Percutaneous or Surgical Repair In Mitral Prolapse And Regurgitation for ≥60 Year-olds (PRIMARY)

NCT05051033 | Active Not Recruiting DMC FDA Device

• 2 other identifiers: STUDY-21-012465U01HL088942
• Study Type: interventional
• Target: 450
• Locations: 5 countries
• Sites: 62

Brief Summary

This is a prospective, multicenter, open-label, randomized trial comparing mitral valve (MV) transcatheter edge-to-edge repair (TEER) to surgical repair (1:1 ratio) in patients with primary, degenerative mitral regurgitation (MR). The trial will be conducted in the U.S., Canada, Germany, Spain, and the United Kingdom, and is designed as a strategy trial. Thus, all devices legally marketed for TEER of primary degenerative MR in a particular country are eligible to be used in this trial.

Conditions

Mitral Valve Regurgitation

Keywords

surgical mitral valve repair; transcatheter edge-to-edge repair

Outcome Measures

Primary Outcomes (1)

• All-cause mortality, valve re-intervention, hospitalizations and urgent visits for heart failure, or onset of ≥ 2+ MR (by transthoracic echocardiogram (TTE)) composite score.

  All-cause mortality, valve re-intervention, hospitalizations/urgent visits for heart failure (without a blanking period), or onset of ≥ 2+ MR (by transthoracic echocardiogram (TTE)) from randomization to a minimum of 3 years post intervention. Composite score will be expressed as a Z-score - The Z-Score is a statistical measurement of a score's relationship to the mean in a group of scores. A Z-score of 0 is equal to the mean, with negative numbers indicating values lower than the mean and positive values higher than the mean.

  3 years post intervention

Secondary Outcomes (27)

• Adequacy of MR correction

  one year post intervention

• Kansas City Cardiomyopathy Questionnaire (KCCQ)

  up to 10 years post intervention

• Procedure failure

  End of procedure

• Procedure failure

  10 years post randomization

• All-cause mortality

  5 years post randomization

Study Arms (2)

Surgical mitral valve repair

ACTIVE COMPARATOR

Patients who are randomized to the surgical arm will undergo mitral surgery.

Procedure: Mitral valve repair

Transcatheter edge-to-edge repair

ACTIVE COMPARATOR

In the transcatheter edge-to-edge repair arm, patients will be treated with a commercially-approved edge-to-edge mitral repair device.

Device: Transcatheter edge-to-edge repair

Interventions

Mitral valve repair PROCEDURE

Patients who are randomized to the surgical arm will undergo mitral surgery. Mitral surgery will be conducted using general anesthesia and cardiopulmonary bypass. Mitral surgery may be performed via a sternotomy or a right thoracotomy approach with or without robotic assistance. Standard techniques commonly include a ring or band annuloplasty to correct and prevent annular dilatation; leaflet prolapse and redundancy may be corrected by leaflet resection techniques and / or chordal reconstruction.

Also known as: Mitral valve surgery

Surgical mitral valve repair

Transcatheter edge-to-edge repair DEVICE

Patients will be treated with a commercially-approved edge-to-edge mitral repair device. The steerable guide catheter (guide) is inserted into the femoral vein and advanced across the inter-atrial septum using image guided puncture. Fluoroscopic and echocardiographic guidance will be used to visualize the devices and assess the repair. The guide is positioned over the MV and the clip/clasp delivery system is inserted into the guide and positioned over the MV in accordance with the manufacturer's instructions. The delivery catheter is advanced until the clip/clasp emerges from the tip of the guide into the left atrium. The catheter is manipulated using the control handle until the clip/clasp is correctly oriented with respect to the line of coaptation of the mitral valve. The clip/clasp is opened, and advanced across the mitral valve into the left ventricle then pulled back to grasp the leaflets.

Also known as: TEER

Transcatheter edge-to-edge repair

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Adult patients ≥60 years with moderately-severe or severe (3+ or 4+/4+) primary degenerative (Carpentier type II) MR defined by transthoracic echocardiography
• Clinical indication for MV intervention and anatomic candidate for both surgical MV repair and transcatheter edge-to-edge repair (TEER) per local heart team assessment with central eligibility committee verification
• Patients across the surgical risk spectrum (low, intermediate, and high risk) depending on local heart team assessment and central eligibility committee verification (see ACC/AHA 2020 guidelines for the management of patients with valvular heart disease)
• Patients with AF who meet an indication for a concomitant ablation procedure be included provided the local heart team and central eligibility committee decide they are eligible for both catheter-based and surgical ablation.
• Ability to perform 6-minute walk test (6MWT) and complete Kansas City Cardiomyopathy Questionnaire (KCCQ) instrument
• Non-degenerative types of primary MR (e.g., cleft leaflet)
• Secondary or functional MR
• Hypertrophic obstructive cardiomyopathy
• Presence of an IVC filter or permanent pacing/ICD leads that would interfere with TEER per local heart team assessment
• Known allergic reactions to intravenous contrast
• Febrile illness within 30-days prior to randomization
• Any absolute contraindication to transesophageal echocardiography
• Any contraindication to systemic heparinization including active bleeding diatheses, and heparin induced thrombocytopenia
• Patients with CAD requiring revascularization
• Any prior mitral valve intervention or any prior repair of atrial septal defect

Sponsors & Collaborators

• Annetine Gelijns: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (62)

Keck Hospital of the University of Southern California

Los Angeles, California, 90033, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Piedmont Heart Institute

Atlanta, Georgia, 30309, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Ochsner Clinic

New Orleans, Louisiana, 70121, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

The Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's

Boston, Massachusetts, 02115, United States

Location

University of Michigan Hospital

Ann Arbor, Michigan, 48109, United States

Location

Saint Luke's Hospital of Kansas City/MidAmerica Heart and Lung Surgeons

Kansas City, Missouri, 64111, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

New York-Presbyterian/Columbia University Medical Center

New York, New York, 10032, United States

Location

Weill Cornell Medicine/ New York-Presbyterian Hospital

New York, New York, 10065, United States

Location

Northwell Health

New York, New York, 21287, United States

Location

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Baylor, Scott and White

Dallas, Texas, 75246, United States

Location

University of Virginia Medical Center

Charlottesville, Virginia, 22903, United States

Location

West Virginia University Hospital

Morgantown, West Virginia, 26506, United States

Location

University of British Columbia, Providence Health Care, St. Paul's Hospital

Vancouver, British Columbia, BC V6E 1M7, Canada

Location

London Health Sciences

London, Ontario, ON N6A 5W9, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Unity Health Toronto (St. Michael's Hospital)

Toronto, Ontario, M5B 1W8St, Canada

Location

Institut Universitaire de Cardiologie et de Pneumologie de Quebec (Laval University)

Québec, Quebec, QC G1V 4G5, Canada

Location

Universitätsklinikum Köln

Cologne, Berlin-kölnische Allee, 50969, Germany

Location

Herz- und Diabeteszentrum NRW

Bad Oeynhausen, North Rhine-Westphalia, 32545, Germany

Location

Universitätsklinikum Köln

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Kerckhoff Klinik Bad Nauheim

Bad Nauheim, 61231, Germany

Location

Schüchtermann-Klinik Bad Rothenfelde

Bad Rothenfelde, 49214, Germany

Location

Deutsches Herzzentrum der Charité

Berlin, 13353, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Asklepios Klinik St. Georg Hamburg

Hamburg, 20099, Germany

Location

Universitätsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitätsklinikum Jena

Jena, 07747, Germany

Location

Universitätsklinikum Schleswig-Holstein Campus Kiel

Kiel, 24105, Germany

Location

Herzzentrum Leipzig

Leipzig, 04289, Germany

Location

Universitätsklinikum Schleswig-Holstein Campus Lübeck

Lübeck, 23538, Germany

Location

Deutsches Herzzentrum München

München, 80636, Germany

Location

Hospital Alvaro Cunqueiro

Vigo, Galacia, 36204, Spain

Location

Hospital Clinic De Barcelona

Barcelona, 08036, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Central de Asturias

Oviedo, 33011, Spain

Location

Royal Papworth Hospital NHS Foundation Trust

Cambridge, England, CB2 0AY, United Kingdom

Location

The Leeds Teaching Hospitals NHS Trust

Leeds, England, LS1 3EX, United Kingdom

Location

St. Thomas Guy's and St Thomas' NHS Foundation Trust

London, England, SE1 7EH, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, England, SE5 9RS, United Kingdom

Location

Royal Brompton and Harefield Guy's and St Thomas' NHS Foundation Trust

London, England, SW3 6NP, United Kingdom

Location

Manchester University NHS Foundation Trust

Manchester, England, M23 9LT, United Kingdom

Location

University Hospitals Sussex NHS Foundation Trust

Worthing, West Sussex, BN2 5BE, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2TH, United Kingdom

Location

Golden Jubilee University National Hospital

Clydebank, G81 4DY, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Headington, OX3 9DU, United Kingdom

Location

Barts Health NHS Trust

London, E1 8PR, United Kingdom

Location

South Tees Hospitals NHS Foundation Trust

Middlesbrough, TS4 3BW, United Kingdom

Location

South Tees Hospital NHS Foundation Trust

Middlesbrough, United Kingdom

Location

Related Links

• PRIMARY Ancillary Substudy

MeSH Terms

Conditions

Mitral Valve Insufficiency

Interventions

Mitral Valve Annuloplasty

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Cardiac Valve Annuloplasty; Cardiac Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Thoracic Surgical Procedures

Study Officials

• Joanna Chikwe, MD

  Cedars Sinai

  STUDY DIRECTOR

• Martin Leon, MD

  Columbia University

  STUDY DIRECTOR

• Patrick O'Gara, MD

  Brigham and Women's Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chair, Department of Population Health Science & Policy Edmond A. Guggenheim Professor of Health Policy Co-Director, InCHOIR

Model Details: Eligible and consented patients will be randomized 1:1 to a TEER versus surgical repair. Patient randomization will be stratified by clinical site and by surgical risk profile, namely low, intermediate, and high surgical risk. Primary effectiveness will be analyzed by intention-to-treat; that is, the patients will be grouped by their assignment at randomization whether or not they actually received the treatment to which they were assigned.

Study Record Dates

• First Submitted: September 10, 2021
• First Posted: September 21, 2021
• Study Start: February 21, 2022
• Primary Completion (Estimated): November 15, 2028
• Study Completion (Estimated): November 15, 2030
• Last Updated: June 24, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: De-identified study data sets must be submitted to the designated NHLBI Program Official no later than 3 years after the end of the clinical activity (final patient follow-up, etc.) or 2 years after the main paper of the trial has been published, whichever comes first. Data are prepared by the study coordinating center and sent to the designated PO for review prior to release.
• Access Criteria: Anyone who wishes to access the data. Any purpose. Data are available indefinitely at link included in the URL field below.

Locations

US (24); DE (16); ES (4); GB (13); CA (5)