EXPLORE FMR: Early Feasibility Study of the PLAR Implant and Delivery System to Treat Functional Mitral Regurgitation

Early Feasibility Study of the PLAR Implant and Delivery System to Treat Functional Mitral Regurgitation (EXPLORE FMR)

An early feasibility study to evaluate the safety and feasibility of the PLAR Implant and Delivery System to treat severe functional mitral regurgitation and to gather preliminary data on its performance thereby providing guidance for future clinical development. The study is a single-arm registry with the last follow-up visit at 5 years post-intervention. The study will enroll up to 10 patients at one (1) center in Brazil.

Study Overview

• Status: Not yet recruiting
• Conditions: Functional Mitral Regurgitation
• Intervention / Treatment: Device: Transcatheter mitral valve repair (PLAR Implant and Delivery System)

Detailed Description

Percutaneous approaches to treat MR promise to provide a sufficient reduction in MR without the risks typically associated with open heart surgery.

Furthermore there is an unmet clinical need for patients with severe MR who are refused or denied surgery due to high risk. Percutaneous therapy provides a novel alternative treatment option for these patients with the aim of reducing morbidity and mortality over and above current medical therapy. The Polares Medical PLAR Implant and Delivery System is a catheter-based technology designed to permanently implant a prosthesis using a transvenous / transseptal approach to augment the posterior mitral valve leaflet and improve coaptation with the anterior leaflet. Approved edge-to-edge repair has already been shown to be a viable alternative for high risk MR patients. However treatment with these devices is limited to specific anatomies and often requires multiple devices which increases clinical risk, adds to procedural time, and can result in residual MR. The PLAR Implant and Delivery System has been designed to overcome and mitigate some of these shortfalls.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 years of age or older
2. Greater than moderate functional mitral regurgitation (Grade 3+ or higher) as confirmed by transesophageal echocardiography (TEE) within 90 days prior to study procedure
3. Patient must present with an STS Score less than 10%
4. High surgical risk for conventional mitral repair or replacement due to morphological criteria (e.g. leaflet or annulus calcifications), but operable, as assessed by the local heart team comprised of a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced in treating mitral valve disease and heart failure
5. New York Heart Association (NYHA) Functional Class III or IV
6. Patient willing to participate in study and provide signed IRB/EC-approved informed consent
7. Treating physician and patient agree that patient is able to return for all required post-procedure follow-up visits

Exclusion Criteria:

1. Severe tricuspid regurgitation
2. Severe aortic stenosis or insufficiency
3. Severe mitral annulus calcification
4. Diseased mitral anterior leaflet such as flail / prolapse/ heavy calcification
5. Implanted vena cava filter
6. Femoral veins with severe angulation and calcification
7. Contraindication for transesophageal echocardiography (TEE) or MDCT scan
8. Active infection or endocarditis
9. Previous mitral valve surgery
10. Prior orthotopic heart transplantation
11. Pulmonary artery systolic hypertension > 70mmHg
12. Evidence of intra-cardiac, inferior vena cava (IVC) or femoral venous thrombus
13. Left ventricular ejection fraction (LVEF) < 30%
14. Implant or revision of any pacing device < 30 days prior to intervention
15. Symptomatic coronary artery disease treated < 30 days prior to study procedure
16. Myocardial infarction requiring intervention < 30 days prior to study procedure
17. Infiltrative cardiomyopathies (e.g., amyloidosis, hemochromatosis, sarcoidosis), hypertrophic or restrictive cardiomyopathies, and constrictive pericarditis
18. Active peptic ulcer or upper gastrointestinal bleeding < 90 days prior to study procedure
19. Stroke < 180 days prior to study procedure
20. Severe renal insufficiency (creatinine > 3.0 mg/dL) or patient requiring dialysis
21. Cardiogenic shock at time of enrolment
22. Hemodynamic instability requiring inotropic support or mechanical heart assistance
23. Concurrent medical condition with a life expectancy of less than 2 years
24. Pregnancy at time of enrolment
25. History of bleeding diathesis or coagulopathy or leukopenia (WBC < 3,000 mcL) or acute anemia (Hb < 9 g/dL) or thrombocytopenia (platelets < 50,000 cells mcL)
26. Known hypersensitivity or contraindication to aspirin, heparin, ticlopidine or clopidogrel, nitinol, tantalum or allergy to contrast agents that cannot be pre-medicated
27. Severe dementia or lack of capacity due to conditions that result in either inability to provide informed consent for the trial/procedure, prevent independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up assessments
28. Emergency situations
29. Company employees or their immediate family members
30. Patient is under guardianship
31. Patient is participating in another clinical study for which follow-up is currently ongoing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single-arm study of PLAR Implant and Delivery System; All enrolled patients will receive the study device	Device: Transcatheter mitral valve repair (PLAR Implant and Delivery System); The PLAR Implant is placed on the mitral valve posterior annulus using its delivery system via femoral vein access and a transeptal puncture; Other Names: TMVr

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of all-cause mortality	Primary safety outcome	30-days follow-up
Incidence of change from baseline to moderate or less mitral regurgitation (Grade 2+ or less) as evaluated by 2D TTE Primary performance endpoint	Primary performance endpoint	30-days follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of major safety events as defined by MVARC2 definitions	Secondary safety endpoint	Follow-up at 30 days, at 6 and 12 months, and at 2, 3, 4 and 5 years
Technical success rate per MVARC2 definitions	All of the following must be present for technical success: Absence of procedure mortality; Successful access, delivery and retrieval of investigation delivery system; Successful deployment and correct positioning of intended implant(s); Freedom from emergency surgery/re-intervention related to device or access procedure	Technical success is measured immediately following the procedure
Procedure success rate per MVARC2 definitions	Both of the following must be present for procedure success: Device success; Absence of major device or procedure-related serious adverse events as below:DeathStrokeLife-threatening bleedMajor vascular complicationMajor cardiac structural complicationStage 2 or 3 AKIMI or coronary ischemia requiring PCI or CABGShock, heart or respiratory failure requiring IV vasopressors, mechanical intervention or prolonged intubationValve-related dysfunction, migration, thrombosis, or other complication requiring surgery or repeat intervention	Procedure success is measured at 30 days follow-up
Device success rate per MVARC 2 definitions	All of the following must be present for device success: Absence of procedure mortality or stroke; Proper placement and positioning of device; Freedom from unplanned re-intervention related to device or access procedure • Continued intended safety and performance of the device as below:No evidence of structural or functional failureNo device technical failure issues/complicationsMR reduction to moderate or less without stenosis	Device success is measured at 30 days, at 6 and 12 months, and at 2, 3, 4, and 5 years follow-up
Patient success rate per MVARC2 definitions	All of the following must be present for patient success: Device success; Patient returned to pre-procedure setting; No rehospitalization or reintervention for mitral regurgitation or heart failure; Functional improvement from baseline by one or more NYHA class; 6MWT improvement from baseline by 50 metres or more	Patient success is measured at 12 months follow-up

Collaborators and Investigators

• Sponsor: Polares Medical SA
• Collaborators: Polares Medical, Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2021
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: December 21, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Actual): December 22, 2020
• Last Update Submitted That Met QC Criteria: December 21, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Mitral Valve Insufficiency
• Other Study ID Numbers: 202004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Clinical trial results will be shared with investigators once study is enrolled and trial data is prepared for presentation at a medical conference or for publication in a medical journal.

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.: Yes