1/8280 (0%) 1
    Cervical spinal stenosis 2/8212 (0%) 2 0/8280 (0%) 0
    Diabetic amyotrophy 1/8212 (0%) 1 0/8280 (0%) 0
    Dupuytren's contracture 1/8212 (0%) 1 0/8280 (0%) 0
    Exostosis 1/8212 (0%) 1 0/8280 (0%) 0
    Extraskeletal ossification 1/8212 (0%) 1 0/8280 (0%) 0
    Fasciitis 1/8212 (0%) 1 0/8280 (0%) 0
    Foot deformity 3/8212 (0%) 3 1/8280 (0%) 1
    Fracture nonunion 0/8212 (0%) 0 1/8280 (0%) 1
    Gouty arthritis 1/8212 (0%) 1 3/8280 (0%) 3
    Haemarthrosis 1/8212 (0%) 1 0/8280 (0%) 0
    Hip deformity 1/8212 (0%) 1 0/8280 (0%) 0
    Inguinal mass 1/8212 (0%) 1 0/8280 (0%) 0
    Intervertebral disc degeneration 1/8212 (0%) 1 3/8280 (0%) 3
    Intervertebral disc disorder 3/8212 (0%) 3 4/8280 (0%) 5
    Intervertebral disc displacement 1/8212 (0%) 1 1/8280 (0%) 1
    Intervertebral disc protrusion 13/8212 (0.2%) 14 9/8280 (0.1%) 10
    Joint ankylosis 1/8212 (0%) 1 0/8280 (0%) 0
    Joint stiffness 0/8212 (0%) 0 1/8280 (0%) 1
    Lumbar spinal stenosis 3/8212 (0%) 3 6/8280 (0.1%) 6
    Mobility decreased 1/8212 (0%) 1 0/8280 (0%) 0
    Monarthritis 0/8212 (0%) 0 1/8280 (0%) 1
    Muscle spasms 1/8212 (0%) 1 0/8280 (0%) 0
    Muscular weakness 0/8212 (0%) 0 4/8280 (0%) 4
    Musculoskeletal chest pain 32/8212 (0.4%) 35 23/8280 (0.3%) 23
    Musculoskeletal pain 4/8212 (0%) 4 3/8280 (0%) 3
    Myalgia 1/8212 (0%) 1 1/8280 (0%) 1
    Myopathy 1/8212 (0%) 1 2/8280 (0%) 2
    Myositis 0/8212 (0%) 0 1/8280 (0%) 1
    Neck pain 1/8212 (0%) 1 0/8280 (0%) 0
    Neuropathic arthropathy 0/8212 (0%) 0 1/8280 (0%) 1
    Osteitis 1/8212 (0%) 1 0/8280 (0%) 0
    Osteoarthritis 40/8212 (0.5%) 42 49/8280 (0.6%) 51
    Osteochondritis 1/8212 (0%) 1 0/8280 (0%) 0
    Osteochondrosis 1/8212 (0%) 1 0/8280 (0%) 0
    Osteolysis 1/8212 (0%) 1 0/8280 (0%) 0
    Osteonecrosis 3/8212 (0%) 3 2/8280 (0%) 2
    Osteoporotic fracture 0/8212 (0%) 0 1/8280 (0%) 1
    Pain in extremity 5/8212 (0.1%) 5 8/8280 (0.1%) 8
    Pathological fracture 1/8212 (0%) 1 1/8280 (0%) 1
    Polymyalgia rheumatica 1/8212 (0%) 1 0/8280 (0%) 0
    Polymyositis 1/8212 (0%) 1 0/8280 (0%) 0
    Rhabdomyolysis 4/8212 (0%) 4 2/8280 (0%) 2
    Rheumatoid arthritis 2/8212 (0%) 2 0/8280 (0%) 0
    Rotator cuff syndrome 2/8212 (0%) 2 3/8280 (0%) 3
    Scoliosis 1/8212 (0%) 1 0/8280 (0%) 0
    Spinal column stenosis 3/8212 (0%) 3 2/8280 (0%) 2
    Spinal disorder 0/8212 (0%) 0 1/8280 (0%) 1
    Spinal osteoarthritis 6/8212 (0.1%) 6 7/8280 (0.1%) 7
    Spondylitis 1/8212 (0%) 1 1/8280 (0%) 1
    Synovial cyst 1/8212 (0%) 1 0/8280 (0%) 0
    Synovitis 1/8212 (0%) 1 0/8280 (0%) 0
    Tendonitis 1/8212 (0%) 1 1/8280 (0%) 1
    Tenosynovitis 1/8212 (0%) 1 0/8280 (0%) 0
    Vertebral column mass 0/8212 (0%) 0 1/8280 (0%) 1
    Vertebral foraminal stenosis 1/8212 (0%) 1 0/8280 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Abdominal neoplasm 0/8212 (0%) 0 1/8280 (0%) 1
    Acute myeloid leukaemia 2/8212 (0%) 4 0/8280 (0%) 0
    Adenocarcinoma of the cervix 1/8212 (0%) 1 0/8280 (0%) 0
    Adenocarcinoma pancreas 1/8212 (0%) 1 1/8280 (0%) 1
    Adenoma benign 0/8212 (0%) 0 2/8280 (0%) 2
    Adrenal adenoma 1/8212 (0%) 1 1/8280 (0%) 1
    Angiocentric lymphoma 0/8212 (0%) 0 1/8280 (0%) 2
    B-cell lymphoma 1/8212 (0%) 1 3/8280 (0%) 3
    Basal cell carcinoma 42/8212 (0.5%) 57 52/8280 (0.6%) 58
    Basosquamous carcinoma 0/8212 (0%) 0 1/8280 (0%) 1
    Benign neoplasm of bladder 0/8212 (0%) 0 2/8280 (0%) 2
    Benign neoplasm of choroid 1/8212 (0%) 1 0/8280 (0%) 0
    Benign neoplasm of thyroid gland 1/8212 (0%) 1 0/8280 (0%) 0
    Benign ovarian tumour 0/8212 (0%) 0 1/8280 (0%) 1
    Benign renal neoplasm 0/8212 (0%) 0 1/8280 (0%) 1
    Benign salivary gland neoplasm 0/8212 (0%) 0 1/8280 (0%) 1
    Bile duct cancer 2/8212 (0%) 2 0/8280 (0%) 0
    Bladder cancer 9/8212 (0.1%) 9 12/8280 (0.1%) 13
    Bladder cancer recurrent 5/8212 (0.1%) 5 2/8280 (0%) 2
    Bladder cancer stage II 1/8212 (0%) 1 0/8280 (0%) 0
    Bladder neoplasm 4/8212 (0%) 4 2/8280 (0%) 2
    Bladder transitional cell carcinoma 3/8212 (0%) 3 2/8280 (0%) 2
    Bladder transitional cell carcinoma stage II 1/8212 (0%) 1 0/8280 (0%) 0
    Blast crisis in myelogenous leukaemia 0/8212 (0%) 0 1/8280 (0%) 1
    Bone neoplasm malignant 0/8212 (0%) 0 1/8280 (0%) 1
    Bowen's disease 2/8212 (0%) 2 0/8280 (0%) 0
    Brain cancer metastatic 0/8212 (0%) 0 1/8280 (0%) 1
    Breast cancer 2/8212 (0%) 2 0/8280 (0%) 0
    Breast cancer female 12/8212 (0.1%) 12 10/8280 (0.1%) 10
    Breast cancer metastatic 0/8212 (0%) 0 1/8280 (0%) 1
    Breast neoplasm 2/8212 (0%) 2 0/8280 (0%) 0
    Bronchial carcinoma 1/8212 (0%) 1 4/8280 (0%) 4
    Burkitt's lymphoma 0/8212 (0%) 0 1/8280 (0%) 1
    Carcinoid tumour of the gastrointestinal tract 1/8212 (0%) 1 0/8280 (0%) 0
    Central nervous system lymphoma 0/8212 (0%) 0 1/8280 (0%) 1
    Cervix carcinoma 0/8212 (0%) 0 1/8280 (0%) 1
    Choroid melanoma 1/8212 (0%) 1 2/8280 (0%) 2
    Chronic lymphocytic leukaemia 1/8212 (0%) 1 4/8280 (0%) 4
    Chronic myeloid leukaemia 1/8212 (0%) 1 0/8280 (0%) 0
    Colon adenoma 2/8212 (0%) 2 2/8280 (0%) 3
    Colon cancer 18/8212 (0.2%) 18 13/8280 (0.2%) 13
    Colon cancer metastatic 2/8212 (0%) 2 3/8280 (0%) 4
    Colon neoplasm 1/8212 (0%) 1 0/8280 (0%) 0
    Colorectal cancer 1/8212 (0%) 1 0/8280 (0%) 0
    Diffuse large B-cell lymphoma 1/8212 (0%) 1 0/8280 (0%) 0
    Endometrial cancer 4/8212 (0%) 4 2/8280 (0%) 2
    Endometrial cancer stage IV 0/8212 (0%) 0 1/8280 (0%) 1
    Gallbladder cancer metastatic 1/8212 (0%) 1 0/8280 (0%) 0
    Gastric cancer 9/8212 (0.1%) 11 6/8280 (0.1%) 6
    Gastric cancer recurrent 0/8212 (0%) 0 1/8280 (0%) 1
    Gastric neoplasm 1/8212 (0%) 1 0/8280 (0%) 0
    Gastrointestinal cancer metastatic 1/8212 (0%) 1 0/8280 (0%) 0
    Gastrointestinal carcinoma 1/8212 (0%) 1 1/8280 (0%) 1
    Gastrointestinal neoplasm 1/8212 (0%) 1 0/8280 (0%) 0
    Gastrointestinal tract adenoma 0/8212 (0%) 0 1/8280 (0%) 1
    Glioblastoma 2/8212 (0%) 2 0/8280 (0%) 0
    Haemangioma 1/8212 (0%) 1 0/8280 (0%) 0
    Head and neck cancer 0/8212 (0%) 0 1/8280 (0%) 1
    Hepatic cancer metastatic 2/8212 (0%) 2 0/8280 (0%) 0
    Hepatic neoplasm 1/8212 (0%) 1 0/8280 (0%) 0
    Hepatic neoplasm malignant 4/8212 (0%) 4 7/8280 (0.1%) 7
    Hepatic neoplasm malignant recurrent 1/8212 (0%) 1 0/8280 (0%) 0
    Hodgkin's disease 1/8212 (0%) 1 0/8280 (0%) 0
    Hodgkin's disease nodular sclerosis stage unspecified 1/8212 (0%) 1 0/8280 (0%) 0
    Keratoacanthoma 0/8212 (0%) 0 2/8280 (0%) 2
    Laryngeal cancer 2/8212 (0%) 2 0/8280 (0%) 0
    Laryngeal cancer stage I 1/8212 (0%) 1 0/8280 (0%) 0
    Leiomyosarcoma 0/8212 (0%) 0 1/8280 (0%) 1
    Lentigo maligna 0/8212 (0%) 0 1/8280 (0%) 1
    Leukaemia 2/8212 (0%) 2 0/8280 (0%) 0
    Lip neoplasm malignant stage unspecified 0/8212 (0%) 0 1/8280 (0%) 1
    Lipoma 1/8212 (0%) 1 0/8280 (0%) 0
    Liposarcoma 0/8212 (0%) 0 1/8280 (0%) 1
    Lung adenocarcinoma 5/8212 (0.1%) 5 2/8280 (0%) 2
    Lung adenocarcinoma metastatic 2/8212 (0%) 2 0/8280 (0%) 0
    Lung adenocarcinoma stage III 1/8212 (0%) 1 0/8280 (0%) 0
    Lung cancer metastatic 4/8212 (0%) 4 6/8280 (0.1%) 6
    Lung carcinoma cell type unspecified recurrent 0/8212 (0%) 0 1/8280 (0%) 1
    Lung carcinoma cell type unspecified stage 0 1/8212 (0%) 1 0/8280 (0%) 0
    Lung carcinoma cell type unspecified stage III 0/8212 (0%) 0 1/8280 (0%) 1
    Lung neoplasm 1/8212 (0%) 1 6/8280 (0.1%) 6
    Lung neoplasm malignant 15/8212 (0.2%) 16 19/8280 (0.2%) 20
    Lung squamous cell carcinoma stage II 0/8212 (0%) 0 1/8280 (0%) 1
    Lung squamous cell carcinoma stage unspecified 2/8212 (0%) 2 4/8280 (0%) 4
    Lymphoma 3/8212 (0%) 3 5/8280 (0.1%) 5
    Malignant melanoma 9/8212 (0.1%) 9 11/8280 (0.1%) 11
    Malignant melanoma in situ 0/8212 (0%) 0 1/8280 (0%) 1
    Malignant palate neoplasm 0/8212 (0%) 0 1/8280 (0%) 1
    Malignant peritoneal neoplasm 0/8212 (0%) 0 1/8280 (0%) 1
    Malignant urinary tract neoplasm 1/8212 (0%) 1 0/8280 (0%) 0
    Melanocytic naevus 1/8212 (0%) 1 0/8280 (0%) 0
    Meningioma 0/8212 (0%) 0 1/8280 (0%) 1
    Mesothelioma 0/8212 (0%) 0 1/8280 (0%) 1
    Mesothelioma malignant 0/8212 (0%) 0 1/8280 (0%) 1
    Metastases to bone 0/8212 (0%) 0 1/8280 (0%) 1
    Metastases to liver 0/8212 (0%) 0 1/8280 (0%) 1
    Metastases to lung 0/8212 (0%) 0 1/8280 (0%) 1
    Metastases to peritoneum 1/8212 (0%) 1 0/8280 (0%) 0
    Metastatic bronchial carcinoma 0/8212 (0%) 0 1/8280 (0%) 1
    Metastatic gastric cancer 1/8212 (0%) 1 2/8280 (0%) 2
    Metastatic neoplasm 0/8212 (0%) 0 1/8280 (0%) 1
    Monoclonal gammopathy 1/8212 (0%) 1 0/8280 (0%) 0
    Multiple myeloma 2/8212 (0%) 2 2/8280 (0%) 2
    Myelodysplastic syndrome 2/8212 (0%) 2 0/8280 (0%) 0
    Myeloproliferative disorder 1/8212 (0%) 1 0/8280 (0%) 0
    Neoplasm malignant 0/8212 (0%) 0 2/8280 (0%) 2
    Neuroendocrine carcinoma 1/8212 (0%) 1 0/8280 (0%) 0
    Non-Hodgkin's lymphoma 2/8212 (0%) 2 0/8280 (0%) 0
    Non-small cell lung cancer 0/8212 (0%) 0 1/8280 (0%) 1
    Non-small cell lung cancer metastatic 2/8212 (0%) 2 0/8280 (0%) 0
    Ocular neoplasm 0/8212 (0%) 0 1/8280 (0%) 1
    Oesophageal cancer metastatic 1/8212 (0%) 1 0/8280 (0%) 0
    Oesophageal carcinoma 1/8212 (0%) 1 1/8280 (0%) 1
    Ovarian adenoma 0/8212 (0%) 0 1/8280 (0%) 1
    Ovarian cancer metastatic 1/8212 (0%) 1 1/8280 (0%) 1
    Ovarian fibroma 1/8212 (0%) 1 0/8280 (0%) 0
    Ovarian neoplasm 0/8212 (0%) 0 1/8280 (0%) 1
    Pancreatic carcinoma 8/8212 (0.1%) 8 2/8280 (0%) 2
    Pancreatic carcinoma metastatic 2/8212 (0%) 2 1/8280 (0%) 1
    Pancreatic neoplasm 0/8212 (0%) 0 1/8280 (0%) 1
    Pancreatic neuroendocrine tumour metastatic 1/8212 (0%) 1 0/8280 (0%) 0
    Plasmacytoma 1/8212 (0%) 1 0/8280 (0%) 0
    Polycythaemia vera 3/8212 (0%) 3 0/8280 (0%) 0
    Prostate cancer 34/8212 (0.4%) 34 41/8280 (0.5%) 43
    Prostate cancer metastatic 4/8212 (0%) 4 1/8280 (0%) 1
    Prostate cancer recurrent 2/8212 (0%) 2 1/8280 (0%) 1
    Prostate cancer stage II 1/8212 (0%) 1 0/8280 (0%) 0
    Prostate cancer stage IV 1/8212 (0%) 1 0/8280 (0%) 0
    Prostatic adenoma 1/8212 (0%) 1 1/8280 (0%) 1
    Rectal cancer 6/8212 (0.1%) 6 0/8280 (0%) 0
    Rectal cancer metastatic 1/8212 (0%) 1 0/8280 (0%) 0
    Rectal neoplasm 1/8212 (0%) 1 0/8280 (0%) 0
    Renal cancer 4/8212 (0%) 4 4/8280 (0%) 4
    Renal cancer metastatic 1/8212 (0%) 1 1/8280 (0%) 1
    Renal cell carcinoma 8/8212 (0.1%) 8 4/8280 (0%) 4
    Renal cell carcinoma stage IV 0/8212 (0%) 0 1/8280 (0%) 1
    Renal neoplasm 1/8212 (0%) 1 3/8280 (0%) 3
    Retroperitoneal neoplasm 0/8212 (0%) 0 1/8280 (0%) 1
    Rhabdomyosarcoma 0/8212 (0%) 0 1/8280 (0%) 1
    Sarcoma metastatic 1/8212 (0%) 1 0/8280 (0%) 0
    Sinonasal papilloma 1/8212 (0%) 2 0/8280 (0%) 0
    Skin cancer 2/8212 (0%) 2 5/8280 (0.1%) 5
    Small cell lung cancer metastatic 3/8212 (0%) 4 2/8280 (0%) 2
    Small cell lung cancer stage unspecified 4/8212 (0%) 4 1/8280 (0%) 1
    Small intestine carcinoma metastatic 1/8212 (0%) 1 0/8280 (0%) 0
    Squamous cell carcinoma 30/8212 (0.4%) 32 18/8280 (0.2%) 19
    Squamous cell carcinoma of skin 6/8212 (0.1%) 6 7/8280 (0.1%) 7
    Superficial spreading melanoma stage unspecified 1/8212 (0%) 1 0/8280 (0%) 0
    Testis cancer 1/8212 (0%) 1 0/8280 (0%) 0
    Thyroid adenoma 0/8212 (0%) 0 1/8280 (0%) 1
    Thyroid cancer 3/8212 (0%) 3 0/8280 (0%) 0
    Thyroid neoplasm 2/8212 (0%) 2 2/8280 (0%) 2
    Transitional cell carcinoma 6/8212 (0.1%) 7 1/8280 (0%) 1
    Uterine cancer 1/8212 (0%) 1 4/8280 (0%) 4
    Uterine leiomyoma 1/8212 (0%) 1 1/8280 (0%) 1
    Vascular neoplasm 0/8212 (0%) 0 1/8280 (0%) 1
    Nervous system disorders
    Amnesia 0/8212 (0%) 0 1/8280 (0%) 1
    Amyotrophic lateral sclerosis 1/8212 (0%) 1 0/8280 (0%) 0
    Aphasia 0/8212 (0%) 0 1/8280 (0%) 1
    Arachnoid cyst 0/8212 (0%) 0 1/8280 (0%) 1
    Ataxia 1/8212 (0%) 1 1/8280 (0%) 1
    Balance disorder 0/8212 (0%) 0 1/8280 (0%) 1
    Basal ganglia haemorrhage 1/8212 (0%) 1 1/8280 (0%) 1
    Brain injury 0/8212 (0%) 0 1/8280 (0%) 1
    Brain mass 1/8212 (0%) 1 0/8280 (0%) 0
    Brain stem haemorrhage 1/8212 (0%) 1 0/8280 (0%) 0
    Carotid arteriosclerosis 0/8212 (0%) 0 1/8280 (0%) 1
    Carotid artery aneurysm 1/8212 (0%) 1 0/8280 (0%) 0
    Carotid artery disease 0/8212 (0%) 0 3/8280 (0%) 4
    Carotid artery occlusion 1/8212 (0%) 2 3/8280 (0%) 3
    Carotid artery stenosis 11/8212 (0.1%) 11 29/8280 (0.4%) 29
    Carotid sinus syndrome 1/8212 (0%) 1 0/8280 (0%) 0
    Carpal tunnel syndrome 3/8212 (0%) 3 1/8280 (0%) 2
    Cerebral arteriosclerosis 0/8212 (0%) 0 1/8280 (0%) 1
    Cerebral circulatory failure 0/8212 (0%) 0 1/8280 (0%) 1
    Cerebral haemorrhage 2/8212 (0%) 2 2/8280 (0%) 2
    Cerebral infarction 1/8212 (0%) 1 1/8280 (0%) 1
    Cerebral ischaemia 0/8212 (0%) 0 1/8280 (0%) 1
    Cerebral microangiopathy 0/8212 (0%) 0 1/8280 (0%) 1
    Cerebrovascular accident 14/8212 (0.2%) 14 12/8280 (0.1%) 12
    Cerebrovascular disorder 2/8212 (0%) 2 3/8280 (0%) 3
    Cerebrovascular insufficiency 1/8212 (0%) 1 1/8280 (0%) 1
    Cervical myelopathy 1/8212 (0%) 1 0/8280 (0%) 0
    Cervical root pain 0/8212 (0%) 0 1/8280 (0%) 1
    Cervicobrachial syndrome 2/8212 (0%) 2 1/8280 (0%) 1
    Cognitive disorder 1/8212 (0%) 1 0/8280 (0%) 0
    Coma 1/8212 (0%) 1 0/8280 (0%) 0
    Complex partial seizures 0/8212 (0%) 0 2/8280 (0%) 2
    Convulsion 4/8212 (0%) 4 3/8280 (0%) 3
    Dementia 0/8212 (0%) 0 2/8280 (0%) 3
    Dementia Alzheimer's type 1/8212 (0%) 1 0/8280 (0%) 0
    Demyelinating polyneuropathy 0/8212 (0%) 0 1/8280 (0%) 1
    Diabetic encephalopathy 1/8212 (0%) 1 0/8280 (0%) 0
    Diabetic neuropathy 6/8212 (0.1%) 6 7/8280 (0.1%) 7
    Dizziness 10/8212 (0.1%) 11 16/8280 (0.2%) 16
    Dysarthria 1/8212 (0%) 1 0/8280 (0%) 0
    Encephalitis 1/8212 (0%) 1 0/8280 (0%) 0
    Encephalomalacia 0/8212 (0%) 0 1/8280 (0%) 1
    Encephalopathy 1/8212 (0%) 1 1/8280 (0%) 1
    Epilepsy 7/8212 (0.1%) 8 2/8280 (0%) 2
    Fahr's disease 1/8212 (0%) 1 0/8280 (0%) 0
    Guillain-Barre syndrome 1/8212 (0%) 2 0/8280 (0%) 0
    Haemorrhage intracranial 2/8212 (0%) 2 1/8280 (0%) 1
    Haemorrhagic stroke 1/8212 (0%) 1 4/8280 (0%) 4
    Headache 0/8212 (0%) 0 2/8280 (0%) 2
    Hemiparesis 2/8212 (0%) 2 4/8280 (0%) 4
    Hemiplegia 0/8212 (0%) 0 1/8280 (0%) 1
    Hemisensory neglect 0/8212 (0%) 0 1/8280 (0%) 1
    Hepatic encephalopathy 2/8212 (0%) 2 1/8280 (0%) 1
    Hydrocephalus 0/8212 (0%) 0 1/8280 (0%) 1
    Hypertensive encephalopathy 1/8212 (0%) 1 0/8280 (0%) 0
    Hypoxic-ischaemic encephalopathy 1/8212 (0%) 1 0/8280 (0%) 0
    IIIrd nerve paresis 0/8212 (0%) 0 1/8280 (0%) 1
    IVth nerve paralysis 0/8212 (0%) 0 1/8280 (0%) 1
    Intracranial aneurysm 0/8212 (0%) 0 1/8280 (0%) 1
    Intraventricular haemorrhage 1/8212 (0%) 1 0/8280 (0%) 0
    Ischaemic neuropathy 0/8212 (0%) 0 1/8280 (0%) 1
    Ischaemic stroke 1/8212 (0%) 1 4/8280 (0%) 4
    Lacunar infarction 2/8212 (0%) 2 1/8280 (0%) 1
    Lumbar radiculopathy 2/8212 (0%) 2 1/8280 (0%) 1
    Mental impairment 0/8212 (0%) 0 1/8280 (0%) 1
    Metabolic encephalopathy 0/8212 (0%) 0 1/8280 (0%) 1
    Migraine 0/8212 (0%) 0 1/8280 (0%) 1
    Monoplegia 0/8212 (0%) 0 1/8280 (0%) 1
    Movement disorder 1/8212 (0%) 1 0/8280 (0%) 0
    Myasthenia gravis 1/8212 (0%) 1 0/8280 (0%) 0
    Nerve root compression 0/8212 (0%) 0 1/8280 (0%) 1
    Neuralgia 1/8212 (0%) 2 0/8280 (0%) 0
    Neurological symptom 1/8212 (0%) 1 0/8280 (0%) 0
    Neuropathy peripheral 2/8212 (0%) 2 2/8280 (0%) 2
    Occipital neuralgia 0/8212 (0%) 0 1/8280 (0%) 1
    Optic neuritis 0/8212 (0%) 0 1/8280 (0%) 1
    Orthostatic intolerance 1/8212 (0%) 1 0/8280 (0%) 0
