RESPOND Post Market Study (RESPOND)

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

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.

Study Overview

• Status: Completed
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Device: Lotus Valve System

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.

• Study Type: Observational
• Enrollment (Actual): 1064

Contacts and Locations

Study Locations

• Colombia
  • Cali, Colombia
    • Angiografia De Occidente S.A.
  • Floridablanca, Colombia
    • Fundacion Cardiovascular de Colombia
• Finland
  • Helsinki, Finland, 00290 HUS
    • Helsinki University Central Hospital/Meilahti Hospital
  • Turku, Finland, 20521
    • Turku University Hospital
• Germany
  • Bad Segeberg, Germany, 23795
    • Herz-Kreislauf-Zentrum Segeberger Kliniken GmbH
  • Berlin, Germany, 10249
    • Vivantes Klinikum Im Friedrichshain
  • Berlin, Germany, 13353
    • Charite Campus Virchow Klinikum
  • Berlin, Germany, 24105
    • Deutsches Herzzentrum Berlin
  • Bonn, Germany, 53113
    • Herz- und Gefäß-Klinik Bonn
  • Hamburg, Germany
    • Asklepios Klinik St. Georg
  • Leipzig, Germany, 04289
    • Herzzentrum Universität Leipzig
  • Munich, Germany, 81377
    • University Hospital Munich
  • Munich, Germany, 80636
    • Deutsches Herzzentrum München
  • Rostock, Germany, 10249
    • Universitätsklinikum Rostock
  • Siegburg, Germany, 53721
    • HELIOS Clinic
  • Ulm, Germany, 69120
    • Universitatsklinikum Ulm
  • NRW
    • Bonn, NRW, Germany, 53105
      • Universitätsklinikum Bonn
  • Rheinland Pfalz
    • Trier, Rheinland Pfalz, Germany, 76133
      • Krankenhaus d. Barmherzigen Brüder
• Israel
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center
• Italy
  • Milano, Italy, 20132
    • Ospedale San Raffaele
  • Mi
    • Milan, Mi, Italy, 20149
      • IRCC Policlinico San Donato
  • PD
    • Padova, PD, Italy, 35100
      • Azienda Ospedaliera Universtitaria di Padova
  • PI
    • Pisa, PI, Italy, 56124
      • Azienda Ospedaliera Universtiatia Pisana (AOUP) Ospedale Cisanello
• Netherlands
  • Rotterdam, Netherlands
    • Erasmus Medical Center
  • EM
    • Nieuwegein, EM, Netherlands, 3430
      • Dept. of Cardiology Sint-Antonius ziekenhuis
• New Zealand
  • Hamilton, New Zealand, 3240
    • Waikato Hospital
• Norway
  • Bergen, Norway, 5021
    • Haukeland Universitetssjukehus
• Poland
  • Poznań, Poland, 61-848
    • I Klinika Kardiologii Uniwersytetu Medycznego W Poznaiu
  • Warsaw, Poland, 04-628
    • National Institute of Cardiology
• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • San Sebastián, Spain, 20011
    • Policlinica Gipuzkoa
• Sweden
  • Gothenburg, Sweden, 413 45
    • Sahlgrenska University Hospital
• Switzerland
  • Bern, Switzerland, CH-3010
    • Inselspital - Universitätsspital Bern
• United Kingdom
  • Brighton, United Kingdom, BN2 5BE
    • Royal Sussex County Hospital
  • Leeds, United Kingdom, LS1 3EX
    • Leeds Teaching Hospitals NHS
  • Leicester, United Kingdom, LE3 9QP
    • Glenfield Hospital
  • London, United Kingdom, SE5 9RS
    • King's College Hospital London
  • London, United Kingdom, SE1 7EH
    • Clinical Trials Practitioner
  • London, United Kingdom, SW17 0QT
    • Cardiovascular & Cell Sciences Research Institute
  • Wolverhampton, United Kingdom, WV10 0QP
    • New Cross Hospital
  • England
    • Oxford, England, United Kingdom, OX3 9DU
      • John Radcliffe Infirmary Oxford II

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Lotus Valve; 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; 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.
Lotus with Depth Guard; 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; 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.

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

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Investigators: Principal Investigator: Nicolas Van Mieghem, MD, Erasmus Medical Center; Principal Investigator: Volkmar Falk, MD, PhD, German Heart Center Berlin

Publications and helpful links

General Publications

• Van Mieghem NM, Wohrle J, Hildick-Smith D, Bleiziffer S, Blackman DJ, Abdel-Wahab M, Gerckens U, Linke A, Ince H, Wenaweser P, Allocco DJ, Meredith IT, Falk V. Use of a Repositionable and Fully Retrievable Aortic Valve in Routine Clinical Practice: The RESPOND Study and RESPOND Extension Cohort. JACC Cardiovasc Interv. 2019 Jan 14;12(1):38-49. doi: 10.1016/j.jcin.2018.10.052.
• Falk V, Wohrle J, Hildick-Smith D, Bleiziffer S, Blackman DJ, Abdel-Wahab M, Gerckens U, Linke A, Ince H, Wenaweser P, Allocco DJ, Dawkins KD, Van Mieghem NM. Safety and efficacy of a repositionable and fully retrievable aortic valve used in routine clinical practice: the RESPOND Study. Eur Heart J. 2017 Dec 1;38(45):3359-3366. doi: 10.1093/eurheartj/ehx297.

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2014
• Primary Completion (Actual): April 4, 2017
• Study Completion (Actual): May 18, 2021

Study Registration Dates

• First Submitted: January 6, 2014
• First Submitted That Met QC Criteria: January 8, 2014
• First Posted (Estimate): January 9, 2014

Study Record Updates

• Last Update Posted (Actual): November 19, 2021
• Last Update Submitted That Met QC Criteria: November 18, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Aortic stenosis; High risk; Real world; Valve; Lotus
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: TP6461

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The data and study protocol for this clinical trial may be made available to other researchers in accordance with the Boston Scientific Data Sharing Policy (http://www.bostonscientific.com/en-US/data-sharing-requests.html).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No