Evaluation of the Long- Term Effects of Spiriva on Lung Function in COPD Patients

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00144339
First received: September 2, 2005
Last updated: May 15, 2014
Last verified: April 2014
Results First Received: February 21, 2009  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Primary Purpose: Treatment
Condition: Pulmonary Disease, Chronic Obstructive
Interventions: Drug: tiotropium
Drug: placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
09 Jan 2003 – 22 Feb 2008; 490 centers in 37 countries

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Placebo once daily
Tiotropium Bromide Inhalation Capsules 18 mcg once daily

Participant Flow:   Overall Study
    Placebo     Tiotropium Bromide Inhalation Capsules 18 mcg  
STARTED     3006     2986  
COMPLETED     1648     1887  
NOT COMPLETED     1358     1099  
Adverse Event                 746                 627  
Protocol Violation                 75                 48  
Withdrawal by Subject                 403                 300  
Lost to Follow-up                 76                 64  
unknown                 58                 60  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Once daily
Tiotropium Bromide Inhalation Capsules 18 mcg Once daily
Total Total of all reporting groups

Baseline Measures
    Placebo     Tiotropium Bromide Inhalation Capsules 18 mcg     Total  
Number of Participants  
[units: participants]
  3006     2986     5992  
Age  
[units: years]
Mean ± Standard Deviation
  64.52  ± 8.48     64.50  ± 8.41     64.51  ± 8.45  
Gender  
[units: participants]
     
Female     784     735     1519  
Male     2222     2251     4473  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 30 to 4 Years   [ Time Frame: From day 30 to 4 years ]

2.  Primary:   Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 30 to 4 Years   [ Time Frame: From day 30 to 4 years ]

3.  Secondary:   Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment   [ Time Frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days. ]

4.  Secondary:   Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment   [ Time Frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days ]

5.  Secondary:   Pre-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 30 to 4 Years   [ Time Frame: From day 30 to 4 years ]

6.  Secondary:   Post-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 30 to 4 Years   [ Time Frame: From day 30 to 4 years ]

7.  Secondary:   Pre-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 30 to 4 Years   [ Time Frame: From day 30 to 4 years ]

8.  Secondary:   Post-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 30 to 4 Years   [ Time Frame: From day 30 to 4 years ]

9.  Secondary:   Rate of Decline of St George's Respiratory Questionnaire (SGRQ) Total Score   [ Time Frame: From month 6 to 4 years ]

10.  Secondary:   Pre-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment   [ Time Frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days. ]

11.  Secondary:   Post-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment   [ Time Frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days ]

12.  Secondary:   Pre-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment   [ Time Frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days ]

13.  Secondary:   Post-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment   [ Time Frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days ]

14.  Secondary:   Time to First Exacerbation   [ Time Frame: From Day 1 to 4 years ]

15.  Secondary:   Number of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Per Patient Year   [ Time Frame: Day 1 to 4 years ]

16.  Secondary:   Number and Percentage of Patients With at Least One Chronic Obstructive Pulmonary Disease (COPD) Exacerbation   [ Time Frame: Day 1 to 4 years ]

17.  Secondary:   Number of Exacerbation Days Per Patient Year   [ Time Frame: Day 1 to 4 years ]

18.  Secondary:   Time to First COPD Exacerbation Leading to Hospitalization (for 25% Patients)   [ Time Frame: Day 1 to 4 years ]

19.  Secondary:   Number and Percentage of Patients With at Least on COPD Exacerbation Leading to Hospitalization   [ Time Frame: From Day 1 to 4 years ]

20.  Secondary:   Number of Exacerbation Leading to Hospitalization   [ Time Frame: From Day 1 to 4 years ]

21.  Secondary:   Days of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization   [ Time Frame: From Day 1 to 4 years ]

22.  Secondary:   Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 1   [ Time Frame: Month 1 ]

23.  Secondary:   Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 1   [ Time Frame: Month 1 ]

24.  Secondary:   Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 6   [ Time Frame: Month 6 ]

25.  Secondary:   Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 6   [ Time Frame: Month 6 ]

26.  Secondary:   Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 12   [ Time Frame: Month 12 ]

27.  Secondary:   Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 12   [ Time Frame: Month 12 ]

28.  Secondary:   Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 18   [ Time Frame: Month 18 ]

29.  Secondary:   Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 18   [ Time Frame: Month 18 ]

30.  Secondary:   Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 24   [ Time Frame: Month 24 ]

31.  Secondary:   Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 24   [ Time Frame: Month 24 ]

32.  Secondary:   Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 30   [ Time Frame: Month 30 ]

33.  Secondary:   Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 30   [ Time Frame: Month 30 ]

34.  Secondary:   Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 36   [ Time Frame: Month 36 ]

35.  Secondary:   Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 36   [ Time Frame: Month 36 ]

36.  Secondary:   Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 42   [ Time Frame: Month 42 ]

37.  Secondary:   Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 42   [ Time Frame: Month 42 ]

38.  Secondary:   Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 48   [ Time Frame: Month 48 ]

39.  Secondary:   Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 48   [ Time Frame: Month 48 ]

40.  Secondary:   Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 1   [ Time Frame: Month 1 ]

41.  Secondary:   Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 1   [ Time Frame: Month 1 ]

42.  Secondary:   Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 6   [ Time Frame: Month 6 ]

43.  Secondary:   Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 6   [ Time Frame: Month 6 ]

44.  Secondary:   Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 12   [ Time Frame: Month 12 ]

45.  Secondary:   Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 12   [ Time Frame: Month 12 ]

46.  Secondary:   Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 18   [ Time Frame: Month 18 ]

47.  Secondary:   Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 18   [ Time Frame: Month 18 ]

48.  Secondary:   Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 24   [ Time Frame: Month 24 ]

49.  Secondary:   Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 24   [ Time Frame: Month 24 ]

50.  Secondary:   Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 30   [ Time Frame: Month 30 ]

51.  Secondary:   Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 30   [ Time Frame: Month 30 ]

52.  Secondary:   Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 36   [ Time Frame: Month 36 ]

53.  Secondary:   Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 36   [ Time Frame: Month 36 ]

54.  Secondary:   Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 42   [ Time Frame: Month 42 ]

55.  Secondary:   Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 42   [ Time Frame: Month 42 ]

56.  Secondary:   Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 48   [ Time Frame: Month 48 ]

57.  Secondary:   Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 48   [ Time Frame: Month 48 ]

58.  Secondary:   Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 1   [ Time Frame: Month 1 ]

59.  Secondary:   Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 1   [ Time Frame: Month 1 ]

60.  Secondary:   Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 6   [ Time Frame: Month 6 ]

61.  Secondary:   Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 6   [ Time Frame: Month 6 ]

62.  Secondary:   Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 12   [ Time Frame: Month 12 ]

63.  Secondary:   Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 12   [ Time Frame: Month 12 ]

64.  Secondary:   Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 18   [ Time Frame: Month 18 ]

65.  Secondary:   Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 18   [ Time Frame: Month 18 ]

66.  Secondary:   Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 24   [ Time Frame: Month 24 ]

67.  Secondary:   Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 24   [ Time Frame: Month 24 ]

68.  Secondary:   Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 30   [ Time Frame: Month 30 ]

69.  Secondary:   Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 30   [ Time Frame: Month 30 ]

70.  Secondary:   Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 36   [ Time Frame: Month 36 ]

71.  Secondary:   Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 36   [ Time Frame: Month 36 ]

72.  Secondary:   Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 42   [ Time Frame: Month 42 ]

73.  Secondary:   Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 42   [ Time Frame: Month 42 ]

74.  Secondary:   Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 48   [ Time Frame: Month 48 ]

75.  Secondary:   Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 48   [ Time Frame: Month 48 ]

76.  Secondary:   Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 6   [ Time Frame: Month 6 ]

77.  Secondary:   Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 12   [ Time Frame: Month 12 ]

78.  Secondary:   Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 18   [ Time Frame: Month 18 ]

79.  Secondary:   Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 24   [ Time Frame: Month 24 ]

80.  Secondary:   Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 30   [ Time Frame: Month 30 ]

81.  Secondary:   Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 36   [ Time Frame: Month 36 ]

82.  Secondary:   Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 42   [ Time Frame: Month 42 ]

83.  Secondary:   Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 48   [ Time Frame: Month 48 ]

84.  Secondary:   Number and Percentage of Participants With All Cause Death and Time to Event Analysis (On-treatment)   [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days between Day 1 and 4 years plus 30 days ]

85.  Secondary:   Number and Percentage of Participants With All Cause Death (Including Vital Status Follow-up, Cutoff at 1470 Days)   [ Time Frame: Day 1 to day 1470 ]

86.  Secondary:   Number and Percentage of Participants With Lower Respiratory Death (On-treatment; Adjudicated Primary Cause)   [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days between Day 1 and 4 years plus 30 days ]

87.  Secondary:   Number and Percentage of Participants With a Lower Respiratory Death (Adjudicated; Including Vital Status Follow-up, Cutoff at 1470 Days)   [ Time Frame: Day 1 to day 1470 ]

88.  Post-Hoc:   Number and Percentage of Participants With All Cause Death (Including Vital Status Follow-up, Cutoff at 1440 Days)   [ Time Frame: Day 1 to day 1440 ]

89.  Other Pre-specified:   Incidence Rate of Serious Adverse Event (System Organ Class = Cardiac Disorders)   [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days ]

90.  Other Pre-specified:   Incidence Rate of Serious Adverse Event (Preferred Term = Angina)   [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days ]

91.  Other Pre-specified:   Incidence Rate of Serious Adverse Event (Preferred Term = Atrial Fibrillation)   [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days ]

92.  Other Pre-specified:   Incidence Rate of Serious Adverse Event (Preferred Term = Cardiac Failure)   [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days ]

93.  Other Pre-specified:   Incidence Rate of Serious Adverse Event (Preferred Term = Cardiac Failure Congestive)   [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days ]

94.  Other Pre-specified:   Incidence Rate of Serious Adverse Event (Preferred Term = Coronary Artery Disease)   [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days ]

95.  Other Pre-specified:   Incidence Rate of Serious Adverse Event (Preferred Term = Myocardial Infarction)   [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days ]

96.  Other Pre-specified:   Incidence Rate of Serious Adverse Event (System Organ Class = Lower Respiratory System Disorders)   [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days ]

97.  Other Pre-specified:   Incidence Rate of Serious Adverse Event (Preferred Term = Bronchitis)   [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days ]

98.  Other Pre-specified:   Incidence Rate of Serious Adverse Event (Preferred Term = Chronic Obstructive Pulmonary Disease (COPD) Exacerbation)   [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days ]

99.  Other Pre-specified:   Incidence Rate of Serious Adverse Event (Preferred Term = Dyspnoea)   [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days ]

100.  Other Pre-specified:   Incidence Rate of Serious Adverse Event (Preferred Term = Pneumonia)   [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days ]

101.  Other Pre-specified:   Incidence Rate of Serious Adverse Event (Preferred Term = Respiratory Failure)   [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days ]


  Serious Adverse Events
  Hide Serious Adverse Events

Time Frame From first drug administration until 30 days after last drug administration
Additional Description The Dictionary used to report the adverse events is Sponsor-defined based on the MedDRA version 11.0

Reporting Groups
  Description
Placebo Once daily
Tiotropium Bromide Inhalation Capsules 18 mcg Once daily

Serious Adverse Events
    Placebo     Tiotropium Bromide Inhalation Capsules 18 mcg  
Total, serious adverse events      
# participants affected     1509     1540  
Blood and lymphatic system disorders      
Anaemia † 1    
# participants affected / at risk     11/3006 (0.37%)     19/2986 (0.64%)  
Coagulopathy † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Disseminated intravascular coagulation † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Febrile neutropenia † 1    
# participants affected / at risk     2/3006 (0.07%)     1/2986 (0.03%)  
Haemolytic anaemia † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Haemorrhagic anaemia † 1    
# participants affected / at risk     4/3006 (0.13%)     0/2986 (0.00%)  
Hypocoagulable state † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Iron deficiency anaemia † 1    
# participants affected / at risk     4/3006 (0.13%)     2/2986 (0.07%)  
Leukocytosis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Leukopenia † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Lymphadenopathy † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Microcytic anaemia † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Neutropenia † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Polycythaemia † 1    
# participants affected / at risk     1/3006 (0.03%)     2/2986 (0.07%)  
Splenic haemorrhage † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Splenic lesion † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Splenic vein thrombosis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Splenomegaly † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Thrombocytopenia † 1    
# participants affected / at risk     3/3006 (0.10%)     0/2986 (0.00%)  
Cardiac disorders      
Accelerated idioventricular rhythm † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Acute coronary syndrome † 1    
# participants affected / at risk     2/3006 (0.07%)     6/2986 (0.20%)  
Acute right ventricular failure † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Angina † 1    
# participants affected / at risk     31/3006 (1.03%)     48/2986 (1.61%)  
Aortic valve disease † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Aortic valve incompetence † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Aortic valve stenosis † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Arrhythmia † 1    
# participants affected / at risk     10/3006 (0.33%)     7/2986 (0.23%)  
Arrhythmia supraventricular † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Arteriosclerosis coronary artery † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Atrial Fibrillation † 1    
# participants affected / at risk     67/3006 (2.23%)     69/2986 (2.31%)  
Atrial tachycardia † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Atrial thrombosis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Atrioventricular block † 1    
# participants affected / at risk     1/3006 (0.03%)     3/2986 (0.10%)  
Atrioventricular block complete † 1    
# participants affected / at risk     4/3006 (0.13%)     5/2986 (0.17%)  
Atrioventricular block first degree † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Atrioventricular block second degree † 1    
# participants affected / at risk     3/3006 (0.10%)     1/2986 (0.03%)  
Bradycardia † 1    
# participants affected / at risk     5/3006 (0.17%)     1/2986 (0.03%)  
Bundle branch block left † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Bundle branch block right † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Cardiac aneurysm † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Cardiac arrest † 1    
# participants affected / at risk     11/3006 (0.37%)     6/2986 (0.20%)  
Cardiac asthma † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Cardiac disorder † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Cardiac failure † 1    
# participants affected / at risk     42/3006 (1.40%)     57/2986 (1.91%)  
Cardiac failure acute † 1    
# participants affected / at risk     3/3006 (0.10%)     4/2986 (0.13%)  
Cardiac failure chronic † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Cardiac failure congestive † 1    
# participants affected / at risk     42/3006 (1.40%)     27/2986 (0.90%)  
Cardiac tamponade † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Cardiac valve disease † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Cardiac ventricular disorder † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Cardio-respiratory arrest † 1    
# participants affected / at risk     7/3006 (0.23%)     6/2986 (0.20%)  
Cardiogenic shock † 1    
# participants affected / at risk     3/3006 (0.10%)     4/2986 (0.13%)  
Cardiomegaly † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Cardiomyopathy † 1    
# participants affected / at risk     3/3006 (0.10%)     2/2986 (0.07%)  
Cardiopulmonary failure † 1    
# participants affected / at risk     12/3006 (0.40%)     10/2986 (0.33%)  
Conduction disorder † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Cor pulmonale † 1    
# participants affected / at risk     15/3006 (0.50%)     12/2986 (0.40%)  
Cor pulmonale acute † 1    
# participants affected / at risk     2/3006 (0.07%)     2/2986 (0.07%)  
Cor pulmonale chronic † 1    
# participants affected / at risk     2/3006 (0.07%)     4/2986 (0.13%)  
Coronary artery disease † 1    
# participants affected / at risk     32/3006 (1.06%)     20/2986 (0.67%)  
Coronary artery embolism † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Coronary artery insufficiency † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Coronary artery occlusion † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Coronary artery restenosis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Coronary artery stenosis † 1    
# participants affected / at risk     6/3006 (0.20%)     4/2986 (0.13%)  
Coronary artery thrombosis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Diastolic dysfunction † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Extrasystoles † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Hypertensive cardiomyopathy † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Hypertensive heart disease † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Intracardiac thrombus † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Ischaemic cardiomyopathy † 1    
# participants affected / at risk     3/3006 (0.10%)     2/2986 (0.07%)  
Left ventricular dysfunction † 1    
# participants affected / at risk     2/3006 (0.07%)     1/2986 (0.03%)  
Left ventricular failure † 1    
# participants affected / at risk     5/3006 (0.17%)     6/2986 (0.20%)  
Mitral valve incompetence † 1    
# participants affected / at risk     3/3006 (0.10%)     2/2986 (0.07%)  
Myocardial infarction † 1    
# participants affected / at risk     84/3006 (2.79%)     65/2986 (2.18%)  
Myocardial ischaemia † 1    
# participants affected / at risk     13/3006 (0.43%)     10/2986 (0.33%)  
Myocarditis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Palpitations † 1    
# participants affected / at risk     2/3006 (0.07%)     2/2986 (0.07%)  
Pericardial haemorrhage † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Pericarditis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Right ventricular failure † 1    
# participants affected / at risk     6/3006 (0.20%)     4/2986 (0.13%)  
Sick sinus syndrome † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Supraventricular extrasystoles † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Supraventricular tachycardia † 1    
# participants affected / at risk     8/3006 (0.27%)     8/2986 (0.27%)  
Tachyarrhythmia † 1    
# participants affected / at risk     2/3006 (0.07%)     5/2986 (0.17%)  
Tachycardia † 1    
# participants affected / at risk     6/3006 (0.20%)     4/2986 (0.13%)  
Torsade de pointes † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Tricuspid valve incompetence † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Ventricular arrhythmia † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Ventricular extrasystoles † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Ventricular fibrillation † 1    
# participants affected / at risk     9/3006 (0.30%)     3/2986 (0.10%)  
Ventricular hypokinesia † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Ventricular tachycardia † 1    
# participants affected / at risk     7/3006 (0.23%)     7/2986 (0.23%)  
Congenital, familial and genetic disorders      
Adenomatous polyposis coli † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Arteriovenous malformation † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Atrial septal defect † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Congenital myopathy † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Dermoid cyst † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Dolichocolon † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Gastrointestinal angiodysplasia † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Gastrointestinal angiodysplasia haemorrhagic † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Gastrointestinal arteriovenous malformation † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Hydrocele † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Neurofibromatosis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Phimosis † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Pyloric stenosis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Ear and labyrinth disorders      
Deafness † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Hypoacusis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Otosclerosis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Sudden hearing loss † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Vertigo † 1    
# participants affected / at risk     8/3006 (0.27%)     8/2986 (0.27%)  
Vertigo positional † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Vestibular disorder † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Endocrine disorders      
Adrenal insufficiency † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Adrenal mass † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Diabetes insipidus † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Hyperparathyroidism † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Hyperthyroidism † 1    
# participants affected / at risk     2/3006 (0.07%)     1/2986 (0.03%)  
Thyroid disorder † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Eye disorders      
Amaurosis fugax † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Blindness unilateral † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Cataract † 1    
# participants affected / at risk     21/3006 (0.70%)     23/2986 (0.77%)  
Conjunctivitis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Eye haemorrhage † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Eye pain † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Glaucoma † 1    
# participants affected / at risk     1/3006 (0.03%)     2/2986 (0.07%)  
Iridocele † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Optic ischaemic neuropathy † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Retinal detachment † 1    
# participants affected / at risk     1/3006 (0.03%)     2/2986 (0.07%)  
Retinal tear † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Retinal vein occlusion † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Vision blurred † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Visual disturbance † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Vitreous haemorrhage † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Gastrointestinal disorders      
Abdominal adhesions † 1    
# participants affected / at risk     2/3006 (0.07%)     2/2986 (0.07%)  
Abdominal discomfort † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Abdominal distension † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Abdominal hernia † 1    
# participants affected / at risk     2/3006 (0.07%)     5/2986 (0.17%)  
Abdominal pain † 1    
# participants affected / at risk     18/3006 (0.60%)     18/2986 (0.60%)  
Abdominal strangulated hernia † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Appendicitis perforated † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Ascites † 1    
# participants affected / at risk     3/3006 (0.10%)     1/2986 (0.03%)  
Coeliac disease † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Colitis † 1    
# participants affected / at risk     3/3006 (0.10%)     0/2986 (0.00%)  
Colitis ischaemic † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Colitis ulcerative † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Colonic polyp † 1    
# participants affected / at risk     4/3006 (0.13%)     5/2986 (0.17%)  
Constipation † 1    
# participants affected / at risk     3/3006 (0.10%)     3/2986 (0.10%)  
Crohn's disease † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Dental caries † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Diarrhoea † 1    
# participants affected / at risk     12/3006 (0.40%)     5/2986 (0.17%)  
Diverticular perforation † 1    
# participants affected / at risk     2/3006 (0.07%)     1/2986 (0.03%)  
Diverticulum † 1    
# participants affected / at risk     4/3006 (0.13%)     5/2986 (0.17%)  
Diverticulum intestinal † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Diverticulum intestinal haemorrhagic † 1    
# participants affected / at risk     1/3006 (0.03%)     3/2986 (0.10%)  
Duodenal perforation † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Duodenal polyp † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Duodenal ulcer † 1    
# participants affected / at risk     4/3006 (0.13%)     3/2986 (0.10%)  
Duodenal ulcer haemorrhage † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Duodenitis † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Dyspepsia † 1    
# participants affected / at risk     1/3006 (0.03%)     2/2986 (0.07%)  
Dysphagia † 1    
# participants affected / at risk     3/3006 (0.10%)     2/2986 (0.07%)  
Enterocolitis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Erosive duodenitis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Faecal incontinence † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Faecaloma † 1    
# participants affected / at risk     2/3006 (0.07%)     2/2986 (0.07%)  
Femoral hernia † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Femoral hernia, obstructive † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Flatulence † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Gastric haemorrhage † 1    
# participants affected / at risk     3/3006 (0.10%)     2/2986 (0.07%)  
Gastric polyps † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Gastric ulcer † 1    
# participants affected / at risk     6/3006 (0.20%)     3/2986 (0.10%)  
Gastric ulcer haemorrhage † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Gastric varices haemorrhage † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Gastric volvulus † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Gastritis † 1    
# participants affected / at risk     5/3006 (0.17%)     9/2986 (0.30%)  
Gastritis erosive † 1    
# participants affected / at risk     1/3006 (0.03%)     3/2986 (0.10%)  
Gastritis haemorrhagic † 1    
# participants affected / at risk     2/3006 (0.07%)     1/2986 (0.03%)  
Gastrointestinal haemorrhage † 1    
# participants affected / at risk     16/3006 (0.53%)     11/2986 (0.37%)  
Gastrooesophageal reflux disease † 1    
# participants affected / at risk     2/3006 (0.07%)     2/2986 (0.07%)  
Gastrooesophagitis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Haematemesis † 1    
# participants affected / at risk     4/3006 (0.13%)     2/2986 (0.07%)  
Haematochezia † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Haemorrhoids † 1    
# participants affected / at risk     5/3006 (0.17%)     2/2986 (0.07%)  
Hiatus hernia † 1    
# participants affected / at risk     0/3006 (0.00%)     5/2986 (0.17%)  
Ileitis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Ileus † 1    
# participants affected / at risk     7/3006 (0.23%)     9/2986 (0.30%)  
Ileus paralytic † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Inguinal hernia † 1    
# participants affected / at risk     21/3006 (0.70%)     20/2986 (0.67%)  
Inguinal hernia, obstructive † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Internal hernia † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Intestinal angina † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Intestinal fistula † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Intestinal haemorrhage † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Intestinal infarction † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Intestinal ischaemia † 1    
# participants affected / at risk     2/3006 (0.07%)     1/2986 (0.03%)  
Intestinal mucosal hypertrophy † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Intestinal obstruction † 1    
# participants affected / at risk     2/3006 (0.07%)     9/2986 (0.30%)  
Intestinal perforation † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Intestinal polyp † 1    
# participants affected / at risk     3/3006 (0.10%)     1/2986 (0.03%)  
Intra-abdominal haematoma † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Irritable bowel syndrome † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Large intestinal haemorrhage † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Large intestine perforation † 1    
# participants affected / at risk     1/3006 (0.03%)     4/2986 (0.13%)  
Loose tooth † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Lower gastrointestinal haemorrhage † 1    
# participants affected / at risk     3/3006 (0.10%)     1/2986 (0.03%)  
Malabsorption † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Mallory-Weiss syndrome † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Mechanical ileus † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Melaena † 1    
# participants affected / at risk     7/3006 (0.23%)     4/2986 (0.13%)  
Mouth cyst † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Mouth ulceration † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Nausea † 1    
# participants affected / at risk     0/3006 (0.00%)     5/2986 (0.17%)  
Odynophagia † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Oesophageal stenosis † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Oesophageal varices haemorrhage † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Oesophagitis † 1    
# participants affected / at risk     2/3006 (0.07%)     1/2986 (0.03%)  
Oesophagitis ulcerative † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Pancreatic duct obstruction † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Pancreatitis † 1    
# participants affected / at risk     6/3006 (0.20%)     5/2986 (0.17%)  
Pancreatitis acute † 1    
# participants affected / at risk     3/3006 (0.10%)     3/2986 (0.10%)  
Pancreatitis chronic † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Parotid lipomatosis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Peptic ulcer † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Peptic ulcer haemorrhage † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Peritonitis † 1    
# participants affected / at risk     1/3006 (0.03%)     4/2986 (0.13%)  
Pneumoperitoneum † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Polyp colorectal † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Rectal discharge † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Rectal haemorrhage † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Rectal polyp † 1    
# participants affected / at risk     2/3006 (0.07%)     1/2986 (0.03%)  
Reflux oesophagitis † 1    
# participants affected / at risk     0/3006 (0.00%)     3/2986 (0.10%)  
Salivary gland calculus † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Salivary gland mass † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Small intestinal obstruction † 1    
# participants affected / at risk     4/3006 (0.13%)     4/2986 (0.13%)  
Small intestinal perforation † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Stomach discomfort † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Stomatitis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Subileus † 1    
# participants affected / at risk     4/3006 (0.13%)     1/2986 (0.03%)  
Umbilical hernia † 1    
# participants affected / at risk     4/3006 (0.13%)     2/2986 (0.07%)  
Umbilical hernia, obstructive † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Upper gastrointestinal haemorrhage † 1    
# participants affected / at risk     5/3006 (0.17%)     3/2986 (0.10%)  
Varices oesophageal † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Volvulus † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Vomiting † 1    
# participants affected / at risk     1/3006 (0.03%)     5/2986 (0.17%)  
General disorders      
Accidental death † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Adverse drug reaction † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Asthenia † 1    
# participants affected / at risk     6/3006 (0.20%)     7/2986 (0.23%)  
Cardiac death † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Chest discomfort † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Chest pain † 1    
# participants affected / at risk     19/3006 (0.63%)     23/2986 (0.77%)  
Cyst rupture † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Death † 1    
# participants affected / at risk     24/3006 (0.80%)     31/2986 (1.04%)  
Fatigue † 1    
# participants affected / at risk     2/3006 (0.07%)     2/2986 (0.07%)  
General physical health deterioration † 1    
# participants affected / at risk     5/3006 (0.17%)     3/2986 (0.10%)  
Impaired healing † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Influenza like illness † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Multi-organ disorder † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Multi-organ failure † 1    
# participants affected / at risk     10/3006 (0.33%)     6/2986 (0.20%)  
Multimorbidity † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Non-cardiac chest pain † 1    
# participants affected / at risk     20/3006 (0.67%)     18/2986 (0.60%)  
Oedema † 1    
# participants affected / at risk     14/3006 (0.47%)     8/2986 (0.27%)  
Pain † 1    
# participants affected / at risk     1/3006 (0.03%)     2/2986 (0.07%)  
Perforated ulcer † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Polyp † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Pyrexia † 1    
# participants affected / at risk     6/3006 (0.20%)     9/2986 (0.30%)  
Sudden cardiac death † 1    
# participants affected / at risk     2/3006 (0.07%)     1/2986 (0.03%)  
Sudden death † 1    
# participants affected / at risk     11/3006 (0.37%)     10/2986 (0.33%)  
Ulcer † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Hepatobiliary disorders      
Acute hepatic failure † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Bile duct obstruction † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Bile duct stone † 1    
# participants affected / at risk     2/3006 (0.07%)     6/2986 (0.20%)  
Biliary colic † 1    
# participants affected / at risk     0/3006 (0.00%)     3/2986 (0.10%)  
Biliary dyskinesia † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Cholangitis † 1    
# participants affected / at risk     2/3006 (0.07%)     1/2986 (0.03%)  
Cholangitis acute † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Cholecystitis † 1    
# participants affected / at risk     5/3006 (0.17%)     7/2986 (0.23%)  
Cholecystitis acute † 1    
# participants affected / at risk     4/3006 (0.13%)     6/2986 (0.20%)  
Cholecystitis chronic † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Cholelithiasis † 1    
# participants affected / at risk     18/3006 (0.60%)     11/2986 (0.37%)  
Cholelithiasis obstructive † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Cholestasis † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Chronic hepatitis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Gallbladder disorder † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Hepatic cirrhosis † 1    
# participants affected / at risk     0/3006 (0.00%)     3/2986 (0.10%)  
Hepatic failure † 1    
# participants affected / at risk     1/3006 (0.03%)     2/2986 (0.07%)  
Hepatic function abnormal † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Hepatitis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Hepatitis acute † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Hepatitis alcoholic † 1    
# participants affected / at risk     2/3006 (0.07%)     1/2986 (0.03%)  
Hepatomegaly † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Jaundice † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Jaundice cholestatic † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Immune system disorders      
Anaphylactic reaction † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Anaphylactic shock † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Food allergy † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Hypersensitivity † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Infections and infestations      
Abdominal infection † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Abdominal sepsis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Abdominal wall abscess † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Abscess † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Abscess intestinal † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Abscess limb † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Appendiceal abscess † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Appendicitis † 1    
# participants affected / at risk     2/3006 (0.07%)     9/2986 (0.30%)  
Arthritis infective † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Bacteraemia † 1    
# participants affected / at risk     1/3006 (0.03%)     2/2986 (0.07%)  
Bacterial infection † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Biliary tract infection † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Cellulitis † 1    
# participants affected / at risk     12/3006 (0.40%)     9/2986 (0.30%)  
Cholecystitis infective † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Clostridial infection † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Clostridium difficile colitis † 1    
# participants affected / at risk     3/3006 (0.10%)     1/2986 (0.03%)  
Corynebacterium infection † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Cystitis escherichia † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Dengue fever † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Dermo-hypodermitis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Device related infection † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Diverticulitis † 1    
# participants affected / at risk     8/3006 (0.27%)     7/2986 (0.23%)  
Empyema † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Endocarditis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Enterococcal sepsis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Erysipelas † 1    
# participants affected / at risk     0/3006 (0.00%)     5/2986 (0.17%)  
Escherichia sepsis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Fungaemia † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Fungal infection † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Gangrene † 1    
# participants affected / at risk     3/3006 (0.10%)     0/2986 (0.00%)  
Gastritis viral † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Gastroenteritis † 1    
# participants affected / at risk     3/3006 (0.10%)     5/2986 (0.17%)  
Gastroenteritis Escherichia coli † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Gastroenteritis salmonella † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Gastroenteritis viral † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Groin abscess † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Haemorrhoid infection † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Helicobacter infection † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Herpes zoster † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Herpes zoster infection neurological † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Hydrocele male infected † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Incision site infection † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Infection † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Intertrigo candida † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Intervertebral discitis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Joint abscess † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Klebsiella sepsis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Localised infection † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Meningitis † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Meningitis listeria † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Meningococcal bacteraemia † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Mycobacterial infection † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Necrotising fasciitis † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Neutropenic sepsis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Nosocomial infection † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Oesophageal candidiasis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Orchitis † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Oropharyngeal candidiasis † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Osteomyelitis † 1    
# participants affected / at risk     1/3006 (0.03%)     3/2986 (0.10%)  
Otitis media † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Parotitis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Perianal abscess † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Periodontal infection † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Periorbital cellulitis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Perirectal abscess † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Peritoneal abscess † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Peritoneal infection † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Pneumococcal sepsis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Post procedural infection † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Post procedural pneumonia † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Postoperative wound infection † 1    
# participants affected / at risk     2/3006 (0.07%)     3/2986 (0.10%)  
Pseudomonas infection † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Sepsis † 1    
# participants affected / at risk     26/3006 (0.86%)     16/2986 (0.54%)  
Sepsis syndrome † 1    
# participants affected / at risk     1/3006 (0.03%)     2/2986 (0.07%)  
Septic shock † 1    
# participants affected / at risk     11/3006 (0.37%)     9/2986 (0.30%)  
Skin infection † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Staphylococcal infection † 1    
# participants affected / at risk     1/3006 (0.03%)     2/2986 (0.07%)  
Staphylococcal sepsis † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Subcutaneous abscess † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Toxic shock syndrome † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Tuberculosis † 1    
# participants affected / at risk     4/3006 (0.13%)     4/2986 (0.13%)  
Urinary tract infection † 1    
# participants affected / at risk     17/3006 (0.57%)     24/2986 (0.80%)  
Urosepsis † 1    
# participants affected / at risk     3/3006 (0.10%)     1/2986 (0.03%)  
Wound infection † 1    
# participants affected / at risk     1/3006 (0.03%)     2/2986 (0.07%)  
Wound infection staphylococcal † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Wound sepsis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Injury, poisoning and procedural complications      
Abdominal injury † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Accident † 1    
# participants affected / at risk     0/3006 (0.00%)     3/2986 (0.10%)  
Acetabulum fracture † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Alcohol poisoning † 1    
# participants affected / at risk     4/3006 (0.13%)     3/2986 (0.10%)  
Anaemia postoperative † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Anastomotic stenosis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Ankle fracture † 1    
# participants affected / at risk     5/3006 (0.17%)     6/2986 (0.20%)  
Arteriovenous fistula site complication † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Arteriovenous fistula site haemorrhage † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Back injury † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Bladder injury † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Brain contusion † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Brain herniation † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Burn of internal organs † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Bursa injury † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Cardiac pacemaker malfunction † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Caustic injury † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Cervical vertebral fracture † 1    
# participants affected / at risk     0/3006 (0.00%)     4/2986 (0.13%)  
Chest injury † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Concussion † 1    
# participants affected / at risk     2/3006 (0.07%)     7/2986 (0.23%)  
Contusion † 1    
# participants affected / at risk     3/3006 (0.10%)     5/2986 (0.17%)  
Decerebration † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Delayed recovery from anaesthesia † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Device failure † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Device malfunction † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Dislocation of joint prosthesis † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Drug toxicity † 1    
# participants affected / at risk     4/3006 (0.13%)     1/2986 (0.03%)  
Face injury † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Facial bones fracture † 1    
# participants affected / at risk     3/3006 (0.10%)     2/2986 (0.07%)  
Fall † 1    
# participants affected / at risk     12/3006 (0.40%)     19/2986 (0.64%)  
Femoral neck fracture † 1    
# participants affected / at risk     5/3006 (0.17%)     9/2986 (0.30%)  
Femur fracture † 1    
# participants affected / at risk     6/3006 (0.20%)     7/2986 (0.23%)  
Fibula fracture † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Foot fracture † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Foreign body trauma † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Fracture † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Gastrointestinal disorder postoperative † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Gastrointestinal injury † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Hand fracture † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Head injury † 1    
# participants affected / at risk     3/3006 (0.10%)     1/2986 (0.03%)  
Hip fracture † 1    
# participants affected / at risk     8/3006 (0.27%)     9/2986 (0.30%)  
Humerus fracture † 1    
# participants affected / at risk     3/3006 (0.10%)     3/2986 (0.10%)  
Ilium fracture † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Incision site haemorrhage † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Incisional hernia † 1    
# participants affected / at risk     2/3006 (0.07%)     1/2986 (0.03%)  
Injury † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Internal injury † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Joint dislocation † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Joint injury † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Joint sprain † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Limb injury † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Lower limb fracture † 1    
# participants affected / at risk     0/3006 (0.00%)     4/2986 (0.13%)  
Lumbar vertebral fracture † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Meniscus lesion † 1    
# participants affected / at risk     2/3006 (0.07%)     2/2986 (0.07%)  
Multiple injuries † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Neck injury † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Operative haemorrhage † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Overdose † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Pacemaker complication † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Pancreatic injury † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Patella fracture † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Pelvic fracture † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Post gastric surgery syndrome † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Post procedural bile leak † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Post procedural fistula † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Post procedural haemorrhage † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Post-traumatic pain † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Postoperative ileus † 1    
# participants affected / at risk     3/3006 (0.10%)     2/2986 (0.07%)  
Postoperative wound complication † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Procedural hypotension † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Pubic rami fracture † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Radius fracture † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Rib fracture † 1    
# participants affected / at risk     6/3006 (0.20%)     9/2986 (0.30%)  
Road traffic accident † 1    
# participants affected / at risk     1/3006 (0.03%)     8/2986 (0.27%)  
Scapula fracture † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Shunt thrombosis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Skin injury † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Skin laceration † 1    
# participants affected / at risk     3/3006 (0.10%)     4/2986 (0.13%)  
Skull fracture † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Spinal compression fracture † 1    
# participants affected / at risk     6/3006 (0.20%)     8/2986 (0.27%)  
Spinal fracture † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Stent occlusion † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Stent-graft endoleak † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Subdural haematoma † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Subdural haemorrhage † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Synovial rupture † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Tendon injury † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Tendon rupture † 1    
# participants affected / at risk     0/3006 (0.00%)     3/2986 (0.10%)  
Therapeutic agent toxicity † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Thermal burn † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Thoracic vertebral fracture † 1    
# participants affected / at risk     2/3006 (0.07%)     2/2986 (0.07%)  
Thrombosis in device † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Tibia fracture † 1    
# participants affected / at risk     2/3006 (0.07%)     1/2986 (0.03%)  
Traumatic brain injury † 1    
# participants affected / at risk     0/3006 (0.00%)     3/2986 (0.10%)  
Traumatic fracture † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Ulna fracture † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Ulnar nerve injury † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Upper limb fracture † 1    
# participants affected / at risk     1/3006 (0.03%)     5/2986 (0.17%)  
Urinary tract injury † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Vaccination complication † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Vascular bypass dysfunction † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Vascular graft occlusion † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Vena cava injury † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Wound † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Wound dehiscence † 1    
# participants affected / at risk     0/3006 (0.00%)     4/2986 (0.13%)  
Wound secretion † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Wrist fracture † 1    
# participants affected / at risk     5/3006 (0.17%)     2/2986 (0.07%)  
Investigations      
Blood calcium decreased † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Blood creatine phosphokinase increased † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Blood glucose increased † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Blood pressure increased † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Blood sodium decreased † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Body temperature increased † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
C-reactive protein increased † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Cardiac murmur † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Electrocardiogram QT prolonged † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Heart rate irregular † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Hepatic enzyme increased † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
International normalised ratio increased † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Investigation † 1    
# participants affected / at risk     0/3006 (0.00%)     5/2986 (0.17%)  
Oxygen saturation decreased † 1    
# participants affected / at risk     1/3006 (0.03%)     2/2986 (0.07%)  
Physical examination † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Platelet count decreased † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Prostatic specific antigen increased † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Urine calcium increased † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Urine output decreased † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Weight decreased † 1    
# participants affected / at risk     3/3006 (0.10%)     3/2986 (0.10%)  
White blood cell count decreased † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
White blood cell count increased † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Metabolism and nutrition disorders      
Acidosis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Anorexia † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Cachexia † 1    
# participants affected / at risk     4/3006 (0.13%)     1/2986 (0.03%)  
Dehydration † 1    
# participants affected / at risk     10/3006 (0.33%)     14/2986 (0.47%)  
Diabetes mellitus † 1    
# participants affected / at risk     7/3006 (0.23%)     8/2986 (0.27%)  
Diabetes mellitus inadequate control † 1    
# participants affected / at risk     1/3006 (0.03%)     3/2986 (0.10%)  
Diabetic ketoacidosis † 1    
# participants affected / at risk     3/3006 (0.10%)     0/2986 (0.00%)  
Electrolyte imbalance † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Failure to thrive † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Food intolerance † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Gout † 1    
# participants affected / at risk     1/3006 (0.03%)     2/2986 (0.07%)  
Hyperglycaemia † 1    
# participants affected / at risk     3/3006 (0.10%)     1/2986 (0.03%)  
Hyperkalaemia † 1    
# participants affected / at risk     3/3006 (0.10%)     3/2986 (0.10%)  
Hypertriglyceridaemia † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Hypoglycaemia † 1    
# participants affected / at risk     4/3006 (0.13%)     3/2986 (0.10%)  
Hypokalaemia † 1    
# participants affected / at risk     5/3006 (0.17%)     2/2986 (0.07%)  
Hypomagnesaemia † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Hyponatraemia † 1    
# participants affected / at risk     6/3006 (0.20%)     5/2986 (0.17%)  
Hypophosphataemia † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Hypovolaemia † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Malnutrition † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Metabolic acidosis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Obesity † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Polydipsia † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Type 2 diabetes mellitus † 1    
# participants affected / at risk     0/3006 (0.00%)     3/2986 (0.10%)  
Musculoskeletal and connective tissue disorders      
Arthralgia † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Arthritis † 1    
# participants affected / at risk     1/3006 (0.03%)     3/2986 (0.10%)  
Back pain † 1    
# participants affected / at risk     10/3006 (0.33%)     8/2986 (0.27%)  
Bone cyst † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Bone pain † 1    
# participants affected / at risk     2/3006 (0.07%)     1/2986 (0.03%)  
Bursitis † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Costochondritis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Dupuytren's contracture † 1    
# participants affected / at risk     1/3006 (0.03%)     2/2986 (0.07%)  
Facet joint syndrome † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Foot deformity † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Fracture nonunion † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Intervertebral disc degeneration † 1    
# participants affected / at risk     1/3006 (0.03%)     2/2986 (0.07%)  
Intervertebral disc displacement † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Intervertebral disc protrusion † 1    
# participants affected / at risk     3/3006 (0.10%)     6/2986 (0.20%)  
Joint swelling † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Loose body in joint † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Lumbar spinal stenosis † 1    
# participants affected / at risk     1/3006 (0.03%)     3/2986 (0.10%)  
Metatarsalgia † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Muscle spasms † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Muscular weakness † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Musculoskeletal chest pain † 1    
# participants affected / at risk     4/3006 (0.13%)     7/2986 (0.23%)  
Myalgia † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Myalgia intercostal † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Myopathy steroid † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Neck pain † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Osteoarthritis † 1    
# participants affected / at risk     20/3006 (0.67%)     28/2986 (0.94%)  
Osteonecrosis † 1    
# participants affected / at risk     1/3006 (0.03%)     3/2986 (0.10%)  
Osteopenia † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Osteoporosis † 1    
# participants affected / at risk     1/3006 (0.03%)     4/2986 (0.13%)  
Osteoporotic fracture † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Pain in extremity † 1    
# participants affected / at risk     3/3006 (0.10%)     1/2986 (0.03%)  
Pathological fracture † 1    
# participants affected / at risk     3/3006 (0.10%)     0/2986 (0.00%)  
Periarthritis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Polymyositis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Rhabdomyolysis † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Rheumatoid arthritis † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Rotator cuff syndrome † 1    
# participants affected / at risk     3/3006 (0.10%)     3/2986 (0.10%)  
Spinal column stenosis † 1    
# participants affected / at risk     2/3006 (0.07%)     1/2986 (0.03%)  
Spinal osteoarthritis † 1    
# participants affected / at risk     8/3006 (0.27%)     3/2986 (0.10%)  
Spondylitis † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Spondylolisthesis † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Synovial cyst † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Tendonitis † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Acoustic neuroma † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Acute leukaemia † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Adenocarcinoma † 1    
# participants affected / at risk     3/3006 (0.10%)     3/2986 (0.10%)  
Adenocarcinoma pancreas † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Adrenal neoplasm † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
B-cell lymphoma † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Basal cell carcinoma † 1    
# participants affected / at risk     22/3006 (0.73%)     23/2986 (0.77%)  
Basosquamous carcinoma † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Basosquamous carcinoma of skin † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Benign colonic neoplasm † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Benign salivary gland neoplasm † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Bile duct cancer † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Bladder adenocarcinoma stage unspecified † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Bladder cancer † 1    
# participants affected / at risk     7/3006 (0.23%)     11/2986 (0.37%)  
Bladder cancer recurrent † 1    
# participants affected / at risk     1/3006 (0.03%)     3/2986 (0.10%)  
Bladder cancer stage II † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Bladder cancer stage IV † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Bladder neoplasm † 1    
# participants affected / at risk     6/3006 (0.20%)     5/2986 (0.17%)  
Bladder transitional cell carcinoma † 1    
# participants affected / at risk     3/3006 (0.10%)     5/2986 (0.17%)  
Bone cancer metastatic † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Bone neoplasm malignant † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Bowen's disease † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Brain neoplasm † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Breast cancer † 1    
# participants affected / at risk     6/3006 (0.20%)     8/2986 (0.27%)  
Breast cancer female † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Breast cancer metastatic † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Breast cancer recurrent † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Breast neoplasm † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Carcinoid tumour of the small bowel † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Carcinoma in situ of bladder † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Cerebellar tumour † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Cervix carcinoma † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Chronic lymphocytic leukaemia † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Chronic myeloid leukaemia † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Colon cancer † 1    
# participants affected / at risk     10/3006 (0.33%)     11/2986 (0.37%)  
Colon cancer metastatic † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Colon cancer stage II † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Colon neoplasm † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Colorectal cancer † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Gallbladder cancer † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Gastric adenoma † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Gastric cancer † 1    
# participants affected / at risk     7/3006 (0.23%)     2/2986 (0.07%)  
Gastric cancer recurrent † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Gastric cancer stage 0 † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Gastric cancer stage I † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Gastric cancer stage III † 1    
# participants affected / at risk     1/3006 (0.03%)     1/2986 (0.03%)  
Gastric neoplasm † 1    
# participants affected / at risk     3/3006 (0.10%)     0/2986 (0.00%)  
Gastrointestinal carcinoma † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Gastrointestinal neoplasm † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Gastrointestinal tract adenoma † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Glioblastoma † 1    
# participants affected / at risk     2/3006 (0.07%)     0/2986 (0.00%)  
Head and neck cancer † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Hepatic cancer metastatic † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Hepatic neoplasm † 1    
# participants affected / at risk     3/3006 (0.10%)     2/2986 (0.07%)  
Hepatic neoplasm malignant † 1    
# participants affected / at risk     3/3006 (0.10%)     4/2986 (0.13%)  
Hodgkin's disease † 1    
# participants affected / at risk     1/3006 (0.03%)     0/2986 (0.00%)  
Large intestine carcinoma † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Lentigo maligna stage unspecified † 1    
# participants affected / at risk     0/3006 (0.00%)     2/2986 (0.07%)  
Leukaemia † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Lip neoplasm † 1    
# participants affected / at risk     0/3006 (0.00%)     1/2986 (0.03%)  
Lipoma † 1    
# participants affected / at risk     1/3006 (0.03%)