Clinical trial NCT04098328: Early Feasibility EXperience of Posterior Leaflet RestOration to REduce Mitral Regurgitation
Official title: Early Feasibility EXperience of Posterior Leaflet RestOration to REduce Mitral Regurgitation (EXPLORE MR)
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Mitral Regurgitation
Mitral Valve Disease
Mitral Valve Insufficiency
Lead sponsor: Polares Medical SA
Sponsor class: INDUSTRY
First posted: 2019-09-23
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Inoperable or high surgical risk patients with symptomatic degenerative or functional mitral regurgitation (Grade 3+ or higher) with mitral valve anatomy deemed unsuitable, or off-label, to be treated with an approved edge-to-edge repair system.

Brief summary: Early feasibility study, single-arm registry design

Detailed description: First-In-Human

Eligibility criteria: Inclusion Criteria:

1. 18 years of age or older.
2. Greater than moderate degenerative or 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) 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. Mitral valve anatomy deemed unsuitable to be treated with an approved edge-to-edge repair system (e.g., retracted posterior leaflet, lack of leaflet tissue, calcified or cleft posterior leaflet) 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
6. Patient is approved by an independent Patient Eligibility Committee
7. New York Heart Association (NYHA) Functional Class III or IV
8. Patient willing to participate in study and provide signed EC-approved informed consent.
9. Treating physician and patient agree that patient is able to return for all required post- procedure follow-up visits
10. Women of child-bearing potential have a negative pregnancy test

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

Primary outcomes:
measure: Primary safety endpoint
timeFrame: 30 days
measure: Improvement from baseline mitral regurgitation
timeFrame: 30 days
Secondary outcomes:
measure: Technical success according to MVARC2 criteria
timeFrame: 24 hours
measure: Procedure success according to MVARC2 criteria
timeFrame: 30 days
measure: Device success according to MVARC2 criteria
timeFrame: 30 days, 6 and 12 months, and 2 - 5 years post treatment
measure: Patient success according to MVARC2 criteria
timeFrame: 30 days, 6 and 12 months, and 2 - 5 years post treatment
measure: Rate (%) of major adverse events as defined by MVARC2 criteria
timeFrame: Procedure, discharge/7 days, 30 days, 6 and 12 months, and 2 - 5 years post treatment
Other outcomes:
Locations:
city: Dortmund
country: Germany
facility: St. Johannes Hospital
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
Study officials:
affiliation: Polares Medical
name: Laura A Brenton
role: STUDY_DIRECTOR
affiliation: MarienKrankenhaus & Asklepios Klinik St. Georg, Hamburg (DE)
name: Ulrich Schaefer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Inselspital Bern, Bern (CH)
name: Stephan Windecker, MD
role: PRINCIPAL_INVESTIGATOR
References: