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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Mitral Valve Regurgitation
• Intervention / Treatment: Procedure: Mitral valve repair; Device: Transcatheter edge-to-edge repair

Detailed Description

The primary aim of this study is to evaluate the long-term effectiveness and safety of MV TEER compared with surgical repair in patients with primary, degenerative MR. The secondary aim is to analyze the relationship between the adequacy of MR correction at one-year post intervention and longer-term clinical outcomes (death, heart failure hospitalizations/urgent care visits, valve re-interventions, and quality of life). The tertiary aim of this trial is to evaluate a range of patient-centered outcomes (quality of life, functional status, and discharge location) of transcatheter edge-to-edge MV repair compared with MV surgical repair in patients with primary, degenerative mitral regurgitation. This study is closely integrated with the PRIMARY Ancillary Substudy (NCT07103733)

The patient population for this trial consists of adult patients with severe, primary degenerative MR for whom the local heart team has verified that an indication for MV intervention is present and for whom both transcatheter edge-to-edge and surgical repair strategies are anatomically feasible.

Because the use of the commercial edge-to-edge mitral repair device in the U.S. is approved only in patients considered to be at prohibitive risk of MV surgery by a heart team, use of such devices in this trial is considered investigational by the FDA. As such, this trial will be conducted under an Investigational Device Exemption (IDE).

Outcomes will be measured from randomization over a period of 5 years post intervention. The estimated enrollment period is 36 months, and all patients will be followed from randomization for up to 10 years post intervention for particular endpoints. Long-term follow-up will include leveraging administrative datasets linked to clinical trial data.

• Study Type: Interventional
• Enrollment (Actual): 450
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, BC V6E 1M7
      • University of British Columbia, Providence Health Care, St. Paul's Hospital
  • Ontario
    • London, Ontario, Canada, ON N6A 5W9
      • London Health Sciences
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute
    • Toronto, Ontario, Canada, M5B 1W8St
      • Unity Health Toronto (St. Michael's Hospital)
  • Quebec
    • Québec, Quebec, Canada, QC G1V 4G5
      • Institut Universitaire de Cardiologie et de Pneumologie de Quebec (Laval University)
• Germany
  • Bad Nauheim, Germany, 61231
    • Kerckhoff Klinik Bad Nauheim
  • Bad Rothenfelde, Germany, 49214
    • Schüchtermann-Klinik Bad Rothenfelde
  • Berlin, Germany, 13353
    • Deutsches Herzzentrum der Charité
  • Frankfurt, Germany, 60590
    • Universitätsklinikum Frankfurt
  • Freiburg im Breisgau, Germany, 79106
    • Universitätsklinikum Freiburg
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg Eppendorf
  • Hamburg, Germany, 20099
    • Asklepios Klinik St. Georg Hamburg
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Jena, Germany, 07747
    • Universitätsklinikum Jena
  • Kiel, Germany, 24105
    • Universitätsklinikum Schleswig-Holstein Campus Kiel
  • Leipzig, Germany, 04289
    • Herzzentrum Leipzig
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein Campus Lübeck
  • München, Germany, 80636
    • Deutsches Herzzentrum München
  • Berlin-kölnische Allee
    • Cologne, Berlin-kölnische Allee, Germany, 50969
      • Universitätsklinikum Köln
  • North Rhine-Westphalia
    • Bad Oeynhausen, North Rhine-Westphalia, Germany, 32545
      • Herz- und Diabeteszentrum NRW
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Universitätsklinikum Köln
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Madrid, Spain, 28040
    • Hospital Clínico San Carlos
  • Oviedo, Spain, 33011
    • Hospital Central de Asturias
  • Galacia
    • Vigo, Galacia, Spain, 36204
      • Hospital Alvaro Cunqueiro
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • University Hospitals Birmingham NHS Foundation Trust
  • Clydebank, United Kingdom, G81 4DY
    • Golden Jubilee University National Hospital
  • Headington, United Kingdom, OX3 9DU
    • Oxford University Hospitals NHS Foundation Trust
  • London, United Kingdom, E1 8PR
    • Barts Health NHS Trust
  • Middlesbrough, United Kingdom, TS4 3BW
    • South Tees Hospitals NHS Foundation Trust
  • Middlesbrough, United Kingdom
    • South Tees Hospital NHS Foundation Trust
  • England
    • Cambridge, England, United Kingdom, CB2 0AY
      • Royal Papworth Hospital NHS Foundation Trust
    • Leeds, England, United Kingdom, LS1 3EX
      • The Leeds Teaching Hospitals NHS Trust
    • London, England, United Kingdom, SE5 9RS
      • King's College Hospital NHS Foundation Trust
    • London, England, United Kingdom, SE1 7EH
      • St. Thomas Guy's and St Thomas' NHS Foundation Trust
    • London, England, United Kingdom, SW3 6NP
      • Royal Brompton and Harefield Guy's and St Thomas' NHS Foundation Trust
    • Manchester, England, United Kingdom, M23 9LT
      • Manchester University NHS Foundation Trust
  • West Sussex
    • Worthing, West Sussex, United Kingdom, BN2 5BE
      • University Hospitals Sussex NHS Foundation Trust
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Los Angeles, California, United States, 90033
      • Keck Hospital of the University of Southern California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • Stanford, California, United States, 94305
      • Stanford University
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Atlanta, Georgia, United States, 30309
      • Piedmont Heart Institute
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City/MidAmerica Heart and Lung Surgeons
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10032
      • New York-Presbyterian/Columbia University Medical Center
    • New York, New York, United States, 21287
      • Northwell Health
    • New York, New York, United States, 10065
      • Weill Cornell Medicine/ New York-Presbyterian Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor, Scott and White
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Medical Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

