REPRISE I: REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus™ Valve SystEm

• Sponsor: Boston Scientific Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01383720
• Collaborator: (none)
• Enrollment: 11
• Locations: 3
• Arm: 1
• Duration (Months): 61.2
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a prospective, single-arm feasibility study designed to assess the acute safety and performance of the Lotus Valve System for transcatheter aortic valve replacement in symptomatic patients with calcified aortic valve stenosis and who are at high risk for surgical intervention.

Condition or Disease	Intervention/Treatment	Phase
Aortic Valve Stenosis; Aortic Valve Calcification; Aortic Valve Disease	Device: Lotus Valve System	N/A

Detailed Description

The incidence of aortic stenosis is increasing due to the aging of the world-wide population and the lack of drug therapies to prevent, halt, or effectively slow the stenotic process. Transcatheter aortic valve replacement has become a viable alternative for treatment of severe symptomatic aortic stenosis in selected patients who are unsuitable candidates for surgical valve replacement. The Lotus Valve System is designed to enable precise placement and minimize or eliminate the paravalvular regurgitation and associated adverse events seen with earlier generation devices. The REPRISE I study assesses acute safety and performance.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus™ Valve SystEm
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 9, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lotus Valve System Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis	Device: Lotus Valve System; The Lotus Valve System includes the Lotus Valve, a bovine tissue tri-leaflet bioprosthetic aortic valve, and the Lotus Delivery Catheter for guidance and placement.

Outcome Measures

Primary Outcome Measures

1. Clinical Procedural Success [Discharge or 7 days post-procedure, whichever comes first]

   Clinical procedural success defined as successful implantation of a Lotus Valve System (Device Success) without in-hospital Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) through discharge or 7 days post-procedure, whichever comes first.

Secondary Outcome Measures

1. Device Performance Endpoint-Repositioning [procedure]

   Successful repositioning of the Lotus Valve System if repositioning is attempted

2. Device Performance Endpoint-Valve Retrieval, if Attempted [procedure]

   Successful retrieval of the Lotus Valve System if retrieval is attempted

3. Central Aortic Regurgitation [Discharge or 7 days post-procedure, whichever comes first]

   As determined by echocardiography

4. Paravalvular Aortic Regurgitation [Discharge or 7 days post-procedure, whichever comes first]

   As determined by echocardiography

Other Outcome Measures

1. Successful Access, Device Delivery, Deployment and Positioning and Retrieval of Delivery System [Procedure]

2. Intended Performance of the Lotus Valve [At time of discharge or 7 days post procedure]

   Aortic valve area >1.0 cm2 plus either a mean aortic valve gradient <20 mmHg or peak velocity <3m/sec, without moderate or severe prosthetic valve aortic regurgitation

3. Single Valve Implanted in the Proper Anatomical Location [procedure]

4. No Major Adverse Cardiovascular and Cerebrovascular Events Through Discharge [Discharge or 7 days post-procedure, whichever comes first]

   Major adverse cardiovascular or cerebrovascular events include all-cause mortality, periprocedural myocardial infarction ≤72 hours, major stroke, urgent/emergent conversion to surgery or repeat procedure for valve-related dysfunction

5. Mean Aortic Valve Gradient [Discharge or 7 days post-procedure, whichever comes first]

   As determined by echocardiography

6. Aortic Valve Area [Discharge or 7 days post-procedure, whichever comes first]

   As determined by echocardiography

7. Death [Discharge or 7 days post-procedure, whichever comes first]

8. Peri-procedural Myocardial Infarction [72 hours]

   Peri-Procedural Myocardial Infarction (≤72 hours after the index procedure) New ischemic symptoms (e.g., chest pain or shortness of breath), or new ischemic signs (e.g. ventricular arrhythmias, new or worsening heart failure, new ST-segment changes, hemodynamic instability, or imaging evidence of new loss of viable myocardium or new wall motion abnormality), AND Elevated cardiac biomarkers (preferably creatine kinase-myoglobin band) within 72 h after the index procedure, consisting of two or more post-procedure samples that are > 0.6 to 8 h apart with a 20% increase in the second sample and a peak value exceeding 10X the 99th percentile upper reference limit (URL), or a peak value exceeding 5X the 99th percentile URL with new pathological Q waves in at least 2 contiguous leads

9. Major Stroke [Discharge or 7 days post-procedure, whichever comes first]

   Confirmed with a Modified Rankin score >/= 2 at 30 and 90 days

10. Urgent/Emergent Conversion to Surgery or Repeat Procedure for Valve-related Dysfunction [Discharge or 7 days post-procedure, whichever comes first]

11. Major Vascular Complication [Discharge or 7 days post-procedure, whichever comes first]

    Any thoracic aortic dissection Access site or access-related vascular injury (dissection, stenosis, perforation, rupture, arterio-venous fistula, pseudoaneurysm, hematoma, irreversible nerve injury, or compartment syndrome) leading to either death, need for significant blood transfusions (≥4 units), unplanned percutaneous or surgical intervention, or irreversible end-organ damage (e.g. hypogastric artery occlusion causing visceral ischemia or spinal artery injury causing neurologic impairment) Distal embolization (non-cerebral) from a vascular source requiring surgery or resulting in amputation or irreversible end-organ damage

12. New Conduction Disturbances or Arrhythmias Requiring Permanent Pacemaker [Discharge or 7 days post-procedure, whichever comes first]

13. Bleeding [Discharge or 7 days post-procedure, whichever comes first]

    Life-threatening or Disabling Bleeding Fatal bleeding OR Bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, or pericardial necessitating pericardiocentesis, or intramuscular with compartment syndrome OR Bleeding causing hypovolemic shock or severe hypotension requiring vasopressors or surgery OR Overt source of bleeding with drop in hemoglobin of ≥5 g/dL or whole blood or packed red blood cells (RBC) transfusion ≥4 units Major Bleeding 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 AND Does not meet criteria of life-threatening or disabling bleeding

14. Acute Kidney Injury - Stage 2 or 3 [Discharge or 7 days post-procedure, whichever comes first]

    Stage 2: Increase in serum creatinine to 200-300% (2.0-3.0 times increase compared with baseline). Stage 3: Increase in serum creatinine to ≥ 300% (> 3 times increase compared with baseline) or serum creatinine of ≥ 4.0 mg/d (≥ 354 μmol/L) with an acute increase of at least 0.5 mg/dl (44 μmol/L). Subjects receiving renal replacement therapy are considered to meet Stage 3 criteria irrespective of other criteria.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 70 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patient must be at least 70 years of age or older, and meets all of the criteria below.

2. Patient has documented calcified native aortic valve stenosis, defined with an initial aortic valve area (AVA) of <1.0 cm2 (or AVA index of <0.6 cm2/m2), and a mean pressure gradient >40 mmHg or a jet velocity >4 m/s, as measured by echocardiography.

3. The patient is considered at high risk for surgical aortic valve replacement with an STS (Society of Thoracic Surgeons) score ≥8% or a EuroSCORE ≥20%, or documented multidisciplinary heart team agreement that the patient is at high risk for surgery due to frailty and/or coexisting comorbidities.

4. Symptomatic aortic valve stenosis with New York Heart Association (NYHA) Functional Class ≥ II.

5. Patient has a documented aortic annulus size between 19 and 22 mm (able to accommodate the 23 mm Lotus™ Valve). Pre-procedure measurement by transthoracic echocardiography (TTE) is required. Other imaging modalities (e.g., transesophageal echocardiography (TEE), CT scan) can be used in an adjunctive manner.

6. Patient (or legal representative) understands the trial requirements and the treatment procedures, and provides written informed consent.

7. Patient agrees and is capable of returning to the study hospital for all required scheduled follow up visits.

Exclusion Criteria:

1. Patient has a congenital unicuspid or bicuspid aortic valve.

2. Patient with an acute myocardial infarction (MI) within 30 days of the index procedure (defined as Q wave MI, or non-Q wave MI with total creatine kinase (CK) elevation ≥ twice normal in the presence of CK-MB elevation and/or troponin level elevation (WHO definition)).

3. Patient has had a cerebrovascular accident (CVA) or transient ischemic attack (TIA) within the past 6 months, or has any permanent neurologic defect prior to study enrollment.

4. Patient is on dialysis or has serum creatinine level >3.0 mg/dL.

5. Patient has a pre-existing prosthetic heart valve (aortic or mitral) or a prosthetic ring in any position.

6. Patient has >2+ mitral regurgitation or >2+ aortic regurgitation (ie., patient cannot have more than moderate mitral or aortic regurgitation).

7. Moderate to severe pulmonary hypertension (PA systolic pressure >60 mm Hg) as assessed by transthoracic echocardiography.

8. Patient has a need for emergency surgery for any reason.

9. Patient has a history of endocarditis within 12 months of index procedure or evidence of an active systemic infection or sepsis.

10. Patient has echocardiographic evidence of intra-cardiac mass, thrombus or vegetation.

11. Patient has Hgb <9 g/dL, platelet count <100,000 cells/mm3 or >700,000 cells/mm3, and white blood cell (WBC) count <3,000 cells/mm3.

12. Patient is receiving chronic (≥72 hours) anticoagulation therapy (e.g., heparin, warfarin) and who cannot tolerate concomitant therapy with aspirin and clopidogrel (patients who require chronic anticoagulation must be treated with either aspirin or clopidogrel).

13. Patient has active peptic ulcer disease, gastrointestinal (GI) bleed within the past 3 months, other bleeding diathesis or coagulopathy or will refuse transfusions.

14. Patient is contraindicated for transesophageal echocardiography (TEE).

15. Patient has known hypersensitivity to contrast agents that cannot be adequately pre-medicated, or has known hypersensitivity to aspirin, all thienopyridines, heparin, nickel, titanium, or polyurethanes.

16. Patient has a life expectancy of less than 12 months due to non-cardiac, co-morbid conditions based on the assessment of the investigator at the time of enrollment.

17. Patient has other cardiac devices or hardware with which the study device will interfere with device placement (per physician judgment).

18. Patient has hypertrophic obstructive cardiomyopathy.

19. Patient has any therapeutic invasive cardiac procedure within 30 days prior to the index procedure.

20. Untreated clinically significant coronary artery disease requiring revascularization.

21. Patient has documented left ventricular ejection fraction (LVEF) <30%.

22. Patient is in cardiogenic shock or has hemodynamic instability requiring inotropic support or mechanical support devices.

23. Patient has severe peripheral vascular disease (including aneurysm defined as maximal luminal diameter >5cm or with documented presence of thrombus, marked tortuosity, narrowing of the abdominal aorta, severe unfolding of the thoracic aorta or thick (>5mm), protruding or ulcerated atheroma in the aortic arch) or symptomatic carotid or vertebral disease.

24. Patient has a femoral artery lumen of <6.0 mm or severe iliofemoral tortuosity or calcification that would prevent safe placement of the introducer sheath.

25. Current problems with substance abuse (e.g. alcohol, cocaine, heroin, etc).

26. Patient is participating in another investigational drug or device study that has not reached its primary endpoint.

27. Patient has preexisting untreated conduction system disorders: Type II second-degree atrioventricular (AV) block, bifascicular or trifascicular block.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
2	St. Vincent's Hospital	Melbourne	Victoria	Australia	3040
3	Southern Health Monash Medical Centre	Melbourne	Victoria	Australia	3168

Sponsors and Collaborators

• Boston Scientific Corporation

Investigators

• Principal Investigator: Ian Meredith, MBBS, PhD, Southern Health, Monash Medical Centre

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Boston Scientific Corporation
• ClinicalTrials.gov Identifier: NCT01383720
• Other Study ID Numbers: TP3659
• First Posted: Jun 28, 2011
• Last Update Posted: Jun 20, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Boston Scientific Corporation: Aortic Valve Stenosis; Transcatheter Aortic Valve Replacement
• Additional relevant MeSH terms: Aortic Valve Stenosis; Aortic Valve Disease

Study Results

Participant Flow

Recruitment Details	Patients were identified by their physicians as meeting the study inclusion/exclusion criteria.
Pre-assignment Detail	Screening materials from patients identified by the investigators as having met the inclusion and exclusion criteria were reviewed by a Case Review Committee to assess and confirm eligibility.

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Period Title: Overall Study
STARTED	11
Primary Endpoint (Discharge/7 Days)	11
COMPLETED	11
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Overall Participants	11
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	11 100%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	83.0 (3.6)
Sex: Female, Male (Count of Participants)
Female	11 100%
Male	0 0%
Region of Enrollment (participants) [Number]
Australia	11 100%
General Medical History (participants) [Number]
Diabetes mellitus (current)	5 45.5%
Hyperlipidemia (medically treated)	8 72.7%
Hypertension (medically treated)	10 90.9%
History of peripheral vascular disease	1 9.1%
Dialysis dependent renal failure	0 0%
Chronic obstructive pulmonary disease	1 9.1%
Cardiac History (participants) [Number]
Coronary artery disease	5 45.5%
Previous percutaneous coronary intervention	2 18.2%
Previous coronary artery bypass graft surgery	0 0%
History of atrial fibrillation	5 45.5%
New York Heart Association Class (participants) [Number]
Class I	0 0%
Class II	6 54.5%
Class III	5 45.5%
Class IV	0 0%
Modified Rankin Scale (participants) [Number]
0	10 90.9%
1	0 0%
2	1 9.1%
3 or higher	0 0%
Neurological History (participants) [Number]
Transient Ischemic Attack	1 9.1%
Cerebrovascular Accident	2 18.2%
Aortic valve area (effective orifice area) (cm^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm^2]	0.68 (0.19)
Mean Aortic Valve Gradient (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	53.9 (20.9)
Left Ventricular Ejection Fraction (percent of LVEF) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent of LVEF]	62.3 (7.6)
Aortic regurgitation (moderate or severe) (participants) [Number]
Number [participants]	4 36.4%
Mitral Regurgitation (moderate or severe) (participants) [Number]
Number [participants]	3 27.3%
Body mass index (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	27.6 (6.0)
Serum Albumin (g/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/dL]	3.9 (0.4)
5-Meter Gait Speed (seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [seconds]	8.2 (4.9)
Maximum Grip Strength Average (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	15.3 (5.7)
Katz Index (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.9 (0.3)
Mini-Cognitive Assessment for Dementia (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	3.3 (1.5)
Charlson Comorbidity Index Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	1.8 (1.7)
Society of Thoracic Surgeons (STS) Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.9 (2.5)
EuroScore (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	9.5 (4.4)

Outcome Measures

1. Primary Outcome

Title	Clinical Procedural Success
Description	Clinical procedural success defined as successful implantation of a Lotus Valve System (Device Success) without in-hospital Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) through discharge or 7 days post-procedure, whichever comes first.
Time Frame	Discharge or 7 days post-procedure, whichever comes first

Outcome Measure Data

Analysis Population Description

Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
Number [participants]	9 81.8%

2. Secondary Outcome

Title	Device Performance Endpoint-Repositioning
Description	Successful repositioning of the Lotus Valve System if repositioning is attempted
Time Frame	procedure

Outcome Measure Data

Analysis Population Description

Patients in whom repositioning of the Lotus Valve was attempted

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	4
Number [participants]	4 36.4%

3. Secondary Outcome

Title	Device Performance Endpoint-Valve Retrieval, if Attempted
Description	Successful retrieval of the Lotus Valve System if retrieval is attempted
Time Frame	procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
Number [participants]	NA NaN

4. Secondary Outcome

Title	Central Aortic Regurgitation
Description	As determined by echocardiography
Time Frame	Discharge or 7 days post-procedure, whichever comes first

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
None	10 90.9%
Trivial	1 9.1%
Mild	0 0%
Moderate or Severe	0 0%

5. Secondary Outcome

Title	Paravalvular Aortic Regurgitation
Description	As determined by echocardiography
Time Frame	Discharge or 7 days post-procedure, whichever comes first

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
None	8 72.7%
Trivial	1 9.1%
Mild	2 18.2%
Moderate or Severe	0 0%

6. Other Pre-specified Outcome

Title	Successful Access, Device Delivery, Deployment and Positioning and Retrieval of Delivery System
Time Frame	Procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
Number [participants]	11 100%

7. Other Pre-specified Outcome

Title	Intended Performance of the Lotus Valve
Description	Aortic valve area >1.0 cm2 plus either a mean aortic valve gradient <20 mmHg or peak velocity <3m/sec, without moderate or severe prosthetic valve aortic regurgitation
Time Frame	At time of discharge or 7 days post procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
Number [participants]	10 90.9%

8. Other Pre-specified Outcome

Title	Single Valve Implanted in the Proper Anatomical Location
Time Frame	procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
Number [participants]	11 100%

9. Other Pre-specified Outcome

Title	No Major Adverse Cardiovascular and Cerebrovascular Events Through Discharge
Description	Major adverse cardiovascular or cerebrovascular events include all-cause mortality, periprocedural myocardial infarction ≤72 hours, major stroke, urgent/emergent conversion to surgery or repeat procedure for valve-related dysfunction
Time Frame	Discharge or 7 days post-procedure, whichever comes first

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
Number [participants]	10 90.9%

10. Other Pre-specified Outcome

Title	Mean Aortic Valve Gradient
Description	As determined by echocardiography
Time Frame	Discharge or 7 days post-procedure, whichever comes first

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
Mean (Standard Deviation) [mm Hg]	13.7 (3.7)

11. Other Pre-specified Outcome

Title	Aortic Valve Area
Description	As determined by echocardiography
Time Frame	Discharge or 7 days post-procedure, whichever comes first

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
Mean (Standard Deviation) [cm^2]	1.53 (0.18)

12. Other Pre-specified Outcome

Title	Death
Time Frame	Discharge or 7 days post-procedure, whichever comes first

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
Number [participants]	0 0%

13. Other Pre-specified Outcome

Title	Peri-procedural Myocardial Infarction
Description	Peri-Procedural Myocardial Infarction (≤72 hours after the index procedure) New ischemic symptoms (e.g., chest pain or shortness of breath), or new ischemic signs (e.g. ventricular arrhythmias, new or worsening heart failure, new ST-segment changes, hemodynamic instability, or imaging evidence of new loss of viable myocardium or new wall motion abnormality), AND Elevated cardiac biomarkers (preferably creatine kinase-myoglobin band) within 72 h after the index procedure, consisting of two or more post-procedure samples that are > 0.6 to 8 h apart with a 20% increase in the second sample and a peak value exceeding 10X the 99th percentile upper reference limit (URL), or a peak value exceeding 5X the 99th percentile URL with new pathological Q waves in at least 2 contiguous leads
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
Number [participants]	0 0%

14. Other Pre-specified Outcome

Title	Major Stroke
Description	Confirmed with a Modified Rankin score >/= 2 at 30 and 90 days
Time Frame	Discharge or 7 days post-procedure, whichever comes first

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
Number [participants]	1 9.1%

15. Other Pre-specified Outcome

Title	Urgent/Emergent Conversion to Surgery or Repeat Procedure for Valve-related Dysfunction
Time Frame	Discharge or 7 days post-procedure, whichever comes first

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
Number [participants]	0 0%

16. Other Pre-specified Outcome

Title	Major Vascular Complication
Description	Any thoracic aortic dissection Access site or access-related vascular injury (dissection, stenosis, perforation, rupture, arterio-venous fistula, pseudoaneurysm, hematoma, irreversible nerve injury, or compartment syndrome) leading to either death, need for significant blood transfusions (≥4 units), unplanned percutaneous or surgical intervention, or irreversible end-organ damage (e.g. hypogastric artery occlusion causing visceral ischemia or spinal artery injury causing neurologic impairment) Distal embolization (non-cerebral) from a vascular source requiring surgery or resulting in amputation or irreversible end-organ damage
Time Frame	Discharge or 7 days post-procedure, whichever comes first

