Inspiris Resilia Durability Registry (INDURE)

Clinical Outcomes of Patients Under the Age of Sixty Undergoing INSPIRIS RESILIA Aortic Valve Replacement

Prospective, open-label, multicenter, European registry with a follow-up of 5 years to assess the clinical outcomes of patients younger than 60 years who undergo surgical AVR with the INSPIRIS RESILIA Aortic Valve™.

Study Overview

• Status: Active, not recruiting
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Device: AVR with or without CABG

Detailed Description

The INSPIRIS RESILIA Aortic Valve™ is a stented tri-leaflet valve comprised of bovine pericardial tissue. The tissue is created by treating bovine pericardial tissue with Edwards Integrity Preservation. It incorporates a stable capping anticalcification process, which blocks residual aldehyde groups known to bind with calcium. Tissue preservation with glycerol allows the valve to be stored without a traditional liquid-based solution, such as glutaraldehyde. Therefore, valve is stored under dry packaging conditions and consequently does not require rinsing prior to implantation.

The novel tissue preservation technology significantly improves hemodynamic and anticalcification properties compared with the standard Perimount valve in an ovine model. In this registry, data is collected over a period of 5 years to demonstrate these properties in a clinical real-life setting. Clinical outcomes, hemodynamic as well as safety parameters and quality of life data are documented into e-CRF at baseline, surgery, pre-discharge, 3-6 months and annually up to year 5.

The required sample size was calculated using the online calculator at http://www.surveysystem.com/sscalc.htm. It was estimated, from COMMENCE Trial dataset that freedom from time-related valve safety events at 1 year (composite endpoint according to VARC-2) is around 0.915. The following table illustrates 95% CIs at different levels of risk:

Sample Size Observed freedom from event 95%CI 400 0.900 ± 0.0294 400 0.910 ± 0.0280 400 0.915 ± 0.0214 400 0.920 ± 0.0266 400 0.930 ± 0.0250

20% of registry sites will be monitored with 100% source data verification

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

Study Locations

• Austria
  • St. Pölten, Austria, 3100
    • University Clinics St. Pölten
  • Vienna, Austria, 1090
    • Medical University Vienna
  • Vienna, Austria, 1080
    • Heart Center Hietzing
• Belgium
  • Leuven, Belgium
    • KU Leuven
• Canada
  • Montréal, Canada, H1T 1C8
    • Institut de Cardiologie de Montréal, Université de Montréal
  • Québec, Canada, G1V 0A6
    • Laval University
• France
  • Marseille, France, 13005
    • Hopital de la Timone
  • Nantes, France, 44100
    • L'institut du thorax - CHU (Centre Hospitalier Universitaire de Nantes)
  • Rennes, France, 35033
    • Centre Hospitalier Universitaire (CHU) de Rennes
  • Tours, France
    • CHRU - Hospital Trousseau
• Germany
  • Leipzig, Germany
    • Heart Center Leipzig
  • Baden-Württemberg
    • Freiburg, Baden-Württemberg, Germany, 79106
      • UNIVERSITÄTSKLINIKUM FREIBURG, Universitäts-Herzzentrum Herz- und Gefäßchirurgie
• Italy
  • Florence, Italy, 50139
    • University Hospital Careggi
  • Milano, Italy, 20138
    • Centro Cardiologico Monzino
  • Roma, Italy
    • European Hospital Rome
  • Salerno, Italy, 84131
    • AOU San Giovanni di Dio e Ruggi d'Aragona
• Netherlands
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus Medisch Centrum
• Spain
  • Murcia, Spain, 30120
    • University Hospital Virgen de la Arrixaca
• United Kingdom
  • Edinburgh, United Kingdom, EH1 3EG
    • NHS Lothian
  • Glenfield, United Kingdom, LE3 9QP
    • Glenfield Hospital
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients under the age of 60 with an indication for surgical AVR who will receive an Edwards INSPIRIS RESILIA aortic valve prosthesis.

Description

Inclusion Criteria:

1. Age 18 to 60 years inclusive
2. Subject requiring a planned replacement of their native aortic valve as indicated in a preoperative evaluation
3. Subject is scheduled to undergo planned aortic valve replacement with or without concomitant root replacement and/or coronary bypass surgery
4. Subject is scheduled to attend yearly follow-up visits at the registry center up to 5 years follow-up
5. Subject provides written informed consent prior to the procedure

Exclusion Criteria:

1. Active endocarditis/myocarditis or endocarditis/myocarditis within 3 months prior to the scheduled aortic valve replacement surgery
2. Previous aortic valve replacement
3. Valve implantation is not possible in accordance with the device IFU
4. Subject has a life expectancy ≤ 12 months for any reason

Intraoperative Exclusion criteria:

1. Valve implantation is not possible in accordance with the device IFU

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-related valve safety	Composite endpoint according to VARC-2 depicted as freedom from event: SVD (structural valve deterioration); Valve-related dysfunction; Requirement of repeat procedure; Prosthetic valve endocarditis; Prosthetic valve thrombosis; Thromboembolic events (e.g. stroke); Valve-related VARC bleeding	Year 1
Freedom from severe SVD (structural valve deterioration)	Freedom from stage 3 SVD including stenosis and regurgitation determined by echocardiography	Year 5

Collaborators and Investigators

• Sponsor: Institut für Pharmakologie und Präventive Medizin
• Collaborators: Edwards Lifesciences
• Investigators: Study Director: Peter Bramlage, Professor, CEO IPPMed; Principal Investigator: Ruggero dePaulis, Professor, European Hospital Rome, Italy; Principal Investigator: Bart Meuris, Professor, UZ Leuven, Belgium

Publications and helpful links

General Publications

• Flameng W, Hermans H, Verbeken E, Meuris B. A randomized assessment of an advanced tissue preservation technology in the juvenile sheep model. J Thorac Cardiovasc Surg. 2015 Jan;149(1):340-5. doi: 10.1016/j.jtcvs.2014.09.062. Epub 2014 Sep 28.
• Puskas JD, Bavaria JE, Svensson LG, Blackstone EH, Griffith B, Gammie JS, Heimansohn DA, Sadowski J, Bartus K, Johnston DR, Rozanski J, Rosengart T, Girardi LN, Klodell CT, Mumtaz MA, Takayama H, Halkos M, Starnes V, Boateng P, Timek TA, Ryan W, Omer S, Smith CR; COMMENCE Trial Investigators. The COMMENCE trial: 2-year outcomes with an aortic bioprosthesis with RESILIA tissue. Eur J Cardiothorac Surg. 2017 Sep 1;52(3):432-439. doi: 10.1093/ejcts/ezx158.
• Kappetein AP, Head SJ, Genereux P, Piazza N, van Mieghem NM, Blackstone EH, Brott TG, Cohen DJ, Cutlip DE, van Es GA, Hahn RT, Kirtane AJ, Krucoff MW, Kodali S, Mack MJ, Mehran R, Rodes-Cabau J, Vranckx P, Webb JG, Windecker S, Serruys PW, Leon MB; Valve Academic Research Consortium-2. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. EuroIntervention. 2012 Nov 22;8(7):782-95. doi: 10.4244/EIJV8I7A121.
• Dvir D, Bourguignon T, Otto CM, Hahn RT, Rosenhek R, Webb JG, Treede H, Sarano ME, Feldman T, Wijeysundera HC, Topilsky Y, Aupart M, Reardon MJ, Mackensen GB, Szeto WY, Kornowski R, Gammie JS, Yoganathan AP, Arbel Y, Borger MA, Simonato M, Reisman M, Makkar RR, Abizaid A, McCabe JM, Dahle G, Aldea GS, Leipsic J, Pibarot P, Moat NE, Mack MJ, Kappetein AP, Leon MB; VIVID (Valve in Valve International Data) Investigators. Standardized Definition of Structural Valve Degeneration for Surgical and Transcatheter Bioprosthetic Aortic Valves. Circulation. 2018 Jan 23;137(4):388-399. doi: 10.1161/CIRCULATIONAHA.117.030729.
• Capodanno D, Petronio AS, Prendergast B, Eltchaninoff H, Vahanian A, Modine T, Lancellotti P, Sondergaard L, Ludman PF, Tamburino C, Piazza N, Hancock J, Mehilli J, Byrne RA, Baumbach A, Kappetein AP, Windecker S, Bax J, Haude M. Standardized definitions of structural deterioration and valve failure in assessing long-term durability of transcatheter and surgical aortic bioprosthetic valves: a consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) endorsed by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur J Cardiothorac Surg. 2017 Sep 1;52(3):408-417. doi: 10.1093/ejcts/ezx244. No abstract available.
• Meuris B, Borger MA, Bourguignon T, Siepe M, Grabenwoger M, Laufer G, Binder K, Polvani G, Stefano P, Coscioni E, van Leeuwen W, Demers P, Dagenais F, Canovas S, Theron A, Langanay T, Roussel JC, Wendler O, Mariscalco G, Pessotto R, Botta B, Bramlage P, de Paulis R. Durability of bioprosthetic aortic valves in patients under the age of 60 years - rationale and design of the international INDURE registry. J Cardiothorac Surg. 2020 May 27;15(1):119. doi: 10.1186/s13019-020-01155-6.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2019
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: September 10, 2018
• First Submitted That Met QC Criteria: September 11, 2018
• First Posted (Actual): September 12, 2018

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Surgical valve
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: HVT-R18-IND

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO