Clinical trial NCT03666741: Inspiris Resilia Durability Registry
Official title: Clinical Outcomes of Patients Under the Age of Sixty Undergoing INSPIRIS RESILIA Aortic Valve Replacement
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Aortic Valve Stenosis
Keywords: Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Surgical valve
Lead sponsor: Institut für Pharmakologie und Präventive Medizin
Sponsor class: NETWORK
Collaborators: name: Edwards Lifesciences
First posted: 2018-09-12
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

Brief summary: 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™.

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

Eligibility criteria: 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

Primary outcomes:
measure: Time-related valve safety
timeFrame: Year 1
measure: Freedom from severe SVD (structural valve deterioration)
timeFrame: Year 5
Secondary outcomes:
Other outcomes:
Locations:
city: St. Pölten
country: Austria
facility: University Clinics St. Pölten
city: Vienna
country: Austria
facility: Heart Center Hietzing
city: Vienna
country: Austria
facility: Medical University Vienna
city: Leuven
country: Belgium
facility: KU Leuven
city: Montréal
country: Canada
facility: Institut de Cardiologie de Montréal, Université de Montréal
city: Québec
country: Canada
facility: Laval University
city: Marseille
country: France
facility: Hopital de la Timone
city: Nantes
country: France
facility: L'institut du thorax - CHU (Centre Hospitalier Universitaire de Nantes)
city: Rennes
country: France
facility: Centre Hospitalier Universitaire (CHU) de Rennes
city: Tours
country: France
facility: CHRU - Hospital Trousseau
city: Freiburg
country: Germany
facility: UNIVERSITÄTSKLINIKUM FREIBURG, Universitäts-Herzzentrum Herz- und Gefäßchirurgie
state: Baden-Württemberg
city: Leipzig
country: Germany
facility: Heart Center Leipzig
city: Florence
country: Italy
facility: University Hospital Careggi
city: Milano
country: Italy
facility: Centro Cardiologico Monzino
city: Roma
country: Italy
facility: European Hospital Rome
city: Salerno
country: Italy
facility: AOU San Giovanni di Dio e Ruggi d'Aragona
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Murcia
country: Spain
facility: University Hospital Virgen de la Arrixaca
city: Edinburgh
country: United Kingdom
facility: NHS Lothian
city: Glenfield
country: United Kingdom
facility: Glenfield Hospital
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
Study officials:
affiliation: CEO IPPMed
name: Peter Bramlage, Professor
role: STUDY_DIRECTOR
affiliation: European Hospital Rome, Italy
name: Ruggero dePaulis, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: UZ Leuven, Belgium
name: Bart Meuris, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.