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
Number [participants]	1 9.1%

17. Other Pre-specified Outcome

Title	New Conduction Disturbances or Arrhythmias Requiring Permanent Pacemaker
Time Frame	Discharge or 7 days post-procedure, whichever comes first

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
Number [participants]	4 36.4%

18. Other Pre-specified Outcome

Title	Bleeding
Description	Life-threatening or Disabling Bleeding Fatal bleeding OR Bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, or pericardial necessitating pericardiocentesis, or intramuscular with compartment syndrome OR Bleeding causing hypovolemic shock or severe hypotension requiring vasopressors or surgery OR Overt source of bleeding with drop in hemoglobin of ≥5 g/dL or whole blood or packed red blood cells (RBC) transfusion ≥4 units Major Bleeding 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 AND Does not meet criteria of life-threatening or disabling bleeding
Time Frame	Discharge or 7 days post-procedure, whichever comes first

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
Life-threatening or disabling	0 0%
Major	2 18.2%

19. Other Pre-specified Outcome

Title	Acute Kidney Injury - Stage 2 or 3
Description	Stage 2: Increase in serum creatinine to 200-300% (2.0-3.0 times increase compared with baseline). Stage 3: Increase in serum creatinine to ≥ 300% (> 3 times increase compared with baseline) or serum creatinine of ≥ 4.0 mg/d (≥ 354 μmol/L) with an acute increase of at least 0.5 mg/dl (44 μmol/L). Subjects receiving renal replacement therapy are considered to meet Stage 3 criteria irrespective of other criteria.
Time Frame	Discharge or 7 days post-procedure, whichever comes first

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
Measure Participants	11
Number [participants]	0 0%

Adverse Events

Time Frame	After 1 year index procedure
Arm/Group Title	Lotus Valve System
Arm/Group Description	Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
All Cause Mortality
	Lotus Valve System
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lotus Valve System
	Affected / at Risk (%)	# Events
Total	6/11 (54.5%)
Cardiac disorders
Atrioventricular block complete	2/11 (18.2%)	2
Bradycardia	1/11 (9.1%)	1
Pericardial effusion	1/11 (9.1%)	1
Ventricular fibrillation	1/11 (9.1%)	1
Nervous system disorders
Ischaemic stroke	1/11 (9.1%)	1
Renal and urinary disorders
Renal failure acute	1/11 (9.1%)	1
Vascular disorders
Haematoma	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Lotus Valve System
	Affected / at Risk (%)	# Events
Total	11/11 (100%)
Blood and lymphatic system disorders
Anaemia	1/11 (9.1%)	1
Cardiac disorders
Bundle branch block left	7/11 (63.6%)	7
Myocardial infarction	1/11 (9.1%)	1
Gastrointestinal disorders
Constipation	1/11 (9.1%)	1
General disorders
Chest discomfort	1/11 (9.1%)	1
Pyrexia	1/11 (9.1%)	1
Secretion discharge	1/11 (9.1%)	1
Immune system disorders
Drug hypersensitivity	1/11 (9.1%)	1
Infections and infestations
Otitis externa	1/11 (9.1%)	1
Urinary tract infection	1/11 (9.1%)	1
Injury, poisoning and procedural complications
Arterial injury	1/11 (9.1%)	1
Investigations
Hepatic enzyme increased	1/11 (9.1%)	1
Nervous system disorders
Dizziness	1/11 (9.1%)	1
Psychiatric disorders
Confusional state	1/11 (9.1%)	1
Delirium	1/11 (9.1%)	1
Skin and subcutaneous tissue disorders
Petechiae	1/11 (9.1%)	1
Vascular disorders
Haematoma	3/11 (27.3%)	3
Peripheral artery dissection	1/11 (9.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Principal Investigator (PI) shall have the right to publish the results, provided that before publishing, the PI shall submit copies of any proposed publication or presentation to the Sponsor for review at least 45 days in advance of submission for publication or presentation to a publisher or other third party. Sponsor reserves the right to delete any confidential information or other proprietary information of Sponsor from the proposed publication or presentation.