PRIMARY Ancillary Substudy

August 14, 2025 updated by: Annetine Gelijns

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

The PRIMARY trial (NCT05051033), which compares mitral valve repair (MVr) to transcatheter-edge-to-edge-repair (TEER), offers a platform for conducting mechanistic studies to develop early insights into the pathophysiological processes by which mitral valve prolapse (MVP) can impact left ventricular (LV) myocardial structure and function, and, thereby, predispose to arrhythmias and sudden death. Such insights are key to identifying interventions to reduce the long-term sequelae of heart failure (HF) and arrhythmias, as well as delineate optimal therapeutic approaches for different patient sub-groups.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is an ancillary study of a multicenter randomized clinical trial comparing MVr to TEER for degenerative mitral regurgitation (MR) involving up to 250 patients from the parent trial. All patients will receive rhythm monitoring, up to 200 patients will receive pre/post intervention CMR, all patients in the parent trial will undergo a transthoracic echocardiogram (TTE) (as part of the randomized controlled trial (RCT)), and 60 surgical patients will undergo tissue biopsies. The study is being conducted in highly experienced clinical centers in the U.S., Canada, Germany, the U.K. and Spain. The estimated enrollment period is 12-18 months. Outcomes will be measured from baseline to 12 months after randomization.

This mechanistic ancillary study has the following aims:

  1. To compare the impact of MVr and TEER on disordered ventricular biomechanics and myocardial fibrosis that predispose to ventricular arrhythmias, using speckle tracking strain echocardiography, cardiac magnetic resonance imaging (CMR), and rhythm monitoring pre- and post-mitral valve (MV) intervention. The research team hypothesize's that a treatment strategy that more effectively and durably reduces MVP and MR will lead to improved ventricular mechanics, limit progression of myocardial fibrosis and decrease the burden of ventricular arrhythmias and HF.
  2. To compare the impact of MVr and TEER on recurrent/residual MR, LV and left atrial (LA) reverse remodeling with baseline and 1-year post-intervention CMR, and to use quantitative CMR myocardial tissue phenotyping as a predictor of response to MVr and TEER.
  3. To construct functional pre-operative CMR fingerprints that recapitulate the mechanical state of the heart to develop individualized computational models, which will be altered in silico based on the proposed treatment plan, to predict patients' response to therapy. These results will be validated against post-operative outcome data to test the validity of this approach for predicting treatment response.
  4. To explore the relationships among gene products, structural variables, and post-operative clinical outcomes, including reverse remodeling, using tissue obtained at surgery from ventricular myocardium.

Study Type

Interventional

Enrollment (Estimated)

250

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Germany
      • Berlin, Germany, 13353
        • Recruiting
        • Deutsches Herzzentrum der Charité
        • Principal Investigator:
          • Volkmar Falk
        • Contact:
      • Leipzig, Germany, 04289
        • Recruiting
        • Herzzentrum Leipzig
        • Principal Investigator:
          • Michael Borger
        • Contact:
  • United Kingdom
    • Cambridge
      • Trumpington, Cambridge, United Kingdom
        • Recruiting
        • Royal Papworth Hospital NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Patrick Calvert
    • England
      • Leeds, England, United Kingdom, LS9 7TF
        • Recruiting
        • The Leeds Teaching Hospitals Nhs Trust
        • Contact:
        • Principal Investigator:
          • Chris Malkin
    • London
      • Whitechapel, London, United Kingdom
        • Recruiting
        • Barts Health NHS Trust
        • Contact:
        • Principal Investigator:
          • Dincer Aktuerk
    • Manchester
      • Oxford, Manchester, United Kingdom
        • Recruiting
        • Manchester University NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Mamta Buch
    • Middlesbrough
      • Marton, Middlesbrough, United Kingdom
        • Recruiting
        • South Tees Hospitals NHS Foundation Trust
        • Principal Investigator:
          • Enoch Akowuah, MD
        • Contact:
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 9DU
        • Recruiting
        • Oxford University Hospitals NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Rana Sayeed
    • West Sussex
      • Worthing, West Sussex, United Kingdom, BN11 2DH
        • Recruiting
        • University Hospitals Sussex NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Ish Ahmed
  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai
        • Principal Investigator:
          • Joanna Chikwe, MD
        • Contact:
      • Los Angeles, California, United States, 90033
        • Recruiting
        • Keck Hospital of the University of Southern California
        • Principal Investigator:
          • Vaughn Starnes, MD
        • Contact:
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California San Francisco
        • Principal Investigator:
          • Sammy Elmariah, MD
        • Contact:
      • Stanford, California, United States, 94305
        • Recruiting
        • Stanford University
        • Principal Investigator:
          • Jack Boyd, MD
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30309
    • Maine
      • Portland, Maine, United States, 04102
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • The Johns Hopkins Hospital
        • Principal Investigator:
          • James Gammie, MD
        • Contact:
          • Zyriah Robinson
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Serguei Melnitchouk, MD
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan Hospital
        • Principal Investigator:
          • Gorav Ailawadi
        • Contact:
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Recruiting
        • Saint Luke's Hospital of Kansas City/MidAmerica Heart and Lung Surgeons
        • Principal Investigator:
          • Keith Allen, MD
        • Contact:
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Weill Cornell Medicine/ New York-Presbyterian Hospital
        • Contact:
        • Principal Investigator:
          • Stephanie Mick, MD
        • Principal Investigator:
          • Donald Glower
      • New York, New York, United States, 10075
        • Recruiting
        • Northwell--Lenox Hill, North Shore, South Shore, Staten Island University Hospital
        • Principal Investigator:
          • Nirav Patel, MD
        • Contact:
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Hospital
        • Contact:
        • Principal Investigator:
          • Donald Glower, MD
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Contact:
        • Principal Investigator:
          • Marc Gilinov, MD
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University of Virginia Medical Center
        • Principal Investigator:
          • John Saxon, MD
        • Contact:
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Recruiting
        • West Virginia University Hospital
        • Principal Investigator:
          • Vinay Badhwar, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients who meet all eligibility criteria and are randomized in the parent PRIMARY trial.
  • For the ancillary biospecimen study, patients who are randomized to MVr in the parent trial.

Exclusion Criteria:

  • Severe claustrophobia not controlled with sedation.
  • Prior adverse reaction to gadolinium administration.
  • Patients with an implantable subcutaneous cardioverter defibrillator and/or cardiac resynchronization therapy device with defibrillator may be excluded as they typically produce substantial artifacts on cardiac MRI making assessment very challenging.
  • Known allergic reaction to adhesives or hydrogels or with family history of adhesive skin allergies (for patients undergoing rhythm monitoring).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Mitral valve repair
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.
Procedure: Cardiac Magnetic Resonance Imaging
Non-invasive imaging test that uses powerful magnets and radio waves to create detailed pictures of the heart without using radiation.
Other Names:
  • CMR
Device: ZioPatch Monitoring
ZioPatch is a small, wearable heart monitor that sticks to the chest and records the heart's electrical activity continuously for up to 14 days. It helps doctors detect irregular heart rhythms (arrhythmias) without the need for bulky wires or equipment.
Other Names:
  • iRhythm Monitoring
Procedure: Myocardial Tissue Biopsy
During the MVr procedure, surgeons will biopsy approximately 50 μg of tissue from the endocardial and subendocardial myocardium in the inferobasilar and control areas using a surgical rongeur.
Other Names:
  • Heart Bioplsy
Active Comparator: Transcatheter edge-to-edge repair
Patients will be treated with a commercially-approved edge-to-edge mitral repair device.
Procedure: Cardiac Magnetic Resonance Imaging
Non-invasive imaging test that uses powerful magnets and radio waves to create detailed pictures of the heart without using radiation.
Other Names:
  • CMR
Device: ZioPatch Monitoring
ZioPatch is a small, wearable heart monitor that sticks to the chest and records the heart's electrical activity continuously for up to 14 days. It helps doctors detect irregular heart rhythms (arrhythmias) without the need for bulky wires or equipment.
Other Names:
  • iRhythm Monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence of Myocardial Fibrosis
Time Frame: 1 year post index procedure.
Myocardial fibrosis is the buildup of excess fibrous connective tissue in the heart muscle often resulting from chronic injury or stress. It can impair the heart's ability to contract and relax properly leading to reduced cardiac function.
1 year post index procedure.
Presence of Ventricular Arrythmia
Time Frame: 1 year post index procedure.
A ventricular arrhythmia is an abnormal heart rhythm that starts in the lower chambers of the heart (the ventricles). It can cause the heart to beat too fast, which may reduce blood flow to the body and, in some cases, be life-threatening.
1 year post index procedure.
Proteomics
Time Frame: 1 year post index procedure.
Proteomics is the large-scale study of proteins, which are essential molecules that carry out most functions in the body. By analyzing proteins in tissues or fluids, scientists can better understand diseases, identify biomarkers, and discover new treatment targets.
1 year post index procedure.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Computational and Predictive Models of Treatment Outcome
Time Frame: 1 year post index procedure.
specific treatment. These tools help doctors make more personalized and effective care decisions based on patterns found in large sets of medical information.
1 year post index procedure.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Annetine Gelijns

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Study Director: Martin Leon, MD, Columbia University
  • Study Director: Joanna Chikwe, MD, Cedars-Sinai

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 16, 2023

Primary Completion (Estimated)

June 30, 2027

Study Completion (Estimated)

June 30, 2027

Study Registration Dates

First Submitted

July 22, 2025

First Submitted That Met QC Criteria

August 1, 2025

First Posted (Actual)

August 5, 2025

Study Record Updates

Last Update Posted (Actual)

August 19, 2025

Last Update Submitted That Met QC Criteria

August 14, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GCO 08-1078 ANC
  • 5U01HL088942-17 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data shared will be in aggregate.

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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