Safety and Efficacy Study of Lotus Valve for Transcatheter Aortic Valve Replacement (REPRISE III)

• ClinicalTrials.gov Identifier: NCT02202434
• Recruitment Status: Active, not recruiting
• First Posted: July 29, 2014
• Results First Posted: July 30, 2019
• Last Update Posted: July 15, 2020
• Sponsor: Boston Scientific Corporation
• Information provided by (Responsible Party): Boston Scientific Corporation

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Aortic Stenosis
• Interventions: Device: Lotus Valve System; Device: CoreValve/Evolut R Transcatheter Aortic Valve Replacement System; Device: LOTUS Edge Valve System
• Enrollment: 1425

Participant Flow

Recruitment Details	912 subjects randomized from 22Sep2014 to 24Dec2015. 102 subjects enrolled in the Roll-in cohort. 295 subjects enrolled in the US CAS from 25Feb2016 to 23Feb2017. Enrollment in the LOTUS Edge Valve System – Single-arm Edge Nested Reg is ongoing. Enrollment in the LOTUS Edge Valve System – Single-arm 29mm Reg and Roll-in Cohorts has not begun.
Pre-assignment Details	The non-randomized Roll-In phase with only the test device was for centers with no previous experience implanting the Lotus Valve System. Each performed at least two Roll-In cases before starting RCT. Only cohorts that have completed enrollment, reached primary endpoint and were submitted for regulatory approval are included in the Results Section

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Period Title: Overall Study
Started	607	305	102	295
Completed	498	236	87	258
Not Completed	109	69	15	37
Reason Not Completed
Death	70	39	13	27
Lost to Follow-up	1	1	1	0
Physician Decision	2	3	0	0
Withdrawal by Subject	13	14	1	4
Completed Study	1	0	0	0
Visit Missed	21	12	0	5
Other	1	0	0	1

Baseline Characteristics

Arm/Group Title		Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort	Total
Arm/Group Description		Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Total of all reporting groups
Overall Number of Baseline Participants		607	305	102	295	1309
Baseline Analysis Population Description		Data are reported separately for each cohort as pooled mean and standard deviations across cohorts do not provide meaningful data.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years	Number Analyzed	607 participants	305 participants	102 participants	295 participants	1309 participants
Lotus Valve System - Randomized		82.8 (7.1)	0 (0)	0 (0)	0 (0)	82.8 (7.1)
CoreValve TAVR System - Randomize		0 (0)	82.9 (7.6)	0 (0)	0 (0)	82.9 (7.6)
Lotus Valve System - Single-arm Roll-in Cohort		0 (0)	0 (0)	83.6 (6.9)	0 (0)	83.6 (6.9)
Lotus Valve System - Single-arm Continued Access		0 (0)	0 (0)	0 (0)	81.7 (6.6)	81.7 (6.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	607 participants	305 participants	102 participants	295 participants	1309 participants
	Female	304 50.1%	159 52.1%	52 51.0%	137 46.4%	652 49.8%
	Male	303 49.9%	146 47.9%	50 49.0%	158 53.6%	657 50.2%
Race/Ethnicity, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	607 participants	305 participants	102 participants	295 participants	1309 participants
American Indian or Alaska Native		1 0.2%	0 0.0%	1 1.0%	1 0.3%	3 0.2%
Asian		3 0.5%	2 0.7%	0 0.0%	4 1.4%	9 0.7%
Black, of African Heritage		17 2.8%	11 3.6%	4 3.9%	13 4.4%	45 3.4%
Caucasian		537 88.5%	271 88.9%	93 91.2%	271 91.9%	1172 89.5%
Hispanic or Latino		18 3.0%	2 0.7%	4 3.9%	6 2.0%	30 2.3%
Native Hawaiian or other Pacific Islander		2 0.3%	1 0.3%	0 0.0%	0 0.0%	3 0.2%
Other		3 0.5%	4 1.3%	0 0.0%	1 0.3%	8 0.6%
Unknown or Not Reported		28 4.6%	14 4.6%	1 1.0%	0 0.0%	43 3.3%
		[1] Measure Description: Subjects were allowed to select more than one option.
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	607 participants	305 participants	102 participants	295 participants	1309 participants
Canada		1	1	2	0	4
Netherlands		4	2	0	0	6
United States		531	261	100	295	1187
Australia		15	8	0	0	23
France		23	13	0	0	36
Germany		33	20	0	0	53
Society of Thoracic Surgeons (STS) Risk Score [1]; Mean (Standard Deviation); Unit of measure: Percent	Number Analyzed	607 participants	305 participants	102 participants	295 participants	1309 participants
Lotus Valve System - Randomized		6.7 (4.0)	0 (0)	0 (0)	0 (0)	6.7 (4.0)
CoreValve TAVR System - Randomized		0 (0)	6.9 (4.1)	0 (0)	0 (0)	6.9 (4.1)
Lotus Valve System - Single-arm Roll-in Cohort		0 (0)	0 (0)	7.0 (4.9)	0 (0)	7.0 (4.9)
Lotus Valve System - Single-arm Continued Access		0 (0)	0 (0)	0 (0)	5.4 (2.9)	5.4 (2.9)
		[1] Measure Description: The Society of Thoracic Surgeons Score is a risk model used to predict a subject’s risk of mortality and morbidities for the most commonly performed cardiac surgeries. The model is a percentage score from 0 to 100 where a lower score means a lower risk and higher score means a higher risk.
European System for Cardiac Operative Risk Evaluation (EuroSCORE) [1]; Mean (Standard Deviation); Unit of measure: Percent	Number Analyzed	607 participants	305 participants	102 participants	295 participants	1309 participants
Lotus Valve System - Randomized		6.4 (5.5)	0 (0)	0 (0)	0 (0)	6.4 (5.5)
CoreValve TAVR System - Randomized		0 (0)	6.4 (5.5)	0 (0)	0 (0)	6.4 (5.5)
Lotus Valve System - Single-arm Roll-in Cohort		0 (0)	0 (0)	6.4 (6.5)	0 (0)	6.4 (6.5)
Lotus Valve System - Single-arm Continued Access		0 (0)	0 (0)	0 (0)	5.3 (5.9)	5.3 (5.9)
		[1] Measure Description: The European System for Cardiac Operative Risk Evaluation is a risk model where if a risk factor is present in a subject, a weight or number is assigned. The weights are added to give an approximate percent predicted mortality. A higher score means a higher risk and a lower score means a lower risk.
New York Heart Association (NYHA) Classification [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	607 participants	305 participants	102 participants	295 participants	1309 participants
	NYHA I	0	0	0	0	0
	NYHA II	174	98	22	108	402
	NYHA III	386	186	70	171	813
	NYHA IV	47	21	10	16	94
		[1] Measure Description: New York Heart Association Classification is a system for defining cardiac disease and related functional limitations into four broad categorizations. The categories range from NYHA I (No limitations) to NYHA IV (inability to carry out any physical activity without discomfort).

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Events Included in the Primary Safety Endpoint
Description	Composite of all-cause mortality, stroke, life-threatening and major bleeding events, stage 2 or 3 acute kidney injury, or major vascular complications
Time Frame	30 days following procedure

Outcome Measure Data

Analysis Population Description

Implanted population - all subjects who sign an Informed Consent Form, are enrolled in the trial, and are implanted with the assigned, randomized study device. The Primary and Secondary Endpoints (Outcome Measures 1-3) are only applicable to the two Randomized arms of the study.