The patient population for this trial consists of adults with severe, primary degenerative MR for whom the local heart team has verified that an indication for MV intervention is present and for whom both transcatheter edge-to-edge and surgical repair strategies are anatomically feasible. Specific inclusion and exclusion criteria are listed below. All patients who meet eligibility criteria will be included in the study regardless of gender, race, or ethnicity.

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Any prior MV intervention or any prior repair of atrial septal defect
• Need for any of the following concomitant procedures: aortic valve or aortic surgery, tricuspid valve surgery
• Need for any emergency intervention or surgery
• Active endocarditis
• Hemodynamic instability defined as cardiac index <2.0 l/min/m2 or systolic blood pressure <90mmHg or need for inotropic support or any mechanical circulatory support
• Left ventricular ejection fraction <25%
• Intracardiac mass or thrombus
• Co-morbid medical or oncologic condition for which local heart team believes that survival beyond 2 years is unlikely
• Active substance abuse
• Suspected inability to adhere to follow-up
• Treatment with another investigational drug or other intervention, assessment of which has not completed the primary endpoint or that clinically interferes with the present study endpoints.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Surgical mitral valve repair; Patients who are randomized to the surgical arm will undergo mitral surgery.	Procedure: Mitral valve repair; 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.; Other Names: Mitral valve surgery
Active Comparator: Transcatheter edge-to-edge repair; 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; 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.; Other Names: TEER

