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Safety and Efficacy Continued Access Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in Very High Risk Subjects and High Risk Subjects Who Need Aortic Valve Replacement

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01531374
Recruitment Status : Completed
First Posted : February 10, 2012
Results First Posted : July 18, 2017
Last Update Posted : November 10, 2020
Sponsor:
Information provided by (Responsible Party):
Medtronic Cardiovascular

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Severe Aortic Stenosis
Intervention Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Enrollment 2777
Recruitment Details Between February 21, 2012 and April 15, 2014, 1658 subjects were enrolled in the Continued Access Extreme Risk Study at 45 centers in the US. Between October 19, 2012 and August 12, 2014, 1119 subjects were enrolled in the High Risk Study at the same 45 US centers.
Pre-assignment Details  
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Period Title: Overall Study
Started 1285 373 1119
Completed 921 231 836
Not Completed 364 142 283
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk Total
Hide Arm/Group Description

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

 Total of all reporting groups
Overall Number of Baseline Participants 1257 367 1108 2732
Hide Baseline Analysis Population Description
A total of 1658 Extreme Risk subjects were enrolled; 1257 Iliofemoral and 367 Non-Iliofemoral had an attempted implant procedure. A total of 1119 High Risk subjects were enrolled; however, 1108 subjects had an attempted implant procedure. The baseline data presented are for subjects with an attempted implant.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1257 participants 367 participants 1108 participants 2732 participants
83.5  (8.1) 81.9  (8.2) 83.6  (7.1) 83.3  (7.7)
[1]
Measure Description: Participant Population= Consisted of all subjects with an attempted implant procedure.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1257 participants 367 participants 1108 participants 2732 participants
Female
568
  45.2%
185
  50.4%
456
  41.2%
1209
  44.3%
Male
689
  54.8%
182
  49.6%
652
  58.8%
1523
  55.7%
[1]
Measure Description: Participant Population= Consisted of all subjects with an attempted implant procedure.
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1257 participants 367 participants 1108 participants 2732 participants
Hispanic or Latino
37
   2.9%
4
   1.1%
38
   3.4%
79
   2.9%
Not Hispanic or Latino
1206
  95.9%
360
  98.1%
1056
  95.3%
2622
  96.0%
Unknown or Not Reported
14
   1.1%
3
   0.8%
14
   1.3%
31
   1.1%
[1]
Measure Description: Participant Population= Consisted of all subjects with an attempted implant procedure.
Body Surface Area   [1] 
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 1257 participants 367 participants 1108 participants 2732 participants
1.9  (0.3) 1.8  (0.3) 1.9  (0.2) 1.9  (0.3)
[1]
Measure Description: Participant Population= Consisted of all subjects with an attempted implant procedure.
New York Heart Association (NYHA) Classification   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 1257 participants 367 participants 1108 participants 2732 participants
NYHA Classification I 0 0 0 0
NYHA Classification II 159 45 180 384
NYHA Classification III 881 248 811 1940
NYHA Classification IV 217 74 117 408
[1]
Measure Description:

NYHA Classification:

Class I: Subjects with cardiac disease but without resulting limitations of physical activity.

Class I: Subjects with cardiac disease resulting in slight limitation of physical activity.

Class III: Subjects with cardiac disease resulting in marked limitation of physical activity.

Class IV: Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort.
Society of Thoracic Surgeons (STS) Risk Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Percent of predicted mortality
Number Analyzed 1257 participants 367 participants 1108 participants 2732 participants
9.1  (5.1) 10.2  (5.6) 7.7  (3.3) 8.7  (4.6)
[1]
Measure Description: The Society of Thoracic Surgeons (STS) risk model predicts the risk of operative mortality and morbidity after adult cardiac surgery on the basis of patient demographic and clinical variables. After information has been entered on a given case, the online STS risk calculator provides a risk percentage for each of the outcomes. The risk percentage estimates the chance of a specific outcome for a patient with the indicated risk factors. A higher score indicates a higher risk. A lower score indicates a lower risk.
Logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percent of predicted mortality
Number Analyzed 1257 participants 367 participants 1108 participants 2732 participants
24.2  (17.1) 24.2  (17.1) 20.3  (13.5) 22.6  (15.9)
[1]
Measure Description: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is a method of calculating predicted operative mortality for patients undergoing cardiac surgery. If a risk factor is present, a weight/number is assigned. The weights are added to give an approximate percent of predicted mortality. A higher score indicates a higher risk. A lower score indicates a lower risk.
1.Primary Outcome
Title Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality
Hide Description All-cause Death or Major Stroke (Extreme Risk- Medtronic CoreValve® System); All-cause Mortality (High Risk Surgical- Medtronic CoreValve® System vs. Surgical Valve)
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participant Population = Consisted of all subjects with an attempted implant procedure.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1257 367 1108
Measure Type: Number
Unit of Measure: percentage of participants, Kaplan-Meier
22.5 30.8 17.8
2.Secondary Outcome
Title Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)
Hide Description

MACCE is defined as a composite of:

  • All-Cause Death
  • Myocardial Infarction (MI)
  • All Stroke
  • Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)
Time Frame 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Hide Outcome Measure Data
Hide Analysis Population Description
Participant Population = Consisted of all subjects with an attempted implant procedure.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1257 367 1108
Measure Type: Number
Unit of Measure: percentage of participants, Kaplan-Meier
30 day 9.1 16.1 8.9
6 month 19.2 28.4 17.2
1 year 26.6 36.2 24.3
3.Secondary Outcome
Title The Occurrence of Individual MACCE Components
Hide Description

Individual MACCE Components Include:

  • All Cause Mortality
  • MI
  • All stroke
  • Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)
Time Frame 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Hide Outcome Measure Data
Hide Analysis Population Description
Participant Population = Consisted of all subjects with an attempted implant procedure.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1257 367 1108
Measure Type: Number
Unit of Measure: percentage of participants, Kaplan-Meier
30 day All Cause Mortality 4.5 9.6 4.9
30 day MI 1.1 1.4 0.4
30 day Stroke 4.6 5.9 4.7
30 day Reintervention 0.6 0.8 0.4
6 month All Cause Mortality 13.7 20.8 12.0
6 month MI 1.6 2.7 1.0
6 month Stroke 6.6 8.2 7.0
6 month Reintervention 0.9 0.8 0.8
1 year All Cause Mortality 21.0 29.4 17.8
1 year MI 2.2 3.8 1.9
1 year Stroke 7.3 9.2 8.7
1 year Reintervention 1.0 1.2 0.8
4.Secondary Outcome
Title Major Adverse Events (MAEs)
Hide Description

MAEs Include:

  • MACCE
  • Acute Kidney Injury
  • Cardiac Tamponade
  • Prosthetic Valve Dysfunction
  • Cardiogenic Shock
  • Valve Endocarditis
  • Life-Threatening, Disabling or Major Bleeding
  • Major Vascular Complication
  • Cardiac Perforation
  • Device Migration/Valve Embolism
Time Frame 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Hide Outcome Measure Data
Hide Analysis Population Description
Participant Population = Consisted of all subjects with an attempted implant procedure.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1257 367 1108
Measure Type: Number
Unit of Measure: percentage of participants, Kaplan-Meier
30 day 46.3 67.4 48.1
6 month 53.0 73.1 54.5
1 year 57.7 76.4 59.3
5.Secondary Outcome
Title Conduction Disturbance Requiring Permanent Pacemaker Implantation
Hide Description [Not Specified]
Time Frame 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Hide Outcome Measure Data
Hide Analysis Population Description
Participant Population = Consisted of all subjects with an attempted implant procedure.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1257 367 1108
Measure Type: Number
Unit of Measure: percentage of participants, Kaplan-Meier
30 day 27.2 23.0 28.8
6 month 29.7 24.6 30.5
1 year 31.1 25.5 32.1
6.Secondary Outcome
Title Change From Baseline in NYHA Class
Hide Description

Change from baseline (continuous variable). A positive number corresponds to NYHA worsening; a negative number corresponds to NYHA improvement.

NYHA Classification:

Class I: Subjects with cardiac disease but without resulting limitations of physical activity.

Class I: Subjects with cardiac disease resulting in slight limitation of physical activity.

Class III: Subjects with cardiac disease resulting in marked limitation of physical activity.

