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

Mitral Valve Regurgitation Clinical Trial

— PRIMARY  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05051033
• Other study ID #: STUDY-21-01246
• Secondary ID: 5U01HL088942
• Status: Recruiting
• Phase: N/A
• Start date: February 21, 2022
• Est. completion date: January 2032

Study information

• Verified date: March 2024
• Source: Icahn School of Medicine at Mount Sinai
• Contact: Chari Ponder, RN, BSN
• Phone: (646) 899-8106
• Email: chari.ponder[@]mountsinai.org
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: January 2032
• Est. primary completion date: January 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Mitral Valve Insufficiency
• Mitral Valve Regurgitation
• Prolapse

Intervention

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.

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.

Locations

Country	Name	City	State
Canada	London Health Sciences	London	Ontario
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Quebec (Laval University)	Quebec City	Quebec
Germany	Kerckhoff Klinik Bad Nauheim	Bad Nauheim
Germany	Schüchtermann-Klinik Bad Rothenfelde	Bad Rothenfelde
Germany	Deutsches Herzzentrum Berlin	Berlin
Germany	Deutsches Herzzentrum der Charité	Berlin
Germany	Universitätsklinikum Frankfurt	Frankfurt
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	Asklepios Klinik St. Georg Hamburg	Hamburg
Germany	Universitätsklinikum Hamburg Eppendorf	Hamburg
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Jena	Jena
Germany	Universitätsklinikum Schleswig-Holstein Campus Kiel	Kiel
Germany	Herzzentrum Leipzig	Leipzig
Germany	Lübeck	Lübeck
Germany	Deutsches Herzzentrum München	München
United Kingdom	South Tees Hospitals NHS Foundation Trust	Middlesbrough
United States	University of Michigan Hospital	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Piedmont Heart Institute	Atlanta	Georgia
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	Brigham and Women's	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Medical Center	Charlottesville	Virginia
United States	Cleveland Clinic	Cleveland	Ohio
United States	Baylor, Scott and White	Dallas	Texas
United States	Duke University Hospital	Durham	North Carolina
United States	Saint Luke's Hospital of Kansas City/MidAmerica Heart and Lung Surgeons	Kansas City	Missouri
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Keck Hospital of the University of Southern California	Los Angeles	California
United States	West Virginia University Hospital	Morgantown	West Virginia
United States	Ochsner Clinic	New Orleans	Louisiana
United States	Northwell Health	New York	New York
United States	Nyph/Cumc	New York	New York
United States	Weill Cornell Medicine/ New York-Presbyterian Hospital	New York	New York
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Maine Medical Center	Portland	Maine
United States	University of California San Francisco	San Francisco	California
United States	Stanford University	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Annetine Gelijns	National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause mortality, valve re-intervention, hospitalizations and urgent visits for heart failure, or onset of = 3+ MR (by transthoracic echocardiogram (TTE)) composite score.	Composite score of all-cause mortality, valve re-intervention, hospitalizations and urgent visits for heart failure, or onset of = 3+ MR (by transthoracic echocardiogram (TTE)) from randomization to a minimum follow-up of 3 years post randomization (including a one-month post intervention blanking period for HF hospitalizations/urgent visits).; 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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	All-cause mortality	All-cause mortality through 5 years post randomization	5 years post randomization
Secondary	All-cause mortality	All-cause mortality from randomization through 10 years post intervention	10 years post intervention
Secondary	Cardiovascular and non-cardiovascular mortality	Cardiovascular and non-cardiovascular mortality from randomization through 5 years post intervention	5 years post intervention
Secondary	Cardiovascular and non-cardiovascular mortality	Cardiovascular and non-cardiovascular mortality from randomization through 10 years post intervention	10 years post intervention
Secondary	Valve re-interventions	Valve re-interventions through 5 years post intervention	5 years post intervention
Secondary	Valve re-interventions	Valve re-interventions through 10 years post intervention	10 years post intervention
Secondary	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
Secondary	MR grade	Mitral Regurgitation (MR) grade as mild, moderate, or severe. (grade I-IV, with higher grade indicating poorer health outcomes.)	through 5 years post intervention
Secondary	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.	through 5 years post intervention
Secondary	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.	through 5 years post intervention
Secondary	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.	through 5 years post intervention
Secondary	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.	through 5 years post intervention
Secondary	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.	through 5 years post intervention
Secondary	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.	through 5 years post intervention
Secondary	Forward stroke volume	The forward stroke volume is the volume entering the aorta.	through 5 years post intervention
Secondary	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	through 5 years post intervention
Secondary	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
Secondary	Length of stay (LOS)	Length of stay as measured by number of days hospitalized.	through 10 years post intervention
Secondary	ICU days of index hospitalization	Number of ICU days of index hospitalization	through 10 years post intervention
Secondary	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
Secondary	Cost	Costs associated with the index hospitalization as well as follow-up readmissions will be measured.	through 10 years post intervention
Secondary	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