Mitral Valve RegurgitationPRIMARYNCT05051033
Percutaneous or Surgical Repair In Mitral Prolapse And Regurgitation for ≥60 Year-olds (PRIMARY)
A study testing Mitral valve repair and Transcatheter edge-to-edge repair in people with Mitral Valve Regurgitation, run by Annetine Gelijns at 67 sites in 5 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Mitral Valve Regurgitation
- What is being tested?
- Mitral valve repair and Transcatheter edge-to-edge repair
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 450 participants
- Where
- 67 sitesin 5 countries
- Study dates
- 21 Feb 2022to 31 Jan 2034
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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.
Trial locations and contacts
67 sites in 5 countries.
67 sites in 5 countries
United States29 sites
University of Michigan Hospital
Ann Arbor, Michigan, 48109
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Piedmont Heart Institute
Atlanta, Georgia, 30309
Emory University
Atlanta, Georgia, 30322
The Johns Hopkins Hospital
Baltimore, Maryland, 21287
Northwell - South Shore
Bay Shore, New York, 11706
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's
Boston, Massachusetts, 02115
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Virginia Medical Center
Charlottesville, Virginia, 22903
Cleveland Clinic
Cleveland, Ohio, 44195
Baylor, Scott and White
Dallas, Texas, 75246
Duke University Hospital
Durham, North Carolina, 27710
Saint Luke's Hospital of Kansas City/MidAmerica Heart and Lung Surgeons
Kansas City, Missouri, 64111
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Keck Hospital of the University of Southern California
Los Angeles, California, 90033
Cedars Sinai Medical Center
Los Angeles, California, 90048
Northwell Health - North Shore
Manhasset, New York, 11030
West Virginia University Hospital
Morgantown, West Virginia, 26506
Ochsner Clinic
New Orleans, Louisiana, 70121
New York-Presbyterian/Columbia University Medical Center
New York, New York, 10032
Weill Cornell Medicine/ New York-Presbyterian Hospital
New York, New York, 10065
Northwell Health - Lenox Hill
New York, New York, 10075
Northwell Health
New York, New York, 21287
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Maine Medical Center
Portland, Maine, 04102
University of California San Francisco
San Francisco, California, 94143
Stanford University
Stanford, California, 94305
Northwell Staten Island University Hospital
Staten Island, New York, 10305
Germany15 sites
Kerckhoff Klinik Bad Nauheim
Bad Nauheim, 61231
Schüchtermann-Klinik Bad Rothenfelde
Bad Rothenfelde, 49214
Deutsches Herzzentrum der Charité
Berlin, 13353
Universitätsklinikum Köln
Cologne, Berlin-kölnische Allee, 50969
Universitätsklinikum Köln
Cologne, North Rhine-Westphalia, 50937
Universitätsklinikum Frankfurt
Frankfurt, 60590
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106
Asklepios Klinik St. Georg Hamburg
Hamburg, 20099
Universitätsklinikum Hamburg Eppendorf
Hamburg, 20246
Universitätsklinikum Heidelberg
Heidelberg, 69120
Universitätsklinikum Jena
Jena, 07747
Universitätsklinikum Schleswig-Holstein Campus Kiel
Kiel, 24105
Herzzentrum Leipzig
Leipzig, 04289
Universitätsklinikum Schleswig-Holstein Campus Lübeck
Lübeck, 23538
Deutsches Herzzentrum München
München, 80636
United Kingdom13 sites
University Hospitals Birmingham NHS Foundation Trust
Birmingham, B15 2TH
University Hospital Bristol and Weston NHS Foundation Trust
Bristol, BS1 3NU
Royal Papworth Hospital NHS Foundation Trust
Cambridge, England, CB2 0AY
Golden Jubilee University National Hospital
Clydebank, G81 4DY
Oxford University Hospitals NHS Foundation Trust
Headington, OX3 9DU
The Leeds Teaching Hospitals NHS Trust
Leeds, England, LS1 3EX
St. Thomas Guy's and St Thomas' NHS Foundation Trust
London, England, SE1 7EH
King's College Hospital NHS Foundation Trust
London, England, SE5 9RS
Royal Brompton and Harefield Guy's and St Thomas' NHS Foundation Trust
London, England, SW3 6NP
Barts Health NHS Trust
London, E1 8PR
Manchester University NHS Foundation Trust
Manchester, England, M23 9LT
South Tees Hospitals NHS Foundation Trust
Middlesbrough, TS4 3BW
University Hospitals Sussex NHS Foundation Trust
Worthing, West Sussex, BN2 5BE
Canada5 sites
London Health Sciences
London, Ontario, ON N6A 5W9
University of Ottawa Heart Institute
Ottawa, Ontario, K1Y 4W7
Institut Universitaire de Cardiologie et de Pneumologie de Quebec (Laval University)
Québec, Quebec, QC G1V 4G5
Unity Health Toronto (St. Michael's Hospital)
Toronto, Ontario, M5B 1W8St
University of British Columbia, Providence Health Care, St. Paul's Hospital
Vancouver, British Columbia, BC V6E 1M7
Spain5 sites
Hospital Clinic De Barcelona
Barcelona, 08036
Hospital Clínico San Carlos
Madrid, 28040
Hospital Central de Asturias
Oviedo, 33011
Hospital Universitari Son Espases.