Class IV: Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort.
Time Frame Baseline to 30 days, baseline to 6 months, baseline to 1 year. The 2-5 year outcome data will be reported once data set is complete.
Hide Outcome Measure Data
Hide Analysis Population Description
Participant Population = Consisted of all subjects with an attempted implant procedure.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1257 367 1108
Mean (Standard Deviation)
Unit of Measure: average classification level change
Baseline to 30 days -1.2  (0.8) -1.1  (0.9) -1.2  (0.8)
Baseline to 6 month -1.4  (0.8) -1.4  (0.8) -1.4  (0.8)
Baseline to 1 year -1.4  (0.8) -1.4  (0.9) -1.4  (0.8)
7.Secondary Outcome
Title Change From Baseline in Distance Walked During 6-Minute Walk Test (6MWT)
Hide Description Change in distance walked during 6MWT from baseline
Time Frame Baseline to 30 days, baseline to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participant Population = Consisted of all subjects with an attempted implant procedure.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1257 367 1108
Mean (Standard Deviation)
Unit of Measure: meters
Baseline to 30 day 46.3  (116.4) 4.0  (110.4) 38.1  (100.0)
Baseline to 1 year 58.8  (121.2) 28.5  (137.4) 55.5  (117.9)
8.Secondary Outcome
Title Ratio of Days Alive Out of Hospital at 365 Days Post Procedure Versus Total Days Alive
Hide Description [Not Specified]
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participant Population= Consisted of all subjects with an attempted implant procedure.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1257 367 1108
Mean (Standard Deviation)
Unit of Measure: ratio of days alive and out of hospital
0.8  (0.3) 0.7  (0.4) 0.8  (0.3)
9.Secondary Outcome
Title Quality of Life (QoL) Change
Hide Description

QoL summary score change from baseline using the following measures:

  • Kansas City Cardiomyopathy Questionnaire (KCCQ): Quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
  • 12 Item Short Form Health Survey (SF-12): Measures functional health and well-being. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
  • European QoL (EQ-5D): Measures 5 domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that can be converted to utilities using an algorithm. Utilities range from 0 to 1, with 1 representing perfect health, and 0 corresponding to the worst imaginable health state.
Time Frame 30 day, 6 month, 1 year. The 2-5 year outcome data will be reported once data set is complete.
Hide Outcome Measure Data
Hide Analysis Population Description
Participant Population = Consisted of all subjects with an attempted implant procedure.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1257 367 1108
Mean (Standard Deviation)
Unit of Measure: units on a scale
30 day KCCQ- Overall 26.3  (26.4) 19.9  (29.8) 19.9  (25.0)
30 day KCCQ- Clinical 21.7  (26.6) 16.5  (30.2) 16.6  (24.0)
30 day SF-12-Physical 7.1  (10.7) 5.1  (10.7) 5.7  (10.2)
30 day SF-12-Mental 6.0  (13.9) 4.5  (14.5) 3.0  (12.4)
30 day EQ-5D 0.10  (0.26) 0.07  (0.30) 0.05  (0.21)
6 month KCCQ- Overall 31.7  (27.3) 29.6  (28.5) 26.2  (25.0)
6 month KCCQ- Clinical 25.8  (27.7) 23.2  (28.5) 20.8  (24.7)
6 month SF-12-Physical 7.6  (11.1) 6.8  (11.4) 7.1  (10.7)
6 month SF-12-Mental 6.9  (13.9) 7.9  (14.9) 4.4  (11.8)
6 month EQ-5D 0.10  (0.25) 0.11  (0.27) 0.06  (0.21)
1 year KCCQ- Overall 30.0  (27.5) 28.7  (27.5) 27.1  (24.7)
1 year KCCQ- Clinical 23.8  (27.9) 21.7  (27.2) 21.0  (24.0)
1 year SF-12-Physical 6.6  (11.7) 6.4  (11.4) 6.6  (11.1)
1 year SF-12-Mental 6.6  (13.9) 6.4  (13.8) 4.7  (12.3)
1 year EQ-5D 0.08  (0.26) 0.08  (0.27) 0.05  (0.21)
10.Secondary Outcome
Title Echocardiographic Assessment of Valve Performance
Hide Description

Using the following measure:

• Effective Orifice Area (EOA) analyzed overall per Extreme Risk or High Risk. Iliofemoral access and non-iliofemoral access are not reported separate because this is a valve performance measurement.
Time Frame 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Hide Outcome Measure Data
Hide Analysis Population Description
Participant Population = Consisted of all subjects with a valve implanted.
Arm/Group Title Extreme Risk: Implanted Cohort High Risk: Implanted Cohort
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1615 1102
Mean (Standard Deviation)
Unit of Measure: cm^2
30 day 1.77  (0.53) 1.77  (0.51)
6 month 1.75  (0.54) 1.78  (0.49)
1 year 1.78  (0.54) 1.77  (0.51)
11.Secondary Outcome
Title Echocardiographic Assessment of Valve Performance
Hide Description

Using the following measure:

• Transvalvular Mean Gradient analyzed overall per Extreme Risk or High Risk. Iliofemoral access and non-iliofemoral access are not reported separate because this is a valve performance measurement.
Time Frame 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Hide Outcome Measure Data
Hide Analysis Population Description
Participant Population= Consisted of all subjects with a valve implanted.
Arm/Group Title Extreme Risk: Implanted Cohort High Risk: Implanted Cohort
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1615 1102
Mean (Standard Deviation)
Unit of Measure: mmHg
30 day 8.20  (4.26) 8.02  (3.53)
6 month 7.98  (3.63) 7.97  (3.48)
1 year 7.72  (3.40) 8.12  (3.93)
12.Secondary Outcome
Title Echocardiographic Assessment of Valve Performance
Hide Description

Using the following measure:

- Degree of Aortic Valve Regurgitation (Transvalvular and Paravalvular) analyzed overall per Extreme Risk or High Risk. Iliofemoral access and non-iliofemoral access are not reported separate because this is a valve performance measurement.
Time Frame 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Hide Outcome Measure Data
Hide Analysis Population Description
Participant Population = Consisted of all subjects with a valve implanted.
Arm/Group Title Extreme Risk: Implanted Cohort High Risk: Implanted Cohort
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1615 1102
Measure Type: Number
Unit of Measure: percentage of participants
30 day Total Aortic Regurgitation- None 26.5 28.7
30 day Total Aortic Regurgitation- Mild 66.3 65.2
30 day Total Aortic Regurgitation- Moderate 6.9 5.8
30 day Total Aortic Regurgitation- Severe 0.3 0.3
6 month Total Aortic Regurgitation- None 35.1 37.8
6 month Total Aortic Regurgitation- Mild 58.5 58.1
6 month Total Aortic Regurgitation- Moderate 6.1 4.0
6 month Total Aortic Regurgitation- Severe 0.2 0.1
1 year Total Aortic Regurgitation- None 39.8 39.9
1 year Total Aortic Regurgitation- Mild 54.9 56.0
1 year Total Aortic Regurgitation- Moderate 5.1 3.8
1 year Total Aortic Regurgitation- Severe 0.2 0.3
13.Secondary Outcome
Title Aortic Valve Hospitalizations
Hide Description [Not Specified]
Time Frame 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Hide Outcome Measure Data
Hide Analysis Population Description
Participant Population = Consisted of all subjects with an attempted implant procedure.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1257 367 1108
Measure Type: Number
Unit of Measure: percentage of participants, Kaplan-Meier
30 day 6.2 5.5 5.6
6 month 12.5 12.9 11.8
1 year 17.1 16.5 15.4
14.Secondary Outcome
Title Cardiovascular Deaths and Valve-Related Deaths
Hide Description [Not Specified]
Time Frame 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
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Participant Population = Consisted of all subjects with an attempted implant procedure.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1257 367 1108
Measure Type: Number
Unit of Measure: percentage of participants, Kaplan-Meier
30 day Cardiovascular Deaths 4.4 9.3 4.6
30 day Valve Related Deaths 1.9 4.2 2.4
6 month Cardiovascular Deaths 11.3 16.3 9.4
6 month Valve Related Deaths 3.9 5.7 3.8
1 year Cardiovascular Deaths 16.6 22.0 13.0
1 year Valve Related Deaths 5.5 6.4 4.2
15.Secondary Outcome
Title Strokes and Transient Ischemic Attacks (TIAs)
Hide Description Strokes (of any severity) and TIAs
Time Frame 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Hide Outcome Measure Data
Hide Analysis Population Description
Participant Population = Consisted of all subjects with an attempted implant procedure.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1257 367 1108
Measure Type: Number
Unit of Measure: percentage of participants, Kaplan-Meier
30 day Stroke 4.6 5.9 4.7
30 day TIA 0.7 0.3 0.7
6 month Stroke 6.6 8.2 6.8
6 month TIA 1.4 0.9 2.2
1 year Stroke 7.3 9.2 8.7
1 year TIA 2.0 0.9 2.9
16.Secondary Outcome
Title Index Procedure Related MAEs
Hide Description [Not Specified]
Time Frame Procedure
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Participant Population = Consisted of all subjects with an attempted implant procedure.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1257 367 1108
Measure Type: Number
Unit of Measure: percentage of participants
46.4 66.6 48.1
17.Secondary Outcome
Title Length of Index Procedure Hospital Stay
Hide Description [Not Specified]
Time Frame Number of days from admission to discharge
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Participant Population = Consisted of all subjects with an attempted implant procedure.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1257 367 1108
Mean (Standard Deviation)
Unit of Measure: days
7.6  (6.9) 10.7  (8.7) 7.6  (5.9)
18.Secondary Outcome
Title Device Success
Hide Description

Defined as:

  • Successful vascular access, delivery and deployment of the device, and successful retrieval of the delivery system,
  • Correct position of the device in the proper anatomical location (placement in the annulus with no impedance on device function),
  • Intended performance of the prosthetic valve (aortic valve area > 1.2 cm2 for 26, 29 and 31mm valves, ≥ 0.9 cm2 for 23mm valve (by echocardiography using the continuity equation) and mean aortic valve gradient < 20 mmHg or peak velocity < 3 m/sec, without moderate or severe prosthetic valve aortic regurgitation)
  • Only one valve implanted in the proper anatomical location
Time Frame Number of days from admission to discharge
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Participant Population= Consisted of all subjects with a TAVR index procedure who were evaluable for device success.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1252 365 1104
Measure Type: Number
Unit of Measure: percentage of participants
84.9 88.1 87.9
19.Secondary Outcome
Title Procedural Success
Hide Description Defined as device success and absence of in-hospital MACCE.
Time Frame Number of days from admission to discharge
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Hide Analysis Population Description
Participant Population = Consisted of all subjects with an index procedure who were evaluable for procedural success.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1252 365 1104
Measure Type: Number
Unit of Measure: percentage of participants
79.7 76.8 82.3
20.Secondary Outcome
Title Prosthetic Valve Dysfunction (PVD)
Hide Description

PVD was defined according to VARC using the site reported echocardiography assessments including aortic regurgitation (AR) and aortic stenosis (AS) evaluations. Total AR reported as moderate or severe was considered PVD. AS was defined as significant stenosis and considered PVD if one of the following was met:

  • Peak velocity >4 m/s
  • Mean gradient >35 mmHg
  • EOA < 0.8 cm2
  • TVIV1 / TVIV2 < 0.25
Time Frame 30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Hide Outcome Measure Data
Hide Analysis Population Description
Participant Population = Consisted of all subjects with a valve implanted.
Arm/Group Title Extreme Risk: Iliofemoral Extreme Risk: Non-Iliofemoral High Risk
Hide Arm/Group Description:

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Overall Number of Participants Analyzed 1251 364 1102
Measure Type: Number
Unit of Measure: Percentage of participants
30 day Aortic Stenosis 1.0 0.8 0.9
30 day Aortic Regurgitation 3.0 1.9 2.0
6 month Aortic Stenosis 2.2 0.8 2.0
6 month Aortic Regurgitation 5.0 3.3 3.1
1 year Aortic Stenosis 2.8 1.6 2.5
1 year Aortic Regurgitation 5.8 3.8 4.5
Time Frame Adverse events (AEs) were collected from study enrollment to study closure, up to 5 years.
Adverse Event Reporting Description All new or worsening AEs were collected through1 year. After 1 year, serious AEs, major AEs, cardiovascular events, device-related AEs, device related technical observations, unanticipated adverse device effects, strokes, and deaths were collected. AE data reported are Clinical Event Committee adjudicated AEs for subjects with an attempted implant.
 
Arm/Group Title Extreme Risk: TAVI Iliofemoral Extreme Risk: TAVI Non-Iliofemoral High Risk: TAVI
Hide Arm/Group Description

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
All-Cause Mortality
Extreme Risk: TAVI Iliofemoral Extreme Risk: TAVI Non-Iliofemoral High Risk: TAVI
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
Extreme Risk: TAVI Iliofemoral Extreme Risk: TAVI Non-Iliofemoral High Risk: TAVI
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1117/1257 (88.86%)      359/367 (97.82%)      1004/1108 (90.61%)    
Blood and lymphatic system disorders       
Anaemia Deficiencies † 1  7/1257 (0.56%)  7 3/367 (0.82%)  3 6/1108 (0.54%)  6
Anaemias Due To Chronic Disorders † 1  2/1257 (0.16%)  2 3/367 (0.82%)  3 2/1108 (0.18%)  2
Anaemias † 1  340/1257 (27.05%)  420 150/367 (40.87%)  182 265/1108 (23.92%)  319
Coagulopathies † 1  9/1257 (0.72%)  9 6/367 (1.63%)  6 6/1108 (0.54%)  6
Haemolyses † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 1/1108 (0.09%)  1
Leukocytoses † 1  9/1257 (0.72%)  9 4/367 (1.09%)  4 13/1108 (1.17%)  13
Lymphatic System Disorders † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 1/1108 (0.09%)  1
Marrow Depression And Hypoplastic Anaemias † 1  3/1257 (0.24%)  3 4/367 (1.09%)  7 2/1108 (0.18%)  2
Spleen Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 2/1108 (0.18%)  2
Thrombocytopenias † 1  34/1257 (2.70%)  34 17/367 (4.63%)  17 20/1108 (1.81%)  21
Cardiac disorders       
Aortic Valvular Disorders † 1  143/1257 (11.38%)  153 26/367 (7.08%)  29 103/1108 (9.30%)  108
Cardiac Conduction Disorders † 1  293/1257 (23.31%)  311 63/367 (17.17%)  66 277/1108 (25.00%)  296
Cardiac Disorders † 1  13/1257 (1.03%)  13 5/367 (1.36%)  5 13/1108 (1.17%)  13
Cardiac Signs And Symptoms † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 3/1108 (0.27%)  3
Cardiac Valve Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Cardiomyopathies † 1  16/1257 (1.27%)  16 3/367 (0.82%)  3 6/1108 (0.54%)  7
Coronary Artery Disorders † 1  26/1257 (2.07%)  28 7/367 (1.91%)  8 10/1108 (0.90%)  11
Heart Failures † 1  329/1257 (26.17%)  531 105/367 (28.61%)  147 248/1108 (22.38%)  346
Ischaemic Coronary Artery Disorders † 1  91/1257 (7.24%)  102 26/367 (7.08%)  30 78/1108 (7.04%)  97
Left Ventricular Failures † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Mitral Valvular Disorders † 1  36/1257 (2.86%)  37 3/367 (0.82%)  3 28/1108 (2.53%)  30
Myocardial Disorders † 1  6/1257 (0.48%)  6 5/367 (1.36%)  5 9/1108 (0.81%)  9
Pericardial Disorders † 1  22/1257 (1.75%)  24 8/367 (2.18%)  9 30/1108 (2.71%)  33
Pulmonary Valvular Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Rate And Rhythm Disorders † 1  75/1257 (5.97%)  77 20/367 (5.45%)  21 50/1108 (4.51%)  54
Right Ventricular Failures † 1  4/1257 (0.32%)  4 1/367 (0.27%)  1 4/1108 (0.36%)  4
Supraventricular Arrhythmias † 1  152/1257 (12.09%)  184 47/367 (12.81%)  55 119/1108 (10.74%)  137
Tricuspid Valvular Disorders † 1  11/1257 (0.88%)  11 1/367 (0.27%)  1 5/1108 (0.45%)  5
Ventricular Arrhythmias And Cardiac Arrest † 1  139/1257 (11.06%)  150 43/367 (11.72%)  49 104/1108 (9.39%)  113
Congenital, familial and genetic disorders       
Cardiac Malpositions Congenital † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Cardiac Septal Defects Congenital † 1  2/1257 (0.16%)  3 0/367 (0.00%)  0 3/1108 (0.27%)  3
Cardiovascular Disorders Congenital † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Male Reproductive Tract Disorders Congenital † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Vascular Anomalies Congenital † 1  2/1257 (0.16%)  2 1/367 (0.27%)  1 0/1108 (0.00%)  0
Ear and labyrinth disorders       
Eustachian Tube Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
External Ear Disorders † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 0/1108 (0.00%)  0
Inner Ear Signs And Symptoms † 1  7/1257 (0.56%)  7 3/367 (0.82%)  3 2/1108 (0.18%)  2
Middle Ear Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Endocrine disorders       
Thyroid Disorders † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Thyroid Hyperfunction Disorders † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Thyroid Hypofunction Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 4/1108 (0.36%)  4
Eye disorders       
Blindness (Excl Colour Blindness) † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Cataract Conditions † 1  5/1257 (0.40%)  6 0/367 (0.00%)  0 6/1108 (0.54%)  6
Conjunctival And Corneal Bleeding And Vascular Disorders † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Corneal Structural Change, Deposit And Degeneration † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Lens Structural Change, Deposit And Degeneration (Excl Cataracts) † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Lid, Lash And Lacrimal Structural Disorders † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Ocular Bleeding And Vascular Disorders † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 2/1108 (0.18%)  3
Partial Vision Loss † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Retinal Bleeding And Vascular Disorders (Excl Retinopathy) † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 4/1108 (0.36%)  4
Retinal Structural Change, Deposit And Degeneration † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 2/1108 (0.18%)  2
Retinal, Choroid And Vitreous Infections And Inflammations † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Visual Disorders † 1  2/1257 (0.16%)  2 2/367 (0.54%)  2 3/1108 (0.27%)  3
Gastrointestinal disorders       
Abdominal Findings Abnormal † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Abdominal Hernias, Site Unspecified † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 1/1108 (0.09%)  1
Abdominal Wall Conditions † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 2/1108 (0.18%)  2
Acute And Chronic Pancreatitis † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 0/1108 (0.00%)  0
Anal And Rectal Pains † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Benign Neoplasms Gastrointestinal (Excl Oral Cavity) † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 2/1108 (0.18%)  2
Colitis (Excl Infective) † 1  4/1257 (0.32%)  5 3/367 (0.82%)  3 4/1108 (0.36%)  4
Dental And Periodontal Infections And Inflammations † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 1/1108 (0.09%)  1
Dental Disorders † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 0/1108 (0.00%)  0
Diaphragmatic Hernias † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 1/1108 (0.09%)  1
Diarrhoea (Excl Infective) † 1  9/1257 (0.72%)  9 2/367 (0.54%)  2 5/1108 (0.45%)  5
Diverticula † 1  3/1257 (0.24%)  3 2/367 (0.54%)  2 4/1108 (0.36%)  4
Duodenal And Small Intestinal Stenosis And Obstruction † 1  7/1257 (0.56%)  7 1/367 (0.27%)  1 5/1108 (0.45%)  7
Duodenal Ulcers And Perforation † 1  4/1257 (0.32%)  4 0/367 (0.00%)  0 1/1108 (0.09%)  1
Dyspeptic Signs And Symptoms † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Faecal Abnormalities † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 9/1108 (0.81%)  9
Flatulence, Bloating And Distension † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 0/1108 (0.00%)  0
Gastric And Oesophageal Haemorrhages † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 2/1108 (0.18%)  2
Gastric Ulcers And Perforation † 1  5/1257 (0.40%)  5 1/367 (0.27%)  1 0/1108 (0.00%)  0
Gastritis (Excl Infective) † 1  5/1257 (0.40%)  5 3/367 (0.82%)  3 2/1108 (0.18%)  2
Gastrointestinal And Abdominal Pains (Excl Oral And Throat) † 1  17/1257 (1.35%)  19 4/367 (1.09%)  4 14/1108 (1.26%)  15
Gastrointestinal Atonic And Hypomotility Disorders † 1  14/1257 (1.11%)  15 0/367 (0.00%)  0 6/1108 (0.54%)  7
Gastrointestinal Disorders † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 0/1108 (0.00%)  0
Gastrointestinal Dyskinetic Disorders † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 0/1108 (0.00%)  0
Gastrointestinal Fistulae † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Gastrointestinal Inflammatory Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Gastrointestinal Necrosis And Gangrene (Excl Gangrenous Hernia) † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 2/1108 (0.18%)  2
Gastrointestinal Signs And Symptoms † 1  35/1257 (2.78%)  35 12/367 (3.27%)  13 16/1108 (1.44%)  17
Gastrointestinal Stenosis And Obstruction † 1  3/1257 (0.24%)  3 2/367 (0.54%)  2 7/1108 (0.63%)  7
Gastrointestinal Ulcers And Perforation, Site Unspecified † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 2/1108 (0.18%)  2
Gastrointestinal Vascular Occlusion And Infarction † 1  3/1257 (0.24%)  3 2/367 (0.54%)  2 6/1108 (0.54%)  6
Gingival Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Haemorrhoids And Gastrointestinal Varices (Excl Oesophageal) † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 4/1108 (0.36%)  4
Inguinal Hernias † 1  5/1257 (0.40%)  6 2/367 (0.54%)  2 5/1108 (0.45%)  5
Intestinal Haemorrhages † 1  9/1257 (0.72%)  10 3/367 (0.82%)  3 9/1108 (0.81%)  9
Intestinal Ulcers And Perforation † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 1/1108 (0.09%)  2
Large Intestinal Stenosis And Obstruction † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Nausea And Vomiting Symptoms † 1  11/1257 (0.88%)  11 6/367 (1.63%)  8 12/1108 (1.08%)  12
Non-Site Specific Gastrointestinal Haemorrhages † 1  98/1257 (7.80%)  121 26/367 (7.08%)  35 71/1108 (6.41%)  84
Oesophageal Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Oesophageal Stenosis And Obstruction † 1  6/1257 (0.48%)  6 0/367 (0.00%)  0 1/1108 (0.09%)  2
Oesophageal Ulcers And Perforation † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 0/1108 (0.00%)  0
Oesophagitis (Excl Infective) † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Peritoneal And Retroperitoneal Disorders † 1  5/1257 (0.40%)  5 2/367 (0.54%)  2 4/1108 (0.36%)  4
Peritoneal And Retroperitoneal Haemorrhages † 1  5/1257 (0.40%)  5 1/367 (0.27%)  1 9/1108 (0.81%)  9
Tongue Disorders † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 0/1108 (0.00%)  0
Umbilical Hernias † 1  1/1257 (0.08%)  1 2/367 (0.54%)  2 0/1108 (0.00%)  0
General disorders       
Administration Site Reactions † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 2/1108 (0.18%)  2
Asthenic Conditions † 1  31/1257 (2.47%)  33 8/367 (2.18%)  10 23/1108 (2.08%)  25
Body Temperature Altered † 1  2/1257 (0.16%)  2 1/367 (0.27%)  1 1/1108 (0.09%)  1
Complications Associated With Device † 1  5/1257 (0.40%)  5 1/367 (0.27%)  1 7/1108 (0.63%)  9
Death And Sudden Death † 1  49/1257 (3.90%)  49 18/367 (4.90%)  18 38/1108 (3.43%)  38
Device Issues † 1  130/1257 (10.34%)  140 17/367 (4.63%)  19 93/1108 (8.39%)  103
Device Malfunction Events † 1  7/1257 (0.56%)  7 2/367 (0.54%)  2 7/1108 (0.63%)  7
Device Physical Property And Chemical Issues † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Febrile Disorders † 1  24/1257 (1.91%)  24 5/367 (1.36%)  5 15/1108 (1.35%)  15
Gait Disturbances † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 2/1108 (0.18%)  2
General Signs And Symptoms † 1  20/1257 (1.59%)  20 4/367 (1.09%)  4 11/1108 (0.99%)  11
Healing Abnormal † 1  4/1257 (0.32%)  4 1/367 (0.27%)  1 1/1108 (0.09%)  1
Hernias † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 2/1108 (0.18%)  2
Implant And Catheter Site Reactions † 1  4/1257 (0.32%)  5 1/367 (0.27%)  2 9/1108 (0.81%)  9
Inflammations † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 5/1108 (0.45%)  5
Injection Site Reactions † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Mucosal Findings Abnormal † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Oedema † 1  31/1257 (2.47%)  32 7/367 (1.91%)  8 15/1108 (1.35%)  17
Pain And Discomfort † 1  67/1257 (5.33%)  85 14/367 (3.81%)  18 40/1108 (3.61%)  41
Product Physical Issues † 1  6/1257 (0.48%)  6 0/367 (0.00%)  0 0/1108 (0.00%)  0
Therapeutic And Nontherapeutic Responses † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 3/1108 (0.27%)  3
Ulcers † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 2/1108 (0.18%)  2
Vascular Complications Associated With Device † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Hepatobiliary disorders       
Bile Duct Infections And Inflammations † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 0/1108 (0.00%)  0
Cholecystitis And Cholelithiasis † 1  11/1257 (0.88%)  11 4/367 (1.09%)  4 7/1108 (0.63%)  7
Cholestasis And Jaundice † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 1/1108 (0.09%)  1
Gallbladder Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Hepatic And Hepatobiliary Disorders † 1  1/1257 (0.08%)  1 2/367 (0.54%)  2 1/1108 (0.09%)  1
Hepatic Failure And Associated Disorders † 1  7/1257 (0.56%)  7 0/367 (0.00%)  0 5/1108 (0.45%)  5
Hepatic Fibrosis And Cirrhosis † 1  4/1257 (0.32%)  4 0/367 (0.00%)  0 0/1108 (0.00%)  0
Hepatic Vascular Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Hepatobiliary Signs And Symptoms † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Hepatocellular Damage And Hepatitis † 1  4/1257 (0.32%)  4 1/367 (0.27%)  1 5/1108 (0.45%)  5
Obstructive Bile Duct Disorders (Excl Neoplasms) † 1  4/1257 (0.32%)  4 3/367 (0.82%)  3 1/1108 (0.09%)  1
Immune system disorders       
Acute And Chronic Sarcoidosis † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Allergic Conditions † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 2/1108 (0.18%)  2
Allergies To Foods, Food Additives, Drugs And Other Chemicals † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Infections and infestations       
Abdominal And Gastrointestinal Infections † 1  14/1257 (1.11%)  14 2/367 (0.54%)  2 9/1108 (0.81%)  9
Aspergillus Infections † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Atypical Mycobacterial Infections † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 1/1108 (0.09%)  1
Bacterial Infections † 1  54/1257 (4.30%)  66 17/367 (4.63%)  22 37/1108 (3.34%)  42
Bone And Joint Infections † 1  11/1257 (0.88%)  12 2/367 (0.54%)  2 7/1108 (0.63%)  7
Candida Infections † 1  1/1257 (0.08%)  1 2/367 (0.54%)  2 1/1108 (0.09%)  1
Cardiac Infections † 1  15/1257 (1.19%)  16 5/367 (1.36%)  5 10/1108 (0.90%)  10
Clostridia Infections † 1  19/1257 (1.51%)  23 9/367 (2.45%)  12 11/1108 (0.99%)  13
Dental And Oral Soft Tissue Infections † 1  2/1257 (0.16%)  2 1/367 (0.27%)  1 3/1108 (0.27%)  5
Ear Infections † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Enterobacter Infections † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Enterococcal Infections † 1  2/1257 (0.16%)  2 1/367 (0.27%)  1 3/1108 (0.27%)  4
Escherichia Infections † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 2/1108 (0.18%)  2
Eye And Eyelid Infections † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Fungal Infections † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Haemophilus Infections † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Helicobacter Infections † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 0/1108 (0.00%)  0
Hepatobiliary And Spleen Infections † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Herpes Viral Infections † 1  4/1257 (0.32%)  4 0/367 (0.00%)  0 5/1108 (0.45%)  5
Infections † 1  28/1257 (2.23%)  30 8/367 (2.18%)  8 20/1108 (1.81%)  22
Infectious Disorders Carrier † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 0/1108 (0.00%)  0
Infectious Transmissions † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Influenza Viral Infections † 1  14/1257 (1.11%)  14 2/367 (0.54%)  2 11/1108 (0.99%)  12
Klebsiella Infections † 1  0/1257 (0.00%)  0 2/367 (0.54%)  2 3/1108 (0.27%)  3
Lower Respiratory Tract And Lung Infections † 1  170/1257 (13.52%)  218 61/367 (16.62%)  73 101/1108 (9.12%)  116
Male Reproductive Tract Infections † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  2
Pseudomonal Infections † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 1/1108 (0.09%)  1
Respiratory Syncytial Viral Infections † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Salmonella Infections † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Sepsis, Bacteraemia, Viraemia And Fungaemia † 1  113/1257 (8.99%)  133 35/367 (9.54%)  37 82/1108 (7.40%)  87
Skin Structures And Soft Tissue Infections † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 2/1108 (0.18%)  2
Staphylococcal Infections † 1  15/1257 (1.19%)  17 4/367 (1.09%)  5 8/1108 (0.72%)  8
Streptococcal Infections † 1  1/1257 (0.08%)  1 2/367 (0.54%)  2 5/1108 (0.45%)  5
Upper Respiratory Tract Infections † 1  8/1257 (0.64%)  8 0/367 (0.00%)  0 7/1108 (0.63%)  7
Urinary Tract Infections † 1  112/1257 (8.91%)  132 25/367 (6.81%)  32 58/1108 (5.23%)  67
Vascular Infections † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Viral Infections † 1  6/1257 (0.48%)  6 3/367 (0.82%)  3 2/1108 (0.18%)  2
Injury, poisoning and procedural complications       
Abdominal Injuries † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 2/1108 (0.18%)  2
Cardiac And Vascular Procedural Complications † 1  37/1257 (2.94%)  38 7/367 (1.91%)  7 27/1108 (2.44%)  27
Cardiovascular Injuries † 1  9/1257 (0.72%)  9 3/367 (0.82%)  3 3/1108 (0.27%)  3
Cerebral Injuries † 1  16/1257 (1.27%)  17 4/367 (1.09%)  5 11/1108 (0.99%)  13
Chest And Lung Injuries † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 2/1108 (0.18%)  2
Ear Injuries † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Eye Injuries † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 0/1108 (0.00%)  0
Fractures And Dislocations † 1  7/1257 (0.56%)  8 0/367 (0.00%)  0 1/1108 (0.09%)  1
Gastrointestinal And Hepatobiliary Procedural Complications † 1  1/1257 (0.08%)  1 2/367 (0.54%)  2 0/1108 (0.00%)  0
Limb Injuries (Incl Traumatic Amputation) † 1  3/1257 (0.24%)  3 1/367 (0.27%)  1 5/1108 (0.45%)  5
Lower Limb Fractures And Dislocations † 1  69/1257 (5.49%)  73 9/367 (2.45%)  9 28/1108 (2.53%)  28
Muscle, Tendon And Ligament Injuries † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Nerve Injuries † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 0/1108 (0.00%)  0
Neurological And Psychiatric Procedural Complications † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 0/1108 (0.00%)  0
Non-Site Specific Injuries † 1  63/1257 (5.01%)  67 16/367 (4.36%)  16 48/1108 (4.33%)  51
Non-Site Specific Procedural Complications † 1  78/1257 (6.21%)  82 25/367 (6.81%)  29 52/1108 (4.69%)  54
Overdoses † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 1/1108 (0.09%)  1
Pelvic Fractures And Dislocations † 1  9/1257 (0.72%)  9 0/367 (0.00%)  0 4/1108 (0.36%)  4
Poisoning And Toxicity † 1  4/1257 (0.32%)  4 3/367 (0.82%)  3 5/1108 (0.45%)  5
Renal And Urinary Tract Injuries † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 2/1108 (0.18%)  2
Respiratory Tract And Thoracic Cavity Procedural Complications † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 2/1108 (0.18%)  2
Site Specific Injuries † 1  8/1257 (0.64%)  8 1/367 (0.27%)  1 5/1108 (0.45%)  5
Skin Injuries † 1  21/1257 (1.67%)  24 6/367 (1.63%)  8 12/1108 (1.08%)  13
Skull Fractures, Facial Bone Fractures And Dislocations † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 2/1108 (0.18%)  2
Spinal Fractures And Dislocations † 1  18/1257 (1.43%)  18 1/367 (0.27%)  1 7/1108 (0.63%)  9
Thermal Burns † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Thoracic Cage Fractures And Dislocations † 1  5/1257 (0.40%)  5 1/367 (0.27%)  1 3/1108 (0.27%)  3
Transfusion Related Complications † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 1/1108 (0.09%)  1
Upper Limb Fractures And Dislocations † 1  11/1257 (0.88%)  13 3/367 (0.82%)  3 12/1108 (1.08%)  14
Urinary Tract Procedural Complications † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 0/1108 (0.00%)  0
Investigations       
Blood Counts † 1  7/1257 (0.56%)  7 0/367 (0.00%)  0 4/1108 (0.36%)  4
Blood Gas And Acid Base Analyses † 1  6/1257 (0.48%)  6 7/367 (1.91%)  7 1/1108 (0.09%)  1
Carbohydrate Tolerance Analyses (Incl Diabetes) † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 7/1108 (0.63%)  7
Cardiac Function Diagnostic Procedures † 1  16/1257 (1.27%)  16 4/367 (1.09%)  4 17/1108 (1.53%)  17
Coagulation And Bleeding Analyses † 1  22/1257 (1.75%)  22 6/367 (1.63%)  6 14/1108 (1.26%)  17
Ecg Investigations † 1  3/1257 (0.24%)  3 3/367 (0.82%)  3 1/1108 (0.09%)  1
Faecal Analyses † 1  2/1257 (0.16%)  2 1/367 (0.27%)  1 1/1108 (0.09%)  1
Heart Rate And Pulse Investigations † 1  4/1257 (0.32%)  4 0/367 (0.00%)  0 2/1108 (0.18%)  2
Hepatobiliary Histopathology Procedures † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Liver Function Analyses † 1  2/1257 (0.16%)  2 2/367 (0.54%)  2 1/1108 (0.09%)  1
Metabolism Tests † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 1/1108 (0.09%)  1
Mineral And Electrolyte Analyses † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 3/1108 (0.27%)  4
Musculoskeletal And Soft Tissue Histopathology Procedures † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Physical Examination Procedures † 1  3/1257 (0.24%)  3 2/367 (0.54%)  2 0/1108 (0.00%)  0
Platelet Analyses † 1  3/1257 (0.24%)  3 1/367 (0.27%)  1 0/1108 (0.00%)  0
Protein Analyses † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Red Blood Cell Analyses † 1  11/1257 (0.88%)  12 5/367 (1.36%)  5 8/1108 (0.72%)  9
Renal Function Analyses † 1  10/1257 (0.80%)  10 1/367 (0.27%)  1 5/1108 (0.45%)  5
Respiratory And Pulmonary Function Diagnostic Procedures † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Respiratory Tract And Thoracic Imaging Procedures † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Skeletal And Cardiac Muscle Analyses † 1  9/1257 (0.72%)  10 3/367 (0.82%)  3 5/1108 (0.45%)  5
Urinalysis † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 2/1108 (0.18%)  2
Urinary Tract Function Analyses † 1  5/1257 (0.40%)  5 2/367 (0.54%)  2 5/1108 (0.45%)  5
Vascular Auscultatory Investigations † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 0/1108 (0.00%)  0
Vascular Tests (Incl Blood Pressure) † 1  8/1257 (0.64%)  9 1/367 (0.27%)  1 2/1108 (0.18%)  2
White Blood Cell Analyses † 1  4/1257 (0.32%)  4 0/367 (0.00%)  0 2/1108 (0.18%)  2
Metabolism and nutrition disorders       
Appetite Disorders † 1  3/1257 (0.24%)  3 1/367 (0.27%)  1 0/1108 (0.00%)  0
Calcium Metabolism Disorders † 1  1/1257 (0.08%)  3 2/367 (0.54%)  2 3/1108 (0.27%)  3
Chloride Imbalance † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Diabetes Mellitus (Incl Subtypes) † 1  4/1257 (0.32%)  4 2/367 (0.54%)  3 4/1108 (0.36%)  4
Diabetic Complications † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Disorders Of Purine Metabolism † 1  6/1257 (0.48%)  7 0/367 (0.00%)  0 8/1108 (0.72%)  9
Electrolyte Imbalance † 1  12/1257 (0.95%)  12 3/367 (0.82%)  3 4/1108 (0.36%)  4
General Nutritional Disorders † 1  31/1257 (2.47%)  32 12/367 (3.27%)  12 10/1108 (0.90%)  10
Hyperglycaemic Conditions † 1  18/1257 (1.43%)  20 8/367 (2.18%)  8 15/1108 (1.35%)  15
Hypoglycaemic Conditions † 1  13/1257 (1.03%)  13 9/367 (2.45%)  10 8/1108 (0.72%)  8
Magnesium Metabolism Disorders † 1  0/1257 (0.00%)  0 3/367 (0.82%)  3 2/1108 (0.18%)  2
Metabolic Acidoses (Excl Diabetic Acidoses) † 1  6/1257 (0.48%)  6 2/367 (0.54%)  2 4/1108 (0.36%)  4
Metabolic Alkaloses † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 2/1108 (0.18%)  2
Mixed Acid-Base Disorders † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 3/1108 (0.27%)  3
Phosphorus Metabolism Disorders † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 1/1108 (0.09%)  1
Potassium Imbalance † 1  34/1257 (2.70%)  37 10/367 (2.72%)  12 25/1108 (2.26%)  26
Protein Metabolism Disorders † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 0/1108 (0.00%)  0
Sodium Imbalance † 1  21/1257 (1.67%)  23 2/367 (0.54%)  2 20/1108 (1.81%)  23
Total Fluid Volume Decreased † 1  37/1257 (2.94%)  37 13/367 (3.54%)  14 29/1108 (2.62%)  30
Total Fluid Volume Increased † 1  35/1257 (2.78%)  36 10/367 (2.72%)  10 23/1108 (2.08%)  23
Musculoskeletal and connective tissue disorders       
Arthropathies † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 3/1108 (0.27%)  3
Bone Disorders † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 0/1108 (0.00%)  0
Bursal Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Connective Tissue Disorders (Excl Le) † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 1/1108 (0.09%)  1
Crystal Arthropathic Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Extremity Deformities † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Joint Related Disorders † 1  2/1257 (0.16%)  3 0/367 (0.00%)  0 0/1108 (0.00%)  0
Joint Related Signs And Symptoms † 1  10/1257 (0.80%)  10 3/367 (0.82%)  3 9/1108 (0.81%)  9
Muscle Infections And Inflammations † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Muscle Pains † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Muscle Related Signs And Symptoms † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Muscle Weakness Conditions † 1  8/1257 (0.64%)  8 4/367 (1.09%)  4 5/1108 (0.45%)  5
Musculoskeletal And Connective Tissue Pain And Discomfort † 1  38/1257 (3.02%)  43 8/367 (2.18%)  8 23/1108 (2.08%)  25
Musculoskeletal And Connective Tissue Signs And Symptoms † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 2/1108 (0.18%)  2
Myopathies † 1  3/1257 (0.24%)  3 2/367 (0.54%)  2 3/1108 (0.27%)  3
Osteoarthropathies † 1  6/1257 (0.48%)  8 1/367 (0.27%)  1 13/1108 (1.17%)  15
Rheumatoid Arthropathies † 1  1/1257 (0.08%)  2 1/367 (0.27%)  1 0/1108 (0.00%)  0
Soft Tissue Disorders † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 3/1108 (0.27%)  3
Spine And Neck Deformities † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 2/1108 (0.18%)  2
Tendon Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
B-Cell Lymphomas † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Bile Duct Neoplasms Malignant † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 0/1108 (0.00%)  0
Bladder Neoplasms Malignant † 1  5/1257 (0.40%)  5 1/367 (0.27%)  1 1/1108 (0.09%)  1
Bone Neoplasms Malignant (Excl Sarcomas) † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Breast And Nipple Neoplasms Malignant † 1  5/1257 (0.40%)  5 0/367 (0.00%)  0 2/1108 (0.18%)  2
Burkitt's Lymphomas † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Cardiovascular Neoplasms Benign † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Central Nervous System Neoplasms Malignant † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 2/1108 (0.18%)  2
Colonic Neoplasms Malignant † 1  6/1257 (0.48%)  6 0/367 (0.00%)  0 4/1108 (0.36%)  4
Hepatic Neoplasms Malignant † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 0/1108 (0.00%)  0
Leiomyosarcomas † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Leukaemias Acute Myeloid † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Leukaemias Chronic Lymphocytic † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 2/1108 (0.18%)  2
Leukaemias † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 2/1108 (0.18%)  2
Lip And Oral Cavity Neoplasms Malignant † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 0/1108 (0.00%)  0
Lymphomas Unspecified † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Mantle Cell Lymphomas † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Metastases To Specified Sites † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 2/1108 (0.18%)  2
Multiple Myelomas † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Myelodysplastic Syndromes † 1  0/1257 (0.00%)  0 2/367 (0.54%)  3 4/1108 (0.36%)  4
Myeloproliferative Disorders (Excl Leukaemias) † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Neoplasms Malignant Site Unspecified † 1  9/1257 (0.72%)  9 3/367 (0.82%)  3 6/1108 (0.54%)  6
Nervous System Neoplasms Unspecified Malignancy † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 1/1108 (0.09%)  1
Non-Small Cell Neoplasms Malignant Of The Respiratory Tract Cell Type Specified † 1  0/1257 (0.00%)  0 2/367 (0.54%)  2 0/1108 (0.00%)  0
Oesophageal Neoplasms Malignant † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 1/1108 (0.09%)  1
Oncologic Complications And Emergencies † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Pancreatic Neoplasms Malignant (Excl Islet Cell And Carcinoid) † 1  0/1257 (0.00%)  0 2/367 (0.54%)  2 3/1108 (0.27%)  3
Prostatic Neoplasms Malignant † 1  4/1257 (0.32%)  4 1/367 (0.27%)  1 2/1108 (0.18%)  2
Rectal Neoplasms Malignant † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 0/1108 (0.00%)  0
Renal Neoplasms Malignant † 1  2/1257 (0.16%)  2 1/367 (0.27%)  1 2/1108 (0.18%)  2
Respiratory Tract And Pleural Neoplasms Malignant Cell Type Unspecified † 1  6/1257 (0.48%)  7 7/367 (1.91%)  7 2/1108 (0.18%)  2
Skin Melanomas (Excl Ocular) † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 0/1108 (0.00%)  0
Skin Neoplasms Benign † 1  1/1257 (0.08%)  2 0/367 (0.00%)  0 0/1108 (0.00%)  0
Skin Neoplasms Malignant And Unspecified (Excl Melanoma) † 1  6/1257 (0.48%)  6 0/367 (0.00%)  0 3/1108 (0.27%)  3
Small Intestinal Neoplasms Malignant † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Soft Tissue Sarcomas Histology Unspecified † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Thyroid Neoplasms Malignant † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Urinary Tract Neoplasms Malignant † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Uterine Neoplasms Benign † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Uterine Neoplasms Malignant † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Vulval Neoplasms Malignant † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Nervous system disorders       
Acute Polyneuropathies † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Alzheimer's Disease (Incl Subtypes) † 1  1/1257 (0.08%)  1 2/367 (0.54%)  2 0/1108 (0.00%)  0
Autonomic Nervous System Disorders † 1  1/1257 (0.08%)  2 0/367 (0.00%)  0 0/1108 (0.00%)  0
Central Nervous System Aneurysms † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 1/1108 (0.09%)  1
Central Nervous System Haemorrhages And Cerebrovascular Accidents † 1  98/1257 (7.80%)  105 30/367 (8.17%)  33 79/1108 (7.13%)  86
Central Nervous System Vascular Disorders † 1  10/1257 (0.80%)  11 2/367 (0.54%)  3 7/1108 (0.63%)  7
Cerebellar Coordination And Balance Disturbances † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 1/1108 (0.09%)  1
Coma States † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 1/1108 (0.09%)  1
Cortical Dysfunction † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 1/1108 (0.09%)  1
Dementia (Excl Alzheimer's Type) † 1  5/1257 (0.40%)  5 0/367 (0.00%)  0 5/1108 (0.45%)  5
Disturbances In Consciousness † 1  42/1257 (3.34%)  46 13/367 (3.54%)  14 32/1108 (2.89%)  33
Dyskinesias And Movement Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Encephalopathies † 1  27/1257 (2.15%)  29 8/367 (2.18%)  8 13/1108 (1.17%)  13
Encephalopathies Toxic And Metabolic † 1  22/1257 (1.75%)  22 1/367 (0.27%)  1 14/1108 (1.26%)  14
Facial Cranial Nerve Disorders † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 2/1108 (0.18%)  2
Generalised Tonic-Clonic Seizures † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Headaches † 1  10/1257 (0.80%)  10 1/367 (0.27%)  1 8/1108 (0.72%)  9
Hydrocephalic Conditions † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Lumbar Spinal Cord And Nerve Root Disorders † 1  2/1257 (0.16%)  2 1/367 (0.27%)  1 1/1108 (0.09%)  1
Memory Loss (Excl Dementia) † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 1/1108 (0.09%)  1
Mental Impairment (Excl Dementia And Memory Loss) † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Mononeuropathies † 1  2/1257 (0.16%)  2 2/367 (0.54%)  2 0/1108 (0.00%)  0
Motor Neurone Diseases † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 0/1108 (0.00%)  0
Multiple Sclerosis Acute And Progressive † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Myelitis (Incl Infective) † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Nervous System Disorders † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 0/1108 (0.00%)  0
Neurological Signs And Symptoms † 1  32/1257 (2.55%)  34 6/367 (1.63%)  6 18/1108 (1.62%)  19
Neuromuscular Junction Dysfunction † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Paralysis And Paresis (Excl Cranial Nerve) † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 4/1108 (0.36%)  4
Parkinson's Disease And Parkinsonism † 1  3/1257 (0.24%)  4 0/367 (0.00%)  0 1/1108 (0.09%)  1
Peripheral Neuropathies † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 1/1108 (0.09%)  1
Seizures And Seizure Disorders † 1  12/1257 (0.95%)  18 3/367 (0.82%)  3 5/1108 (0.45%)  5
Sensory Abnormalities † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 5/1108 (0.45%)  5
Speech And Language Abnormalities † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Spinal Cord And Nerve Root Disorders † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 1/1108 (0.09%)  1
Structural Brain Disorders † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 1/1108 (0.09%)  1
Transient Cerebrovascular Events † 1  30/1257 (2.39%)  34 5/367 (1.36%)  6 24/1108 (2.17%)  27
Tremor (Excl Congenital) † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 2/1108 (0.18%)  2
Trigeminal Disorders † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Vagus Nerve Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Psychiatric disorders       
Abnormal Behaviour † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Anxiety Disorders † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Anxiety Symptoms † 1  8/1257 (0.64%)  10 4/367 (1.09%)  4 10/1108 (0.90%)  11
Behaviour And Socialisation Disturbances † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Bipolar Disorders † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 0/1108 (0.00%)  0
Confusion And Disorientation † 1  24/1257 (1.91%)  24 10/367 (2.72%)  10 20/1108 (1.81%)  20
Deliria † 1  14/1257 (1.11%)  14 1/367 (0.27%)  1 9/1108 (0.81%)  9
Delusional Symptoms † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 2/1108 (0.18%)  2
Depressive Disorders † 1  6/1257 (0.48%)  6 1/367 (0.27%)  1 4/1108 (0.36%)  4
Disturbances In Initiating And Maintaining Sleep † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 2/1108 (0.18%)  2
Eating Disorders † 1  0/1257 (0.00%)  0 2/367 (0.54%)  2 0/1108 (0.00%)  0
Mental Disorders † 1  56/1257 (4.46%)  64 19/367 (5.18%)  21 29/1108 (2.62%)  29
Panic Attacks And Disorders † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 2/1108 (0.18%)  2
Perception Disturbances † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 0/1108 (0.00%)  0
Psychiatric Symptoms † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 0/1108 (0.00%)  0
Psychotic Disorder † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 2/1108 (0.18%)  2
Speech Articulation And Rhythm Disturbances † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Stress Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Substance-Related Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Suicidal And Self-Injurious Behaviour † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 1/1108 (0.09%)  1
Renal and urinary disorders       
Bladder And Urethral Symptoms † 1  51/1257 (4.06%)  57 6/367 (1.63%)  8 48/1108 (4.33%)  49
Bladder Disorders † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 4/1108 (0.36%)  4
Genital And Urinary Tract Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Myoneurogenic Bladder Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Nephropathies And Tubular Disorders † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 2/1108 (0.18%)  2
Renal Disorders † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 1/1108 (0.09%)  1
Renal Failure And Impairment † 1  208/1257 (16.55%)  263 76/367 (20.71%)  94 154/1108 (13.90%)  181
Renal Failure Complications † 1  2/1257 (0.16%)  2 1/367 (0.27%)  1 1/1108 (0.09%)  1
Renal Lithiasis † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 6/1108 (0.54%)  7
Renal Neoplasms † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Renal Obstructive Disorders † 1  4/1257 (0.32%)  4 1/367 (0.27%)  1 0/1108 (0.00%)  0
Renal Vascular And Ischaemic Conditions † 1  2/1257 (0.16%)  2 1/367 (0.27%)  1 4/1108 (0.36%)  4
Structural And Obstructive Urethral Disorders (Excl Congenital) † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 3/1108 (0.27%)  3