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedure failure	Procedure failure defined as residual moderately severe or severe (3+ or 4+/4+) MR at the end of the procedure, or conversion of a TEER to an open surgical repair or replacement, or conversion of a surgical mitral valve repair to a mitral valve replacement procedure.	10 years post randomization
All-cause mortality	All-cause mortality through 5 years post randomization	5 years post randomization
Adequacy of MR correction	Adequacy of MR correction at one year post intervention, defined as < 2+ MR as assessed by TTE	one year post intervention
Kansas City Cardiomyopathy Questionnaire (KCCQ)	Disease-specific quality of life as measured by the KCCQ at 6-month time intervals up to 5 years. KCCQ has 23 items that map to 7 domains: symptom frequency; symptom burden; symptom stability; physical limitations; social limitations; quality of life; and self-efficacy. The symptom frequency and symptom burden domains are merged into a total symptom score, which can be combined with the physical limitation domain to create a clinical summary score. All scores are scaled 0 to 100, with higher scores indicating better health outcome.	up to 10 years post intervention
Procedure failure	Procedure failure defined as residual moderately severe or severe (3+ or 4+/4+) MR at the end of the procedure, or conversion of a TEER to an open surgical repair or replacement, or conversion of a surgical mitral valve repair to a mitral valve replacement procedure.	End of procedure
All-cause mortality	All-cause mortality from randomization through 10 years post intervention	10 years post intervention
Cardiovascular and non-cardiovascular mortality	Cardiovascular and non-cardiovascular mortality from randomization through 5 years post intervention	5 years post intervention
Cardiovascular and non-cardiovascular mortality	Cardiovascular and non-cardiovascular mortality from randomization through 10 years post intervention	10 years post intervention
Valve re-interventions	Valve re-interventions through 5 years post intervention	5 years post intervention
Valve re-interventions	Valve re-interventions through 10 years post intervention	10 years post intervention
Serious or protocol-defined adverse events	Serious or protocol-defined adverse events, including stroke, acute kidney injury (AKI), and renal failure, through 5 years	5 years post intervention
EuroQol- 5 Dimension (EQ-5D)	Generic QoL as measured by the EuroQol-5D (EQ-5D). The EQ-5D descriptive system is a preference-based HRQL measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The answers given to ED-5D permit to find 243 unique health states or can be converted into EQ- 5D index an utility scores anchored at 0 for death and 1 for perfect health. The EQ-5D questionnaire also includes a Visual Analog Scale (VAS), by which respondents can report their perceived health status with a grade ranging from 0 (the worst possible health status) to 100 (the best possible health status).	through 10 years post intervention
Length of stay (LOS)	Length of stay as measured by number of days hospitalized.	through 10 years post intervention
ICU days of index hospitalization	Number of ICU days of index hospitalization	through 10 years post intervention
Number and reasons for readmissions	Number and reasons for readmissions, including for valve re-intervention and readmissions/urgent visits for heart failure	through 10 years post intervention
Cost	Costs associated with the index hospitalization as well as follow-up readmissions will be measured.	through 10 years post intervention
Cost-effectiveness	A cost-effectiveness analysis (CEA) comparing cumulative costs and quality-adjusted life years (QALYs) of transcatheter edge-to-edge repair vs surgical repair will be performed from U.S., Canadian, German and United Kingdom health care sector perspectives according to national guidelines.	through 10 years post intervention
6 Minute Walk Test (6MWT)	Functional status as measured by the 6MWT at yearly time intervals over 5 years. 6MT - The distance covered over a time of 6 minutes	up to 5 years post intervention
Number of participants with stroke with disability	Stroke with disability is defined as a modified Rankin score of ≥ 2 and/or major bleeding (BARC Type 3b, 3c and 5) by 30 days post-intervention	30 days post-intervention
MR grade	Mitral Regurgitation (MR) grade as mild, moderate, or severe. (grade I-IV, with higher grade indicating poorer health outcomes.)	up to 6 years post intervention
Left Ventricular Ejection Fraction (LVEF)	Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction.	up to 6 years post intervention
Left Ventricular End Diastolic Dimension (LVEDD)	Left ventricular end diastolic dimension (LVEDD) is the diameter across the left ventricle of the heart at the end of diastole, that is, when the heart muscle is maximally relaxed, and usually corresponds to its largest diameter.	up to 6 years post intervention
Left Ventricular End Systolic Dimension (LVESD)	Left ventricular end systolic dimension (LVESD) is the diameter across the left ventricle of the heart at the end of systole, that is, when the heart muscle is maximally contracted, and usually corresponds to its smallest diameter.	up to 6 years post intervention
Left Ventricular End Diastolic Volume (LVEDV)	Left Ventricular end diastolic volume (LVEDV) is the volume of blood in the left ventricle at the end of the diastole or ventricular filling.	up to 6 years post intervention
Left Ventricular End Systolic Volume (LVESV)	Left Ventricular end systolic volume (LVESV) is the volume of blood in the left ventricle at the end of the systolic ejection phase immediately before the beginning of diastole or ventricular filling.	up to 6 years post intervention
Mitral valve gradient	The valve gradient is the difference in pressure on each side of the valve. When a valve is narrowed (a condition called stenosis), the pressure on the front of the valve builds up as blood is forced through the narrow opening. This causes a larger pressure difference between the front and back of the valve. The valve gradient can be used to determine the severity of the valve disorder.	up to 6 years post intervention
Forward stroke volume	The forward stroke volume is the volume entering the aorta.	up to 6 years post intervention

Collaborators and Investigators

• Sponsor: Annetine Gelijns
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Study Director: Martin Leon, MD, Columbia University; Study Director: Patrick O'Gara, MD, Brigham and Women's Hospital; Study Director: Joanna Chikwe, MD, Cedars Sinai

Publications and helpful links

Helpful Links

• PRIMARY Ancillary Substudy

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2022
• Primary Completion (Estimated): November 15, 2028
• Study Completion (Estimated): November 15, 2030

Study Registration Dates

• First Submitted: September 10, 2021
• First Submitted That Met QC Criteria: September 10, 2021
• First Posted (Actual): September 21, 2021

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: surgical mitral valve repair; transcatheter edge-to-edge repair
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Mitral Valve Insufficiency; Surgical Procedures, Operative; Cardiovascular Surgical Procedures; Cardiac Surgical Procedures; Thoracic Surgical Procedures; Cardiac Valve Annuloplasty; Mitral Valve Annuloplasty
• Other Study ID Numbers: STUDY-21-01246; 5U01HL088942 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing 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.
• IPD Sharing Access Criteria: Anyone who wishes to access the data. Any purpose. Data are available indefinitely at link included in the URL field below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No