SAVR: IMPACT of Pre-existing Comorbidities on Patient Outcomes and Prosthetic Valve Performance in a Real-world Setting. (IMPACT)

Surgical Aortic Valve Replacement: IMPACT of Pre-existing Comorbidities on Patient Outcomes and Prosthetic Valve Performance in a Real-world Setting.

The IMPACT Registry represents a non-interventional, prospective, open-label, multicenter, international registry with a follow-up of 5 years that includes data of patients undergoing aortic valve replacement with the Edwards INSPIRIS RESILIA Aortic Valve™. The IMPACT Registry will be performed in up to 25 participating sites across Germany, Austria and Switzerland. A minimum number of 500 patients (20 patients per center) will be enrolled. Patients will undergo follow-up visits at baseline, surgery, pre-discharge, year 1, year 3 and year 5.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Diseases
• Intervention / Treatment: Device: 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 (Flameng et al., 2015). The RESILIA tissue has been studied in the COMMENCE trial: Two year data show that the NYHA class improved in 65.7% of patients, effective orifice area after implantation was 1.6 ± 0.5 cm2; mean gradient was 10.1 ± 4.3 mmHg; and paravalvular leak was none/trivial in 94.5% of patients (mild to moderate in 0.5%) (Puskas et al., 2017).

On the sizes 19 - 25 mm the INSPIRIS RESILIA Aortic Valve™ has been outfitted with the VFit technology, which incorporates two novel features designed for potential future valve-in-valve procedures: fluoroscopically visible size markers and an expandable cobalt chromium alloy band. No clinical data are available that evaluate the use of the INSPIRIS RESILIA Aortic Valve™ in patients to date.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria
    • Medizinische Universität Innsbruck, Uniklinik für Herzchirurgie
  • Linz, Austria, 4021
    • Kepler Universitätsklinikum Linz
  • Salzburg, Austria
    • • Universitätsklinikum Salzburg, Herzchirurgie, Gefäßchirurgie und endovaskuläre Chirurgie
  • Wels, Austria
    • • Klinikum Wels-Grieskirchen, Herz-, Gefäß- und Thoraxchirurgie
• Germany
  • Koblenz, Germany, 56072
    • BundeswehrKrankenhaus Klinik XVII und XVIII
  • Siegburg, Germany, 53721
    • Helios Klinikum Siegburg
  • Ulm, Germany, 89091
    • Universitätsklinikum Ulm
  • Wuppertal, Germany, 42283
    • Helios Klinikum Wuppertal
  • Bayern
    • Nürnberg, Bayern, Germany, 90471
      • Klinikum Nürnberg
    • Passau, Bayern, Germany, 94032
      • Klinikum Passau/Universität Regensburg
    • Würzburg, Bayern, Germany, 97080
      • Universitätsklinikum Würzburg
  • Hessen
    • Frankfurt, Hessen, Germany, 60590
      • • Universitätsklinikum Frankfurt, Thorax-, Herz- und thorakale Gefässchirurgie
  • NRW
    • Aachen, NRW, Germany, 52074
      • Uniklinik RWTH Aachen
    • Bad Rothenfelde, NRW, Germany
      • Schüchtermann Klinik
    • Bochum, NRW, Germany, 44789
      • Herzzentrum Bergmannsheil
    • Düsseldorf, NRW, Germany, 40225
      • Klinik für Herzchirurgie UKD
    • Essen, NRW, Germany, 45147
      • Universitätsklinikum Essen
  • Niedersachsen
    • Oldenburg, Niedersachsen, Germany, 26133
      • Universitätsklinik für Herzchirurgie
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • • Universitätsklinikum Leipzig, Thorax- und Kardiovaskuläre Chirurgie
• Netherlands
  • Eindhoven, Netherlands
    • Catharina Ziekenhuis, Catharina Hart- en Vaatcentrum
• Switzerland
  • Zürich, Switzerland
    • HerzKlinik Hirslanden, Herz- und thorakale Gefässchirurgie
  • Zürich, Switzerland
    • HerzZentrum Hirslanden, Herz- und Gefässchirurgie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Minimum of 500 patients (20 patients per center) undergoing Surgical Aortic Valve Replacement (SAVR) using the INSPIRIS RESILIA aortic valve™ (all comers).

The required sample size was calculated using the online calculator at http://www.surveysystem.com/sscalc.htm. It was estimated, from the COMMENCE Trial dataset (Puskas et al., 2017) that all-cause mortality is around 1.2% at year 1 and 2.0% at year 2.

Description

Inclusion Criteria:

1. Patient is at least 18 years old
2. Patient has an aortic valve vitium and requires an aortic valve replacement with the Edwards INSPIRIS RESILIA Aortic Valve™
3. Patient is scheduled to attend yearly follow-up visits at the registry center up to 5 years
4. Patient provides written informed consent prior to the procedure and in case of emergency after the procedure.

Exclusion Criteria:

1. Disability and / or other circumstances under which the patient is not capable to understand the nature, significance and scope of the clinical trial
2. Active endocarditis/myocarditis or endocarditis/myocarditis within 3 months prior to the scheduled aortic valve replacement surgery
3. Patient has a life expectancy ≤ 12 months for any reason
4. Valve implantation is not possible in accordance with the device IFU
5. Pregnancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SAVR patients; patients undergoing surgical aortic valve replacement (SAVR) by usage of the INSPIRIS RESILIA Aortic valve™	Device: INSPIRIS RESILIA Aortic Valve™; Collection of patient data from patients undergoing Surgical Aortic Valve Replacement (SAVR) by usage of the INSPIRIS RESILIA aortic valve™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	All-cause mortality after 1 year will be investigated	after 1 year
All-cause mortality	All-cause mortality after 3 years will be investigated	after 3 years
All-cause mortality	All-cause mortality after 5 years will be investigated	after 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	All cause, cardiac and valve-related mortality in the overall study population and in different patient subgroups at all timepoints: Chronic kidney disease, diabetes, hypertension, metabolic syndrome, inflammation	after 1 year
Mortality	All cause, cardiac and valve-related mortality in the overall study population and in different patient subgroups at all timepoints: Chronic kidney disease, diabetes, hypertension, metabolic syndrome, inflammation	after 3 years
Mortality	All cause, cardiac and valve-related mortality in the overall study population and in different patient subgroups at all timepoints: Chronic kidney disease, diabetes, hypertension, metabolic syndrome, inflammation	after 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Maximum pressure gradient (Pmax) over time	Change in Pmax in mmHg as an indicator of patient prosthesis mismatch	after 1 year
Change in Maximum pressure gradient (Pmax) over time	Change in Pmax in mmHg as an indicator of patient prosthesis mismatch	after 3 years
Change in Maximum pressure gradient (Pmax) over time	Change in Pmax in mmHg as an indicator of patient prosthesis mismatch	after 5 years
Change in mean pressure gradient (Pmean) over time	Change in Pmean in mmHg as an indicator of patient prosthesis mismatch	after 1 year
Change in mean pressure gradient (Pmean) over time	Change in Pmean in mmHg as an indicator of patient prosthesis mismatch	after 3 years
Change in mean pressure gradient (Pmean) over time	Change in Pmean in mmHg as an indicator of patient prosthesis mismatch	after 5 years
Change in velocity time integral (VTI) over time	Change in VTI as an indicator of patient prosthesis mismatch	after 1 year
Change in velocity time integral (VTI) over time	Change in VTI as an indicator of patient prosthesis mismatch	after 3 years
Change in velocity time integral (VTI) over time	Change in VTI as an indicator of patient prosthesis mismatch	after 5 years
Change in prostesis opening area (EOA) over time	Change in EOA in mm2 as an indicator of patient prosthesis mismatch	after 1 year
Change in prostesis opening area (EOA) over time	Change in EOA in mm2 as an indicator of patient prosthesis mismatch	after 3 years
Change in prostesis opening area (EOA) over time	Change in EOA in mm2 as an indicator of patient prosthesis mismatch	after 5 years
Change in left ventricular ejection fraction (LVEF) over time	Change in LVEF in % as an indicator of patient prosthesis mismatch	after 1 year
Change in left ventricular ejection fraction (LVEF) over time	Change in LVEF in % as an indicator of patient prosthesis mismatch	after 3 years
Change in left ventricular ejection fraction (LVEF) over time	Change in LVEF in % as an indicator of patient prosthesis mismatch	after 5 years
Occurence of paravalvular leaks	Occurence of paravalvular leaks as an indicator of patient prostheis mismatch	after 1 year
Occurence of paravalvular leaks	Occurence of paravalvular leaks as an indicator of patient prostheis mismatch	after 3 years
Occurence of paravalvular leaks	Occurence of paravalvular leaks as an indicator of patient prostheis mismatch	after 5 years
Occurence of structural valve detioration (SVD) over time	SVD to be determined by imaging methods (e.g. Echocardiography) following Salaun et al. 2018	after 1 year
Occurence of structural valve detioration (SVD) over time	SVD to be determined by imaging methods (e.g. Echocardiography) following Salaun et al. 2018	after 3 years
Occurence of structural valve detioration (SVD) over time	SVD to be determined by imaging methods (e.g. Echocardiography) following Salaun et al. 2018	after 5 years
Occurence of repeat procedures (valve-in-valve reoperation)	Any repeat procedures will be documented and assessed	after 1 year
Occurence of repeat procedures (valve-in-valve reoperation)	Any repeat procedures will be documented and assessed	after 3 years
Occurence of repeat procedures (valve-in-valve reoperation)	Any repeat procedures will be documented and assessed	after 5 years
New York Heart Association (NYHA) functional class compared to baseline	NYHA class will be determined at follow-up visits	after 1 year
New York Heart Association (NYHA) functional class compared to baseline	NYHA class will be determined at follow-up visits	after 3 years
New York Heart Association (NYHA) functional class compared to baseline	NYHA class will be determined at follow-up visits	after 5 years
Freedom from valve-related rehospitalization	any valve related hospitalizations will be documented and assessed	after 1 year
Freedom from valve-related rehospitalization	any valve related hospitalizations will be documented and assessed	after 3 years
Freedom from valve-related rehospitalization	any valve related hospitalizations will be documented and assessed	after 5 years
Need for new pacemaker implant	Any occurence of new pacemaker implant (e. g. when the participant did not have a pacemaker at baseline) will be documented and assessed	after 1 year
Need for new pacemaker implant	Any occurence of new pacemaker implant (e. g. when the participant did not have a pacemaker at the preceding follow-up visit) will be documented and assessed	after 3 years
Need for new pacemaker implant	Any occurence of new pacemaker implant (e. g. when the participant did not have a pacemaker at the preceding follow-up visit) will be documented and assessed	after 5 years

Collaborators and Investigators

• Sponsor: Institut für Pharmakologie und Präventive Medizin
• Collaborators: Edwards Lifesciences
• Investigators: Principal Investigator: Farhad Bakhtiary, Dr. med., Helios Klinik Siegburg; Principal Investigator: Andreas Zierer, Prof. Dr., Kepler University Hosiptal Linz and Hospital Wels-Grieskirchen

Publications and helpful links

General Publications

• Salaun E, Clavel MA, Rodes-Cabau J, Pibarot P. Bioprosthetic aortic valve durability in the era of transcatheter aortic valve implantation. Heart. 2018 Aug;104(16):1323-1332. doi: 10.1136/heartjnl-2017-311582. Epub 2018 May 7.
• Bakhtiary F, Ahmad AE, Autschbach R, Benedikt P, Bonaros N, Borger M, Dewald O, Feyrer R, Geissler HJ, Grunenfelder J, Lam KY, Leyh R, Liebold A, Czesla M, Mehdiani A, Pollari F, Salamate S, Strauch J, Votsch A, Weber A, Wendt D, Botta B, Bramlage P, Zierer A. Impact of pre-existing comorbidities on outcomes of patients undergoing surgical aortic valve replacement - rationale and design of the international IMPACT registry. J Cardiothorac Surg. 2021 Mar 25;16(1):51. doi: 10.1186/s13019-021-01434-w.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2019
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: August 6, 2019
• First Submitted That Met QC Criteria: August 9, 2019
• First Posted (Actual): August 12, 2019

Study Record Updates

• Last Update Posted (Estimated): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Hemodynamics; Surgical Aortic Valve Replacement (SAVR); INSPIRIS RESILIA; Durability
• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: IPPM2019IMPACT

Drug and device information, study documents

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