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

• Sponsor: Medtronic Cardiovascular (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01531374
• Collaborator: (none)
• Enrollment: 2,777
• Locations: 45
• Arms: 3
• Actual Duration (Months): 92.9
• Patients Per Site: 61.7
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the safety and efficacy of the Medtronic CoreValve® System in the treatment of symptomatic severe aortic stenosis in subjects who have a predicted very high risk and high risk for aortic valve surgery.

Condition or Disease	Intervention/Treatment	Phase
Severe Aortic Stenosis	Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 2777 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Medtronic CoreValve® Continued Access Study
• Actual Study Start Date: Feb 21, 2012
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Nov 18, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Extreme Risk: TAVI Iliofemoral Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access	Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Experimental: Extreme Risk: TAVI Non-Iliofemoral Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access	Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Experimental: High Risk: TAVI High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)	Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Outcome Measures

Primary Outcome Measures

1. Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality [1 year]

   All-cause Death or Major Stroke (Extreme Risk- Medtronic CoreValve® System); All-cause Mortality (High Risk Surgical- Medtronic CoreValve® System vs. Surgical Valve)

Secondary Outcome Measures

1. Major Adverse Cardiovascular and Cerebrovascular Event (MACCE) [30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.]

   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)

2. The Occurrence of Individual MACCE Components [30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.]

   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)

3. Major Adverse Events (MAEs) [30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.]

   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

4. Conduction Disturbance Requiring Permanent Pacemaker Implantation [30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.]

5. Change From Baseline in NYHA Class [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.]

   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.

6. Change From Baseline in Distance Walked During 6-Minute Walk Test (6MWT) [Baseline to 30 days, baseline to 1 year]

   Change in distance walked during 6MWT from baseline

7. Ratio of Days Alive Out of Hospital at 365 Days Post Procedure Versus Total Days Alive [1 year]

8. Quality of Life (QoL) Change [30 day, 6 month, 1 year. The 2-5 year outcome data will be reported once data set is complete.]

   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.

9. Echocardiographic Assessment of Valve Performance [30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.]

   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.

10. Echocardiographic Assessment of Valve Performance [30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.]

    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.

11. Echocardiographic Assessment of Valve Performance [30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.]

    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.

12. Aortic Valve Hospitalizations [30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.]

13. Cardiovascular Deaths and Valve-Related Deaths [30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.]

14. Strokes and Transient Ischemic Attacks (TIAs) [30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.]

    Strokes (of any severity) and TIAs

15. Index Procedure Related MAEs [Procedure]

16. Length of Index Procedure Hospital Stay [Number of days from admission to discharge]

17. Device Success [Number of days from admission to discharge]

    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

18. Procedural Success [Number of days from admission to discharge]

    Defined as device success and absence of in-hospital MACCE.

19. Prosthetic Valve Dysfunction (PVD) [30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.]

    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

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. High Risk: Subject must have co-morbidities such that one cardiologist and two cardiac surgeons agree that predicted risk of operative mortality is ≥15% (and predicted operative mortality or serious, irreversible morbidity risk of < 50%) at 30 days.

OR

Extreme Risk: Subject must have co-morbidities such that one cardiologist and two cardiac surgeons agree that medical factors preclude operation, based on a conclusion that the probability of death or serious morbidity exceeds the probability of meaningful improvement. Specifically, the predicted operative risk of death or serious, irreversible morbidity is ≥ 50% at 30 days.

1. Subject has senile degenerative aortic valve stenosis with:

• Mean gradient > 40 mmHg, or jet velocity greater than 4.0 m/sec by either resting or dobutamine stress echocardiogram, or simultaneous pressure recordings at cardiac catheterization (either resting or dobutamine stress), AND

• An initial aortic valve area of ≤ 0.8 cm2 (or aortic valve area index ≤ 0.5 cm2/m2) by resting echocardiogram or simultaneous pressure recordings at cardiac catheterization

1. Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by New York Heart Association (NYHA) Functional Class II or greater.

2. The subject or the subject's legal representative has been informed of the nature of the trial, agrees to its provisions and has provided written informed consent as approved by the IRB of the respective clinical site.

3. The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits.

Exclusion Criteria:

Clinical

1. Evidence of an acute myocardial infarction ≤ 30 days before the intended treatment.

2. Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to the MCS TAVI procedure including bare metal and drug eluting stents.

3. Blood dyscrasias as defined: leukopenia (WBC < 1000mm3), thrombocytopenia (platelet count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy.

4. Untreated clinically significant coronary artery disease requiring revascularization.

5. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support.

6. Need for emergency surgery for any reason.

7. Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20% as measured by resting echocardiogram.

8. Recent (within 6 months) cerebrovascular accident (CVA) or transient ischemic attack (TIA).

9. End stage renal disease requiring chronic dialysis or creatinine clearance < 20 cc/min.

10. Active GI bleeding that would preclude anticoagulation.

11. A known hypersensitivity or contraindication to any of the following which cannot be adequately pre-medicated:

• Aspirin

• Heparin (HIT/HITTS) and bivalirudin

• Nitinol (titanium or nickel)

• Ticlopidine and clopidogrel

• Contrast media

1. Ongoing sepsis, including active endocarditis.

2. Subject refuses a blood transfusion.

3. Life expectancy < 12 months due to associated non-cardiac co-morbid conditions.

4. Other medical, social, or psychological conditions that in the opinion of an Investigator precludes the subject from appropriate consent.

5. Severe dementia (resulting in either inability to provide informed consent for the trial/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits).

6. Currently participating in an investigational drug or another device trial.

7. Symptomatic carotid or vertebral artery disease.

Anatomical

1. High Risk:Native aortic annulus size < 20 mm or > 29 mm per the baseline diagnostic imaging (until 23mm valve enrollment completion/closure in the CoreValve® US Pivotal Trial-High Risk Cohort)

OR

Extreme Risk: Native aortic annulus size < 18 mm or > 29 mm per the baseline diagnostic imaging. (High risk and extreme risk upon 23mm valve enrollment completion/closure in the CoreValve® US Pivotal Trial-High Risk Cohort)

1. Pre-existing prosthetic heart valve any position.

2. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation (3-4+)).

3. Moderate to severe (3-4+) or severe (4+) mitral or severe (4+) tricuspid regurgitation.

4. Moderate to severe mitral stenosis.

5. Hypertrophic obstructive cardiomyopathy.

6. Echocardiographic evidence of new or untreated intracardiac mass, thrombus or vegetation.

7. Severe basal septal hypertrophy with an outflow gradient.

8. Aortic root angulation (angle between plane of aortic valve annulus and horizontal plane/vertebrae) > 70° (for femoral and left subclavian/axillary access) and > 30° (for right subclavian/axillary access).

9. Ascending aorta diameter >43 mm if the aortic annulus diameter is 23-29 mm; ascending aortic diameter > 40 mm if the aortic annulus diameter is 20-23 mm; or an ascending aorta diameter > 34 mm if the aortic annulus diameter is 18-20 mm (Extreme Risk only until 23 mm valve enrollment completion/closure in the CoreValve® US Pivotal Trial-High Risk Cohort).

10. Congenital bicuspid or unicuspid valve verified by echocardiography.

11. Sinus of valsalva anatomy that would prevent adequate coronary perfusion.

Vascular

1. Transarterial access not able to accommodate an 18Fr sheath.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner Good Samaritan	Phoenix	Arizona	United States	85006
2	University of Southern California University Hospital	Los Angeles	California	United States	90033
3	Kaiser Permanente - Los Angeles Medical Center	Los Angeles	California	United States	90072
4	El Camino Hospital	Mountain View	California	United States	94040
5	VA Palo Alto Health Care System	Palo Alto	California	United States	94304
6	Hartford Hospital	Hartford	Connecticut	United States	06102
7	Yale New Haven Hospital	New Haven	Connecticut	United States	06520
8	Washington Hospital Center / Georgetown Hospital	Washington	District of Columbia	United States	20010
9	Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
10	University of Miami Health System / Jackson Memorial Hospital	Miami	Florida	United States	33136
11	Piedmont Heart Institute	Atlanta	Georgia	United States	30309
12	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia	United States	30342
13	Loyola University Medical Center	Maywood	Illinois	United States	60153
14	St. Vincent Heart Center of Indiana	Indianapolis	Indiana	United States	46290
15	Iowa Heart Center	Des Moines	Iowa	United States	50314
16	University of Kansas Hospital	Kansas City	Kansas	United States	66160
17	Cardiovascular Institute of the South/Terrebonne General	Houma	Louisiana	United States	70360
18	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
19	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
20	University of Michigan Health Systems	Ann Arbor	Michigan	United States	48109
21	Detroit Medical Center Cardiovascular Institute	Detroit	Michigan	United States	48201
22	St. John Hospital and Medical Center	Detroit	Michigan	United States	48236
23	Spectrum Health Hospitals	Grand Rapids	Michigan	United States	49503
24	Morristown Memorial Hospital	Morristown	New Jersey	United States	07962
25	North Shore University Hospital/ Long Island Jewish Hospital	Manhasset	New York	United States	11030
26	NYU Langone Medical Center	New York	New York	United States	10016
27	The Mount Sinai Medical Center	New York	New York	United States	10029
28	Lenox Hill Hospital	New York	New York	United States	10075
29	St. Francis Hospital	Roslyn	New York	United States	11576
30	Duke University Medical Center	Durham	North Carolina	United States	27710
31	Wake Forest University - Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
32	University Hospitals - Case Medical Center	Cleveland	Ohio	United States	44106
33	The Ohio State University Medical Center - The Richard M. Ross Heart Hospital	Columbus	Ohio	United States	43210
34	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
35	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
36	Pinnacle Health	Harrisburg	Pennsylvania	United States	17043
37	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
38	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
39	Baylor Heart and Vascular Hospital	Dallas	Texas	United States	75226
40	Texas Heart Institute at St. Luke's Episcopal Hospital	Houston	Texas	United States	77030
41	The Methodist Hospital - The Methodist DeBakey Heart & Vascular Center	Houston	Texas	United States	77030
42	University of Vermont Medical Center	Burlington	Vermont	United States	05458
43	Inova Fairfax Hospital	Falls Church	Virginia	United States	22042
44	Providence Sacred Heart Medical Center	Spokane	Washington	United States	99204
45	St. Luke's Medical Center - Aurora Health Care	Milwaukee	Wisconsin	United States	53215

Sponsors and Collaborators

• Medtronic Cardiovascular

Investigators

• Principal Investigator: David H Adams, MD, Icahn School of Medicine at Mount Sinai

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medtronic Cardiovascular
• ClinicalTrials.gov Identifier: NCT01531374
• Other Study ID Numbers: 10037989DOC REV 1C
• First Posted: Feb 10, 2012
• Last Update Posted: Jun 16, 2022
• Last Verified: May 1, 2022

• Keywords provided by Medtronic Cardiovascular: Valvular Heart Disease; Critical Aortic Stenosis; Severe Aortic Stenosis; Extreme Risk; High Risk; Aortic Valve Replacement
• Additional relevant MeSH terms: Aortic Valve Stenosis; Constriction, Pathologic

Study Results

Participant Flow

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.

Arm/Group Title	Extreme Risk: Iliofemoral	Extreme Risk: Non-Iliofemoral	High Risk
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

Baseline Characteristics

Arm/Group Title	Extreme Risk: Iliofemoral	Extreme Risk: Non-Iliofemoral	High Risk	Total
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 Participants	1257	367	1108	2732
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	83.5 (8.1)	81.9 (8.2)	83.6 (7.1)	83.3 (7.7)
Sex: Female, Male (Count of 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%
Ethnicity (NIH/OMB) (Count of 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%
Unknown or Not Reported	14 1.1%	3 0.8%	14 1.3%	31 1.1%
Body Surface Area (m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [m^2]	1.9 (0.3)	1.8 (0.3)	1.9 (0.2)	1.9 (0.3)
New York Heart Association (NYHA) Classification (participants) [Number]
NYHA Classification I	0 0%	0 0%	0 0%	0 0%
NYHA Classification II	159 12.6%	45 12.3%	180 16.2%	384 14.1%
NYHA Classification III	881 70.1%	248 67.6%	811 73.2%	1940 71%
NYHA Classification IV	217 17.3%	74 20.2%	117 10.6%	408 14.9%
Society of Thoracic Surgeons (STS) Risk Score (Percent of predicted mortality) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percent of predicted mortality]	9.1 (5.1)	10.2 (5.6)	7.7 (3.3)	8.7 (4.6)
Logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) (Percent of predicted mortality) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percent of predicted mortality]	24.2 (17.1)	24.2 (17.1)	20.3 (13.5)	22.6 (15.9)

Outcome Measures

1. Primary Outcome

Title	Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality
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

Outcome Measure Data

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
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)
Measure Participants	1257	367	1108
Number [percentage of participants, Kaplan-Meier]	22.5 1.8%	30.8 8.4%	17.8 1.6%

2. Secondary Outcome

Title	Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)
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.

Outcome Measure Data

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
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)
Measure Participants	1257	367	1108
30 day	9.1 0.7%	16.1 4.4%	8.9 0.8%
6 month	19.2 1.5%	28.4 7.7%	17.2 1.6%
1 year	26.6 2.1%	36.2 9.9%	24.3 2.2%

3. Secondary Outcome

Title	The Occurrence of Individual MACCE Components
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.

Outcome Measure Data

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
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)
Measure Participants	1257	367	1108
30 day All Cause Mortality	4.5 0.4%	9.6 2.6%	4.9 0.4%
30 day MI	1.1 0.1%	1.4 0.4%	0.4 0%
30 day Stroke	4.6 0.4%	5.9 1.6%	4.7 0.4%
30 day Reintervention	0.6 0%	0.8 0.2%	0.4 0%
6 month All Cause Mortality	13.7 1.1%	20.8 5.7%	12.0 1.1%
6 month MI	1.6 0.1%	2.7 0.7%	1.0 0.1%
6 month Stroke	6.6 0.5%	8.2 2.2%	7.0 0.6%
6 month Reintervention	0.9 0.1%	0.8 0.2%	0.8 0.1%
1 year All Cause Mortality	21.0 1.7%	29.4 8%	17.8 1.6%
1 year MI	2.2 0.2%	3.8 1%	1.9 0.2%
1 year Stroke	7.3 0.6%	9.2 2.5%	8.7 0.8%
1 year Reintervention	1.0 0.1%	1.2 0.3%	0.8 0.1%

4. Secondary Outcome

Title	Major Adverse Events (MAEs)
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.

Outcome Measure Data

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
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)
Measure Participants	1257	367	1108
30 day	46.3 3.7%	67.4 18.4%	48.1 4.3%
6 month	53.0 4.2%	73.1 19.9%	54.5 4.9%
1 year	57.7 4.6%	76.4 20.8%	59.3 5.4%

5. Secondary Outcome

Title	Conduction Disturbance Requiring Permanent Pacemaker Implantation
Time Frame	30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.

Outcome Measure Data

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
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)
Measure Participants	1257	367	1108
30 day	27.2 2.2%	23.0 6.3%	28.8 2.6%
6 month	29.7 2.4%	24.6 6.7%	30.5 2.8%
1 year	31.1 2.5%	25.5 6.9%	32.1 2.9%

6. Secondary Outcome

Title	Change From Baseline in NYHA Class
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.

Outcome Measure Data

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
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)
Measure Participants	1257	367	1108
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)
Description	Change in distance walked during 6MWT from baseline
Time Frame	Baseline to 30 days, baseline to 1 year

Outcome Measure Data

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
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)
Measure Participants	1257	367	1108
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
Time Frame	1 year

Outcome Measure Data

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
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)
Measure Participants	1257	367	1108
Mean (Standard Deviation) [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
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.

Outcome Measure Data

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
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)
Measure Participants	1257	367	1108
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
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.

Outcome Measure Data

Analysis Population Description

Participant Population = Consisted of all subjects with a valve implanted.

Arm/Group Title	Extreme Risk: Implanted Cohort	High Risk: Implanted Cohort
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)
Measure Participants	1615	1102
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
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.

Outcome Measure Data

Analysis Population Description

Participant Population= Consisted of all subjects with a valve implanted.

Arm/Group Title	Extreme Risk: Implanted Cohort	High Risk: Implanted Cohort
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)
Measure Participants	1615	1102
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
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.

Outcome Measure Data

Analysis Population Description

Participant Population = Consisted of all subjects with a valve implanted.

Arm/Group Title	Extreme Risk: Implanted Cohort	High Risk: Implanted Cohort
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)
Measure Participants	1615	1102
30 day Total Aortic Regurgitation- None	26.5 2.1%	28.7 7.8%
30 day Total Aortic Regurgitation- Mild	66.3 5.3%	65.2 17.8%
30 day Total Aortic Regurgitation- Moderate	6.9 0.5%	5.8 1.6%
30 day Total Aortic Regurgitation- Severe	0.3 0%	0.3 0.1%
6 month Total Aortic Regurgitation- None	35.1 2.8%	37.8 10.3%
6 month Total Aortic Regurgitation- Mild	58.5 4.7%	58.1 15.8%
6 month Total Aortic Regurgitation- Moderate	6.1 0.5%	4.0 1.1%
6 month Total Aortic Regurgitation- Severe	0.2 0%	0.1 0%
1 year Total Aortic Regurgitation- None	39.8 3.2%	39.9 10.9%
1 year Total Aortic Regurgitation- Mild	54.9 4.4%	56.0 15.3%
1 year Total Aortic Regurgitation- Moderate	5.1 0.4%	3.8 1%
1 year Total Aortic Regurgitation- Severe	0.2 0%	0.3 0.1%

13. Secondary Outcome

Title	Aortic Valve Hospitalizations
Time Frame	30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.

Outcome Measure Data

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
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)
Measure Participants	1257	367	1108
30 day	6.2 0.5%	5.5 1.5%	5.6 0.5%
6 month	12.5 1%	12.9 3.5%	11.8 1.1%
1 year	17.1 1.4%	16.5 4.5%	15.4 1.4%

14. Secondary Outcome

Title	Cardiovascular Deaths and Valve-Related Deaths
Time Frame	30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.

Outcome Measure Data

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
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)
Measure Participants	1257	367	1108
30 day Cardiovascular Deaths	4.4 0.4%	9.3 2.5%	4.6 0.4%
30 day Valve Related Deaths	1.9 0.2%	4.2 1.1%	2.4 0.2%
6 month Cardiovascular Deaths	11.3 0.9%	16.3 4.4%	9.4 0.8%
6 month Valve Related Deaths	3.9 0.3%	5.7 1.6%	3.8 0.3%
1 year Cardiovascular Deaths	16.6 1.3%	22.0 6%	13.0 1.2%
1 year Valve Related Deaths	5.5 0.4%	6.4 1.7%	4.2 0.4%

15. Secondary Outcome

Title	Strokes and Transient Ischemic Attacks (TIAs)
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.

Outcome Measure Data

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
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)
Measure Participants	1257	367	1108
30 day Stroke	4.6 0.4%	5.9 1.6%	4.7 0.4%
30 day TIA	0.7 0.1%	0.3 0.1%	0.7 0.1%
6 month Stroke	6.6 0.5%	8.2 2.2%	6.8 0.6%
6 month TIA	1.4 0.1%	0.9 0.2%	2.2 0.2%
1 year Stroke	7.3 0.6%	9.2 2.5%	8.7 0.8%
1 year TIA	2.0 0.2%	0.9 0.2%	2.9 0.3%

16. Secondary Outcome

Title	Index Procedure Related MAEs
Time Frame	Procedure

Outcome Measure Data

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
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)
Measure Participants	1257	367	1108
Number [percentage of participants]	46.4 3.7%	66.6 18.1%	48.1 4.3%

17. Secondary Outcome

Title	Length of Index Procedure Hospital Stay
Time Frame	Number of days from admission to discharge

Outcome Measure Data

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
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)
Measure Participants	1257	367	1108
Mean (Standard Deviation) [days]	7.6 (6.9)	10.7 (8.7)	7.6 (5.9)

18. Secondary Outcome

Title	Device Success
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

Outcome Measure Data

Analysis Population Description

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
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)
Measure Participants	1252	365	1104
Number [percentage of participants]	84.9 6.8%	88.1 24%	87.9 7.9%

19. Secondary Outcome

Title	Procedural Success
Description	Defined as device success and absence of in-hospital MACCE.
Time Frame	Number of days from admission to discharge

Outcome Measure Data

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
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)
Measure Participants	1252	365	1104
Number [percentage of participants]	79.7 6.3%	76.8 20.9%	82.3 7.4%

20. Secondary Outcome

Title	Prosthetic Valve Dysfunction (PVD)
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.

Outcome Measure Data

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
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)
Measure Participants	1251	364	1102
30 day Aortic Stenosis	1.0 0.1%	0.8 0.2%	0.9 0.1%
30 day Aortic Regurgitation	3.0 0.2%	1.9 0.5%	2.0 0.2%
6 month Aortic Stenosis	2.2 0.2%	0.8 0.2%	2.0 0.2%
6 month Aortic Regurgitation	5.0 0.4%	3.3 0.9%	3.1 0.3%
1 year Aortic Stenosis	2.8 0.2%	1.6 0.4%	2.5 0.2%
1 year Aortic Regurgitation	5.8 0.5%	3.8 1%	4.5 0.4%

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
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 (88.9%)		359/367 (97.8%)		1004/1108 (90.6%)
Blood and lymphatic system disorders
Anaemia Deficiencies	7/1257 (0.6%)	7	3/367 (0.8%)	3	6/1108 (0.5%)	6
Anaemias Due To Chronic Disorders	2/1257 (0.2%)	2	3/367 (0.8%)	3	2/1108 (0.2%)	2
Anaemias	340/1257 (27%)	420	150/367 (40.9%)	182	265/1108 (23.9%)	319
Coagulopathies	9/1257 (0.7%)	9	6/367 (1.6%)	6	6/1108 (0.5%)	6
Haemolyses	0/1257 (0%)	0	1/367 (0.3%)	1	1/1108 (0.1%)	1
Leukocytoses	9/1257 (0.7%)	9	4/367 (1.1%)	4	13/1108 (1.2%)	13
Lymphatic System Disorders	0/1257 (0%)	0	1/367 (0.3%)	1	1/1108 (0.1%)	1
Marrow Depression And Hypoplastic Anaemias	3/1257 (0.2%)	3	4/367 (1.1%)	7	2/1108 (0.2%)	2
Spleen Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	2/1108 (0.2%)	2
Thrombocytopenias	34/1257 (2.7%)	34	17/367 (4.6%)	17	20/1108 (1.8%)	21
Cardiac disorders
Aortic Valvular Disorders	143/1257 (11.4%)	153	26/367 (7.1%)	29	103/1108 (9.3%)	108
Cardiac Conduction Disorders	293/1257 (23.3%)	311	63/367 (17.2%)	66	277/1108 (25%)	296
Cardiac Disorders	13/1257 (1%)	13	5/367 (1.4%)	5	13/1108 (1.2%)	13
Cardiac Signs And Symptoms	1/1257 (0.1%)	1	0/367 (0%)	0	3/1108 (0.3%)	3
Cardiac Valve Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Cardiomyopathies	16/1257 (1.3%)	16	3/367 (0.8%)	3	6/1108 (0.5%)	7
Coronary Artery Disorders	26/1257 (2.1%)	28	7/367 (1.9%)	8	10/1108 (0.9%)	11
Heart Failures	329/1257 (26.2%)	531	105/367 (28.6%)	147	248/1108 (22.4%)	346
Ischaemic Coronary Artery Disorders	91/1257 (7.2%)	102	26/367 (7.1%)	30	78/1108 (7%)	97
Left Ventricular Failures	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Mitral Valvular Disorders	36/1257 (2.9%)	37	3/367 (0.8%)	3	28/1108 (2.5%)	30
Myocardial Disorders	6/1257 (0.5%)	6	5/367 (1.4%)	5	9/1108 (0.8%)	9
Pericardial Disorders	22/1257 (1.8%)	24	8/367 (2.2%)	9	30/1108 (2.7%)	33
Pulmonary Valvular Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Rate And Rhythm Disorders	75/1257 (6%)	77	20/367 (5.4%)	21	50/1108 (4.5%)	54
Right Ventricular Failures	4/1257 (0.3%)	4	1/367 (0.3%)	1	4/1108 (0.4%)	4
Supraventricular Arrhythmias	152/1257 (12.1%)	184	47/367 (12.8%)	55	119/1108 (10.7%)	137
Tricuspid Valvular Disorders	11/1257 (0.9%)	11	1/367 (0.3%)	1	5/1108 (0.5%)	5
Ventricular Arrhythmias And Cardiac Arrest	139/1257 (11.1%)	150	43/367 (11.7%)	49	104/1108 (9.4%)	113
Congenital, familial and genetic disorders
Cardiac Malpositions Congenital	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Cardiac Septal Defects Congenital	2/1257 (0.2%)	3	0/367 (0%)	0	3/1108 (0.3%)	3
Cardiovascular Disorders Congenital	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Male Reproductive Tract Disorders Congenital	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Vascular Anomalies Congenital	2/1257 (0.2%)	2	1/367 (0.3%)	1	0/1108 (0%)	0
Ear and labyrinth disorders
Eustachian Tube Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
External Ear Disorders	2/1257 (0.2%)	2	0/367 (0%)	0	0/1108 (0%)	0
Inner Ear Signs And Symptoms	7/1257 (0.6%)	7	3/367 (0.8%)	3	2/1108 (0.2%)	2
Middle Ear Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Endocrine disorders
Thyroid Disorders	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Thyroid Hyperfunction Disorders	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Thyroid Hypofunction Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	4/1108 (0.4%)	4
Eye disorders
Blindness (Excl Colour Blindness)	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Cataract Conditions	5/1257 (0.4%)	6	0/367 (0%)	0	6/1108 (0.5%)	6
Conjunctival And Corneal Bleeding And Vascular Disorders	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Corneal Structural Change, Deposit And Degeneration	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Lens Structural Change, Deposit And Degeneration (Excl Cataracts)	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Lid, Lash And Lacrimal Structural Disorders	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Ocular Bleeding And Vascular Disorders	0/1257 (0%)	0	0/367 (0%)	0	2/1108 (0.2%)	3
Partial Vision Loss	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Retinal Bleeding And Vascular Disorders (Excl Retinopathy)	3/1257 (0.2%)	3	0/367 (0%)	0	4/1108 (0.4%)	4
Retinal Structural Change, Deposit And Degeneration	2/1257 (0.2%)	2	0/367 (0%)	0	2/1108 (0.2%)	2
Retinal, Choroid And Vitreous Infections And Inflammations	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Visual Disorders	2/1257 (0.2%)	2	2/367 (0.5%)	2	3/1108 (0.3%)	3
Gastrointestinal disorders
Abdominal Findings Abnormal	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Abdominal Hernias, Site Unspecified	3/1257 (0.2%)	3	0/367 (0%)	0	1/1108 (0.1%)	1
Abdominal Wall Conditions	1/1257 (0.1%)	1	1/367 (0.3%)	1	2/1108 (0.2%)	2
Acute And Chronic Pancreatitis	1/1257 (0.1%)	1	1/367 (0.3%)	1	0/1108 (0%)	0
Anal And Rectal Pains	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Benign Neoplasms Gastrointestinal (Excl Oral Cavity)	2/1257 (0.2%)	2	0/367 (0%)	0	2/1108 (0.2%)	2
Colitis (Excl Infective)	4/1257 (0.3%)	5	3/367 (0.8%)	3	4/1108 (0.4%)	4
Dental And Periodontal Infections And Inflammations	2/1257 (0.2%)	2	0/367 (0%)	0	1/1108 (0.1%)	1
Dental Disorders	1/1257 (0.1%)	1	1/367 (0.3%)	1	0/1108 (0%)	0
Diaphragmatic Hernias	2/1257 (0.2%)	2	0/367 (0%)	0	1/1108 (0.1%)	1
Diarrhoea (Excl Infective)	9/1257 (0.7%)	9	2/367 (0.5%)	2	5/1108 (0.5%)	5
Diverticula	3/1257 (0.2%)	3	2/367 (0.5%)	2	4/1108 (0.4%)	4
Duodenal And Small Intestinal Stenosis And Obstruction	7/1257 (0.6%)	7	1/367 (0.3%)	1	5/1108 (0.5%)	7
Duodenal Ulcers And Perforation	4/1257 (0.3%)	4	0/367 (0%)	0	1/1108 (0.1%)	1
Dyspeptic Signs And Symptoms	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Faecal Abnormalities	2/1257 (0.2%)	2	0/367 (0%)	0	9/1108 (0.8%)	9
Flatulence, Bloating And Distension	2/1257 (0.2%)	2	0/367 (0%)	0	0/1108 (0%)	0
Gastric And Oesophageal Haemorrhages	3/1257 (0.2%)	3	0/367 (0%)	0	2/1108 (0.2%)	2
Gastric Ulcers And Perforation	5/1257 (0.4%)	5	1/367 (0.3%)	1	0/1108 (0%)	0
Gastritis (Excl Infective)	5/1257 (0.4%)	5	3/367 (0.8%)	3	2/1108 (0.2%)	2
Gastrointestinal And Abdominal Pains (Excl Oral And Throat)	17/1257 (1.4%)	19	4/367 (1.1%)	4	14/1108 (1.3%)	15
Gastrointestinal Atonic And Hypomotility Disorders	14/1257 (1.1%)	15	0/367 (0%)	0	6/1108 (0.5%)	7
Gastrointestinal Disorders	1/1257 (0.1%)	1	1/367 (0.3%)	1	0/1108 (0%)	0
Gastrointestinal Dyskinetic Disorders	1/1257 (0.1%)	1	1/367 (0.3%)	1	0/1108 (0%)	0
Gastrointestinal Fistulae	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Gastrointestinal Inflammatory Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Gastrointestinal Necrosis And Gangrene (Excl Gangrenous Hernia)	0/1257 (0%)	0	0/367 (0%)	0	2/1108 (0.2%)	2
Gastrointestinal Signs And Symptoms	35/1257 (2.8%)	35	12/367 (3.3%)	13	16/1108 (1.4%)	17
Gastrointestinal Stenosis And Obstruction	3/1257 (0.2%)	3	2/367 (0.5%)	2	7/1108 (0.6%)	7
Gastrointestinal Ulcers And Perforation, Site Unspecified	3/1257 (0.2%)	3	0/367 (0%)	0	2/1108 (0.2%)	2
Gastrointestinal Vascular Occlusion And Infarction	3/1257 (0.2%)	3	2/367 (0.5%)	2	6/1108 (0.5%)	6
Gingival Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Haemorrhoids And Gastrointestinal Varices (Excl Oesophageal)	0/1257 (0%)	0	0/367 (0%)	0	4/1108 (0.4%)	4
Inguinal Hernias	5/1257 (0.4%)	6	2/367 (0.5%)	2	5/1108 (0.5%)	5
Intestinal Haemorrhages	9/1257 (0.7%)	10	3/367 (0.8%)	3	9/1108 (0.8%)	9
Intestinal Ulcers And Perforation	2/1257 (0.2%)	2	0/367 (0%)	0	1/1108 (0.1%)	2
Large Intestinal Stenosis And Obstruction	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Nausea And Vomiting Symptoms	11/1257 (0.9%)	11	6/367 (1.6%)	8	12/1108 (1.1%)	12
Non-Site Specific Gastrointestinal Haemorrhages	98/1257 (7.8%)	121	26/367 (7.1%)	35	71/1108 (6.4%)	84
Oesophageal Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Oesophageal Stenosis And Obstruction	6/1257 (0.5%)	6	0/367 (0%)	0	1/1108 (0.1%)	2
Oesophageal Ulcers And Perforation	1/1257 (0.1%)	1	1/367 (0.3%)	1	0/1108 (0%)	0
Oesophagitis (Excl Infective)	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Peritoneal And Retroperitoneal Disorders	5/1257 (0.4%)	5	2/367 (0.5%)	2	4/1108 (0.4%)	4
Peritoneal And Retroperitoneal Haemorrhages	5/1257 (0.4%)	5	1/367 (0.3%)	1	9/1108 (0.8%)	9
Tongue Disorders	0/1257 (0%)	0	1/367 (0.3%)	1	0/1108 (0%)	0
Umbilical Hernias	1/1257 (0.1%)	1	2/367 (0.5%)	2	0/1108 (0%)	0
General disorders
Administration Site Reactions	2/1257 (0.2%)	2	0/367 (0%)	0	2/1108 (0.2%)	2
Asthenic Conditions	31/1257 (2.5%)	33	8/367 (2.2%)	10	23/1108 (2.1%)	25
Body Temperature Altered	2/1257 (0.2%)	2	1/367 (0.3%)	1	1/1108 (0.1%)	1
Complications Associated With Device	5/1257 (0.4%)	5	1/367 (0.3%)	1	7/1108 (0.6%)	9
Death And Sudden Death	49/1257 (3.9%)	49	18/367 (4.9%)	18	38/1108 (3.4%)	38
Device Issues	130/1257 (10.3%)	140	17/367 (4.6%)	19	93/1108 (8.4%)	103
Device Malfunction Events	7/1257 (0.6%)	7	2/367 (0.5%)	2	7/1108 (0.6%)	7
Device Physical Property And Chemical Issues	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Febrile Disorders	24/1257 (1.9%)	24	5/367 (1.4%)	5	15/1108 (1.4%)	15
Gait Disturbances	3/1257 (0.2%)	3	0/367 (0%)	0	2/1108 (0.2%)	2
General Signs And Symptoms	20/1257 (1.6%)	20	4/367 (1.1%)	4	11/1108 (1%)	11
Healing Abnormal	4/1257 (0.3%)	4	1/367 (0.3%)	1	1/1108 (0.1%)	1
Hernias	1/1257 (0.1%)	1	0/367 (0%)	0	2/1108 (0.2%)	2
Implant And Catheter Site Reactions	4/1257 (0.3%)	5	1/367 (0.3%)	2	9/1108 (0.8%)	9
Inflammations	2/1257 (0.2%)	2	0/367 (0%)	0	5/1108 (0.5%)	5
Injection Site Reactions	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Mucosal Findings Abnormal	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Oedema	31/1257 (2.5%)	32	7/367 (1.9%)	8	15/1108 (1.4%)	17
Pain And Discomfort	67/1257 (5.3%)	85	14/367 (3.8%)	18	40/1108 (3.6%)	41
Product Physical Issues	6/1257 (0.5%)	6	0/367 (0%)	0	0/1108 (0%)	0
Therapeutic And Nontherapeutic Responses	1/1257 (0.1%)	1	1/367 (0.3%)	1	3/1108 (0.3%)	3
Ulcers	0/1257 (0%)	0	0/367 (0%)	0	2/1108 (0.2%)	2
Vascular Complications Associated With Device	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Hepatobiliary disorders
Bile Duct Infections And Inflammations	2/1257 (0.2%)	2	0/367 (0%)	0	0/1108 (0%)	0
Cholecystitis And Cholelithiasis	11/1257 (0.9%)	11	4/367 (1.1%)	4	7/1108 (0.6%)	7
Cholestasis And Jaundice	0/1257 (0%)	0	1/367 (0.3%)	1	1/1108 (0.1%)	1
Gallbladder Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Hepatic And Hepatobiliary Disorders	1/1257 (0.1%)	1	2/367 (0.5%)	2	1/1108 (0.1%)	1
Hepatic Failure And Associated Disorders	7/1257 (0.6%)	7	0/367 (0%)	0	5/1108 (0.5%)	5
Hepatic Fibrosis And Cirrhosis	4/1257 (0.3%)	4	0/367 (0%)	0	0/1108 (0%)	0
Hepatic Vascular Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Hepatobiliary Signs And Symptoms	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Hepatocellular Damage And Hepatitis	4/1257 (0.3%)	4	1/367 (0.3%)	1	5/1108 (0.5%)	5
Obstructive Bile Duct Disorders (Excl Neoplasms)	4/1257 (0.3%)	4	3/367 (0.8%)	3	1/1108 (0.1%)	1
Immune system disorders
Acute And Chronic Sarcoidosis	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Allergic Conditions	1/1257 (0.1%)	1	0/367 (0%)	0	2/1108 (0.2%)	2
Allergies To Foods, Food Additives, Drugs And Other Chemicals	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Infections and infestations
Abdominal And Gastrointestinal Infections	14/1257 (1.1%)	14	2/367 (0.5%)	2	9/1108 (0.8%)	9
Aspergillus Infections	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Atypical Mycobacterial Infections	0/1257 (0%)	0	1/367 (0.3%)	1	1/1108 (0.1%)	1
Bacterial Infections	54/1257 (4.3%)	66	17/367 (4.6%)	22	37/1108 (3.3%)	42
Bone And Joint Infections	11/1257 (0.9%)	12	2/367 (0.5%)	2	7/1108 (0.6%)	7
Candida Infections	1/1257 (0.1%)	1	2/367 (0.5%)	2	1/1108 (0.1%)	1
Cardiac Infections	15/1257 (1.2%)	16	5/367 (1.4%)	5	10/1108 (0.9%)	10
Clostridia Infections	19/1257 (1.5%)	23	9/367 (2.5%)	12	11/1108 (1%)	13
Dental And Oral Soft Tissue Infections	2/1257 (0.2%)	2	1/367 (0.3%)	1	3/1108 (0.3%)	5
Ear Infections	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Enterobacter Infections	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Enterococcal Infections	2/1257 (0.2%)	2	1/367 (0.3%)	1	3/1108 (0.3%)	4
Escherichia Infections	3/1257 (0.2%)	3	0/367 (0%)	0	2/1108 (0.2%)	2
Eye And Eyelid Infections	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Fungal Infections	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Haemophilus Infections	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Helicobacter Infections	2/1257 (0.2%)	2	0/367 (0%)	0	0/1108 (0%)	0
Hepatobiliary And Spleen Infections	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Herpes Viral Infections	4/1257 (0.3%)	4	0/367 (0%)	0	5/1108 (0.5%)	5
Infections	28/1257 (2.2%)	30	8/367 (2.2%)	8	20/1108 (1.8%)	22
Infectious Disorders Carrier	1/1257 (0.1%)	1	1/367 (0.3%)	1	0/1108 (0%)	0
Infectious Transmissions	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Influenza Viral Infections	14/1257 (1.1%)	14	2/367 (0.5%)	2	11/1108 (1%)	12
Klebsiella Infections	0/1257 (0%)	0	2/367 (0.5%)	2	3/1108 (0.3%)	3
Lower Respiratory Tract And Lung Infections	170/1257 (13.5%)	218	61/367 (16.6%)	73	101/1108 (9.1%)	116
Male Reproductive Tract Infections	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	2
Pseudomonal Infections	2/1257 (0.2%)	2	0/367 (0%)	0	1/1108 (0.1%)	1
Respiratory Syncytial Viral Infections	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Salmonella Infections	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Sepsis, Bacteraemia, Viraemia And Fungaemia	113/1257 (9%)	133	35/367 (9.5%)	37	82/1108 (7.4%)	87
Skin Structures And Soft Tissue Infections	1/1257 (0.1%)	1	0/367 (0%)	0	2/1108 (0.2%)	2
Staphylococcal Infections	15/1257 (1.2%)	17	4/367 (1.1%)	5	8/1108 (0.7%)	8
Streptococcal Infections	1/1257 (0.1%)	1	2/367 (0.5%)	2	5/1108 (0.5%)	5
Upper Respiratory Tract Infections	8/1257 (0.6%)	8	0/367 (0%)	0	7/1108 (0.6%)	7
Urinary Tract Infections	112/1257 (8.9%)	132	25/367 (6.8%)	32	58/1108 (5.2%)	67
Vascular Infections	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Viral Infections	6/1257 (0.5%)	6	3/367 (0.8%)	3	2/1108 (0.2%)	2
Injury, poisoning and procedural complications
Abdominal Injuries	1/1257 (0.1%)	1	0/367 (0%)	0	2/1108 (0.2%)	2
Cardiac And Vascular Procedural Complications	37/1257 (2.9%)	38	7/367 (1.9%)	7	27/1108 (2.4%)	27
Cardiovascular Injuries	9/1257 (0.7%)	9	3/367 (0.8%)	3	3/1108 (0.3%)	3
Cerebral Injuries	16/1257 (1.3%)	17	4/367 (1.1%)	5	11/1108 (1%)	13
Chest And Lung Injuries	3/1257 (0.2%)	3	0/367 (0%)	0	2/1108 (0.2%)	2
Ear Injuries	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Eye Injuries	3/1257 (0.2%)	3	0/367 (0%)	0	0/1108 (0%)	0
Fractures And Dislocations	7/1257 (0.6%)	8	0/367 (0%)	0	1/1108 (0.1%)	1
Gastrointestinal And Hepatobiliary Procedural Complications	1/1257 (0.1%)	1	2/367 (0.5%)	2	0/1108 (0%)	0
Limb Injuries (Incl Traumatic Amputation)	3/1257 (0.2%)	3	1/367 (0.3%)	1	5/1108 (0.5%)	5
Lower Limb Fractures And Dislocations	69/1257 (5.5%)	73	9/367 (2.5%)	9	28/1108 (2.5%)	28
Muscle, Tendon And Ligament Injuries	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Nerve Injuries	0/1257 (0%)	0	1/367 (0.3%)	1	0/1108 (0%)	0
Neurological And Psychiatric Procedural Complications	1/1257 (0.1%)	1	1/367 (0.3%)	1	0/1108 (0%)	0
Non-Site Specific Injuries	63/1257 (5%)	67	16/367 (4.4%)	16	48/1108 (4.3%)	51
Non-Site Specific Procedural Complications	78/1257 (6.2%)	82	25/367 (6.8%)	29	52/1108 (4.7%)	54
Overdoses	1/1257 (0.1%)	1	1/367 (0.3%)	1	1/1108 (0.1%)	1
Pelvic Fractures And Dislocations	9/1257 (0.7%)	9	0/367 (0%)	0	4/1108 (0.4%)	4
Poisoning And Toxicity	4/1257 (0.3%)	4	3/367 (0.8%)	3	5/1108 (0.5%)	5
Renal And Urinary Tract Injuries	0/1257 (0%)	0	0/367 (0%)	0	2/1108 (0.2%)	2
Respiratory Tract And Thoracic Cavity Procedural Complications	1/1257 (0.1%)	1	1/367 (0.3%)	1	2/1108 (0.2%)	2
Site Specific Injuries	8/1257 (0.6%)	8	1/367 (0.3%)	1	5/1108 (0.5%)	5
Skin Injuries	21/1257 (1.7%)	24	6/367 (1.6%)	8	12/1108 (1.1%)	13
Skull Fractures, Facial Bone Fractures And Dislocations	1/1257 (0.1%)	1	1/367 (0.3%)	1	2/1108 (0.2%)	2
Spinal Fractures And Dislocations	18/1257 (1.4%)	18	1/367 (0.3%)	1	7/1108 (0.6%)	9
Thermal Burns	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Thoracic Cage Fractures And Dislocations	5/1257 (0.4%)	5	1/367 (0.3%)	1	3/1108 (0.3%)	3
Transfusion Related Complications	2/1257 (0.2%)	2	0/367 (0%)	0	1/1108 (0.1%)	1
Upper Limb Fractures And Dislocations	11/1257 (0.9%)	13	3/367 (0.8%)	3	12/1108 (1.1%)	14
Urinary Tract Procedural Complications	0/1257 (0%)	0	1/367 (0.3%)	1	0/1108 (0%)	0
Investigations
Blood Counts	7/1257 (0.6%)	7	0/367 (0%)	0	4/1108 (0.4%)	4
Blood Gas And Acid Base Analyses	6/1257 (0.5%)	6	7/367 (1.9%)	7	1/1108 (0.1%)	1
Carbohydrate Tolerance Analyses (Incl Diabetes)	1/1257 (0.1%)	1	1/367 (0.3%)	1	7/1108 (0.6%)	7
Cardiac Function Diagnostic Procedures	16/1257 (1.3%)	16	4/367 (1.1%)	4	17/1108 (1.5%)	17
Coagulation And Bleeding Analyses	22/1257 (1.8%)	22	6/367 (1.6%)	6	14/1108 (1.3%)	17
Ecg Investigations	3/1257 (0.2%)	3	3/367 (0.8%)	3	1/1108 (0.1%)	1
Faecal Analyses	2/1257 (0.2%)	2	1/367 (0.3%)	1	1/1108 (0.1%)	1
Heart Rate And Pulse Investigations	4/1257 (0.3%)	4	0/367 (0%)	0	2/1108 (0.2%)	2
Hepatobiliary Histopathology Procedures	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Liver Function Analyses	2/1257 (0.2%)	2	2/367 (0.5%)	2	1/1108 (0.1%)	1
Metabolism Tests	0/1257 (0%)	0	1/367 (0.3%)	1	1/1108 (0.1%)	1
Mineral And Electrolyte Analyses	1/1257 (0.1%)	1	0/367 (0%)	0	3/1108 (0.3%)	4
Musculoskeletal And Soft Tissue Histopathology Procedures	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Physical Examination Procedures	3/1257 (0.2%)	3	2/367 (0.5%)	2	0/1108 (0%)	0
Platelet Analyses	3/1257 (0.2%)	3	1/367 (0.3%)	1	0/1108 (0%)	0
Protein Analyses	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Red Blood Cell Analyses	11/1257 (0.9%)	12	5/367 (1.4%)	5	8/1108 (0.7%)	9
Renal Function Analyses	10/1257 (0.8%)	10	1/367 (0.3%)	1	5/1108 (0.5%)	5
Respiratory And Pulmonary Function Diagnostic Procedures	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Respiratory Tract And Thoracic Imaging Procedures	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Skeletal And Cardiac Muscle Analyses	9/1257 (0.7%)	10	3/367 (0.8%)	3	5/1108 (0.5%)	5
Urinalysis	1/1257 (0.1%)	1	0/367 (0%)	0	2/1108 (0.2%)	2
Urinary Tract Function Analyses	5/1257 (0.4%)	5	2/367 (0.5%)	2	5/1108 (0.5%)	5
Vascular Auscultatory Investigations	3/1257 (0.2%)	3	0/367 (0%)	0	0/1108 (0%)	0
Vascular Tests (Incl Blood Pressure)	8/1257 (0.6%)	9	1/367 (0.3%)	1	2/1108 (0.2%)	2
White Blood Cell Analyses	4/1257 (0.3%)	4	0/367 (0%)	0	2/1108 (0.2%)	2
Metabolism and nutrition disorders
Appetite Disorders	3/1257 (0.2%)	3	1/367 (0.3%)	1	0/1108 (0%)	0
Calcium Metabolism Disorders	1/1257 (0.1%)	3	2/367 (0.5%)	2	3/1108 (0.3%)	3
Chloride Imbalance	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Diabetes Mellitus (Incl Subtypes)	4/1257 (0.3%)	4	2/367 (0.5%)	3	4/1108 (0.4%)	4
Diabetic Complications	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Disorders Of Purine Metabolism	6/1257 (0.5%)	7	0/367 (0%)	0	8/1108 (0.7%)	9
Electrolyte Imbalance	12/1257 (1%)	12	3/367 (0.8%)	3	4/1108 (0.4%)	4
General Nutritional Disorders	31/1257 (2.5%)	32	12/367 (3.3%)	12	10/1108 (0.9%)	10
Hyperglycaemic Conditions	18/1257 (1.4%)	20	8/367 (2.2%)	8	15/1108 (1.4%)	15
Hypoglycaemic Conditions	13/1257 (1%)	13	9/367 (2.5%)	10	8/1108 (0.7%)	8
Magnesium Metabolism Disorders	0/1257 (0%)	0	3/367 (0.8%)	3	2/1108 (0.2%)	2
Metabolic Acidoses (Excl Diabetic Acidoses)	6/1257 (0.5%)	6	2/367 (0.5%)	2	4/1108 (0.4%)	4
Metabolic Alkaloses	0/1257 (0%)	0	1/367 (0.3%)	1	2/1108 (0.2%)	2
Mixed Acid-Base Disorders	1/1257 (0.1%)	1	1/367 (0.3%)	1	3/1108 (0.3%)	3
Phosphorus Metabolism Disorders	2/1257 (0.2%)	2	0/367 (0%)	0	1/1108 (0.1%)	1
Potassium Imbalance	34/1257 (2.7%)	37	10/367 (2.7%)	12	25/1108 (2.3%)	26
Protein Metabolism Disorders	2/1257 (0.2%)	2	0/367 (0%)	0	0/1108 (0%)	0
Sodium Imbalance	21/1257 (1.7%)	23	2/367 (0.5%)	2	20/1108 (1.8%)	23
Musculoskeletal and connective tissue disorders
Arthropathies	3/1257 (0.2%)	3	0/367 (0%)	0	3/1108 (0.3%)	3
Bone Disorders	2/1257 (0.2%)	2	0/367 (0%)	0	0/1108 (0%)	0
Bursal Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Connective Tissue Disorders (Excl Le)	2/1257 (0.2%)	2	0/367 (0%)	0	1/1108 (0.1%)	1
Crystal Arthropathic Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Extremity Deformities	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Joint Related Disorders	2/1257 (0.2%)	3	0/367 (0%)	0	0/1108 (0%)	0
Joint Related Signs And Symptoms	10/1257 (0.8%)	10	3/367 (0.8%)	3	9/1108 (0.8%)	9
Muscle Infections And Inflammations	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Muscle Pains	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Muscle Related Signs And Symptoms	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Muscle Weakness Conditions	8/1257 (0.6%)	8	4/367 (1.1%)	4	5/1108 (0.5%)	5
Musculoskeletal And Connective Tissue Pain And Discomfort	38/1257 (3%)	43	8/367 (2.2%)	8	23/1108 (2.1%)	25
Musculoskeletal And Connective Tissue Signs And Symptoms	1/1257 (0.1%)	1	0/367 (0%)	0	2/1108 (0.2%)	2
Myopathies	3/1257 (0.2%)	3	2/367 (0.5%)	2	3/1108 (0.3%)	3
Osteoarthropathies	6/1257 (0.5%)	8	1/367 (0.3%)	1	13/1108 (1.2%)	15
Rheumatoid Arthropathies	1/1257 (0.1%)	2	1/367 (0.3%)	1	0/1108 (0%)	0
Soft Tissue Disorders	2/1257 (0.2%)	2	0/367 (0%)	0	3/1108 (0.3%)	3
Spine And Neck Deformities	1/1257 (0.1%)	1	0/367 (0%)	0	2/1108 (0.2%)	2
Tendon Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-Cell Lymphomas	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Bile Duct Neoplasms Malignant	0/1257 (0%)	0	1/367 (0.3%)	1	0/1108 (0%)	0
Bladder Neoplasms Malignant	5/1257 (0.4%)	5	1/367 (0.3%)	1	1/1108 (0.1%)	1
Bone Neoplasms Malignant (Excl Sarcomas)	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Breast And Nipple Neoplasms Malignant	5/1257 (0.4%)	5	0/367 (0%)	0	2/1108 (0.2%)	2
Burkitt's Lymphomas	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Cardiovascular Neoplasms Benign	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Central Nervous System Neoplasms Malignant	1/1257 (0.1%)	1	0/367 (0%)	0	2/1108 (0.2%)	2
Colonic Neoplasms Malignant	6/1257 (0.5%)	6	0/367 (0%)	0	4/1108 (0.4%)	4
Hepatic Neoplasms Malignant	1/1257 (0.1%)	1	1/367 (0.3%)	1	0/1108 (0%)	0
Leiomyosarcomas	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Leukaemias Acute Myeloid	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Leukaemias Chronic Lymphocytic	1/1257 (0.1%)	1	1/367 (0.3%)	1	2/1108 (0.2%)	2
Leukaemias	0/1257 (0%)	0	0/367 (0%)	0	2/1108 (0.2%)	2
Lip And Oral Cavity Neoplasms Malignant	2/1257 (0.2%)	2	0/367 (0%)	0	0/1108 (0%)	0
Lymphomas Unspecified	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Mantle Cell Lymphomas	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Metastases To Specified Sites	0/1257 (0%)	0	0/367 (0%)	0	2/1108 (0.2%)	2
Multiple Myelomas	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Myelodysplastic Syndromes	0/1257 (0%)	0	2/367 (0.5%)	3	4/1108 (0.4%)	4
Myeloproliferative Disorders (Excl Leukaemias)	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Neoplasms Malignant Site Unspecified	9/1257 (0.7%)	9	3/367 (0.8%)	3	6/1108 (0.5%)	6
Nervous System Neoplasms Unspecified Malignancy	1/1257 (0.1%)	1	1/367 (0.3%)	1	1/1108 (0.1%)	1
Non-Small Cell Neoplasms Malignant Of The Respiratory Tract Cell Type Specified	0/1257 (0%)	0	2/367 (0.5%)	2	0/1108 (0%)	0
Oesophageal Neoplasms Malignant	1/1257 (0.1%)	1	1/367 (0.3%)	1	1/1108 (0.1%)	1
Oncologic Complications And Emergencies	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Pancreatic Neoplasms Malignant (Excl Islet Cell And Carcinoid)	0/1257 (0%)	0	2/367 (0.5%)	2	3/1108 (0.3%)	3
Prostatic Neoplasms Malignant	4/1257 (0.3%)	4	1/367 (0.3%)	1	2/1108 (0.2%)	2
Rectal Neoplasms Malignant	2/1257 (0.2%)	2	0/367 (0%)	0	0/1108 (0%)	0
Renal Neoplasms Malignant	2/1257 (0.2%)	2	1/367 (0.3%)	1	2/1108 (0.2%)	2
Respiratory Tract And Pleural Neoplasms Malignant Cell Type Unspecified	6/1257 (0.5%)	7	7/367 (1.9%)	7	2/1108 (0.2%)	2
Skin Melanomas (Excl Ocular)	1/1257 (0.1%)	1	1/367 (0.3%)	1	0/1108 (0%)	0
Skin Neoplasms Benign	1/1257 (0.1%)	2	0/367 (0%)	0	0/1108 (0%)	0
Skin Neoplasms Malignant And Unspecified (Excl Melanoma)	6/1257 (0.5%)	6	0/367 (0%)	0	3/1108 (0.3%)	3
Small Intestinal Neoplasms Malignant	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Soft Tissue Sarcomas Histology Unspecified	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Thyroid Neoplasms Malignant	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Urinary Tract Neoplasms Malignant	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Uterine Neoplasms Benign	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Uterine Neoplasms Malignant	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Vulval Neoplasms Malignant	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Nervous system disorders