    Paraesthesia 2/8212 (0%) 2 2/8280 (0%) 2
    Parkinson's disease 1/8212 (0%) 1 3/8280 (0%) 3
    Parkinsonism 0/8212 (0%) 0 1/8280 (0%) 1
    Polyneuropathy 3/8212 (0%) 3 0/8280 (0%) 0
    Presyncope 4/8212 (0%) 4 5/8280 (0.1%) 5
    Radicular pain 1/8212 (0%) 1 0/8280 (0%) 0
    Radicular syndrome 0/8212 (0%) 0 1/8280 (0%) 1
    Sciatica 2/8212 (0%) 2 1/8280 (0%) 1
    Sensory disturbance 1/8212 (0%) 1 0/8280 (0%) 0
    Speech disorder 1/8212 (0%) 1 0/8280 (0%) 0
    Spinal cord infarction 0/8212 (0%) 0 1/8280 (0%) 1
    Subarachnoid haemorrhage 2/8212 (0%) 2 4/8280 (0%) 4
    Syncope 32/8212 (0.4%) 33 37/8280 (0.4%) 39
    Tension headache 0/8212 (0%) 0 1/8280 (0%) 1
    Thalamus haemorrhage 1/8212 (0%) 1 0/8280 (0%) 0
    Toxic encephalopathy 0/8212 (0%) 0 1/8280 (0%) 1
    Transient ischaemic attack 60/8212 (0.7%) 64 48/8280 (0.6%) 49
    Ulnar nerve palsy 0/8212 (0%) 0 1/8280 (0%) 1
    Uraemic encephalopathy 1/8212 (0%) 1 0/8280 (0%) 0
    VIIth nerve paralysis 4/8212 (0%) 4 8/8280 (0.1%) 8
    Vascular dementia 1/8212 (0%) 1 1/8280 (0%) 1
    Vascular encephalopathy 0/8212 (0%) 0 1/8280 (0%) 1
    Vertebral artery stenosis 0/8212 (0%) 0 1/8280 (0%) 1
    Vertebrobasilar insufficiency 3/8212 (0%) 3 3/8280 (0%) 3
    Vocal cord paralysis 1/8212 (0%) 1 0/8280 (0%) 0
    White matter lesion 0/8212 (0%) 0 1/8280 (0%) 1
    Psychiatric disorders
    Adjustment disorder 0/8212 (0%) 0 1/8280 (0%) 1
    Adjustment disorder with depressed mood 1/8212 (0%) 1 0/8280 (0%) 0
    Agitation 1/8212 (0%) 1 0/8280 (0%) 0
    Alcoholism 1/8212 (0%) 1 0/8280 (0%) 0
    Anxiety 0/8212 (0%) 0 3/8280 (0%) 3
    Bipolar disorder 1/8212 (0%) 2 2/8280 (0%) 2
    Completed suicide 2/8212 (0%) 2 1/8280 (0%) 1
    Confusional state 2/8212 (0%) 2 7/8280 (0.1%) 8
    Delirium 1/8212 (0%) 1 2/8280 (0%) 2
    Depression 6/8212 (0.1%) 8 5/8280 (0.1%) 5
    Drug abuse 1/8212 (0%) 1 0/8280 (0%) 0
    Hallucination 1/8212 (0%) 1 0/8280 (0%) 0
    Insomnia 1/8212 (0%) 1 0/8280 (0%) 0
    Major depression 1/8212 (0%) 2 0/8280 (0%) 0
    Mental status changes 5/8212 (0.1%) 5 7/8280 (0.1%) 8
    Psychosomatic disease 1/8212 (0%) 1 0/8280 (0%) 0
    Psychotic disorder 0/8212 (0%) 0 2/8280 (0%) 2
    Stress 1/8212 (0%) 1 0/8280 (0%) 0
    Suicidal ideation 2/8212 (0%) 2 0/8280 (0%) 0
    Suicide attempt 4/8212 (0%) 4 3/8280 (0%) 3
    Renal and urinary disorders
    Acute prerenal failure 1/8212 (0%) 1 2/8280 (0%) 2
    Azotaemia 2/8212 (0%) 2 3/8280 (0%) 3
    Bladder outlet obstruction 2/8212 (0%) 2 0/8280 (0%) 0
    Calculus bladder 2/8212 (0%) 2 0/8280 (0%) 0
    Calculus ureteric 7/8212 (0.1%) 8 5/8280 (0.1%) 7
    Calculus urinary 0/8212 (0%) 0 2/8280 (0%) 2
    Cystitis haemorrhagic 2/8212 (0%) 2 0/8280 (0%) 0
    Cystitis noninfective 0/8212 (0%) 0 1/8280 (0%) 1
    Diabetic nephropathy 0/8212 (0%) 0 3/8280 (0%) 3
    Glomerulonephritis membranoproliferative 1/8212 (0%) 1 0/8280 (0%) 0
    Glomerulonephritis membranous 1/8212 (0%) 1 0/8280 (0%) 0
    Haematuria 7/8212 (0.1%) 7 5/8280 (0.1%) 6
    Hydronephrosis 1/8212 (0%) 1 1/8280 (0%) 1
    Lupus nephritis 1/8212 (0%) 1 0/8280 (0%) 0
    Nephrolithiasis 11/8212 (0.1%) 11 13/8280 (0.2%) 16
    Nephropathy 0/8212 (0%) 0 2/8280 (0%) 2
    Nephropathy toxic 1/8212 (0%) 1 1/8280 (0%) 1
    Nephrotic syndrome 1/8212 (0%) 1 1/8280 (0%) 1
    Renal artery stenosis 3/8212 (0%) 3 0/8280 (0%) 0
    Renal colic 0/8212 (0%) 0 2/8280 (0%) 2
    Renal cyst 1/8212 (0%) 1 0/8280 (0%) 0
    Renal failure 20/8212 (0.2%) 20 23/8280 (0.3%) 23
    Renal failure acute 65/8212 (0.8%) 71 80/8280 (1%) 89
    Renal failure chronic 17/8212 (0.2%) 18 18/8280 (0.2%) 19
    Renal impairment 24/8212 (0.3%) 25 22/8280 (0.3%) 25
    Renal infarct 1/8212 (0%) 1 0/8280 (0%) 0
    Renal mass 1/8212 (0%) 1 0/8280 (0%) 0
    Renal tubular necrosis 1/8212 (0%) 1 0/8280 (0%) 0
    Stress urinary incontinence 1/8212 (0%) 1 0/8280 (0%) 0
