Clinical trial NCT05051033: Percutaneous or Surgical Repair In Mitral Prolapse And Regurgitation for ≥60 Year-olds (PRIMARY)
Official title: Percutaneous or Surgical Repair In Mitral Prolapse And Regurgitation for ≥60 Year-olds (PRIMARY)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Mitral Valve Regurgitation
Keywords: surgical mitral valve repair
transcatheter edge-to-edge repair
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2021-09-21
Enrollment: 450
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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 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.

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.

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.

Eligibility criteria: 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 ≥65 yrs 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 MV transcatheter edge-to-edge and surgical repair per local heart team assessment
* Patients across the surgical risk spectrum (low, intermediate, and high risk) depending on the local heart team assessment (see 2020 ACC/AHA guidelines for the management of patients with valvular heart disease)
* Patients with AF who meet an indication for concomitant ablation may be included provided the local heart team verifies 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 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 meaningful 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 its primary endpoint or that clinically interferes with the present study endpoints.

Primary outcomes:
measure: All-cause mortality, valve re-intervention, hospitalizations and urgent visits for heart failure, or onset of ≥ 3+ MR (by transthoracic echocardiogram (TTE)) composite score.
timeFrame: 3 years post intervention
Secondary outcomes:
measure: Adequacy of MR correction
timeFrame: one year post intervention
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: up to 10 years post intervention
measure: Procedure failure
timeFrame: End of procedure
measure: Procedure failure
timeFrame: 10 years post randomization
measure: All-cause mortality
timeFrame: 5 years post randomization
measure: All-cause mortality
timeFrame: 10 years post intervention
measure: Cardiovascular and non-cardiovascular mortality
timeFrame: 5 years post intervention
measure: Cardiovascular and non-cardiovascular mortality
timeFrame: 10 years post intervention
measure: Valve re-interventions
timeFrame: 5 years post intervention
measure: Valve re-interventions
timeFrame: 10 years post intervention
measure: Serious or protocol-defined adverse events
timeFrame: 5 years post intervention
measure: MR grade
timeFrame: through 5 years post intervention
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: through 5 years post intervention
measure: Left Ventricular End Diastolic Dimension (LVEDD)
timeFrame: through 5 years post intervention
measure: Left Ventricular End Systolic Dimension (LVESD)
timeFrame: through 5 years post intervention
measure: Left Ventricular End Diastolic Volume (LVEDV)
timeFrame: through 5 years post intervention
measure: Left Ventricular End Systolic Volume (LVESV)
timeFrame: through 5 years post intervention
measure: Mitral valve gradient
timeFrame: through 5 years post intervention
measure: Forward stroke volume
timeFrame: through 5 years post intervention
measure: 6 Minute Walk Test (6MWT)
timeFrame: through 5 years post intervention
measure: EuroQol- 5 Dimension (EQ-5D)
timeFrame: through 10 years post intervention
measure: Length of stay (LOS)
timeFrame: through 10 years post intervention
measure: ICU days of index hospitalization
timeFrame: through 10 years post intervention
measure: Number and reasons for readmissions
timeFrame: through 10 years post intervention
measure: Cost
timeFrame: through 10 years post intervention
measure: Cost-effectiveness
timeFrame: through 10 years post intervention
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Keck Hospital of the University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: New Orleans
country: United States
facility: Ochsner Clinic
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City/MidAmerica Heart and Lung Surgeons
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Nyph/Cumc
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine/ New York-Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Northwell Health
state: New York
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Baylor, Scott and White
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University Hospital
state: West Virginia
city: London
country: Canada
facility: London Health Sciences
state: Ontario
city: Quebec City
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Quebec (Laval University)
state: Quebec
city: Bad Nauheim
country: Germany
facility: Kerckhoff Klinik Bad Nauheim
city: Bad Rothenfelde
country: Germany
facility: Schüchtermann-Klinik Bad Rothenfelde
city: Berlin
country: Germany
facility: Deutsches Herzzentrum Berlin
city: Berlin
country: Germany
facility: Deutsches Herzzentrum der Charité
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg Hamburg
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein Campus Kiel
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig
city: Lübeck
country: Germany
facility: Lübeck
city: München
country: Germany
facility: Deutsches Herzzentrum München
city: Middlesbrough
country: United Kingdom
facility: South Tees Hospitals NHS Foundation Trust
Study officials:
affiliation: Cedars Sinai
name: Joann Chikwe, MD
role: STUDY_DIRECTOR
affiliation: Columbia University
name: Martin Leon, MD
role: STUDY_DIRECTOR
affiliation: Brigham and Women's Hospital
name: Patrick O'Gara, MD
role: STUDY_DIRECTOR
References: