FORWARD PRO Study Interventional Post-market Study With the Evolut™ PRO System

Prospective, single-arm, multi-center, interventional post-market study. After signing informed consent, eligible subjects will be implanted with the CE marked Evolut™ PRO system.

The investigation purpose is to evaluate the acute and long term clinical performance and safety of Evolut™ PRO in a routine hospital setting in patients with symptomatic native aortic valve stenosis or a stenosed, insufficient, or combined surgical bioprosthetic valve failure necessitating valve replacement within the approved intended use in local geography.

Study Overview

• Status: Completed
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Device: Medtronic CoreValve™ Evolut™ PRO System (Evolut™ PRO System)

Detailed Description

Approximately 600 subjects implanted with the Evolut™ PRO at up to 40 sites in Europe. Other regions may be added depending on the regulatory status of the device.

• Study Type: Observational
• Enrollment (Actual): 638

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • LKH - Universitätsklinikum
• Belgium
  • Antwerp, Belgium
    • Universitair Ziekenhuis Antwerpen
  • Liège, Belgium
    • CHU de Liège - Hôpital du Sart Tilman
• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet
• Finland
  • Turku, Finland
    • Turun yliopistollinen keskussairaala
• France
  • Bordeaux, France
    • CHU Bordeaux
  • Créteil, France
    • Hôpital Henri Mondor
  • Toulouse, France
    • Clinique Pasteur
• Germany
  • Bad Oeynhausen, Germany
    • Herz- und Diabeteszentrum NRW - Ruhr-Universität Bochum
  • Berlin, Germany
    • Deutsches Herzzentrum Berlin
  • Bonn, Germany
    • Universitätsklinikum Bonn
  • Cottbus, Germany
    • Sana-Herzzentrum Cottbus GmbH
  • Dresden, Germany
    • Herzzentrum Dresden GmbH Universitätsklinik
  • Düsseldorf, Germany
    • Universitatsklinikum Dusseldorf
  • Essen, Germany
    • Universitätsklinikum Essen
  • Hamburg, Germany
    • Asklepios Klinik St. Georg
  • Leipzig, Germany
    • Herzzentrum Leipzig GmbH
  • Munich, Germany
    • Deutsches Herzzentrum München Klinik an der TU München
  • Stuttgart, Germany
    • Sana Herzchirurgie Stuttgart GmbH
• Israel
  • Jerusalem, Israel
    • Hadassah Medical Organisation
  • Petah Tikva, Israel
    • Rabin Medical Center - Beilinson Hospital
• Italy
  • Brescia, Italy
    • Azienda Ospedaliera Spedali Civili di Brescia
  • Catania, Italy
    • AOU Presidio Gaspare Rodolico Policlinico
  • Milan, Italy
    • Azienda Ospedaliera Ospedale Niguarda Ca Granda
  • Milan, Italy
    • IRCCS Policlinico San Donato
  • Pisa, Italy
    • Azienda Ospedaliero Universitaria Pisana - Stabilimento di Cisanello
• Netherlands
  • Amsterdam, Netherlands
    • Onze Lieve Vrouwe Gasthuis
  • Eindhoven, Netherlands
    • Catharina Ziekenhuis Eindhoven
  • Rotterdam, Netherlands
    • Erasmus Medisch Centrum
• Norway
  • Oslo, Norway
    • Oslo Universitetssykehus-Ullevål
• Slovenia
  • Ljubljana, Slovenia
    • University Medical Centre
• Spain
  • Málaga, Spain
    • Hospital Universitario Virgen de la Victoria
  • Oviedo, Spain
    • Hospital Universitario Central de Asturias
  • Santiago de Compostela, Spain
    • Complejo Hospitalario Universitario de Santiago de Compostela
• Switzerland
  • Bern, Switzerland
    • Inselspital - Universitätsspital
  • Zurich, Switzerland
    • Universtitätsspital Zürich
• United Kingdom
  • Belfast, United Kingdom
    • Royal Victoria Hospital - Belfast Health and Social Care Trust
  • London, United Kingdom
    • St. George's Hospital
  • Wolverhampton, United Kingdom
    • The Royal Wolverhampton Hospitals NHS - New Cross Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with symptomatic native aortic valve stenosis or a stenosed, insufficient, or combined surgical bioprosthetic valve failure necessitating valve replacement within the approved intended use in local geography.

Description

Inclusion Criteria:

• Symptomatic native aortic valve stenosis or a stenosed, insufficient, or combined surgical bioprosthetic valve failure necessitating valve replacement
• High or greater risk for surgical aortic valve replacement as estimated by the heart team OR, 75 years or older and at intermediate risk for surgical AVR (STS risk score ≥4% or with an estimated hospital mortality ≥4% as assessed by the heart team)
• Acceptable candidate for treatment with the Evolut™ PRO system in conformity with the Instructions for Use and the local regulations
• Able and willing to return to the implanting site at the following follow-up visits: 1-year, 3-year and 5-year
• Written informed consent obtained without assistance from a legal representative prior to enrollment in the study.

Exclusion Criteria:

• Known hypersensitivity or contraindication to aspirin, heparin (HIT/HITTS) and bivalirudin, ticlopidine, clopidogrel, Nitinol (Titanium or Nickel), or sensitivity to contrast media, which cannot be adequately premedicated
• Preexisting mechanical heart valve in aortic position
• Ongoing sepsis, including active endocarditis
• Anatomically not suitable for the Evolut™ PRO system
• Estimated life expectancy of less than 1 year
• Participating in another trial that may influence the outcome of this study
• Need for emergency surgery for any reason
• Inability to understand and respond to the quality of life questionnaire

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	The all-cause mortality rate at 30 days post procedure meets a prespecified performance goal of 5.5%.	30 days post procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total AR	The percentage of subjects graded as none or trace total aortic regurgitation at discharge is greater than a prespecified performance goal of 67.1%.	24 hours to 7 days post procedure (prior to discharge)
VARC-2 composite safety endpoint	Event rate of the VARC-2 composite safety endpoint through 5 years from enrollment until end of study, which includes the following components: All-cause mortality; All stroke (disabling and non-disabling); 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)	through 5 years from enrollment until end of study
Individual components of the VARC-2 composite safety endpoint	Event rates of the individual components of the VARC-2 composite safety endpoint through 5 years until end of study	through 5 years from enrollment until end of study
Rate of new permanent pacemaker implant	Rate of new permanent pacemaker implant at 30 days post procedure	30 days post procedure
Device success rate	Device success rate at 24 hours to 7 days post procedure (prior to discharge), defined according to the VARC-2 guidelines as: Absence of procedural mortality, AND; Correct positioning of a single prosthetic heart valve into the proper anatomical location, AND; Intended performance of the prosthetic heart valve, defined as the absence of patient prosthesis mismatch and mean gradient <20 mmHg (or peak velocity <3 m/sec), AND; No moderate or severe prosthetic valve regurgitation.	24 hours to 7 days post procedure (prior to discharge)
Hemodynamic performance	Hemodynamic performance at 24 hours to 7 days (prior to discharge), 1-year, 3-year and 5-year post procedure, including the mean prosthetic valve gradient as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory.	24 hours to 7 days (prior to discharge), 1-year, 3-year and 5-year post
Hemodynamic performance	Hemodynamic performance at 24 hours to 7 days (prior to discharge), 1-year, 3-year and 5-year post procedure, including the effective orifice area as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory.	24 hours to 7 days (prior to discharge), 1-year, 3-year and 5-year post
Hemodynamic performance	Hemodynamic performance at 24 hours to 7 days (prior to discharge), 1-year, 3-year and 5-year post procedure, including the degree of prosthetic valve regurgitation (transvalvular, paravalvular and total) as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory.	24 hours to 7 days (prior to discharge), 1-year, 3-year and 5-year post
Change in NYHA functional status	Change in NYHA functional status from baseline to 30-day, 1-year, 3-year, and 5-year post procedure	From baseline to 30-day, 1-year, 3-year, and 5-year post procedure
Change in Quality of Life score	Change in Quality of Life score (EQ-5D questionnaire) from baseline to 30-day, and 1-year, 3-year, and 5-year post procedure. The EQ-5D descriptive system comprises five dimensions and each dimension has five levels of severity. The subject is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the five dimensions. The EQ VAS records the subject's self-rated health on a 20 cm vertical, visual analogue scale. The subject marks an X on the scale to indicate how his/her health is TODAY and then writes the number they marked on the scale in the box below.	From baseline to 30-day, and 1-year, 3-year, and 5-year post procedure

Collaborators and Investigators

• Sponsor: Medtronic Cardiovascular

Publications and helpful links

General Publications

• Manoharan G, Grube E, Van Mieghem NM, Brecker S, Fiorina C, Kornowski R, Danenberg H, Ruge H, Thiele H, Lancellotti P, Sondergaard L, Tamburino C, Oh JK, Fan Y, Windecker S. Thirty-day clinical outcomes of the Evolut PRO self-expanding transcatheter aortic valve: the international FORWARD PRO study. EuroIntervention. 2020 Nov 20;16(10):850-857. doi: 10.4244/EIJ-D-20-00279.
• Van Mieghem NM, Windecker S, Manoharan G, Lancellotti P, Tamburino C, Kornowski R, Thiele H, Danenberg H, Fiorina C, Scholtz W, Brecker S, Ruge H, Opdahl A, Amoroso G, Bedogni F, Petronio AS, Nickenig G, Harnath A, Kempfert J, Oh JK, Eisenberg RE, Grube E. Three-Year Outcomes With a Supra-Annular, Self-Expanding Bioprosthesis and a Pericardial Wrap-The FORWARD PRO Study. Catheter Cardiovasc Interv. 2025 Feb;105(3):577-587. doi: 10.1002/ccd.31335. Epub 2024 Dec 16.

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2018
• Primary Completion (Actual): March 6, 2019
• Study Completion (Actual): February 26, 2024

Study Registration Dates

• First Submitted: January 18, 2018
• First Submitted That Met QC Criteria: January 30, 2018
• First Posted (Actual): January 31, 2018

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: MDT17050EVR003

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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