    Tubulointerstitial nephritis 1/8212 (0%) 1 0/8280 (0%) 0
    Ureteric stenosis 2/8212 (0%) 2 2/8280 (0%) 2
    Urethral stenosis 2/8212 (0%) 2 5/8280 (0.1%) 6
    Urinary bladder polyp 0/8212 (0%) 0 2/8280 (0%) 2
    Urinary incontinence 0/8212 (0%) 0 1/8280 (0%) 1
    Urinary retention 4/8212 (0%) 4 8/8280 (0.1%) 8
    Urinary tract obstruction 4/8212 (0%) 4 0/8280 (0%) 0
    Reproductive system and breast disorders
    Acquired hydrocele 1/8212 (0%) 1 1/8280 (0%) 1
    Acquired phimosis 0/8212 (0%) 0 1/8280 (0%) 1
    Balanitis 1/8212 (0%) 1 0/8280 (0%) 0
    Benign prostatic hyperplasia 13/8212 (0.2%) 13 13/8280 (0.2%) 13
    Breast mass 0/8212 (0%) 0 1/8280 (0%) 1
    Cervical polyp 2/8212 (0%) 2 0/8280 (0%) 0
    Colpocele 0/8212 (0%) 0 1/8280 (0%) 1
    Dysfunctional uterine bleeding 0/8212 (0%) 0 1/8280 (0%) 1
    Endometrial hyperplasia 1/8212 (0%) 1 2/8280 (0%) 2
    Epididymitis 0/8212 (0%) 0 2/8280 (0%) 2
    Metrorrhagia 1/8212 (0%) 1 0/8280 (0%) 0
    Ovarian cyst 1/8212 (0%) 1 0/8280 (0%) 0
    Postmenopausal haemorrhage 0/8212 (0%) 0 1/8280 (0%) 1
    Prostatic obstruction 0/8212 (0%) 0 1/8280 (0%) 1
    Prostatitis 4/8212 (0%) 4 1/8280 (0%) 1
    Prostatomegaly 1/8212 (0%) 1 2/8280 (0%) 2
    Rectocele 0/8212 (0%) 0 1/8280 (0%) 1
    Testicular cyst 1/8212 (0%) 1 0/8280 (0%) 0
    Uterine haemorrhage 0/8212 (0%) 0 1/8280 (0%) 1
    Uterine polyp 2/8212 (0%) 2 1/8280 (0%) 1
    Uterine prolapse 2/8212 (0%) 2 1/8280 (0%) 2
    Uterovaginal prolapse 1/8212 (0%) 1 1/8280 (0%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute lung injury 1/8212 (0%) 1 0/8280 (0%) 0
    Acute pulmonary oedema 1/8212 (0%) 1 4/8280 (0%) 4
    Acute respiratory distress syndrome 1/8212 (0%) 1 1/8280 (0%) 1
    Acute respiratory failure 3/8212 (0%) 3 12/8280 (0.1%) 12
    Apnoea 0/8212 (0%) 0 1/8280 (0%) 1
    Aspiration 1/8212 (0%) 1 1/8280 (0%) 1
    Asthma 6/8212 (0.1%) 7 15/8280 (0.2%) 20
    Atelectasis 1/8212 (0%) 1 1/8280 (0%) 1
    Bronchitis chronic 2/8212 (0%) 2 1/8280 (0%) 1
    Bullous lung disease 1/8212 (0%) 1 0/8280 (0%) 0
    Chronic obstructive pulmonary disease 53/8212 (0.6%) 79 71/8280 (0.9%) 88
    Cough 2/8212 (0%) 2 1/8280 (0%) 1
    Dyspnoea 24/8212 (0.3%) 24 18/8280 (0.2%) 19
    Dyspnoea exertional 4/8212 (0%) 4 2/8280 (0%) 2
    Emphysema 1/8212 (0%) 1 0/8280 (0%) 0
    Epistaxis 3/8212 (0%) 3 8/8280 (0.1%) 9
    Haemoptysis 2/8212 (0%) 2 2/8280 (0%) 2
    Haemothorax 3/8212 (0%) 3 0/8280 (0%) 0
    Hydrothorax 2/8212 (0%) 2 0/8280 (0%) 0
    Hypercapnia 0/8212 (0%) 0 1/8280 (0%) 1
    Hypoxia 2/8212 (0%) 2 1/8280 (0%) 1
    Interstitial lung disease 4/8212 (0%) 5 0/8280 (0%) 0
    Laryngeal stenosis 2/8212 (0%) 2 0/8280 (0%) 0
    Lung consolidation 0/8212 (0%) 0 1/8280 (0%) 1
    Lung disorder 0/8212 (0%) 0 1/8280 (0%) 1
    Lung infiltration 1/8212 (0%) 1 0/8280 (0%) 0
    Nasal congestion 1/8212 (0%) 1 0/8280 (0%) 0
    Nasal obstruction 1/8212 (0%) 1 0/8280 (0%) 0
    Nasal polyps 1/8212 (0%) 1 2/8280 (0%) 2
    Nasal septum deviation 1/8212 (0%) 1 0/8280 (0%) 0
    Nocturnal dyspnoea 0/8212 (0%) 0 1/8280 (0%) 1
    Obstructive airways disorder 0/8212 (0%) 0 2/8280 (0%) 3
    Pharyngeal hypertrophy 0/8212 (0%) 0 1/8280 (0%) 1
    Pharyngeal inflammation 1/8212 (0%) 1 0/8280 (0%) 0
    Pleural effusion 8/8212 (0.1%) 9 5/8280 (0.1%) 5
    Pleuritic pain 1/8212 (0%) 1 1/8280 (0%) 1
    Pneumonia aspiration 1/8212 (0%) 1 10/8280 (0.1%) 10
    Pneumonitis 1/8212 (0%) 1 0/8280 (0%) 0
    Pneumothorax 2/8212 (0%) 2 0/8280 (0%) 0
    Pulmonary congestion 1/8212 (0%) 1 2/8280 (0%) 2
    Pulmonary embolism 10/8212 (0.1%) 10 11/8280 (0.1%) 11
    Pulmonary fibrosis 2/8212 (0%) 2 3/8280 (0%) 5
    Pulmonary haemorrhage 0/8212 (0%) 0 1/8280 (0%) 1
    Pulmonary hypertension 5/8212 (0.1%) 5 4/8280 (0%) 4
    Pulmonary oedema 7/8212 (0.1%) 8 8/8280 (0.1%) 8
    Pulmonary sarcoidosis 0/8212 (0%) 0 1/8280 (0%) 1
    Pulmonary toxicity 1/8212 (0%) 1 0/8280 (0%) 0
    Reflux laryngitis 0/8212 (0%) 0 1/8280 (0%) 1
    Respiratory arrest 0/8212 (0%) 0 1/8280 (0%) 1
    Respiratory disorder 0/8212 (0%) 0 2/8280 (0%) 2
    Respiratory distress 1/8212 (0%) 1 1/8280 (0%) 1
    Respiratory failure 11/8212 (0.1%) 13 9/8280 (0.1%) 10
    Sleep apnoea syndrome 6/8212 (0.1%) 6 2/8280 (0%) 2
    Snoring 0/8212 (0%) 0 1/8280 (0%) 1
    Status asthmaticus 1/8212 (0%) 1 0/8280 (0%) 0
    Vocal cord polyp 1/8212 (0%) 1 1/8280 (0%) 1
    Skin and subcutaneous tissue disorders
    Actinic keratosis 1/8212 (0%) 1 0/8280 (0%) 0
    Angioedema 1/8212 (0%) 1 5/8280 (0.1%) 5
    Decubitus ulcer 0/8212 (0%) 0 4/8280 (0%) 4
    Dermatitis contact 0/8212 (0%) 0 1/8280 (0%) 1
    Diabetic foot 23/8212 (0.3%) 25 22/8280 (0.3%) 24
    Diabetic ulcer 2/8212 (0%) 2 1/8280 (0%) 1
    Drug eruption 0/8212 (0%) 0 1/8280 (0%) 1
    Dry gangrene 2/8212 (0%) 2 0/8280 (0%) 0
    Dyshidrosis 1/8212 (0%) 1 0/8280 (0%) 0
    Ecchymosis 2/8212 (0%) 2 0/8280 (0%) 0
    Erythema 0/8212 (0%) 0 1/8280 (0%) 1
    Hyperhidrosis 0/8212 (0%) 0 1/8280 (0%) 1
    Keloid scar 0/8212 (0%) 0 1/8280 (0%) 1
    Leukocytoclastic vasculitis 0/8212 (0%) 0 1/8280 (0%) 1
    Neurodermatitis 1/8212 (0%) 1 0/8280 (0%) 0
    Neuropathic ulcer 1/8212 (0%) 1 1/8280 (0%) 1
    Night sweats 1/8212 (0%) 1 0/8280 (0%) 0
    Panniculitis 0/8212 (0%) 0 1/8280 (0%) 1
    Pemphigoid 0/8212 (0%) 0 2/8280 (0%) 2
    Pruritus 0/8212 (0%) 0 1/8280 (0%) 1
    Psoriasis 1/8212 (0%) 1 0/8280 (0%) 0
    Purpura 1/8212 (0%) 1 0/8280 (0%) 0
    Rash 0/8212 (0%) 0 1/8280 (0%) 1
    Scar pain 0/8212 (0%) 0 1/8280 (0%) 1
    Skin fibrosis 0/8212 (0%) 0 1/8280 (0%) 1
    Skin necrosis 2/8212 (0%) 2 2/8280 (0%) 2
    Skin reaction 0/8212 (0%) 0 1/8280 (0%) 1
    Skin ulcer 22/8212 (0.3%) 24 21/8280 (0.3%) 22
    Stasis dermatitis 2/8212 (0%) 2 0/8280 (0%) 0
    Stevens-Johnson syndrome 1/8212 (0%) 1 0/8280 (0%) 0
    Subcutaneous emphysema 0/8212 (0%) 0 1/8280 (0%) 1
    Toxic epidermal necrolysis 1/8212 (0%) 1 0/8280 (0%) 0
    Urticaria 1/8212 (0%) 1 1/8280 (0%) 1
    Surgical and medical procedures
    Coronary revascularisation 1/8212 (0%) 1 2/8280 (0%) 2
    Percutaneous coronary intervention 1/8212 (0%) 1 0/8280 (0%) 0
    Vascular disorders
    Accelerated hypertension 2/8212 (0%) 2 0/8280 (0%) 0
    Aortic aneurysm 8/8212 (0.1%) 8 4/8280 (0%) 4
    Aortic calcification 0/8212 (0%) 0 1/8280 (0%) 1
    Aortic occlusion 0/8212 (0%) 0 2/8280 (0%) 2
    Aortic stenosis 7/8212 (0.1%) 7 4/8280 (0%) 4
    Arterial insufficiency 1/8212 (0%) 1 0/8280 (0%) 0
    Arterial occlusive disease 0/8212 (0%) 0 1/8280 (0%) 1
    Arteriosclerosis 5/8212 (0.1%) 5 2/8280 (0%) 2
    Arteriovenous fistula 0/8212 (0%) 0 1/8280 (0%) 1
    Blood pressure inadequately controlled 1/8212 (0%) 1 1/8280 (0%) 1
    Circulatory collapse 1/8212 (0%) 1 1/8280 (0%) 1
    Deep vein thrombosis 9/8212 (0.1%) 9 8/8280 (0.1%) 8
    Diabetic macroangiopathy 1/8212 (0%) 1 0/8280 (0%) 0
    Embolism venous 1/8212 (0%) 1 0/8280 (0%) 0
    Extremity necrosis 3/8212 (0%) 3 6/8280 (0.1%) 6
    Femoral artery embolism 1/8212 (0%) 1 0/8280 (0%) 0
    Femoral artery occlusion 7/8212 (0.1%) 8 2/8280 (0%) 2
    Granulomatosis with polyangiitis 0/8212 (0%) 0 1/8280 (0%) 1
    Haematoma 3/8212 (0%) 3 5/8280 (0.1%) 5
    Haemorrhage 0/8212 (0%) 0 3/8280 (0%) 3
    Haemorrhagic infarction 1/8212 (0%) 1 0/8280 (0%) 0
    Hypertension 30/8212 (0.4%) 33 29/8280 (0.4%) 32
    Hypertensive crisis 16/8212 (0.2%) 17 17/8280 (0.2%) 18
    Hypertensive emergency 3/8212 (0%) 3 2/8280 (0%) 2
    Hypoperfusion 0/8212 (0%) 0 1/8280 (0%) 1
    Hypotension 17/8212 (0.2%) 18 19/8280 (0.2%) 22
    Hypovolaemic shock 0/8212 (0%) 0 3/8280 (0%) 3
    Iliac artery occlusion 2/8212 (0%) 2 1/8280 (0%) 1
    Intermittent claudication 10/8212 (0.1%) 11 10/8280 (0.1%) 11
    Necrosis ischaemic 1/8212 (0%) 2 0/8280 (0%) 0
    Orthostatic hypotension 5/8212 (0.1%) 6 6/8280 (0.1%) 6
    Peripheral arterial occlusive disease 43/8212 (0.5%) 49 24/8280 (0.3%) 25
    Peripheral artery aneurysm 3/8212 (0%) 3 1/8280 (0%) 1
    Peripheral artery dissection 0/8212 (0%) 0 1/8280 (0%) 1
    Peripheral artery stenosis 8/8212 (0.1%) 9 18/8280 (0.2%) 20
    Peripheral artery thrombosis 2/8212 (0%) 2 2/8280 (0%) 2
    Peripheral embolism 2/8212 (0%) 2 0/8280 (0%) 0
    Peripheral ischaemia 39/8212 (0.5%) 46 24/8280 (0.3%) 35
    Peripheral vascular disorder 20/8212 (0.2%) 22 21/8280 (0.3%) 24
    Shock 0/8212 (0%) 0 1/8280 (0%) 1
    Shock haemorrhagic 1/8212 (0%) 1 1/8280 (0%) 1
    Subclavian artery occlusion 1/8212 (0%) 1 0/8280 (0%) 0
    Subclavian artery stenosis 2/8212 (0%) 2 0/8280 (0%) 0
    Thrombophlebitis 1/8212 (0%) 1 1/8280 (0%) 1
    Thrombosis 1/8212 (0%) 1 3/8280 (0%) 3
    Varicose vein 1/8212 (0%) 1 2/8280 (0%) 2
    Vascular occlusion 1/8212 (0%) 1 0/8280 (0%) 0
    Vascular stenosis 1/8212 (0%) 1 1/8280 (0%) 1
    Vasculitis 0/8212 (0%) 0 1/8280 (0%) 1
    Venous insufficiency 1/8212 (0%) 1 1/8280 (0%) 1
    Venous thrombosis 0/8212 (0%) 0 1/8280 (0%) 1
    Venous thrombosis limb 1/8212 (0%) 2 0/8280 (0%) 0
    Other (Not Including Serious) Adverse Events
    Placebo Saxagliptin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3641/8212 (44.3%) 3504/8280 (42.3%)
    Blood and lymphatic system disorders
    Anaemia 198/8212 (2.4%) 208 197/8280 (2.4%) 204
    Cardiac disorders
    Angina pectoris 197/8212 (2.4%) 217 171/8280 (2.1%) 188
    Gastrointestinal disorders
    Constipation 164/8212 (2%) 175 170/8280 (2.1%) 183
    Diarrhoea 314/8212 (3.8%) 369 321/8280 (3.9%) 379
    Nausea 182/8212 (2.2%) 215 200/8280 (2.4%) 218
    General disorders
    Fatigue 192/8212 (2.3%) 215 167/8280 (2%) 179
    Oedema peripheral 352/8212 (4.3%) 375 343/8280 (4.1%) 380
    Infections and infestations
    Bronchitis 375/8212 (4.6%) 453 331/8280 (4%) 414
    Influenza 195/8212 (2.4%) 232 199/8280 (2.4%) 230
    Nasopharyngitis 280/8212 (3.4%) 334 293/8280 (3.5%) 341
    Upper respiratory tract infection 324/8212 (3.9%) 398 330/8280 (4%) 408
    Urinary tract infection 323/8212 (3.9%) 431 307/8280 (3.7%) 389
    Metabolism and nutrition disorders
    Diabetes mellitus 666/8212 (8.1%) 834 538/8280 (6.5%) 666
    Hyperglycaemia 278/8212 (3.4%) 327 215/8280 (2.6%) 271
    Musculoskeletal and connective tissue disorders
    Arthralgia 306/8212 (3.7%) 332 313/8280 (3.8%) 354
    Back pain 319/8212 (3.9%) 350 330/8280 (4%) 358
    Musculoskeletal pain 165/8212 (2%) 179 168/8280 (2%) 185
    Pain in extremity 321/8212 (3.9%) 342 264/8280 (3.2%) 298
    Nervous system disorders
    Dizziness 344/8212 (4.2%) 393 374/8280 (4.5%) 485
    Headache 241/8212 (2.9%) 255 208/8280 (2.5%) 240
    Respiratory, thoracic and mediastinal disorders
    Cough 302/8212 (3.7%) 337 258/8280 (3.1%) 282
    Dyspnoea 199/8212 (2.4%) 217 182/8280 (2.2%) 196
    Vascular disorders
    Hypertension 321/8212 (3.9%) 352 349/8280 (4.2%) 379

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    AstraZeneca's Publication Policy, data disclosure and transparency are available at the website: http://www.astrazeneca.com/responsibility/code-and-policies/policies?itemId=4861823&nav=yes. All papers or abstracts must be submitted to the Steering Committee and the SPONSOR, through BRIGHAM, for review of its appropriateness and scientific merit at least six weeks prior to submission to any publication.

    Results Point of Contact

    Name/Title Boaz Hirshberg MD, MBA
    Organization AstraZeneca LP
    Phone 1 302 885 4997
    Email ClinicalTrialTransparency@astrazeneca.com
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT01107886
    Other Study ID Numbers:
    • D1680C00003
    • EudraCT No 2009-017358-10
    First Posted:
    Apr 21, 2010
    Last Update Posted:
    Jul 17, 2014
    Last Verified:
    Jul 1, 2014