RESPOND Post Market Study

Study Overview
=================
Brief Summary
-----------------
The purpose of the RESPOND post market study is to collect real world clinical and device performance outcomes data with the Lotus Valve System used in routine clinical practice to demonstrate that the commercially available Lotus Valve System is a safe and effective treatment for patients with severe calcific aortic stenosis.

Detailed Description
-----------------
The RESPOND study is a prospective, open label, single arm, multi-center, observational post market study designed to collect real world clinical and device performance outcomes data of the commercially available Lotus Valve used in routine clinical practice for the treatment of severe calcific aortic stenosis. Approximately 1000 real-world, consecutive subjects will be enrolled at up to 50 study centers in Europe, Asia Pacific and Central/South America. All enrolled subjects will be contacted for follow-up at 30 days, 1, 2, 3, 4 and 5 years post index valve implantation. Follow-up visit at 1 year post valve implantation should be conducted via outpatient clinic visit. Follow-up visits at 30 days and 2 through 5 years may be conducted in person (preferred) and via telephone interview. Subjects who are not implanted with a Lotus Valve will be followed for safety through 30 days after the initial attempted index procedure. Collection of safety events will include any serious adverse event (SAE) that led to death, serious adverse device effect (SADE), adverse device effect (ADE), unanticipated serious adverse device effect (USADE), and all Valve Academic Research Consortium (VARC) events regardless of seriousness and device relationship through 5 year follow-up. The RESPOND study will be conducted in accordance with the International Organization for Standardization (ISO) 14155: 2011; ethical principles that have their origins in the Declaration of Helsinki; the relevant parts of the International Conference on Harmonization (ICH) Guidelines for Good Clinical Practices (GCP); and pertinent individual country/state/local laws and regulations. An additional cohort of approximately 50 subjects will be enrolled at up to 6 study centers in Europe after enrollment in the main cohort is completed to assess center-driven implantation technique with the commercially available Lotus Valve with Depth Guard technology.

Official Title
-----------------
RESPOND: Re-positionable Lotus Valve System - Post Market Evaluation of Real World Clinical Outcomes

Conditions
-----------------
Aortic Valve Stenosis

Intervention / Treatment
-----------------
* Device: Lotus Valve System


Participation Criteria
=================
Eligibility Criteria
-----------------
Subjects will be evaluated for eligibility by the clinical center's heart team per the local standard of practice in accordance with the Directions for Use.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lotus Valve<br>All subjects who are candidates for Transcatheter Aortic Valve Implantation (TAVI), signed the Informed Consent Form (ICF) and are selected to receive a Lotus Valve. | Device: Lotus Valve System<br>* The Lotus Valve System is indicated to improve aortic valve function for symptomatic subjects with severe calcific aortic stenosis (aortic valve area [AVA] of <1.0 cm2 or index of <0.6 cm2/m2) who are at high risk for standard surgical valve replacement.<br>|
| Lotus with Depth Guard<br>All subjects who are candidates for Transcatheter Aortic Valve Implantation (TAVI), signed the Informed Consent Form (ICF) and are selected to receive a Lotus with Depth Guard. | Device: Lotus Valve System<br>* The Lotus Valve System is indicated to improve aortic valve function for symptomatic subjects with severe calcific aortic stenosis (aortic valve area [AVA] of <1.0 cm2 or index of <0.6 cm2/m2) who are at high risk for standard surgical valve replacement.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Mortality | The primary endpoint is all-cause mortality at 30 days after the implant procedure. The primary safety endpoint will be evaluated on an intention-to-treat (ITT) basis (all subjects enrolled, whether or not a Lotus Valve is implanted). All-cause mortality at 30 days after the implant procedure will be compared to a pre-specified performance goal. | 30 Days | 
| All-cause Mortality | The primary endpoint is all-cause mortality at 1 year after the implant procedure. The primary safety endpoint will be evaluated on an intention-to-treat (ITT) basis (all subjects enrolled, whether or not a Lotus Valve is implanted). A total of 116 subjects died through 1 year (365 days) post procedure (as treated population). 4 additional patients died but were not treated with the study valve system (ITT population). The Lotus Valve cohort is an ongoing study in it's 4 year follow up. The Lotus with Depth Guard cohort ended after 30 day follow up, therefore we have no data at 1 year. | 1 Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Events Included in the Safety Composite Endpoint of All-Cause Mortality and Disabling Stroke | All subjects who are candidates for transcatheter aortic valve implantation (TAVI), signed the Informed Consent Form (ICF) and are selected to receive a Lotus Valve will be evaluated for enrollment in this study (as treated population) The Lotus Valve cohort is an ongoing study in it's 4 year follow up. The Lotus with Depth Guard cohort ended after 30 day follow up, therefore we have no data at 1 year. | 30 Days and 1 year | 
| In-hospital Mortality | In-hospital mortality till discharge | Duration of hospital stay, an expected average of 2 days | 
| Percentage of Participants With Events Included in the VARC Efficacy Composite Endpoint | The VARC efficacy composite at 1 year, including all-cause mortality; all stroke (disabling and non-disabling); re-hospitalization for valve-related symptoms or worsening congestive heart failure (NYHA class III or IV); and prosthetic valve-related dysfunction (mean aortic valve gradient ≥20 mmHg, effective orifice area (EOA) ≤0.9-1.1 cm2 and/or Doppler velocity index (DVI) <0.35 m/s, AND/OR moderate or severe prosthetic valve aortic regurgitation) | 1 Year | 
| Patients With Valve Safety Composite Outcomes at 1 Year | Time related valve safety composite outcomes at 1 year, including structural valve deterioration (valve-related dysfunction requiring repeat procedure [TAVI or SAVR]); prosthetic valve endocarditis; prosthetic valve thrombosis; thromboembolic events (e.g. stroke) and VARC bleeding, unless clearly unrelated to valve therapy based on investigator assessment (e.g. trauma). The Lotus Valve cohort is an ongoing study in it's 4 year follow up. The Lotus with Depth Guard cohort ended after 30 day follow up, therefore we have no data at 1 year. | 1 Year | 
| Patients With VARC Safety Composite Outcomes at 30 Days | Patients with VARC safety composite outcomes at 30 days. VARC safety composite endpoints are defined as: Life-threatening bleeding Acute kidney injury-Stage 2 or 3 (including renal replacement therapy) Coronary artery obstruction requiring intervention Major vascular complication Valve-related dysfunction requiring repeat procedure (BAV, TAVI, or SAVR) New conduction disturbances (LBBB, AVB, RBBB) and need for permanent pacemaker implantation | 30 Days | 
| Patients With Moderate and Severe Paravalvular Aortic Valve Regurgitation | Grade of paravalvular aortic valve regurgitation pre-discharge as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory. The moderate and severe paravalvular aortic regurgitation rate will be compared to a pre-specified performance goal. We don't have a powered analysis for the PVL for RESPOND study. | Duration of hospital stay, an expected average of 2 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lotus, Valve, Real world, Aortic stenosis, High risk