Ureteric Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Urinary Abnormalities † 1  29/1257 (2.31%)  33 9/367 (2.45%)  9 29/1108 (2.62%)  36
Urinary Tract Lithiasis (Excl Renal) † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 2/1108 (0.18%)  2
Reproductive system and breast disorders       
Breast Disorders † 1  2/1257 (0.16%)  2 1/367 (0.27%)  1 0/1108 (0.00%)  0
Cervix Disorders † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Ovarian And Fallopian Tube Cysts And Neoplasms † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Pelvis And Broad Ligament Disorders † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 1/1108 (0.09%)  1
Penile And Scrotal Infections And Inflammations † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Penile Disorders (Excl Erection And Ejaculation) † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 0/1108 (0.00%)  0
Prostatic Neoplasms And Hypertrophy † 1  4/1257 (0.32%)  4 1/367 (0.27%)  1 2/1108 (0.18%)  2
Prostatic Signs, Symptoms And Disorders † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 0/1108 (0.00%)  0
Reproductive Tract Signs And Symptoms † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Scrotal Disorders † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 1/1108 (0.09%)  1
Testicular And Epididymal Disorders † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Vulvovaginal Disorders † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 0/1108 (0.00%)  0
Vulvovaginal Signs And Symptoms † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Breathing Abnormalities † 1  101/1257 (8.04%)  121 31/367 (8.45%)  39 66/1108 (5.96%)  76
Bronchial Conditions † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 1/1108 (0.09%)  2
Bronchospasm And Obstruction † 1  55/1257 (4.38%)  94 26/367 (7.08%)  40 35/1108 (3.16%)  42
Conditions Associated With Abnormal Gas Exchange † 1  25/1257 (1.99%)  26 11/367 (3.00%)  12 22/1108 (1.99%)  23
Coughing And Associated Symptoms † 1  18/1257 (1.43%)  20 6/367 (1.63%)  7 6/1108 (0.54%)  6
Diaphragmatic Disorders † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Laryngeal And Adjacent Sites Disorders (Excl Infections And Neoplasms) † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 0/1108 (0.00%)  0
Laryngeal Spasm, Oedema And Obstruction † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 0/1108 (0.00%)  0
Lower Respiratory Tract Inflammatory And Immunologic Conditions † 1  34/1257 (2.70%)  37 6/367 (1.63%)  7 14/1108 (1.26%)  15
Lower Respiratory Tract Signs And Symptoms † 1  4/1257 (0.32%)  4 1/367 (0.27%)  1 1/1108 (0.09%)  1
Mediastinal Disorders † 1  2/1257 (0.16%)  2 6/367 (1.63%)  6 1/1108 (0.09%)  1
Nasal Disorders † 1  17/1257 (1.35%)  20 11/367 (3.00%)  12 14/1108 (1.26%)  15
Parenchymal Lung Disorders † 1  13/1257 (1.03%)  14 4/367 (1.09%)  4 10/1108 (0.90%)  10
Pharyngeal Disorders (Excl Infections And Neoplasms) † 1  3/1257 (0.24%)  3 0/367 (0.00%)  0 1/1108 (0.09%)  1
Pleural Conditions † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Pneumothorax And Pleural Effusions † 1  106/1257 (8.43%)  137 70/367 (19.07%)  91 75/1108 (6.77%)  92
Pulmonary Hypertensions † 1  7/1257 (0.56%)  7 3/367 (0.82%)  3 8/1108 (0.72%)  9
Pulmonary Oedemas † 1  31/1257 (2.47%)  34 17/367 (4.63%)  17 35/1108 (3.16%)  40
Pulmonary Thrombotic And Embolic Conditions † 1  9/1257 (0.72%)  9 4/367 (1.09%)  5 11/1108 (0.99%)  11
Respiratory Failures (Excl Neonatal) † 1  149/1257 (11.85%)  192 66/367 (17.98%)  77 108/1108 (9.75%)  126
Respiratory Tract Disorders † 1  4/1257 (0.32%)  4 3/367 (0.82%)  3 1/1108 (0.09%)  1
Upper Respiratory Tract Signs And Symptoms † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 1/1108 (0.09%)  1
Skin and subcutaneous tissue disorders       
Bullous Conditions † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Dermal And Epidermal Conditions † 1  7/1257 (0.56%)  7 2/367 (0.54%)  2 2/1108 (0.18%)  2
Dermatitis And Eczema † 1  0/1257 (0.00%)  0 2/367 (0.54%)  2 0/1108 (0.00%)  0
Erythemas † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 2/1108 (0.18%)  2
Exfoliative Conditions † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 0/1108 (0.00%)  0
Hyperkeratoses † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Nail And Nail Bed Conditions (Excl Infections And Infestations) † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Pruritus † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 1/1108 (0.09%)  1
Purpura And Related Conditions † 1  2/1257 (0.16%)  2 1/367 (0.27%)  1 0/1108 (0.00%)  0
Rashes, Eruptions And Exanthems † 1  2/1257 (0.16%)  2 1/367 (0.27%)  1 3/1108 (0.27%)  3
Skin And Subcutaneous Conditions † 1  0/1257 (0.00%)  0 1/367 (0.27%)  1 0/1108 (0.00%)  0
Skin And Subcutaneous Tissue Ulcerations † 1  9/1257 (0.72%)  10 2/367 (0.54%)  2 7/1108 (0.63%)  7
Skin Injuries And Mechanical Dermatoses † 1  5/1257 (0.40%)  5 3/367 (0.82%)  3 1/1108 (0.09%)  1
Skin Preneoplastic Conditions † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Skin Vasculitides † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Skin Vasomotor Conditions † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Surgical and medical procedures       
Arterial Therapeutic Procedures (Excl Aortic) † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Cardiac Device Therapeutic Procedures † 1  8/1257 (0.64%)  8 2/367 (0.54%)  2 3/1108 (0.27%)  3
Haematological Therapeutic Procedures † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Joint Therapeutic Procedures † 1  5/1257 (0.40%)  5 1/367 (0.27%)  1 1/1108 (0.09%)  1
Large Intestine Therapeutic Procedures † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 2/1108 (0.18%)  2
Lens Therapeutic Procedures † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 0/1108 (0.00%)  0
Prostatic Therapeutic Procedures † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Renal Therapeutic Procedures † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Therapeutic Bladder Catheterisation † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Therapeutic Procedures † 1  20/1257 (1.59%)  22 1/367 (0.27%)  1 11/1108 (0.99%)  11
Tracheal Therapeutic Procedures † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Venous Therapeutic Procedures † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Vascular disorders       
Accelerated And Malignant Hypertension † 1  13/1257 (1.03%)  13 2/367 (0.54%)  2 13/1108 (1.17%)  13
Aneurysms And Dissections Non-Site Specific † 1  5/1257 (0.40%)  5 2/367 (0.54%)  2 6/1108 (0.54%)  6
Aortic Aneurysms And Dissections † 1  8/1257 (0.64%)  9 6/367 (1.63%)  6 5/1108 (0.45%)  5
Aortic Embolism And Thrombosis † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Aortic Necrosis And Vascular Insufficiency † 1  3/1257 (0.24%)  3 1/367 (0.27%)  1 1/1108 (0.09%)  1
Arterial And Aortic Injuries † 1  11/1257 (0.88%)  11 0/367 (0.00%)  0 10/1108 (0.90%)  11
Arterial Inflammations † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 0/1108 (0.00%)  0
Blood Pressure Disorders † 1  4/1257 (0.32%)  4 1/367 (0.27%)  1 3/1108 (0.27%)  3
Circulatory Collapse And Shock † 1  7/1257 (0.56%)  7 4/367 (1.09%)  4 4/1108 (0.36%)  4
Haemorrhages † 1  43/1257 (3.42%)  43 16/367 (4.36%)  16 33/1108 (2.98%)  34
Lymphangiopathies † 1  1/1257 (0.08%)  1 1/367 (0.27%)  1 2/1108 (0.18%)  2
Lymphoedemas † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 1/1108 (0.09%)  1
Non-Site Specific Embolism And Thrombosis † 1  9/1257 (0.72%)  10 4/367 (1.09%)  4 7/1108 (0.63%)  7
Non-Site Specific Necrosis And Vascular Insufficiency † 1  6/1257 (0.48%)  6 1/367 (0.27%)  1 4/1108 (0.36%)  5
Non-Site Specific Vascular Disorders † 1  16/1257 (1.27%)  16 10/367 (2.72%)  10 12/1108 (1.08%)  12
Peripheral Aneurysms And Dissections † 1  24/1257 (1.91%)  24 2/367 (0.54%)  2 11/1108 (0.99%)  11
Peripheral Embolism And Thrombosis † 1  20/1257 (1.59%)  20 8/367 (2.18%)  8 17/1108 (1.53%)  19
Peripheral Vascular Disorders † 1  5/1257 (0.40%)  6 5/367 (1.36%)  8 6/1108 (0.54%)  6
Peripheral Vasoconstriction, Necrosis And Vascular Insufficiency † 1  35/1257 (2.78%)  37 16/367 (4.36%)  17 41/1108 (3.70%)  44
Phlebitis † 1  0/1257 (0.00%)  0 0/367 (0.00%)  0 1/1108 (0.09%)  1
Site Specific Necrosis And Vascular Insufficiency † 1  1/1257 (0.08%)  1 0/367 (0.00%)  0 1/1108 (0.09%)  1
Site Specific Vascular Disorders † 1  3/1257 (0.24%)  3 1/367 (0.27%)  1 1/1108 (0.09%)  2
Vascular Hypertensive Disorders † 1  54/1257 (4.30%)  60 22/367 (5.99%)  23 53/1108 (4.78%)  57
Vascular Hypotensive Disorders † 1  137/1257 (10.90%)  157 50/367 (13.62%)  52 90/1108 (8.12%)  93
Vascular Malformations And Acquired Anomalies † 1  2/1257 (0.16%)  2 0/367 (0.00%)  0 1/1108 (0.09%)  1
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Extreme Risk: TAVI Iliofemoral Extreme Risk: TAVI Non-Iliofemoral High Risk: TAVI
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1097/1257 (87.27%)      327/367 (89.10%)      1001/1108 (90.34%)    
Blood and lymphatic system disorders       
Anaemias † 1  244/1257 (19.41%)  259 92/367 (25.07%)  96 260/1108 (23.47%)  267
Leukocytoses † 1  82/1257 (6.52%)  88 38/367 (10.35%)  40 79/1108 (7.13%)  81