PARADIGM: Amplatzer Valvular Plug for PVL Closure (PARADIGM)

PARADIGM PARAvalvular Leak Closure With the Amplatzer Valvular Plug occluDer for Interventional Transcatheter Closure for PVL With Surgical bioloGical and Mechanical Heart Valve

The Paradigm study is a prospective, multicenter, single arm study to demonstrate the safety and effectiveness of the AVP III as a treatment for clinically significant PVLs following surgical implant of a mechanical or biological heart valve implanted in the aortic or mitral position.

Study Overview

• Status: Enrolling by invitation
• Conditions: Paravalvular Aortic Regurgitation
• Intervention / Treatment: Device: Amplatzer Valvular Plug III

Detailed Description

PARADIGM is a prospective, international, multi-center, single arm study to demonstrate the safety and effectiveness of the AVP III for percutaneous, transcatheter closure of PVLs occurring after aortic or mitral valve replacement with a surgically-implanted mechanical or bioprosthetic valve. The study will be conducted at up to 25 clinical sites in the US, EU and Canada, where a total of 200 subjects with a clinically significant PVL will undergo an AVP III implant procedure for PVL closure. Pre-procedural Baseline and follow-up assessments at Discharge, 30 days, 6 months and 1 year will include echocardiography, physical examinations, lab measurements and questionnaires to assess PVL severity, prosthetic valve function, hemolytic anemia, heart failure symptoms, and quality of life. Adverse events will be recorded throughout the study.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Institut de Cardiologie de Quebec (Hôpital Laval)
  • Vancouver, Canada, V6Z 2E8
    • St. Paul's Hospital
  • Quebec
    • Montréal, Quebec, Canada, H1T 1C8
      • Institut de Cardiologie de Montreal (Montreal Heart Inst.)
• Italy
  • Lombard
    • Milano, Lombard, Italy, 20132
      • Ospedale San Raffaele
• Netherlands
  • Utrecht
    • Nieuwegein, Utrecht, Netherlands, 3435 CM
      • St. Antonius Ziekenhuis
• Poland
  • Silesia
    • Katowice, Silesia, Poland, 40-635
      • Gornoslaskie Centrum Medyczne im.prof. Leszka Gieca
• Spain
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Salamanca, Spain
    • Hospital Universitario de Salamanca
• United Kingdom
  • Cambridge, United Kingdom
    • Papworth Hospital NHS Foundation Trust
  • Lothian
    • Edinburgh, Lothian, United Kingdom, EH16 4SA
      • Edinburgh Heart Centre
  • Soeast
    • Brighton, Soeast, United Kingdom, BN25BE
      • The Royal Sussex County Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University Hospital - Univ. of Alabama at Birmingham (UAB)
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46240
      • St. Vincent Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10021
      • Lenox Hill Hospital
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital/Cornell University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Baptist Memorial Hospital
  • Utah
    • Murray, Utah, United States, 84157
      • Intermountain Medical Center
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Carilion Roanoke Memorial Hospital
  • Washington
    • Spokane, Washington, United States, 99202
      • Sacred Heart Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subject is implanted with a mechanical or biological surgical valve in the aortic or mitral position
• Note: Subjects in European countries can only be implanted with a mechanical valve in the aortic or mitral position
• Subject has a clinically significant paravalvular leak with a severity grade of moderate or higher, associated with signs of heart failure and/or hemolysis necessitating recurring blood transfusions.
• Subject has one clinically significant PVL defect that can be closed with a single AVP III as assessed pre-procedurally
• Subject has provided written informed consent
• Subject is ≥18 years old

Exclusion Criteria:

• Subject has a rocking valve or extreme dehiscence of the prosthetic valve involving more than 40% of the sewing ring
• Subject's PVL(s) originates from a transcatheter aortic or mitral valve replacement, or from rapid deployment or sutureless surgical replacement valves
• Subject has a prosthetic aortic valve and prosthetic mitral valve which both have a clinically significant paravalvular leak.
• Subject who is hemodynamically unstable or who cannot undergo an elective procedure
• Subject with active endocarditis or other active infection
• Subject has within the last 6 months a previously documented intracardiac mass, vegetation, tumor, or thrombus which would interfere with placement of the AVP III
• Subject has inadequate vasculature for delivery of the AVP III
• Subject has unsuitable anatomy for PVL closure using the AVP III (such as a PVL associated with an abscess cavity or a pseudoaneurysmal sac) or anatomy where the AVP III would interfere with other intracardiac or intravascular structures (such coronary ostia)
• Subjects who are unable to receive intraprocedural anticoagulant therapy
• Pregnant or nursing subjects or subjects who plan pregnancy during the clinical investigation follow-up period.
• Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements, or impact the scientific soundness of the clinical investigation results.
• Life expectancy is less than 1 year in the opinion of the Investigator
• Incapacitated individuals, defined as persons with mental illnesses or handicaps that impair their ability to provide informed consent, or individuals without legal authority to provide informed consent.
• Individual who are currently participating in an investigational drug or device study that has not reached the primary endpoint or that may confound the results of this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paravalvular Leak Closure; Includes all eligible subjects who undergo an AVP III implant attempt for treatment of significant paravalvular leakage with an echocardiographic severity grade of moderate or higher. This is a single arm study.	Device: Amplatzer Valvular Plug III; Transcatheter closure of a paravalvular leak using Amplatzer Valvular Plug III

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Paravalvular leak closure success rate (percent of subjects)	Defined as AVPIII placement in the intended location without interference with the prosthetic valve or intraprocedural mortality with at least a 2 severity-grade reduction in paravalvular regurgitation at exit from the procedure and freedom from unplanned AVPIII-related transcatheter or surgical reintervention through 30 days post-implant.	30 Days

Collaborators and Investigators

• Sponsor: Abbott Medical Devices
• Investigators: Principal Investigator: Carlos Ruiz, M.D., Ph.D, Hackensack Meridian Health

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: July 10, 2020
• First Submitted That Met QC Criteria: July 27, 2020
• First Posted (Actual): July 28, 2020

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Aortic Valve Insufficiency
• Other Study ID Numbers: ABT-CIP-10309

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: Yes