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	577	297
Measure Type: Number; Unit of Measure: Percent of participants
	20.3	17.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lotus Valve System - Randomized, CoreValve TAVR System - Randomized
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	10.5% non-inferiority margin
Statistical Test of Hypothesis	P-Value	0.0027
	Comments	[Not Specified]
	Method	Farrington-Manning
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	3.1
	Confidence Interval	(1-Sided) 97.5%; 8.32
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Percentage of Participants With Events Included in the Primary Effectiveness Endpoint
Description	Composite of all-cause mortality, disabling stroke, or moderate or greater paravalvular aortic regurgitation (based on core lab assessment).
Time Frame	1 year following procedure

Outcome Measure Data

Analysis Population Description

Non-inferiority analysis - Implanted population - all subjects who sign an Informed Consent Form, are enrolled in the trial, and are implanted with the assigned, randomized study device.

Superiority analysis - Intent to Treat Population The Primary and Secondary Endpoints (Outcome Measures 1-3) are only applicable to the two Randomized arms.

Arm/Group Title		Lotus Valve System - Randomized	CoreValve TAVR System - Randomized
Arm/Group Description:		Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed		607	305
Measure Type: Number; Unit of Measure: Percent of Participants
Implanted	Number Analyzed	577 participants	297 participants
		15.4	25.5
Intent to Treat	Number Analyzed	607 participants	305 participants
		15.8	26.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lotus Valve System - Randomized, CoreValve TAVR System - Randomized
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	9.5% Non-Inferiority margin
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Farrington-Manning
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	-10.1
	Confidence Interval	(1-Sided) 97.5%; -4.41
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lotus Valve System - Randomized, CoreValve TAVR System - Randomized
	Comments	Superiority analysis was only to be run if the non-inferiority analysis was met. Superiority analysis was run on Intent to Treat Population.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0006
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	-10.2
	Confidence Interval	(2-Sided) 95%; -16.3 to -4.0
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Percentage of Participants With Moderate or Greater Paravalvular Aortic Regurgitation
Description	Moderate or greater paravalvular aortic regurgitation based on Independent echocardiographic core lab assessment performed using the Unifying 5-Class Grading Scheme for Aortic Regurgitation by Pibarot et al (J Am Coll Cardiol Img 2015: 8: 340-60). The grading scheme ranges from Trace (the least clinically significant) to severe (the most clinically significant).
Time Frame	1 year following procedure

Outcome Measure Data

Analysis Population Description

ITT - all subjects who sign an Informed Consent Form, are enrolled in the trial, and are randomized, whether or not an assigned study device is implanted.

The Primary and Secondary Endpoints (Outcome Measures 1-3) are only applicable to the two Randomized arms of the study.

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305
Measure Type: Number; Unit of Measure: Percent of Participants
	0.9	6.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lotus Valve System - Randomized, CoreValve TAVR System - Randomized
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	-6.1
	Confidence Interval	(2-Sided) 95%; -9.6 to -2.6
	Estimation Comments	[Not Specified]

4. Other Pre-specified Outcome

Title	Percentage of Participants With Successful Deployment of the Study Valve
Description	Successful deployment of the study valve
Time Frame	at discharge or 7 days post-procedure (whichever comes first)

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
	97.8	99.0	99.0	96.6

5. Other Pre-specified Outcome

Title	Percentage of Participants With Successful Retrieval of the Study Valve if Retrieval is Attempted
Description	Successful retrieval of the study valve if retrieval is attempted
Time Frame	at discharge or 7 days post-procedure (whichever comes first)

Outcome Measure Data

Analysis Population Description

Number of Intent to Treat participants who had Retrieval attempted

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	40	14	5	24
Measure Type: Number; Unit of Measure: Percentage of Participants
	100	92.9	100	100

6. Other Pre-specified Outcome

Title	Percentage of Participants With Successful Repositioning of the Study Valve if Repositioning is Attempted
Description	Successful repositioning of the study valve if repositioning is attempted
Time Frame	at discharge or 7 days post-procedure (whichever comes first)

Outcome Measure Data

Analysis Population Description

Number of Intent to Treat participants who had Repositioning attempted

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	197	35	46	140
Measure Type: Number; Unit of Measure: Percentage of Participants
	100	100	100	97.1

7. Other Pre-specified Outcome

Title	Percentage of Participants With Each Grade of Aortic Valve Regurgitation in Each Location: Paravalvular, Central, and Combined
Description	Grade of aortic valve regurgitation: paravalvular, central, and combined. An Independent echocardiographic core lab assessment was performed using the Unifying 5-Class Grading Scheme for Aortic Regurgitation for the locations paravalvular, central and combined. The grading scheme has a range from Trace to Severe. A grade of Trace is the least clinically significant (better outcome) and a grade of Severe is the most clinically significant (worse outcome).
Time Frame	at discharge or 7 days post-procedure (whichever comes first)

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of Participants
Central - Trace or Greater	15.2	8.7	15.8	15.3
Central - None	84.8	91.3	84.2	84.7
Central - Trace/Trivial	6.1	1.8	6.3	4.0
Central - Mild	4.2	0.7	3.2	4.7
Central - Mild-Moderate	0.0	0.0	0.0	0.0
Central - Moderate	0.0	0.4	1.1	0.0
Central - Moderate-Severe	0.0	0.0	0.0	0.0
Central - Severe	0.0	0.0	0.0	0.0
Central - Moderate or Greater	0.0	0.4	1.1	0.0
Central - AR but Severity Not Evaluable	4.9	5.8	5.3	6.6
Paravalvular - Trace or Greater	26.9	72.6	28.4	28.5
Paravalvular - None	73.1	27.4	71.6	71.5
Paravalvular - Trace/Trivial	10.5	18.1	12.6	2.9
Paravalvular - Mild	11.8	46.9	12.6	18.2
Paravalvular - Mild-Moderate	0.0	0.0	0.0	0.0
Paravalvular - Moderate	0.4	3.6	0.0	0.4
Paravalvular - Moderate-Severe	0.0	0.0	0.0	0.0
Paravalvular - Severe	0.0	0.0	0.0	0.0
Paravalvular - Moderate or Greater	0.4	3.6	0.0	0.4
Paravalvular - AR but Severity Not Evaluable	4.3	4.0	3.2	6.9
Total – Trace or Greater	35.1	73.3	36.8	34.7
Total - None	64.9	26.7	63.2	65.3
Total - Trace/Trivial	17.4	18.4	20.0	8.8
Total - Mild	15.4	48.7	15.8	24.5
Total - Mild-Moderate	0.0	0.0	0.0	0.0
Total - Moderate	0.9	4.3	1.1	0.4
Total - Moderate-Severe	0.0	0.0	0.0	0.0
Total - Severe	0.0	0.0	0.0	0.0
Total - Moderate or Greater	0.9	4.3	1.1	0.4
Total - AR but Severity Not Evaluable	1.4	1.8	0.0	1.1

8. Other Pre-specified Outcome

Title	Percentage of Participants With Clinical Procedural Success
Description	Defined as implantation of the study device in the absence of death, disabling stroke, major vascular complications, and life-threatening or major bleeding
Time Frame	30 days post procedure

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of Participants
	81.4	84.6	81.4	81.0

9. Other Pre-specified Outcome

Title	Percentage of Participants With Procedural Success
Description	Defined as absence of procedural mortality, correct positioning of a single transcatheter valve into the proper anatomical location , intended performance of the study device (effective orifice area [EOA] >0.9 cm2 for body surface area (BSA) <1.6 m2 and EOA >1.1 cm2 for BSA ≥1.6 m2 plus either a mean aortic valve gradient <20 mm Hg or a peak velocity <3m/sec, and no moderate or severe prosthetic valve aortic regurgitation) plus no serious adverse events
Time Frame	30 days post procedure

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
	32.0	39.2	33.3	29.3

10. Other Pre-specified Outcome

Title	Additional Indications of Prosthetic Aortic Valve Performance as Measured by Transthoracic Echocardiography 1
Description	Assessed by an independent core laboratory, including effective orifice area, mean and peak aortic gradients, and peak aortic velocity
Time Frame	assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Mean (Standard Deviation); Unit of Measure: cm^2
Discharge or 7 Days - Aortic Valve Area	1.65 (0.47)	1.96 (0.52)	1.70 (0.49)	1.61 (0.42)
30 Days - Aortic Valve Area	1.59 (0.45)	1.98 (0.51)	1.62 (0.46)	1.55 (0.41)
6 Months - Aortic Valve Area	1.46 (0.46)	1.74 (0.55)	1.55 (0.45)	1.56 (0.47)
1 Year - Aortic Valve Area	1.49 (0.45)	1.69 (0.52)	1.53 (0.49)	1.51 (0.46)

11. Other Pre-specified Outcome

Title	Additional Indications of Prosthetic Aortic Valve Performance as Measured by Transthoracic Echocardiography 2
Description	Assessed by an independent core laboratory - mean and peak aortic gradients
Time Frame	assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Mean (Standard Deviation); Unit of Measure: mmHg
Discharge or 7 Days - Mean Aortic Valve Gradient	12.20 (5.21)	8.19 (3.98)	12.13 (5.13)	12.50 (6.01)
Discharge or 7 Days - Peak Aortic Gradient	22.28 (10.23)	15.21 (7.20)	21.58 (8.55)	22.89 (10.91)
30 Days - Mean Aortic Valve Gradient	12.00 (6.08)	7.25 (3.44)	12.76 (8.24)	12.24 (6.73)
30 Days - Peak Aortic Gradient	21.46 (10.27)	13.59 (6.21)	23.02 (13.43)	22.56 (11.44)
6 Months - Mean Aortic Valve Gradient	11.93 (5.21)	7.89 (4.24)	12.33 (5.89)	12.20 (5.42)
6 Months - Peak Aortic Gradient	22.24 (9.82)	14.84 (7.46)	22.85 (10.60)	22.68 (9.81)
1 Year - Mean Aortic Valve Gradient	12.29 (5.83)	7.89 (3.48)	12.30 (7.39)	12.68 (5.62)
1 Year - Peak Aortic Gradient	22.74 (10.53)	15.22 (6.44)	22.03 (12.05)	23.75 (9.83)

12. Other Pre-specified Outcome

Title	Additional Indications of Prosthetic Aortic Valve Performance as Measured by Transthoracic Echocardiography 3
Description	Assessed by an independent core laboratory - peak aortic velocity
Time Frame	assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Mean (Standard Deviation); Unit of Measure: m/s
Discharge or 7 Days - Peak Aortic Velocity	2.30 (0.48)	1.89 (0.45)	2.28 (0.44)	2.33 (0.53)
30 Days - Peak Aortic Velocity	2.26 (0.46)	1.80 (0.40)	2.33 (0.58)	2.31 (0.53)
6 Months - Peak Aortic Velocity	2.30 (0.46)	1.87 (0.44)	2.32 (0.49)	2.33 (0.49)
1 Year - Peak Aortic Velocity	2.33 (0.51)	1.91 (0.41)	2.28 (0.55)	2.39 (0.47)

13. Other Pre-specified Outcome

Title	Percentage of Participants With Additional Indications of Prosthetic Aortic Valve Performance as Measured by Transthoracic Echocardiography 4
Description	Grade of aortic valve regurgitation: paravalvular, central, and combined. An Independent echocardiographic core lab assessment was performed using the Unifying 5-Class Grading Scheme for Aortic Regurgitation for the locations paravalvular, central and combined. The grading scheme has a range from Trace to Severe. A grade of Trace is the least clinically significant (better outcome) and a grade of Severe is the most clinically significant (worse outcome).
Time Frame	assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
Discharge Paravalvular – Trace or Greater	26.9	72.6	28.4	28.5
Discharge Paravalvular None	73.1	27.4	71.6	71.5
Discharge Paravalvular Trace/Trivial	10.5	18.1	12.6	2.9
Discharge Paravalvular Mild	11.8	46.9	12.6	18.2
Discharge Paravalvular Mild-Moderate	0.0	0.0	0.0	0.0
Discharge Paravalvular Moderate	0.4	3.6	0.0	0.4
Discharge Paravalvular Moderate-Severe	0.0	0.0	0.0	0.0
Discharge Paravalvular Severe	0.0	0.0	0.0	0.0
Discharge Paravalvular Moderate or Greater	0.4	3.6	0.0	0.4
Discharge ParavalvularAR but Severity not evaluabl	4.3	4.0	3.2	6.9
30 Day Paravalvular – Trace or Greater	27.5	75.5	30.0	27.3
30 Day Paravalvular None	72.5	24.5	70.0	72.7
30 Day Paravalvular Trace/Trivial	10.7	14.7	10.0	2.5
30 Day Paravalvular Mild	10.7	48.7	15.0	18.5
30 Day Paravalvular Mild-Moderate	0.0	0.0	0.0	0.0
30 Day Paravalvular Moderate	0.4	7.2	1.0	1.5
30 Day Paravalvular Moderate-Severe	0.2	0.0	0.0	0.0
30 Day Paravalvular Severe	0.0	0.0	0.0	0.0
30 Day Paravalvular Moderate or Greater	0.6	7.2	1.0	1.5
30 Day Paravalvular AR but Severity not evaluable	5.5	4.9	4.0	4.7
6 Month Paravalvular – Trace or Greater	22.3	62.7	23.8	26.9
6 Month Paravalvular None	77.7	37.3	76.2	73.1
6 Month Paravalvular Trace/Trivial	4.2	6.8	7.1	4.3
6 Month Paravalvular Mild	11.5	42.4	14.3	19.8
6 Month Paravalvular Mild-Moderate	0.0	0.0	0.0	0.0
6 Month Paravalvular Moderate	0.4	4.7	0.0	0.0
6 Month Paravalvular Moderate-Severe	0.2	0.0	0.0	0.0
6 Month Paravalvular Severe	0.0	0.0	0.0	0.0
6 Month Paravalvular Moderate or Greater	0.6	4.7	0.0	0.0
6 Month Paravalvular AR but Severity not evaluable	5.9	8.9	2.4	2.8
1 Year Paravalvular – Trace or Greater	20.1	63.0	24.4	20.6
1 Year Paravalvular None	79.9	37.0	75.6	79.4
1 Year Paravalvular Trace/Trivial	5.7	10.5	4.7	3.3
1 Year Paravalvular Mild	11.3	38.8	14.0	12.3
1 Year Paravalvular Mild-Moderate	0.0	0.0	0.0	0.0
1 Year Paravalvular Moderate	0.9	5.9	0.0	1.2
1 Year Paravalvular Moderate-Severe	0.0	0.9	0.0	0.0
1 Year Paravalvular Severe	0.0	0.0	0.0	0.0
1 Year Paravalvular Moderate or Greater	0.9	6.8	0.0	1.2
1 Year Paravalvular AR but Severity not evaluable	2.2	6.8	5.8	3.7