Acute Polyneuropathies	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Alzheimer's Disease (Incl Subtypes)	1/1257 (0.1%)	1	2/367 (0.5%)	2	0/1108 (0%)	0
Autonomic Nervous System Disorders	1/1257 (0.1%)	2	0/367 (0%)	0	0/1108 (0%)	0
Central Nervous System Aneurysms	1/1257 (0.1%)	1	1/367 (0.3%)	1	1/1108 (0.1%)	1
Central Nervous System Haemorrhages And Cerebrovascular Accidents	98/1257 (7.8%)	105	30/367 (8.2%)	33	79/1108 (7.1%)	86
Central Nervous System Vascular Disorders	10/1257 (0.8%)	11	2/367 (0.5%)	3	7/1108 (0.6%)	7
Cerebellar Coordination And Balance Disturbances	3/1257 (0.2%)	3	0/367 (0%)	0	1/1108 (0.1%)	1
Coma States	0/1257 (0%)	0	1/367 (0.3%)	1	1/1108 (0.1%)	1
Cortical Dysfunction	1/1257 (0.1%)	1	1/367 (0.3%)	1	1/1108 (0.1%)	1
Dementia (Excl Alzheimer's Type)	5/1257 (0.4%)	5	0/367 (0%)	0	5/1108 (0.5%)	5
Disturbances In Consciousness	42/1257 (3.3%)	46	13/367 (3.5%)	14	32/1108 (2.9%)	33
Dyskinesias And Movement Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Encephalopathies	27/1257 (2.1%)	29	8/367 (2.2%)	8	13/1108 (1.2%)	13
Encephalopathies Toxic And Metabolic	22/1257 (1.8%)	22	1/367 (0.3%)	1	14/1108 (1.3%)	14
Facial Cranial Nerve Disorders	2/1257 (0.2%)	2	0/367 (0%)	0	2/1108 (0.2%)	2
Generalised Tonic-Clonic Seizures	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Headaches	10/1257 (0.8%)	10	1/367 (0.3%)	1	8/1108 (0.7%)	9
Hydrocephalic Conditions	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Lumbar Spinal Cord And Nerve Root Disorders	2/1257 (0.2%)	2	1/367 (0.3%)	1	1/1108 (0.1%)	1
Memory Loss (Excl Dementia)	2/1257 (0.2%)	2	0/367 (0%)	0	1/1108 (0.1%)	1
Mental Impairment (Excl Dementia And Memory Loss)	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Mononeuropathies	2/1257 (0.2%)	2	2/367 (0.5%)	2	0/1108 (0%)	0
Motor Neurone Diseases	0/1257 (0%)	0	1/367 (0.3%)	1	0/1108 (0%)	0
Multiple Sclerosis Acute And Progressive	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Myelitis (Incl Infective)	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Nervous System Disorders	0/1257 (0%)	0	1/367 (0.3%)	1	0/1108 (0%)	0
Neurological Signs And Symptoms	32/1257 (2.5%)	34	6/367 (1.6%)	6	18/1108 (1.6%)	19
Neuromuscular Junction Dysfunction	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Paralysis And Paresis (Excl Cranial Nerve)	1/1257 (0.1%)	1	1/367 (0.3%)	1	4/1108 (0.4%)	4
Parkinson's Disease And Parkinsonism	3/1257 (0.2%)	4	0/367 (0%)	0	1/1108 (0.1%)	1
Peripheral Neuropathies	2/1257 (0.2%)	2	0/367 (0%)	0	1/1108 (0.1%)	1
Seizures And Seizure Disorders	12/1257 (1%)	18	3/367 (0.8%)	3	5/1108 (0.5%)	5
Sensory Abnormalities	3/1257 (0.2%)	3	0/367 (0%)	0	5/1108 (0.5%)	5
Speech And Language Abnormalities	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Spinal Cord And Nerve Root Disorders	1/1257 (0.1%)	1	1/367 (0.3%)	1	1/1108 (0.1%)	1
Structural Brain Disorders	3/1257 (0.2%)	3	0/367 (0%)	0	1/1108 (0.1%)	1
Transient Cerebrovascular Events	30/1257 (2.4%)	34	5/367 (1.4%)	6	24/1108 (2.2%)	27
Tremor (Excl Congenital)	0/1257 (0%)	0	0/367 (0%)	0	2/1108 (0.2%)	2
Trigeminal Disorders	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Vagus Nerve Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Psychiatric disorders
Abnormal Behaviour	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Anxiety Disorders	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Anxiety Symptoms	8/1257 (0.6%)	10	4/367 (1.1%)	4	10/1108 (0.9%)	11
Behaviour And Socialisation Disturbances	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Bipolar Disorders	0/1257 (0%)	0	1/367 (0.3%)	1	0/1108 (0%)	0
Confusion And Disorientation	24/1257 (1.9%)	24	10/367 (2.7%)	10	20/1108 (1.8%)	20
Deliria	14/1257 (1.1%)	14	1/367 (0.3%)	1	9/1108 (0.8%)	9
Delusional Symptoms	0/1257 (0%)	0	0/367 (0%)	0	2/1108 (0.2%)	2
Depressive Disorders	6/1257 (0.5%)	6	1/367 (0.3%)	1	4/1108 (0.4%)	4
Disturbances In Initiating And Maintaining Sleep	1/1257 (0.1%)	1	0/367 (0%)	0	2/1108 (0.2%)	2
Eating Disorders	0/1257 (0%)	0	2/367 (0.5%)	2	0/1108 (0%)	0
Mental Disorders	56/1257 (4.5%)	64	19/367 (5.2%)	21	29/1108 (2.6%)	29
Panic Attacks And Disorders	0/1257 (0%)	0	0/367 (0%)	0	2/1108 (0.2%)	2
Perception Disturbances	2/1257 (0.2%)	2	0/367 (0%)	0	0/1108 (0%)	0
Psychiatric Symptoms	0/1257 (0%)	0	1/367 (0.3%)	1	0/1108 (0%)	0
Psychotic Disorder	1/1257 (0.1%)	1	0/367 (0%)	0	2/1108 (0.2%)	2
Speech Articulation And Rhythm Disturbances	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Stress Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Substance-Related Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Suicidal And Self-Injurious Behaviour	3/1257 (0.2%)	3	0/367 (0%)	0	1/1108 (0.1%)	1
Renal and urinary disorders
Bladder And Urethral Symptoms	51/1257 (4.1%)	57	6/367 (1.6%)	8	48/1108 (4.3%)	49
Bladder Disorders	0/1257 (0%)	0	0/367 (0%)	0	4/1108 (0.4%)	4
Genital And Urinary Tract Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Myoneurogenic Bladder Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Nephropathies And Tubular Disorders	3/1257 (0.2%)	3	0/367 (0%)	0	2/1108 (0.2%)	2
Renal Disorders	0/1257 (0%)	0	1/367 (0.3%)	1	1/1108 (0.1%)	1
Renal Failure And Impairment	208/1257 (16.5%)	263	76/367 (20.7%)	94	154/1108 (13.9%)	181
Renal Failure Complications	2/1257 (0.2%)	2	1/367 (0.3%)	1	1/1108 (0.1%)	1
Renal Lithiasis	2/1257 (0.2%)	2	0/367 (0%)	0	6/1108 (0.5%)	7
Renal Neoplasms	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Renal Obstructive Disorders	4/1257 (0.3%)	4	1/367 (0.3%)	1	0/1108 (0%)	0
Renal Vascular And Ischaemic Conditions	2/1257 (0.2%)	2	1/367 (0.3%)	1	4/1108 (0.4%)	4
Structural And Obstructive Urethral Disorders (Excl Congenital)	1/1257 (0.1%)	1	0/367 (0%)	0	3/1108 (0.3%)	3
Ureteric Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Urinary Abnormalities	29/1257 (2.3%)	33	9/367 (2.5%)	9	29/1108 (2.6%)	36
Urinary Tract Lithiasis (Excl Renal)	0/1257 (0%)	0	0/367 (0%)	0	2/1108 (0.2%)	2
Reproductive system and breast disorders
Breast Disorders	2/1257 (0.2%)	2	1/367 (0.3%)	1	0/1108 (0%)	0
Cervix Disorders	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Ovarian And Fallopian Tube Cysts And Neoplasms	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Pelvis And Broad Ligament Disorders	0/1257 (0%)	0	1/367 (0.3%)	1	1/1108 (0.1%)	1
Penile And Scrotal Infections And Inflammations	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Penile Disorders (Excl Erection And Ejaculation)	2/1257 (0.2%)	2	0/367 (0%)	0	0/1108 (0%)	0
Prostatic Neoplasms And Hypertrophy	4/1257 (0.3%)	4	1/367 (0.3%)	1	2/1108 (0.2%)	2
Prostatic Signs, Symptoms And Disorders	2/1257 (0.2%)	2	0/367 (0%)	0	0/1108 (0%)	0
Reproductive Tract Signs And Symptoms	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Scrotal Disorders	3/1257 (0.2%)	3	0/367 (0%)	0	1/1108 (0.1%)	1
Testicular And Epididymal Disorders	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Vulvovaginal Disorders	1/1257 (0.1%)	1	1/367 (0.3%)	1	0/1108 (0%)	0
Vulvovaginal Signs And Symptoms	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Respiratory, thoracic and mediastinal disorders
Breathing Abnormalities	101/1257 (8%)	121	31/367 (8.4%)	39	66/1108 (6%)	76
Bronchial Conditions	3/1257 (0.2%)	3	0/367 (0%)	0	1/1108 (0.1%)	2
Bronchospasm And Obstruction	55/1257 (4.4%)	94	26/367 (7.1%)	40	35/1108 (3.2%)	42
Conditions Associated With Abnormal Gas Exchange	25/1257 (2%)	26	11/367 (3%)	12	22/1108 (2%)	23
Coughing And Associated Symptoms	18/1257 (1.4%)	20	6/367 (1.6%)	7	6/1108 (0.5%)	6
Diaphragmatic Disorders	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Laryngeal And Adjacent Sites Disorders (Excl Infections And Neoplasms)	2/1257 (0.2%)	2	0/367 (0%)	0	0/1108 (0%)	0
Laryngeal Spasm, Oedema And Obstruction	2/1257 (0.2%)	2	0/367 (0%)	0	0/1108 (0%)	0
Lower Respiratory Tract Inflammatory And Immunologic Conditions	34/1257 (2.7%)	37	6/367 (1.6%)	7	14/1108 (1.3%)	15
Lower Respiratory Tract Signs And Symptoms	4/1257 (0.3%)	4	1/367 (0.3%)	1	1/1108 (0.1%)	1
Mediastinal Disorders	2/1257 (0.2%)	2	6/367 (1.6%)	6	1/1108 (0.1%)	1
Nasal Disorders	17/1257 (1.4%)	20	11/367 (3%)	12	14/1108 (1.3%)	15
Parenchymal Lung Disorders	13/1257 (1%)	14	4/367 (1.1%)	4	10/1108 (0.9%)	10
Pharyngeal Disorders (Excl Infections And Neoplasms)	3/1257 (0.2%)	3	0/367 (0%)	0	1/1108 (0.1%)	1
Pleural Conditions	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Pneumothorax And Pleural Effusions	106/1257 (8.4%)	137	70/367 (19.1%)	91	75/1108 (6.8%)	92
Pulmonary Hypertensions	7/1257 (0.6%)	7	3/367 (0.8%)	3	8/1108 (0.7%)	9
Pulmonary Oedemas	31/1257 (2.5%)	34	17/367 (4.6%)	17	35/1108 (3.2%)	40
Pulmonary Thrombotic And Embolic Conditions	9/1257 (0.7%)	9	4/367 (1.1%)	5	11/1108 (1%)	11
Respiratory Failures (Excl Neonatal)	149/1257 (11.9%)	192	66/367 (18%)	77	108/1108 (9.7%)	126
Respiratory Tract Disorders	4/1257 (0.3%)	4	3/367 (0.8%)	3	1/1108 (0.1%)	1
Upper Respiratory Tract Signs And Symptoms	0/1257 (0%)	0	1/367 (0.3%)	1	1/1108 (0.1%)	1
Skin and subcutaneous tissue disorders
Bullous Conditions	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Dermal And Epidermal Conditions	7/1257 (0.6%)	7	2/367 (0.5%)	2	2/1108 (0.2%)	2
Dermatitis And Eczema	0/1257 (0%)	0	2/367 (0.5%)	2	0/1108 (0%)	0
Erythemas	2/1257 (0.2%)	2	0/367 (0%)	0	2/1108 (0.2%)	2
Exfoliative Conditions	0/1257 (0%)	0	1/367 (0.3%)	1	0/1108 (0%)	0
Hyperkeratoses	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Nail And Nail Bed Conditions (Excl Infections And Infestations)	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Pruritus	0/1257 (0%)	0	1/367 (0.3%)	1	1/1108 (0.1%)	1
Purpura And Related Conditions	2/1257 (0.2%)	2	1/367 (0.3%)	1	0/1108 (0%)	0
Rashes, Eruptions And Exanthems	2/1257 (0.2%)	2	1/367 (0.3%)	1	3/1108 (0.3%)	3
Skin And Subcutaneous Conditions	0/1257 (0%)	0	1/367 (0.3%)	1	0/1108 (0%)	0
Skin And Subcutaneous Tissue Ulcerations	9/1257 (0.7%)	10	2/367 (0.5%)	2	7/1108 (0.6%)	7
Skin Injuries And Mechanical Dermatoses	5/1257 (0.4%)	5	3/367 (0.8%)	3	1/1108 (0.1%)	1
Skin Preneoplastic Conditions	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Skin Vasculitides	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Skin Vasomotor Conditions	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Surgical and medical procedures
Arterial Therapeutic Procedures (Excl Aortic)	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Cardiac Device Therapeutic Procedures	8/1257 (0.6%)	8	2/367 (0.5%)	2	3/1108 (0.3%)	3
Haematological Therapeutic Procedures	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Joint Therapeutic Procedures	5/1257 (0.4%)	5	1/367 (0.3%)	1	1/1108 (0.1%)	1
Large Intestine Therapeutic Procedures	0/1257 (0%)	0	0/367 (0%)	0	2/1108 (0.2%)	2
Lens Therapeutic Procedures	2/1257 (0.2%)	2	0/367 (0%)	0	0/1108 (0%)	0
Prostatic Therapeutic Procedures	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Renal Therapeutic Procedures	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Therapeutic Bladder Catheterisation	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Therapeutic Procedures	20/1257 (1.6%)	22	1/367 (0.3%)	1	11/1108 (1%)	11
Tracheal Therapeutic Procedures	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Venous Therapeutic Procedures	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Vascular disorders
Accelerated And Malignant Hypertension	13/1257 (1%)	13	2/367 (0.5%)	2	13/1108 (1.2%)	13
Aneurysms And Dissections Non-Site Specific	5/1257 (0.4%)	5	2/367 (0.5%)	2	6/1108 (0.5%)	6
Aortic Aneurysms And Dissections	8/1257 (0.6%)	9	6/367 (1.6%)	6	5/1108 (0.5%)	5
Aortic Embolism And Thrombosis	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Aortic Necrosis And Vascular Insufficiency	3/1257 (0.2%)	3	1/367 (0.3%)	1	1/1108 (0.1%)	1
Arterial And Aortic Injuries	11/1257 (0.9%)	11	0/367 (0%)	0	10/1108 (0.9%)	11
Arterial Inflammations	1/1257 (0.1%)	1	0/367 (0%)	0	0/1108 (0%)	0
Blood Pressure Disorders	4/1257 (0.3%)	4	1/367 (0.3%)	1	3/1108 (0.3%)	3
Circulatory Collapse And Shock	7/1257 (0.6%)	7	4/367 (1.1%)	4	4/1108 (0.4%)	4
Haemorrhages	43/1257 (3.4%)	43	16/367 (4.4%)	16	33/1108 (3%)	34
Lymphangiopathies	1/1257 (0.1%)	1	1/367 (0.3%)	1	2/1108 (0.2%)	2
Lymphoedemas	2/1257 (0.2%)	2	0/367 (0%)	0	1/1108 (0.1%)	1
Non-Site Specific Embolism And Thrombosis	9/1257 (0.7%)	10	4/367 (1.1%)	4	7/1108 (0.6%)	7
Non-Site Specific Necrosis And Vascular Insufficiency	6/1257 (0.5%)	6	1/367 (0.3%)	1	4/1108 (0.4%)	5
Non-Site Specific Vascular Disorders	16/1257 (1.3%)	16	10/367 (2.7%)	10	12/1108 (1.1%)	12
Peripheral Aneurysms And Dissections	24/1257 (1.9%)	24	2/367 (0.5%)	2	11/1108 (1%)	11
Peripheral Embolism And Thrombosis	20/1257 (1.6%)	20	8/367 (2.2%)	8	17/1108 (1.5%)	19
Peripheral Vascular Disorders	5/1257 (0.4%)	6	5/367 (1.4%)	8	6/1108 (0.5%)	6
Peripheral Vasoconstriction, Necrosis And Vascular Insufficiency	35/1257 (2.8%)	37	16/367 (4.4%)	17	41/1108 (3.7%)	44
Phlebitis	0/1257 (0%)	0	0/367 (0%)	0	1/1108 (0.1%)	1
Site Specific Necrosis And Vascular Insufficiency	1/1257 (0.1%)	1	0/367 (0%)	0	1/1108 (0.1%)	1
Site Specific Vascular Disorders	3/1257 (0.2%)	3	1/367 (0.3%)	1	1/1108 (0.1%)	2
Vascular Hypertensive Disorders	54/1257 (4.3%)	60	22/367 (6%)	23	53/1108 (4.8%)	57
Vascular Hypotensive Disorders	137/1257 (10.9%)	157	50/367 (13.6%)	52	90/1108 (8.1%)	93
Vascular Malformations And Acquired Anomalies	2/1257 (0.2%)	2	0/367 (0%)	0	1/1108 (0.1%)	1
Other (Not Including 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	1097/1257 (87.3%)		327/367 (89.1%)		1001/1108 (90.3%)
Blood and lymphatic system disorders
Anaemias	244/1257 (19.4%)	259	92/367 (25.1%)	96	260/1108 (23.5%)	267
Leukocytoses	82/1257 (6.5%)	88	38/367 (10.4%)	40	79/1108 (7.1%)	81
Thrombocytopenias	175/1257 (13.9%)	182	70/367 (19.1%)	74	217/1108 (19.6%)	223
Cardiac disorders
Cardiac Conduction Disorders	286/1257 (22.8%)	335	56/367 (15.3%)	65	331/1108 (29.9%)	387
Heart Failures	96/1257 (7.6%)	107	30/367 (8.2%)	31	68/1108 (6.1%)	74
Rate And Rhythm Disorders	85/1257 (6.8%)	92	28/367 (7.6%)	30	99/1108 (8.9%)	105
Supraventricular Arrhythmias	153/1257 (12.2%)	174	72/367 (19.6%)	81	159/1108 (14.4%)	186
Ventricular Arrhythmias And Cardiac Arrest	64/1257 (5.1%)	69	15/367 (4.1%)	16	66/1108 (6%)	69
Gastrointestinal disorders
Gastrointestinal Atonic And Hypomotility Disorders	66/1257 (5.3%)	70	27/367 (7.4%)	27	74/1108 (6.7%)	78
Nausea And Vomiting Symptoms	57/1257 (4.5%)	61	19/367 (5.2%)	22	45/1108 (4.1%)	51
General disorders
Asthenic Conditions	57/1257 (4.5%)	63	23/367 (6.3%)	25	43/1108 (3.9%)	44
Febrile Disorders	75/1257 (6%)	77	24/367 (6.5%)	25	69/1108 (6.2%)	71
Oedema	93/1257 (7.4%)	102	17/367 (4.6%)	17	85/1108 (7.7%)	95
Pain And Discomfort	72/1257 (5.7%)	86	22/367 (6%)	29	71/1108 (6.4%)	84
Infections and infestations
Lower Respiratory Tract And Lung Infections	67/1257 (5.3%)	75	22/367 (6%)	22	55/1108 (5%)	58
Urinary Tract Infections	149/1257 (11.9%)	182	45/367 (12.3%)	46	141/1108 (12.7%)	164
Injury, poisoning and procedural complications
Non-Site Specific Injuries	86/1257 (6.8%)	93	16/367 (4.4%)	19	68/1108 (6.1%)	77
Non-Site Specific Procedural Complications	74/1257 (5.9%)	80	25/367 (6.8%)	27	87/1108 (7.9%)	92
Investigations
Skeletal And Cardiac Muscle Analyses	52/1257 (4.1%)	54	25/367 (6.8%)	26	42/1108 (3.8%)	43
Metabolism and nutrition disorders
Hyperglycaemic Conditions	33/1257 (2.6%)	34	27/367 (7.4%)	27	46/1108 (4.2%)	46
Magnesium Metabolism Disorders	25/1257 (2%)	25	12/367 (3.3%)	14	64/1108 (5.8%)	65
Potassium Imbalance	84/1257 (6.7%)	96	34/367 (9.3%)	35	87/1108 (7.9%)	99
Sodium Imbalance	61/1257 (4.9%)	68	28/367 (7.6%)	29	58/1108 (5.2%)	63
Musculoskeletal and connective tissue disorders
Musculoskeletal And Connective Tissue Pain And Discomfort	89/1257 (7.1%)	100	29/367 (7.9%)	33	99/1108 (8.9%)	108
Psychiatric disorders
Confusion And Disorientation	57/1257 (4.5%)	59	24/367 (6.5%)	24	68/1108 (6.1%)	69
Renal and urinary disorders
Bladder And Urethral Symptoms	35/1257 (2.8%)	35	13/367 (3.5%)	13	57/1108 (5.1%)	60
Renal Failure And Impairment	165/1257 (13.1%)	199	58/367 (15.8%)	66	201/1108 (18.1%)	223
Respiratory, thoracic and mediastinal disorders
Breathing Abnormalities	77/1257 (6.1%)	81	16/367 (4.4%)	18	64/1108 (5.8%)	67
Parenchymal Lung Disorders	72/1257 (5.7%)	75	25/367 (6.8%)	25	94/1108 (8.5%)	98
Pneumothorax And Pleural Effusions	138/1257 (11%)	146	64/367 (17.4%)	73	168/1108 (15.2%)	187
Pulmonary Oedemas	68/1257 (5.4%)	70	14/367 (3.8%)	14	67/1108 (6%)	69
Vascular disorders
Haemorrhages	55/1257 (4.4%)	57	9/367 (2.5%)	9	61/1108 (5.5%)	62
Vascular Hypertensive Disorders	146/1257 (11.6%)	152	56/367 (15.3%)	58	192/1108 (17.3%)	206
Vascular Hypotensive Disorders	146/1257 (11.6%)	162	45/367 (12.3%)	49	120/1108 (10.8%)	131

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.