Palma de Mallorca, Balearic Islands, 07120
Hospital Alvaro Cunqueiro
Vigo, Galacia, 36204
About this study
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.
Read the 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.
- Conditions
- Mitral Valve Regurgitation
- Being tested
- Mitral valve repair, Transcatheter edge-to-edge repair
- Keywords
- surgical mitral valve repair, transcatheter edge-to-edge repair
- Medical subject headings
- Mitral Valve Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mitral valve repairProcedure or surgery
Also called Mitral valve surgery
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.
Transcatheter edge-to-edge repairDevice
Also called TEER
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.
| Study group | Role | What they receive |
|---|---|---|
| Surgical mitral valve repair | Active comparator | Patients who are randomized to the surgical arm will undergo mitral surgery. Receives: 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. Receives: Device: Transcatheter edge-to-edge repair |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years post intervention
Secondary outcomes (27)
Adequacy of MR correction
Adequacy of MR correction at one year post intervention, defined as < 2+ MR as assessed by TTE
Measured: 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.
Measured: 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.
Measured: End of procedure
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.
Measured: 10 years post randomization
All-cause mortality
All-cause mortality through 5 years post randomization
Measured: 5 years post randomization
All-cause mortality
All-cause mortality from randomization through 10 years post intervention
Measured: 10 years post intervention
Cardiovascular and non-cardiovascular mortality
Cardiovascular and non-cardiovascular mortality from randomization through 5 years post intervention
Measured: 5 years post intervention
Cardiovascular and non-cardiovascular mortality
Cardiovascular and non-cardiovascular mortality from randomization through 10 years post intervention
Measured: 10 years post intervention
Valve re-interventions
Valve re-interventions through 5 years post intervention
Measured: 5 years post intervention
Valve re-interventions
Valve re-interventions through 10 years post intervention
Measured: 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
Measured: 5 years post intervention
MR grade
Mitral Regurgitation (MR) grade as mild, moderate, or severe. (grade I-IV, with higher grade indicating poorer health outcomes.)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: up to 6 years post intervention
Forward stroke volume
The forward stroke volume is the volume entering the aorta.
Measured: up to 6 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
Measured: up to 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).
Measured: through 10 years post intervention
Length of stay (LOS)
Length of stay as measured by number of days hospitalized.
Measured: through 10 years post intervention
ICU days of index hospitalization
Number of ICU days of index hospitalization
Measured: 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
Measured: through 10 years post intervention
Cost
Costs associated with the index hospitalization as well as follow-up readmissions will be measured.
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.
Measured: through 10 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
Measured: 30 days post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2021
- Study start21 Feb 2022
- Primary completion30 Jun 2029 (estimated)
- Study completion31 Jan 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitral Valve RegurgitationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 450 participants (actual)
Sponsor and investigators
- Lead sponsor
- Annetine Gelijns
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor-investigator, Annetine Gelijns, Icahn School of Medicine at Mount Sinai
- Investigators
- Joanna Chikwe, MD, Study director, Cedars SinaiMartin Leon, MD, Study director, Columbia UniversityPatrick O'Gara, MD, Study director, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05051033
- Sponsor's protocol ID
- STUDY-21-01246
- Other IDs
- 5U01HL088942
- Acronym
- PRIMARY
- Status last verified
- Sep 2026
- First submitted
- 10 Sep 2021
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).