14. Other Pre-specified Outcome

Title	Health Status as Evaluated by Quality of Life Questionnaires
Description	SF-12 and Kansas City Cardiomyopathy - Baseline scores and changes from Baseline at 30 days, 6 months and 1 year; SF-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.; 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.
Time Frame	Assessed at Baseline, 1 and 6 months; and 1, 3, and 5 years, at Baseline, 1 and 6 months and 1 Year reported

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Mean (Standard Deviation); Unit of Measure: Score on a scale
Baseline SF-12 Physical Summary Score	31.9 (9.0)	31.2 (8.9)	33.8 (10.5)	32.4 (10.0)
Baseline SF-12 Mental Health Summary Score	49.6 (11.6)	49.0 (11.6)	49.8 (11.0)	50.0 (11.4)
Baseline KC Overall Summary Score	51.9 (23.5)	50.7 (22.1)	52.7 (24.6)	53.5 (22.8)
Baseline KC Clinical Summary Score	55.2 (23.3)	54.9 (21.9)	57.3 (23.7)	57.6 (22.6)
30 Day change from Baseline SF-12 Physical Summary	5.1 (10.5)	6.0 (10.0)	3.3 (10.5)	4.3 (9.8)
30 Day change from Baseline SF-12 Mental Health S	3.4 (12.5)	2.3 (12.6)	1.8 (11.3)	3.2 (10.6)
30 Day change from Baseline KC Overall Summary	20.9 (24.2)	20.2 (24.0)	17.4 (25.6)	18.3 (23.1)
30 Day change from Baseline KC Clinical Summary	17.4 (23.9)	16.6 (22.9)	15.2 (24.5)	14.8 (22.2)
6M change from Baseline SF-12 Physical Summary	5.8 (10.8)	5.6 (10.1)	3.6 (9.8)	4.7 (10.7)
6M change from Baseline SF-12 Mental Health Sum	3.3 (11.2)	3.3 (12.6)	2.8 (10.5)	3.3 (11.6)
6M change from Baseline KC Overal Summary Score	22.9 (23.8)	22.7 (22.6)	23.5 (25.5)	21.2 (23.1)
6M change from Baseline KC Clinical Summary Score	17.8 (22.7)	17.0 (22.2)	17.5 (24.0)	15.9 (22.2)
1Y change from Baseline SF-12 Physical Summary	4.7 (10.9)	5.2 (10.1)	3.0 (10.8)	3.7 (10.6)
1Y change from Baseline SF-12 Mental Health Sum	3.5 (11.5)	3.7 (12.9)	3.2 (12.5)	3.0 (11.1)
1Y change from Baseline KC Overall Summary Score	21.6 (24.4)	21.4 (23.2)	23.2 (26.7)	20.0 (22.2)
1Y change from Baseline KC Clinical Summary Score	16.3 (23.8)	15.0 (21.5)	15.6 (26.8)	14.0 (21.7)

15. Other Pre-specified Outcome

Title	Percentage of Participants With Mortality
Description	All-cause, Cardiovascular, and Non-cardiovascular
Time Frame	assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported.

Outcome Measure Data

Analysis Population Description

Intent to Treat patients with mortality or who were event free with sufficient follow-up for the applicable time point (30 days - at least 23 days of follow-up; 6 months - at least 150 days of follow-up; 1 year - at least 335 days of follow-up).

Arm/Group Title		Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:		Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed		607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
Discharge All Cause Mortality	Number Analyzed	607 participants	305 participants	102 participants	295 participants
		1.3	2.0	0.0	2.0
Discharge Cardiovascular Mortality	Number Analyzed	607 participants	305 participants	102 participants	295 participants
		1.3	2.0	0.0	2.0
Discharge Non-Cardiovascular Mortality	Number Analyzed	607 participants	305 participants	102 participants	295 participants
		0.0	0.0	0.0	0.0
30 Day All Cause Mortality	Number Analyzed	601 participants	303 participants	102 participants	295 participants
		2.5	2.3	0.0	3.4
30 Day Cardiovascular Mortality	Number Analyzed	601 participants	303 participants	102 participants	295 participants
		2.3	2.3	0.0	3.4
30 Day Non-Cardiovascular Mortality	Number Analyzed	601 participants	303 participants	102 participants	295 participants
		0.2	0.0	0.0	0.0
6 Month All Cause Mortality	Number Analyzed	594 participants	300 participants	102 participants	295 participants
		7.7	8.3	8.8	7.1
6 Month Cardiovascular Mortality	Number Analyzed	594 participants	300 participants	102 participants	295 participants
		5.6	6.7	5.9	4.7
6 Month Non-Cardiovascular Mortality	Number Analyzed	594 participants	300 participants	102 participants	295 participants
		2.2	1.7	2.9	2.4
1 Year All Cause Mortality	Number Analyzed	587 participants	297 participants	101 participants	293 participants
		11.9	13.5	12.9	9.2
1 Year Cardiovascular Mortality	Number Analyzed	587 participants	297 participants	101 participants	293 participants
		7.7	9.8	7.9	5.8
1 Year Non-Cardiovascular Mortality	Number Analyzed	587 participants	297 participants	101 participants	293 participants
		4.3	3.7	5.0	3.4

16. Other Pre-specified Outcome

Title	Percentage of Participants With Stroke
Description	Disabling Stroke and Non-disabling Stroke
Time Frame	assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
Discharge All Stroke	4.4	4.3	3.9	5.4
Discharge Disabling Stroke	1.8	3.3	3.9	3.7
Discharge Non-Disabling Stroke	2.6	1.0	0.0	1.7
30 Day All Stroke	4.8	4.3	4.9	6.8
30 Day Disabling Stroke	2.0	3.3	3.9	4.4
30 Day Non-Disabling Stroke	2.8	1.0	1.0	2.4
6 Month All Stroke	5.9	8.3	6.9	8.1
6 Month Disabling Stroke	2.7	6.3	5.9	5.4
6 Month Non-Disabling Stroke	3.2	2.0	1.0	2.7
1 Year All Stroke	7.0	9.4	7.9	8.5
1 Year Disabling Stroke	3.6	7.1	5.9	5.8
1 Year Non-Disabling Stroke	3.6	2.4	2.0	2.7

17. Other Pre-specified Outcome

Title	Percentage of Participants With Myocardial Infarction (MI)
Description	Periprocedural (≤72 hours post index procedure) and spontaneous (>72 hours post index procedure)
Time Frame	assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
Discharge Myocardial Infarction	0.5	1.6	2.0	0.7
Discharge Peri-procedural MI	0.5	1.3	2.0	0.7
Discharge Spontaneous MI	0.0	0.3	0.0	0.0
30 Day Myocardial Infarction	0.7	1.3	2.0	1.0
30 Day Peri-procedural MI	0.5	1.0	2.0	0.7
30 Day Spontaneous MI	0.2	0.3	0.0	0.3
6 Month Myocardial Infarction	2.0	3.0	2.9	3.7
6 Month Peri-procedural MI	0.5	1.3	2.0	0.7
6 Month Spontaneous MI	1.5	2.0	1.0	3.1
1 Year Myocardial Infarction	3.2	4.4	5.0	4.4
1 Year Peri-procedural MI	0.5	1.3	2.0	0.7
1 Year Spontaneous MI	2.7	3.4	3.0	3.8

18. Other Pre-specified Outcome

Title	Percentage of Participants With Bleeding
Description	Life-threatening (or disabling) and major (defined below) Life-threatening or Disabling Bleeding; Fatal bleeding (Bleeding Academic Research Consortium [BARC] type 5124,125); Bleeding in a critical organ, such as intracranial, intraspinal, intraocular, or pericardial necessitating pericardiocentesis, or intramuscular with compartment syndrome (BARC type 3b and 3c); Bleeding causing hypovolemic shock or severe hypotension requiring vasopressors or surgery (BARC type 3b); Overt source of bleeding with drop in hemoglobin of ≥5 g/dL or whole blood or packed red blood cells (RBC) transfusion ≥4 units (BARC type 3b) Major Bleeding (BARC type 3a); Overt bleeding either associated with a drop in the hemoglobin level of at least 3.0g/dL or requiring transfusion of 2 or 3 units of whole blood/RBC, or causing hospitalization or permanent injury, or requiring surgery AND does not meet criteria of life-threatening or disabling bleeding
Time Frame	assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
Discharge Bleeding	11.9	10.5	8.8	9.5
Discharge Life-threatening or Disabling Bleeding	7.2	5.9	7.8	5.4
Discharge Major Bleeding	4.6	4.6	1.0	4.1
30 Day Bleeding	12.8	10.9	11.8	11.9
30 Day Life-threatening or Disabling Bleeding	8.0	5.0	9.8	6.1
30 Day Major Bleeding	4.8	5.9	2.0	5.8
6 Month Bleeding	16.5	17.0	17.6	14.9
6 Month Life-threatening or Disabling Bleeding	9.3	9.0	14.7	8.5
6 Month Major Bleeding	7.2	8.0	2.9	6.8
1 Year Bleeding	18.1	17.8	20.8	19.1
1 Year Life-threatening or Disabling Bleeding	9.9	9.8	16.8	11.3
1 Year Major Bleeding	8.3	8.4	5.0	8.9

19. Other Pre-specified Outcome

Title	Percentage of Participants With Acute Kidney Injury
Description	Acute kidney injury based on the AKIN System Stage 3 (including renal replacement therapy) or Stage 2 Change in serum creatinine (up to 7 days) compared to baseline: Stage 1: Increase in serum creatinine to 150-199% (1.5-1.99 × increase compared with baseline) OR increase of ≥0.3 mg/dl (≥26.4 mmol/L); Stage 2: Increase in serum creatinine to 200-299% (2.0-2.99 × increase compared with baseline); Stage 3: Increase in serum creatinine to ≥300% (>3 × increase compared with baseline) OR serum creatinine of ≥4.0 mg/dL (≥354 mmol/L) with an acute increase of at least 0.5 mg/dL (44 mmol/L) -OR- Based on urine output (up to 7 days): Stage 1: <0.5 ml/kg per hour for >6 but <12 hours; Stage 2: <0.5 ml/kg per hour for >12 but <24 hours; Stage 3: <0.3 ml/kg per hour for ≥24 hours or anuria for ≥12 hours Note 1: Subjects receiving renal replacement therapy are considered to meet Stage 3 criteria irrespective of other criteria.
Time Frame	≤7 days post index procedure

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
Acute Kidney Injury – Stage 2 or Stage 3	2.3	3.6	1.0	0.7
Stage 2	1.0	1.3	0.0	0.0
Stage 3 (including renal replacement therapy)	1.3	2.3	1.0	0.7

20. Other Pre-specified Outcome

Title	Percentage of Participants With Major Vascular Complication
Description	Major vascular complication - including access site related and non access site related
Time Frame	assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
Discharge Major Vascular Complications	6.8	5.6	8.8	7.8
Discharge Access Site Related	4.6	3.6	6.9	4.4
Discharge Not Access Site Related	2.3	2.0	2.9	3.4
30 Day Major Vascular Complications	7.0	5.3	8.8	7.8
30 Day Access Site Related	4.7	3.3	6.9	4.4
30 Day Not Access Site Related	2.5	2.0	2.9	3.4
6 Month Major Vascular Complications	7.6	5.7	8.8	8.1
6 Month Access Site Related	5.1	3.7	6.9	4.4
6 Month Not Access Site Related	2.7	2.0	2.9	3.7
1 Year Major Vascular Complications	7.7	6.1	8.9	8.2
1 Year Access Site Related	5.1	3.7	6.9	4.8
1 Year Not Access Site Related	2.7	2.4	3.0	3.8

21. Other Pre-specified Outcome

Title	Percentage of Participants With Repeat Procedure for Valve-related Dysfunction
Description	Repeat procedure for valve-related dysfunction (surgical or interventional therapy)
Time Frame	assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
Discharge Repeat proc valve-related dysfunction	0.0	0.7	1.0	0.3
30 Day Repeat proc valve-related dysfunction	0.0	1.0	1.0	0.7
6 Month Repeat proc valve-related dysfunction	0.2	1.7	1.0	1.0
1 Year Repeat proc valve-related dysfunction	0.2	2.0	1.0	1.0

22. Other Pre-specified Outcome

Title	Percentage of Participants With Hospitalization for Valve-related Symptoms or Worsening Congestive Heart Failure
Description	Hospitalization for valve-related symptoms or worsening congestive heart failure (New York Hear Association [NYHA] class III or IV)
Time Frame	assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
Discharge	0.8	0.7	1.0	0.0
30 Day	1.7	3.0	4.9	2.4
6 Month	6.7	9.3	9.8	6.4
1 Year	11.2	13.8	13.9	9.6

23. Other Pre-specified Outcome

Title	Percentage of Participants With New Permanent Pacemaker Implantation
Description	New permanent pacemaker implantation resulting from new or worsened conduction disturbances
Time Frame	assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
Discharge	28.2	14.8	27.5	24.1
30 Day	29.1	15.8	28.4	28.1
6 Month	33.3	18.0	29.4	30.2
1 Year	34.2	18.5	30.7	31.1

24. Other Pre-specified Outcome

Title	Percentage of Participants With New Onset of Atrial Fibrillation or Atrial Flutter
Description	New onset of atrial fibrillation or atrial flutter
Time Frame	assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
Discharge	6.4	3.9	4.9	5.1
30 Day	5.8	4.3	5.9	5.1
6 Month	6.6	4.7	5.9	5.1
1 Year	6.6	4.7	5.9	5.1

25. Other Pre-specified Outcome

Title	Percentage of Participants With Coronary Obstruction
Description	Coronary obstruction
Time Frame	≤72 hours post index procedure

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
	0.2	0.7	1.0	0.7

26. Other Pre-specified Outcome

Title	Percentage of Participants With Ventricular Septal Perforation
Description	Ventricular septal perforation
Time Frame	≤72 hours post index procedure

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participant
	0.2	0.0	0.0	0.0

27. Other Pre-specified Outcome

Title	Percentage of Participants With Mitral Apparatus Damage
Description	Mitral apparatus damage
Time Frame	≤72 hours post index procedure

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
	0.0	0.3	0.0	0.0

28. Other Pre-specified Outcome

Title	Percentage of Participants With Cardiac Tamponade
Description	Cardiac tamponade
Time Frame	≤72 hours post index procedure

