PERIGON Pivotal Trial

Not Applicable

Active, not recruiting

Conditions: Aortic Stenosis

Interventions: Device: Model 400 aortic valve bioprosthesis

Registration Number: NCT02088554

Lead Sponsor: Medtronic Cardiac Surgery

Brief Summary: To evaluate the safety and effectiveness of the Model 400 aortic valve bioprosthesis.

Detailed Description: This is a prospective, interventional, non-randomized, worldwide, multi-center trial. A maximum of 1300 subjects were to be implanted at a maximum of 40 sites in the US, Europe and Canada. The trial includes male and female patients of legal age to provide informed consent in the country where they enrolled in the trial, requiring replacement for a diseased, damaged, or malfunctioning native or prosthetic aortic valve. Subjects are followed out to 5 years, and select sites follow subjects out to 12 years. Enrollment closed on 14Jul2017 for all valve sizes. Enrollment was reopened in Apr2019 for the 29mm valve size at a subset of US and Canadian sites to obtain greater patient numbers required by the FDA to support US commercial approval of this valve size. Enrollment for the 29mm valve size closed on 14Feb2023.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 1312

Inclusion Criteria

Patient has moderate or greater aortic stenosis or regurgitation, and there is clinical indication for replacement of their native or prosthetic aortic valve with a bioprosthesis, with or without concomitant procedures, which are limited to any of the following:

i. Left atrial appendage (LAA) ligation ii. CABG (coronary artery bypass grafting) iii. Patent foramen ovale (PFO) closure iv. Ascending aortic aneurysm or dissection repair not requiring circulatory arrest v. Resection of a sub-aortic membrane not requiring myectomy
Patient is geographically stable and willing to return to the implanting site for all follow-up visits
Patient is of legal age to provide informed consent in the country where they enroll in the trial
Patient has been adequately informed of risks and requirements of the trial and is willing and able to provide informed consent for participation in the clinical trial

Exclusion Criteria

Patient has a pre-existing prosthetic valve or annuloplasty device in another position or requires replacement or repair of the mitral, pulmonary or tricuspid valve
Patient has had previous implant and then explant of the Model 400 aortic valve bioprosthesis
Patient presents with active endocarditis, active myocarditis or other systemic infection
Patient has an anatomical abnormality which would increase surgical risk of morbidity or mortality, including:
- Ascending aortic aneurysm or dissection repair requiring circulatory arrest
- Acute Type A aortic dissection
- Ventricular aneurysm
- Porcelain aorta
- Hostile mediastinum
- Hypertrophic obstructive cardiomyopathy (HOCM)
- Documented pulmonary hypertension (systolic >60mmHg)
Patient has a non-cardiac major or progressive disease, with a life expectancy of less than 2 years. These conditions include, but are not limited to:
- Child-Pugh Class C liver disease
- Terminal cancer
- End-stage lung disease
Patient has renal failure, defined as dialysis therapy or glomerular filtration rate(GFR)<30 mL/min/1.73 m2
Patient has hyperparathyroidism
Patient is participating in another investigational device or drug trial or observational competitive study
Patient is pregnant, lactating or planning to become pregnant during the trial period
Patient has a documented history of substance (drug or alcohol) abuse
Patient has greater than mild mitral valve regurgitation or greater than mild tricuspid valve regurgitation as assessed by echocardiography
Patient has systolic ejection fraction (EF)<20% as assessed by echocardiography
Patient has Grade IV Diastolic Dysfunction
Patient has documented bleeding diatheses
Patient has had an acute preoperative neurological deficit or myocardial infarction and has not returned to baseline or stabilized ≥30 days prior to enrollment
Patient requires emergency surgery

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Model 400 aortic valve bioprosthesis	Model 400 aortic valve bioprosthesis	-

