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

• ClinicalTrials.gov Identifier: NCT04053088
• Recruitment Status: Active, not recruiting
• First Posted: August 12, 2019
• Last Update Posted: December 21, 2021
• Sponsor: Institut für Pharmakologie und Präventive Medizin
• Collaborator: Edwards Lifesciences
• Information provided by (Responsible Party): Institut für Pharmakologie und Präventive Medizin

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Cardiovascular Diseases	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 Design

• Study Type: Observational
• Estimated Enrollment: 500 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Surgical Aortic Valve Replacement: IMPACT of Pre-existing Comorbidities on Patient Outcomes and Prosthetic Valve Performance in a Real-world Setting.
• Actual Study Start Date: December 12, 2019
• Estimated Primary Completion Date: March 1, 2026
• Estimated Study Completion Date: August 1, 2026

Groups and Cohorts

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™

Outcome Measures

Primary Outcome Measures :

1. All-cause mortality [ Time Frame: after 1 year ]
   All-cause mortality after 1 year will be investigated
2. All-cause mortality [ Time Frame: after 3 years ]
   All-cause mortality after 3 years will be investigated
3. All-cause mortality [ Time Frame: after 5 years ]
   All-cause mortality after 5 years will be investigated

Secondary Outcome Measures :

1. Mortality [ Time Frame: after 1 year ]
   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
2. Mortality [ Time Frame: after 3 years ]
   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
3. Mortality [ Time Frame: after 5 years ]
   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

Other Outcome Measures:

1. Change in Maximum pressure gradient (Pmax) over time [ Time Frame: after 1 year ]
   Change in Pmax in mmHg as an indicator of patient prosthesis mismatch
2. Change in Maximum pressure gradient (Pmax) over time [ Time Frame: after 3 years ]
   Change in Pmax in mmHg as an indicator of patient prosthesis mismatch
3. Change in Maximum pressure gradient (Pmax) over time [ Time Frame: after 5 years ]
   Change in Pmax in mmHg as an indicator of patient prosthesis mismatch
4. Change in mean pressure gradient (Pmean) over time [ Time Frame: after 1 year ]
   Change in Pmean in mmHg as an indicator of patient prosthesis mismatch
5. Change in mean pressure gradient (Pmean) over time [ Time Frame: after 3 years ]
   Change in Pmean in mmHg as an indicator of patient prosthesis mismatch
6. Change in mean pressure gradient (Pmean) over time [ Time Frame: after 5 years ]
   Change in Pmean in mmHg as an indicator of patient prosthesis mismatch
7. Change in velocity time integral (VTI) over time [ Time Frame: after 1 year ]
   Change in VTI as an indicator of patient prosthesis mismatch
8. Change in velocity time integral (VTI) over time [ Time Frame: after 3 years ]
   Change in VTI as an indicator of patient prosthesis mismatch
9. Change in velocity time integral (VTI) over time [ Time Frame: after 5 years ]
   Change in VTI as an indicator of patient prosthesis mismatch
10. Change in prostesis opening area (EOA) over time [ Time Frame: after 1 year ]
    Change in EOA in mm2 as an indicator of patient prosthesis mismatch
11. Change in prostesis opening area (EOA) over time [ Time Frame: after 3 years ]
    Change in EOA in mm2 as an indicator of patient prosthesis mismatch
12. Change in prostesis opening area (EOA) over time [ Time Frame: after 5 years ]
    Change in EOA in mm2 as an indicator of patient prosthesis mismatch
13. Change in left ventricular ejection fraction (LVEF) over time [ Time Frame: after 1 year ]
    Change in LVEF in % as an indicator of patient prosthesis mismatch
14. Change in left ventricular ejection fraction (LVEF) over time [ Time Frame: after 3 years ]
    Change in LVEF in % as an indicator of patient prosthesis mismatch
15. Change in left ventricular ejection fraction (LVEF) over time [ Time Frame: after 5 years ]
    Change in LVEF in % as an indicator of patient prosthesis mismatch
16. Occurence of paravalvular leaks [ Time Frame: after 1 year ]
    Occurence of paravalvular leaks as an indicator of patient prostheis mismatch
17. Occurence of paravalvular leaks [ Time Frame: after 3 years ]
    Occurence of paravalvular leaks as an indicator of patient prostheis mismatch
18. Occurence of paravalvular leaks [ Time Frame: after 5 years ]
    Occurence of paravalvular leaks as an indicator of patient prostheis mismatch
19. Occurence of structural valve detioration (SVD) over time [ Time Frame: after 1 year ]
    SVD to be determined by imaging methods (e.g. Echocardiography) following Salaun et al. 2018
20. Occurence of structural valve detioration (SVD) over time [ Time Frame: after 3 years ]
    SVD to be determined by imaging methods (e.g. Echocardiography) following Salaun et al. 2018
21. Occurence of structural valve detioration (SVD) over time [ Time Frame: after 5 years ]
    SVD to be determined by imaging methods (e.g. Echocardiography) following Salaun et al. 2018
22. Occurence of repeat procedures (valve-in-valve reoperation) [ Time Frame: after 1 year ]
    Any repeat procedures will be documented and assessed
23. Occurence of repeat procedures (valve-in-valve reoperation) [ Time Frame: after 3 years ]
    Any repeat procedures will be documented and assessed
24. Occurence of repeat procedures (valve-in-valve reoperation) [ Time Frame: after 5 years ]
    Any repeat procedures will be documented and assessed
25. New York Heart Association (NYHA) functional class compared to baseline [ Time Frame: after 1 year ]
    NYHA class will be determined at follow-up visits
26. New York Heart Association (NYHA) functional class compared to baseline [ Time Frame: after 3 years ]
    NYHA class will be determined at follow-up visits
27. New York Heart Association (NYHA) functional class compared to baseline [ Time Frame: after 5 years ]
    NYHA class will be determined at follow-up visits
28. Freedom from valve-related rehospitalization [ Time Frame: after 1 year ]
    any valve related hospitalizations will be documented and assessed
29. Freedom from valve-related rehospitalization [ Time Frame: after 3 years ]
    any valve related hospitalizations will be documented and assessed
30. Freedom from valve-related rehospitalization [ Time Frame: after 5 years ]
    any valve related hospitalizations will be documented and assessed
31. Need for new pacemaker implant [ Time Frame: after 1 year ]
    Any occurence of new pacemaker implant (e. g. when the participant did not have a pacemaker at baseline) will be documented and assessed
32. Need for new pacemaker implant [ Time Frame: after 3 years ]
    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
33. Need for new pacemaker implant [ Time Frame: after 5 years ]
    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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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.

Criteria

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

Contacts and Locations

Locations

Austria

Medizinische Universität Innsbruck, Uniklinik für Herzchirurgie

Innsbruck, Austria

Kepler Universitätsklinikum Linz

Linz, Austria, 4021

• Universitätsklinikum Salzburg, Herzchirurgie, Gefäßchirurgie und endovaskuläre Chirurgie

Salzburg, Austria

• Klinikum Wels-Grieskirchen, Herz-, Gefäß- und Thoraxchirurgie

Wels, Austria

Germany

Klinikum Nürnberg

Nürnberg, Bayern, Germany, 90471

Klinikum Passau/Universität Regensburg

Passau, Bayern, Germany, 94032

Universitätsklinikum Würzburg

Würzburg, Bayern, Germany, 97080

• Universitätsklinikum Frankfurt, Thorax-, Herz- und thorakale Gefässchirurgie

Frankfurt, Hessen, Germany, 60590

Universitätsklinik für Herzchirurgie

Oldenburg, Niedersachsen, Germany, 26133

Uniklinik RWTH Aachen

Aachen, NRW, Germany, 52074

Schüchtermann Klinik

Bad Rothenfelde, NRW, Germany

Herzzentrum Bergmannsheil

Bochum, NRW, Germany, 44789

Klinik für Herzchirurgie UKD

Düsseldorf, NRW, Germany, 40225

Universitätsklinikum Essen

Essen, NRW, Germany, 45147

• Universitätsklinikum Leipzig, Thorax- und Kardiovaskuläre Chirurgie

Leipzig, Sachsen, Germany, 04103

BundeswehrKrankenhaus Klinik XVII und XVIII

Koblenz, Germany, 56072

Helios Klinikum Siegburg

Siegburg, Germany, 53721

Universitätsklinikum Ulm

Ulm, Germany, 89091

Helios Klinikum Wuppertal

Wuppertal, Germany, 42283

Netherlands

Catharina Ziekenhuis, Catharina Hart- en Vaatcentrum

Eindhoven, Netherlands

Switzerland

HerzKlinik Hirslanden, Herz- und thorakale Gefässchirurgie

Zürich, Switzerland

HerzZentrum Hirslanden, Herz- und Gefässchirurgie

Zürich, Switzerland

Sponsors and Collaborators

Institut für Pharmakologie und Präventive Medizin

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

More Information

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Institut für Pharmakologie und Präventive Medizin
• ClinicalTrials.gov Identifier: NCT04053088
• Other Study ID Numbers: IPPM2019IMPACT
• First Posted: August 12, 2019
• Last Update Posted: December 21, 2021
• Last Verified: December 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Institut für Pharmakologie und Präventive Medizin:

Surgical Aortic Valve Replacement (SAVR); INSPIRIS RESILIA; Durability; Hemodynamics

Additional relevant MeSH terms:

Cardiovascular Diseases