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
	2.5	1.3	2.0	1.4

29. Other Pre-specified Outcome

Title	Percentage of Participants With Prosthetic Aortic Valve Malpositioning
Description	Prosthetic aortic valve malpositioning, including valve migration, valve embolization, or ectopic valve deployment
Time Frame	assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
Discharge Prosthetic aortic valve malpositioning	0.0	2.6	0.0	0.0
Discharge Valve Migration	0.0	0.7	0.0	0.0
Discharge Valve Embolization	0.0	2.0	0.0	0.0
Discharge Ectopic Valve Deployment (Procedural)	0.0	0.3	0.0	0.0
30 Day Prosthetic aortic valve malpositioning	0.0	2.6	0.0	0.0
30 Day Valve Migration	0.0	0.7	0.0	0.0
30 Day Valve Embolization	0.0	2.0	0.0	0.0
30 Day Ectopic Valve Deployment (Procedural)	0.0	0.3	0.0	0.0
6 Month Prosthetic aortic valve malpositioning	0.0	2.7	0.0	0.0
6 Month Valve Migration	0.0	0.7	0.0	0.0
6 Month Valve Embolization	0.0	2.0	0.0	0.0
6 Month Ectopic Valve Deployment (Procedural)	0.0	0.3	0.0	0.0
1 Year Prosthetic aortic valve malpositioning	0.0	2.7	0.0	0.0
1 Year Valve Migration	0.0	0.7	0.0	0.0
1 Year Valve Embolization	0.0	2.0	0.0	0.0
1 Year Ectopic Valve Deployment (Procedural)	0.0	0.3	0.0	0.0

30. Other Pre-specified Outcome

Title	Percentage of Participants With Prosthetic Aortic Valve Thrombosis
Description	Prosthetic aortic valve thrombosis
Time Frame	assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
Discharge	0.0	0.0	0.0	1.0
30 Day	0.0	0.0	1.0	1.4
6 Month	1.2	0.0	3.9	2.0
1 Year	1.5	0.0	6.9	2.4

31. Other Pre-specified Outcome

Title	Percentage of Participants With Prosthetic Aortic Valve Endocarditis
Description	Prosthetic aortic valve endocarditis
Time Frame	assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported.

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Lotus Valve System - Randomized	CoreValve TAVR System - Randomized	Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description:	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
Overall Number of Participants Analyzed	607	305	102	295
Measure Type: Number; Unit of Measure: Percentage of participants
Discharge	0.0	0.0	0.0	0.0
30 Day	0.2	0.0	0.0	0.0
6 Month	0.5	0.0	3.9	0.3
1 Year	0.7	0.0	4.0	0.3

Adverse Events

Time Frame	1 Year
Adverse Event Reporting Description	For All Cause Mortality, the at risk population (denominator) is the ITT population who had the event or who were event free with sufficient follow-up (at least 335 days of follow-up). For the SAE/AE tables, the at risk population (denominator) is the full ITT population.
Arm/Group Title	Lotus Valve System - Randomized		CoreValve TAVR System - Randomized		Lotus Valve System - Single-arm Roll-in Cohort		Lotus Valve System - Single-arm Continued Access Cohort
Arm/Group Description	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)		Transcatheter aortic valve replacement (TAVR) with CoreValve Transcatheter Aortic Valve Replacement System CoreValve Transcatheter Aortic Valve Replacement System: Procedure: Transcatheter aortic valve replacement (TAVR)		Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)		Transcatheter aortic valve replacement (TAVR) with Lotus Valve System Lotus Valve System: Procedure: Transcatheter aortic valve replacement (TAVR)
All-Cause Mortality
	Lotus Valve System - Randomized		CoreValve TAVR System - Randomized		Lotus Valve System - Single-arm Roll-in Cohort		Lotus Valve System - Single-arm Continued Access Cohort
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	70/587 (11.93%)		40/297 (13.47%)		13/101 (12.87%)		27/293 (9.22%)
Serious Adverse Events
	Lotus Valve System - Randomized		CoreValve TAVR System - Randomized		Lotus Valve System - Single-arm Roll-in Cohort		Lotus Valve System - Single-arm Continued Access Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	431/607 (71.00%)		207/305 (67.87%)		72/102 (70.59%)		229/295 (77.63%)
Blood and lymphatic system disorders
Anaemia † 1	27/607 (4.45%)	27	5/305 (1.64%)	5	4/102 (3.92%)	4	8/295 (2.71%)	8
Haemorrhagic anaemia † 1	8/607 (1.32%)	8	9/305 (2.95%)	9	0/102 (0.00%)	0	6/295 (2.03%)	6
Thrombocytopenia † 1	5/607 (0.82%)	5	1/305 (0.33%)	1	3/102 (2.94%)	3	9/295 (3.05%)	9
Iron deficiency anaemia † 1	2/607 (0.33%)	2	3/305 (0.98%)	3	0/102 (0.00%)	0	1/295 (0.34%)	1
Heparin-induced thrombocytopenia † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Leukocytosis † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	2/295 (0.68%)	2
Disseminated intravascular coagulation † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Anaemia macrocytic † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Anaemia of malignant disease † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Coagulopathy † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Haemolytic anaemia † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Pancytopenia † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Cardiac disorders
Atrioventricular block complete † 1	135/607 (22.24%)	135	37/305 (12.13%)	37	19/102 (18.63%)	19	62/295 (21.02%)	62
Cardiac failure congestive † 1	62/607 (10.21%)	75	38/305 (12.46%)	54	11/102 (10.78%)	14	23/295 (7.80%)	24
Atrial fibrillation † 1	28/607 (4.61%)	28	7/305 (2.30%)	7	6/102 (5.88%)	6	17/295 (5.76%)	20
Bundle branch block left † 1	22/607 (3.62%)	22	9/305 (2.95%)	9	8/102 (7.84%)	8	15/295 (5.08%)	15
Cardiac arrest † 1	16/607 (2.64%)	16	4/305 (1.31%)	4	3/102 (2.94%)	4	7/295 (2.37%)	8
Cardiac failure † 1	13/607 (2.14%)	15	7/305 (2.30%)	7	1/102 (0.98%)	1	4/295 (1.36%)	4
Atrioventricular block † 1	14/607 (2.31%)	14	9/305 (2.95%)	9	7/102 (6.86%)	7	5/295 (1.69%)	5
Acute myocardial infarction † 1	12/607 (1.98%)	13	8/305 (2.62%)	8	0/102 (0.00%)	0	11/295 (3.73%)	11
Conduction disorder † 1	12/607 (1.98%)	12	8/305 (2.62%)	8	1/102 (0.98%)	1	5/295 (1.69%)	5
Bradycardia † 1	9/607 (1.48%)	9	3/305 (0.98%)	3	1/102 (0.98%)	1	7/295 (2.37%)	7
Pericardial effusion † 1	9/607 (1.48%)	9	5/305 (1.64%)	5	1/102 (0.98%)	1	4/295 (1.36%)	4
Atrioventricular block second degree † 1	8/607 (1.32%)	8	3/305 (0.98%)	3	0/102 (0.00%)	0	7/295 (2.37%)	7
Sick sinus syndrome † 1	8/607 (1.32%)	8	3/305 (0.98%)	3	0/102 (0.00%)	0	1/295 (0.34%)	1
Angina pectoris † 1	6/607 (0.99%)	6	8/305 (2.62%)	8	1/102 (0.98%)	1	4/295 (1.36%)	4
Cardiac tamponade † 1	5/607 (0.82%)	5	1/305 (0.33%)	1	1/102 (0.98%)	1	1/295 (0.34%)	1
Cardiac failure chronic † 1	3/607 (0.49%)	5	3/305 (0.98%)	4	1/102 (0.98%)	1	4/295 (1.36%)	4
Atrioventricular block first degree † 1	4/607 (0.66%)	4	1/305 (0.33%)	1	0/102 (0.00%)	0	2/295 (0.68%)	2
Myocardial infarction † 1	4/607 (0.66%)	4	3/305 (0.98%)	3	3/102 (2.94%)	3	4/295 (1.36%)	4
Ventricular fibrillation † 1	3/607 (0.49%)	3	1/305 (0.33%)	1	1/102 (0.98%)	1	3/295 (1.02%)	3
Mitral valve incompetence † 1	2/607 (0.33%)	3	1/305 (0.33%)	1	2/102 (1.96%)	3	1/295 (0.34%)	1
Angina unstable † 1	3/607 (0.49%)	3	1/305 (0.33%)	1	0/102 (0.00%)	0	1/295 (0.34%)	1
Cardio-respiratory arrest † 1	3/607 (0.49%)	3	3/305 (0.98%)	3	0/102 (0.00%)	0	1/295 (0.34%)	1
Cardiogenic shock † 1	3/607 (0.49%)	3	3/305 (0.98%)	3	0/102 (0.00%)	0	0/295 (0.00%)	0
Cardiac valve disease † 1	3/607 (0.49%)	3	0/305 (0.00%)	0	1/102 (0.98%)	1	3/295 (1.02%)	3
Cardiac failure acute † 1	3/607 (0.49%)	3	1/305 (0.33%)	1	2/102 (1.96%)	2	1/295 (0.34%)	1
Cardiomyopathy † 1	2/607 (0.33%)	2	0/305 (0.00%)	0	1/102 (0.98%)	1	0/295 (0.00%)	0
Coronary artery stenosis † 1	2/607 (0.33%)	2	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Atrial flutter † 1	2/607 (0.33%)	2	1/305 (0.33%)	1	0/102 (0.00%)	0	2/295 (0.68%)	3
Ventricular tachycardia † 1	2/607 (0.33%)	2	3/305 (0.98%)	3	1/102 (0.98%)	1	1/295 (0.34%)	1
Acute coronary syndrome † 1	2/607 (0.33%)	2	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Left ventricular dysfunction † 1	2/607 (0.33%)	2	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Pericarditis † 1	2/607 (0.33%)	2	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Nodal rhythm † 1	2/607 (0.33%)	2	0/305 (0.00%)	0	0/102 (0.00%)	0	2/295 (0.68%)	2
Mitral perforation † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Intracardiac thrombus † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Electromechanical dissociation † 1	1/607 (0.16%)	1	1/305 (0.33%)	1	1/102 (0.98%)	1	0/295 (0.00%)	0
Bundle branch block right † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Myocardial rupture † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Stress cardiomyopathy † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Aortic valve stenosis † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	1/102 (0.98%)	1	3/295 (1.02%)	3
Aortic valve incompetence † 1	1/607 (0.16%)	1	5/305 (1.64%)	5	0/102 (0.00%)	0	0/295 (0.00%)	0
Coronary artery thrombosis † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Myocardial ischaemia † 1	1/607 (0.16%)	1	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Sinus arrhythmia † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Sinus arrest † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Coronary artery occlusion † 1	1/607 (0.16%)	1	2/305 (0.66%)	2	0/102 (0.00%)	0	0/295 (0.00%)	0
Supraventricular tachycardia † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Sinus tachycardia † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Sinus bradycardia † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Ischaemic cardiomyopathy † 1	0/607 (0.00%)	0	2/305 (0.66%)	2	0/102 (0.00%)	0	0/295 (0.00%)	0
Coronary artery disease † 1	0/607 (0.00%)	0	2/305 (0.66%)	2	0/102 (0.00%)	0	1/295 (0.34%)	1
Aortic valve disease † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	2/102 (1.96%)	2	1/295 (0.34%)	1
Arrhythmia † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Arrhythmia supraventricular † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	1/102 (0.98%)	1	1/295 (0.34%)	1
Atrial tachycardia † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Atrial thrombosis † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Bradyarrhythmia † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Mitral valve calcification † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Mitral valve disease † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Tricuspid valve incompetence † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	1/102 (0.98%)	1	0/295 (0.00%)	0
Trifascicular block † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Ventricular asystole † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Congenital, familial and genetic disorders
Peutz-Jeghers syndrome † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Ear and labyrinth disorders
Vertigo † 1	0/607 (0.00%)	0	3/305 (0.98%)	3	0/102 (0.00%)	0	0/295 (0.00%)	0
Deafness † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Endocrine disorders
Hypothyroidism † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Eye disorders
Cataract † 1	2/607 (0.33%)	2	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Vision blurred † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Vitreous haemorrhage † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Gastrointestinal disorders
Gastrointestinal haemorrhage † 1	12/607 (1.98%)	12	9/305 (2.95%)	9	5/102 (4.90%)	5	10/295 (3.39%)	11
Upper gastrointestinal haemorrhage † 1	5/607 (0.82%)	5	2/305 (0.66%)	2	1/102 (0.98%)	1	2/295 (0.68%)	2
Lower gastrointestinal haemorrhage † 1	2/607 (0.33%)	3	4/305 (1.31%)	4	0/102 (0.00%)	0	0/295 (0.00%)	0
Inguinal hernia † 1	3/607 (0.49%)	3	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Ileus † 1	3/607 (0.49%)	3	0/305 (0.00%)	0	1/102 (0.98%)	1	1/295 (0.34%)	1
Diverticulum † 1	3/607 (0.49%)	3	1/305 (0.33%)	1	1/102 (0.98%)	1	0/295 (0.00%)	0
Haemorrhoids † 1	3/607 (0.49%)	3	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Small intestinal obstruction † 1	2/607 (0.33%)	2	1/305 (0.33%)	1	0/102 (0.00%)	0	1/295 (0.34%)	1
Intestinal obstruction † 1	2/607 (0.33%)	2	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Dysphagia † 1	2/607 (0.33%)	2	3/305 (0.98%)	3	0/102 (0.00%)	0	1/295 (0.34%)	1
Haemorrhoidal haemorrhage † 1	2/607 (0.33%)	2	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Diarrhoea † 1	2/607 (0.33%)	2	1/305 (0.33%)	1	0/102 (0.00%)	0	1/295 (0.34%)	1
Colitis ischaemic † 1	2/607 (0.33%)	2	1/305 (0.33%)	1	0/102 (0.00%)	0	1/295 (0.34%)	1
Abdominal pain † 1	2/607 (0.33%)	2	3/305 (0.98%)	3	0/102 (0.00%)	0	1/295 (0.34%)	1
Vomiting † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Peptic ulcer haemorrhage † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Umbilical hernia, obstructive † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Pancreatitis acute † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Pancreatitis † 1	1/607 (0.16%)	1	1/305 (0.33%)	1	0/102 (0.00%)	0	1/295 (0.34%)	1
Oesophagitis haemorrhagic † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Oesophageal spasm † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Melaena † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Intestinal mass † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Intestinal ischaemia † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Inguinal hernia, obstructive † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Haematemesis † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Gastrointestinal ulcer † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Gastrointestinal disorder † 1	1/607 (0.16%)	1	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Gastritis erosive † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Gastric antral vascular ectasia † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Constipation † 1	1/607 (0.16%)	1	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Colonic polyp † 1	1/607 (0.16%)	1	1/305 (0.33%)	1	0/102 (0.00%)	0	1/295 (0.34%)	1
Colitis † 1	1/607 (0.16%)	1	2/305 (0.66%)	2	0/102 (0.00%)	0	1/295 (0.34%)	1
Ascites † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Abdominal pain upper † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Retroperitoneal haematoma † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	1/102 (0.98%)	1	1/295 (0.34%)	1
Abdominal hernia † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Retroperitoneal haemorrhage † 1	1/607 (0.16%)	1	4/305 (1.31%)	4	1/102 (0.98%)	1	3/295 (1.02%)	3
Rectal prolapse † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Rectal haemorrhage † 1	0/607 (0.00%)	0	2/305 (0.66%)	2	1/102 (0.98%)	1	3/295 (1.02%)	3
Enterocolitis haemorrhagic † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Enterocolitis † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Enteritis † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Dyspepsia † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Diverticulum oesophageal † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Coeliac disease † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Abdominal distension † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Abdominal discomfort † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	1/102 (0.98%)	1	0/295 (0.00%)	0
Dental caries † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	1/102 (0.98%)	1	0/295 (0.00%)	0
Diarrhoea haemorrhagic † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Diverticular perforation † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Duodenal ulcer haemorrhage † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Gastric ulcer † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Haematochezia † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	2/295 (0.68%)	2
Nausea † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Oesophageal rupture † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	1/102 (0.98%)	1	0/295 (0.00%)	0
Umbilical hernia † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Volvulus † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
General disorders
Death † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	2/102 (1.96%)	2	2/295 (0.68%)	2
Fatigue † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	1/102 (0.98%)	1	0/295 (0.00%)	0
Systemic inflammatory response syndrome † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Catheter site haemorrhage † 1	8/607 (1.32%)	8	3/305 (0.98%)	3	0/102 (0.00%)	0	1/295 (0.34%)	1
Non-cardiac chest pain † 1	7/607 (1.15%)	7	4/305 (1.31%)	4	0/102 (0.00%)	0	3/295 (1.02%)	3
Asthenia † 1	5/607 (0.82%)	5	1/305 (0.33%)	1	4/102 (3.92%)	4	3/295 (1.02%)	3
Adverse drug reaction † 1	3/607 (0.49%)	3	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
General physical health deterioration † 1	3/607 (0.49%)	3	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Chest pain † 1	3/607 (0.49%)	3	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Catheter site necrosis † 1	2/607 (0.33%)	2	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Catheter site haematoma † 1	2/607 (0.33%)	2	1/305 (0.33%)	1	2/102 (1.96%)	2	8/295 (2.71%)	8
Pain † 1	2/607 (0.33%)	2	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Catheter site related reaction † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Catheter site pain † 1	1/607 (0.16%)	1	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Sudden cardiac death † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Pyrexia † 1	1/607 (0.16%)	1	2/305 (0.66%)	2	0/102 (0.00%)	0	3/295 (1.02%)	3
Oedema peripheral † 1	1/607 (0.16%)	1	3/305 (0.98%)	3	0/102 (0.00%)	0	1/295 (0.34%)	1
Implant site haemorrhage † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Implant site haematoma † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Impaired healing † 1	1/607 (0.16%)	1	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Hernia obstructive † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Multi-organ failure † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Mechanical complication of implant † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Hepatobiliary disorders
Cholelithiasis † 1	2/607 (0.33%)	2	1/305 (0.33%)	1	0/102 (0.00%)	0	1/295 (0.34%)	1
Ischaemic hepatitis † 1	1/607 (0.16%)	1	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Hepatic cirrhosis † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Cholecystitis acute † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Cholangitis † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Biliary dilatation † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Bile duct stone † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Bile duct obstruction † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Liver injury † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Hepatic failure † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	1/102 (0.98%)	1	1/295 (0.34%)	1
Alcoholic liver disease † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Immune system disorders
Anaphylactic reaction † 1	0/607 (0.00%)	0	0/305 (0.00%)	0	1/102 (0.98%)	1	0/295 (0.00%)	0
Infections and infestations
Pneumonia † 1	23/607 (3.79%)	25	13/305 (4.26%)	14	4/102 (3.92%)	4	15/295 (5.08%)	16
Sepsis † 1	18/607 (2.97%)	18	5/305 (1.64%)	5	1/102 (0.98%)	1	7/295 (2.37%)	7
Urinary tract infection † 1	10/607 (1.65%)	10	9/305 (2.95%)	9	4/102 (3.92%)	5	9/295 (3.05%)	11
Septic shock † 1	6/607 (0.99%)	6	4/305 (1.31%)	4	1/102 (0.98%)	1	3/295 (1.02%)	3
Cellulitis † 1	5/607 (0.82%)	5	2/305 (0.66%)	2	4/102 (3.92%)	4	2/295 (0.68%)	2
Bronchitis † 1	4/607 (0.66%)	4	2/305 (0.66%)	2	0/102 (0.00%)	0	0/295 (0.00%)	0
Endocarditis † 1	4/607 (0.66%)	4	2/305 (0.66%)	2	2/102 (1.96%)	2	1/295 (0.34%)	1
Urosepsis † 1	3/607 (0.49%)	4	1/305 (0.33%)	1	3/102 (2.94%)	3	2/295 (0.68%)	2
Catheter site infection † 1	3/607 (0.49%)	3	1/305 (0.33%)	1	0/102 (0.00%)	0	1/295 (0.34%)	2
Staphylococcal sepsis † 1	3/607 (0.49%)	3	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Bacteraemia † 1	3/607 (0.49%)	3	1/305 (0.33%)	1	1/102 (0.98%)	1	4/295 (1.36%)	4
Clostridium difficile colitis † 1	2/607 (0.33%)	2	1/305 (0.33%)	1	0/102 (0.00%)	0	2/295 (0.68%)	2
Catheter site cellulitis † 1	1/607 (0.16%)	2	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Staphylococcal infection † 1	2/607 (0.33%)	2	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Bacterial sepsis † 1	2/607 (0.33%)	2	0/305 (0.00%)	0	1/102 (0.98%)	1	0/295 (0.00%)	0
Bronchiectasis † 1	1/607 (0.16%)	1	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Osteomyelitis acute † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Pneumococcal sepsis † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Bronchopneumonia † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Cellulitis staphylococcal † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Cholecystitis infective † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Gastrointestinal infection † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Clostridial infection † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	1/102 (0.98%)	1	0/295 (0.00%)	0
Clostridium colitis † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Pneumonia klebsiella † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Staphylococcal bacteraemia † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	1/295 (0.34%)	1
Wound infection † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Gastroenteritis † 1	1/607 (0.16%)	1	2/305 (0.66%)	2	0/102 (0.00%)	0	0/295 (0.00%)	0
Device related infection † 1	1/607 (0.16%)	1	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Viral labyrinthitis † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Urinary tract infection bacterial † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Gastrointestinal bacterial infection † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Diabetic foot infection † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Cystitis klebsiella † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Cystitis † 1	1/607 (0.16%)	1	2/305 (0.66%)	2	0/102 (0.00%)	0	0/295 (0.00%)	0
Enterococcal bacteraemia † 1	1/607 (0.16%)	1	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Diverticulitis † 1	1/607 (0.16%)	1	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Lung infection pseudomonal † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Parainfluenzae virus infection † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Gangrene † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Lobar pneumonia † 1	1/607 (0.16%)	1	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Pelvic abscess † 1	1/607 (0.16%)	1	0/305 (0.00%)	0	0/102 (0.00%)	0	0/295 (0.00%)	0
Pleural infection † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Infected skin ulcer † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Gastroenteritis viral † 1	0/607 (0.00%)	0	2/305 (0.66%)	2	0/102 (0.00%)	0	0/295 (0.00%)	0
Escherichia urinary tract infection † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Enterocolitis infectious † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Fungal infection † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Pneumonia viral † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Postoperative wound infection † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Tracheobronchitis † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Appendicitis † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Abdominal wall abscess † 1	0/607 (0.00%)	0	1/305 (0.33%)	1	0/102 (0.00%)	0	0/295 (0.00%)	0
Implant site infection † 1