Primary Outcome Measures

Name	Time	Method
Evaluate the Safety of the Model 400 Avalus Valve With Regard to Valve-related Adverse Events and Death at 1 Year Post-implant	1 year post-implant	Safety of the valve is evaluated by the time-related incidence of valve-related adverse events and death. The following valve-related adverse events are evaluated in this study: Thromboembolism, Thrombosis, Hemorrhage, Paravalvular leak (PVL), Endocarditis, Hemolysis, Structural valve deterioration, Non-structural dysfunction, Reintervention, Explant, and Death. A minimum of 15 participants per valve size are evaluated. The incidence rates will be used to summarize valve-related adverse events and death.
Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Change of New York Heart Association (NYHA) Classification From Baseline Through 1 Year	Discharge (up to 30 days), 3-6 months, and 1 year post-implant	At each timepoint, a minimum of 15 participants per valve size evaluated for change in New York Heart Association (NYHA) functional classification from baseline to 1 year post-procedure. Measure Description: Cardiac Disease with Functional Classes (lower value is more desirable than higher value) I - No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath. II - Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain. III - Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain. IV - Symptoms of heart failure at rest. Any physical activity causes further discomfort.
Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Peak Pressure Gradient (mmHg) From Discharge up to 1 Year	Measured at discharge (up to 30 days), 3-6 months, and 1 year post-implant	A minimum of 15 participants per valve size evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory. The peak pressure gradient is the maximum value measured of flow of blood through the aortic valve as measured in millimeters of mercury.
Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Effective Orifice Area Through 1 Year Post-procedure	Discharge (up to 30 days), 3-6 months, 1 year post-implant	A minimum of 15 participants per valve size evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory. The effective orifice area (EOA) is measured as the minimal cross-sectional area of the blood flow downstream of the aortic valve.
Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Effective Orifice Area Index (EOAI) Through 1 Year Post-implant	Discharge (up to 30 days), 3-6 months, and 1 year post-implant	A minimum of 15 participants per valve size evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory for effective orifice area index (EOAI = EOA/BSA) Effective orifice area index is equal to the effective orifice area (EOA) in cm\^2 divided by body surface area (BSA) in m\^2. The achievement criterion for the effective orifice area index (EOAI) is defined to be ≥0.6 cm\^2/m\^2 12 months after the procedure. This criterion is in accordance with the definition of severe aortic stenosis in the American College of Cardiology (ACC) / American Heart Association (AHA) guidelines for the management of valvular heart disease.
Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Mean Pressure Gradient (mmHg) Through 1 Year Post-implant	Discharge (up to 30 days), 3-6 months, and 1 year post-implant	A minimum of 15 participants per valve size evaluated by transthoracic echocardiography technique and will be assessed by an independent core laboratory. The mean pressure gradient is the average flow of blood through the aortic valve measured in millimeters of mercury.
Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Performance Index (L/Min) Through 1 Year Post-implant	Discharge (up to 30 days), 3-6 months, and 1 year post-implant	A minimum of 15 participants per valve size will have performance index (L/Min) measured by transthoracic echocardiography technique and will be assessed by an independent core laboratory. The performance index is the measurement of the effective orifice area divided by the native orifice area.
Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Cardiac Output (L/Min) Through 1 Year Post-implant	Discharge (up to 30 days), 3-6 months, and 1 year post-implant	Cardiac output is the amount of blood pumped by the heart per minute. A minimum of 15 participants per valve size were evaluated for this outcome measure by transthoracic echocardiography technique and assessed by an independent core laboratory.
Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Cardiac Index (L/Min/m^2) Through 1 Year Post-implant	Discharge (up to 30 days), 3-6 months, and 1 year post-implant	A minimum of 15 participants per valve size evaluated by transthoracic echocardiography technique and will be assessed by an independent core laboratory. The cardiac index is an assessment of the cardiac output based on a patient's size measured by dividing the cardiac output by the patient's body's surface area.

Secondary Outcome Measures

Name	Time	Method
Evaluate the Safety of the Model 400 Avalus Valve With Regard to Valve-related Adverse Events and Death Annually Through 5 Years Post-implant	Annually, at years 2, 3, 4, and 5 post-implant	Safety of the valve is evaluated by the time-related incidence of valve-related adverse events and death. The following valve-related adverse events are evaluated in this study: Thromboembolism, Thrombosis, Hemorrhage, Paravalvular leak (PVL), Endocarditis, Hemolysis, Structural valve deterioration, Non-structural dysfunction, Reintervention, Explant, and Death. The Kaplan-Meier event rates will be used to summarize valve-related adverse events and death. The Kaplan-Meier rate and the corresponding 95% confidence interval will be presented for each visit interval.
Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Mean Pressure Gradient (mmHg) Through 5 Years Post-implant	Annually, at years 2, 3, 4, and 5 post-implant	Evaluated by transthoracic echocardiography technique and will be assessed by an independent core laboratory. The mean pressure gradient is the average flow of blood through the aortic valve measured in millimeters of mercury.
Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Performance Index (L/Min) Through 5 Years Post-implant	Annually, at years 2, 3, 4, and 5 post-implant	Performance index (L/Min) measured by transthoracic echocardiography technique and will be assessed by an independent core laboratory. The performance index is the measurement of the effective orifice area divided by the native orifice area.
Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Cardiac Output (L/Min) Through 5 Years Post-implant	Annually, at years 2, 3, 4, and 5 post-implant	Cardiac output is the amount of blood pumped by the heart per minute, evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory.
Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Change of New York Heart Association (NYHA) Classification From Baseline Through 5 Years Post-implant	Annually, at years 2, 3, 4, and 5 post-implant	At each timepoint, participants were evaluated for change in New York Heart Association (NYHA) functional classification from baseline through 5 years post-procedure. Measure Description: Cardiac Disease with Functional Classes (lower value is more desirable than higher value) I - No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath. II - Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain. III - Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain. IV - Symptoms of heart failure at rest. Any physical activity causes further discomfort.
Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Effective Orifice Area Through 5 Years Post-procedure	Annually, at years 2, 3, 4, and 5 post-implant	Evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory. The effective orifice area (EOA) is measured as the minimal cross-sectional area of the blood flow downstream of the aortic valve.
Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Effective Orifice Area Index (EOAI) Through 5 Years Post-implant	Annually, at years 2, 3, 4, and 5 post-implant	Evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory for effective orifice area index (EOAI = EOA/BSA) Effective orifice area index is equal to the effective orifice area (EOA) in cm\^2 divided by body surface area (BSA) in m\^2. The achievement criterion for the effective orifice area index (EOAI) is defined to be ≥0.6 cm\^2/m\^2 12 months after the procedure. This criterion is in accordance with the definition of severe aortic stenosis in the American College of Cardiology (ACC) / American Heart Association (AHA) guidelines for the management of valvular heart disease.
Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Cardiac Index (L/Min/m^2) Through 5 Years Post-implant	Annually, at years 2, 3, 4, and 5 post-implant	Evaluated by transthoracic echocardiography technique and will be assessed by an independent core laboratory. The cardiac index is an assessment of the cardiac output based on a patient's size measured by dividing the cardiac output by the patient's body's surface area.
Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Peak Pressure Gradient (mmHg) From Discharge up to 5 Years Post-implant	Annually, at years 2, 3, 4, and 5 post-implant	Evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory. The peak pressure gradient is the maximum value measured of flow of blood through the aortic valve as measured in millimeters of mercury.

Trial Locations

Locations (38): Deutsches Herzzentrum München
🇩🇪
Munich, München, Germany
University of Maryland Medical Center
🇺🇸
Baltimore, Maryland, United States
University of Southern California (USC) University Hospital
🇺🇸
Los Angeles, California, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
Riverside Methodist Hospital (OhioHealth)
🇺🇸
Columbus, Ohio, United States
University of Washington Medical Center
🇺🇸
Seattle, Washington, United States
Houston Methodist Hospital
🇺🇸
Houston, Texas, United States
University of Colorado Hospital
🇺🇸
Aurora, Colorado, United States
Minneapolis Heart Institute Foundation
🇺🇸
Minneapolis, Minnesota, United States
Oklahoma Heart Hospital
🇺🇸
Oklahoma City, Oklahoma, United States
Aurora Saint Luke's Medical Center
🇺🇸
Milwaukee, Wisconsin, United States
Hartford Hospital
🇺🇸
Hartford, Connecticut, United States
University of Florida Shands
🇺🇸
Gainesville, Florida, United States
Piedmont Hospital
🇺🇸
Atlanta, Georgia, United States
University of Michigan Cardiovascular Center
🇺🇸
Ann Arbor, Michigan, United States
The Mount Sinai Medical Center
🇺🇸
New York, New York, United States
New York-Presbyterian Hospital/Columbia University Medical Center
🇺🇸
New York, New York, United States
ProMedica Toledo Hospital
🇺🇸
Toledo, Ohio, United States
Cardiothoracic and Vascular Surgeons (CTVS)
🇺🇸
Austin, Texas, United States
University of Ottawa Heart Institute
🇨🇦
Ottawa, Ontario, Canada
London Health Sciences Centre - University Campus
🇨🇦
London, Ontario, Canada
Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ)
🇨🇦
Quebec, Canada
Toronto General Hospital
🇨🇦
Toronto, Canada
Uniklinik Köln
🇩🇪
Cologne, Köln, Germany
Hôpital Cardiologique du Haut-Lévêque
🇫🇷
Bordeaux, France
Hôpital Bichat - Claude Bernard
🇫🇷
Paris, France
Universitäts Klinikum Frankfurt - Goethe-Universität
🇩🇪
Frankfurt, Germany
Medizinische Hochschule Hannover
🇩🇪
Hannover, Germany
Herzzentrum Leipzig GmbH
🇩🇪
Leipzig, Germany
Ospedale San Raffaele - Milano
🇮🇹
Milano, Italy
Leids Universitair Medisch Centrum (LUMC)
🇳🇱
Leiden, Netherlands
Erasmus MC
🇳🇱
Rotterdam, Netherlands
Guy's & St Thomas' NHS Foundation Trust - St Thomas' Hospital
🇬🇧
London, United Kingdom
Inselspital - Universitätsspital Bern
🇨🇭
Bern, Switzerland
Montreal Heart Institute
🇨🇦
Montreal, Quebec, Canada
UniversitätsSpital Zürich
🇨🇭
Zürich, Switzerland
Maimonides Medical Center
🇺🇸
Brooklyn, New York, United States