Clinical trial NCT01940120: EVEREST II Pivotal Study High Risk Registry (HRR)
Official title: A Study of the Evalve® Cardiovascular Valve Repair (MitraClip®) System Endovascular Valve Edge-to-Edge REpair STudy (EVEREST II) EVEREST II High Risk Registry
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mitral Valve Insufficiency
Mitral Valve Regurgitation
Mitral Valve Incompetence
Mitral Regurgitation
Mitral Insufficiency
Keywords: Mitral Valve Insufficiency
Mitral Valve Regurgitation
Mitral Valve Incompetence
Mitral Regurgitation
Mitral Insufficiency
Mitral Valve
MR
Mitral Valve Prolapse
Edge to Edge (E2E)
Alfieri Technique
MitraClip
Functional MR
Degenerative MR
Echocardiogram
Coronary Artery Disease (CAD)
Heart Failure
Heart Attack
EVEREST
EVEREST I
EVEREST II
REALISM
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
First posted: 2013-09-12
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Prospective, multi-center, single arm registry. Clinical follow-up at discharge, 30 days, 6, 12, 18 and 24, months, and 3, 4 and 5 years.

Concurrent Control (CC) group identified retrospectively from the patients screened for the HRR who did not enroll; patient survival determined at 12 months. NCT00209274 (EVEREST II RCT) Intended use Percutaneous reduction of clinically significant mitral regurgitation in symptomatic patients who are considered to be high risk for operative mortality (high surgical risk).

Detailed description: The EVEREST II HRR is a single-arm prospective, multicenter clinical trial enrolling high surgical risk patients of the EVEREST II study (NCT00209274).

Patients were considered high surgical risk if either their Society of Thoracic Surgery (STS) predicted operative mortality risk was ≥ 12%, or the surgeon investigator determined the patient to be high risk (≥ 12% predicted operative mortality risk) due to the presence of, at a minimum, one of the following pre-specified risk factors:

* Porcelain aorta or mobile ascending aortic atheroma
* Post-radiation mediastinum
* Previous mediastinitis
* Functional MR with ejection fraction (EF) \< 40%
* Over 75 years old with EF \< 40%
* Prior re-operation with patent grafts
* Two or more prior chest surgeries
* Hepatic cirrhosis
* Three or more of the following STS high risk factors:

  i. Creatinine \> 2.5 mg/dL ii. Prior chest surgery iii. Age over 75 iv. EF \< 35%

Upon completion of enrollment in the HRR, a process was initiated to ensure patient consent to participate in a Concurrent Control (CC) group was in place. Patients were identified to determine survival through 12 months with current standard of care treatment.CC patients were derived from a cohort of patients screened for enrollment in the HRR,yet did not enroll. All patients had moderate-to-severe (3+) or severe (4+) MR based on transthoracic echocardiography (TTE). To be considered eligible for inclusion in the CC group, the patient had to be classified as high surgical risk using the same criteria used for the HRR. Upon follow-up with the clinical sites, it was determined that some of the initially identified patients with moderate-to-severe (3+) or severe (4+) MR met the criteria for high surgical risk. Of these patients, some were not included due to; lack of Institutional Review Board (IRB) approval at the site, lack of informed consent and unable to be contacted. The remaining patients make up the CC group.

Eligibility criteria: Inclusion Criteria:

Candidates for the high risk arm of the study must meet all of the following inclusion criteria:

* Predicted procedural mortality risk calculated using the STS surgical risk calculator of ≥ 12% or in the judgment of the surgeon investigator the patient is considered a high risk surgical candidate due to the presence of one of the following indications:

  1. Porcelain aorta or mobile ascending aortic atheroma
  2. Post-radiation mediastinum
  3. Previous mediastinitis
  4. Functional MR with EF\<40
  5. Over 75 years old with EF\<40
  6. Re-operation with patent grafts
  7. Two or more prior chest surgeries
  8. Hepatic cirrhosis i Three or more of the following STS high risk factors: i) Creatinine \> 2.5 mg/dL ii) Prior chest surgery iii) Age over 75 iv) EF\<35
* Age 18 years or older.
* Symptomatic moderate to severe (3+) or severe (4+) chronic mitral regurgitation (MR) and in the judgment of the investigator intervention to reduce MR is likely to provide symptomatic relief for the patient. MR is determined as defined in Appendix A of the EVEREST II study protocol. American Society of Anesthesiologists (ASA) physical status classification of ASA IV or lower.
* The primary regurgitant jet originates from malcoaptation of the A2 and P2 scallops of the mitral valve.
* Male or Female. Female subjects of childbearing potential must have a negative pregnancy test within seven (7) days before the procedure.
* The subject or the subject's legal representative has been informed of the nature of the study and agrees to its provisions and has provided written informed consent as approved by the Institutional Review Board of the respective clinical site.
* The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits.
* Transseptal catheterization is determined to be feasible by the treating physician.

Exclusion Criteria:

Candidates will be excluded from the study if any of the following conditions are present:

* Evidence of an acute myocardial infarction in the prior 2 weeks of the intended treatment (defined as: Q wave or non-Q wave infarction having creatine kinase (CK) enzymes ≥ two times (2X) the upper laboratory normal limit with the presence of a Creatine Kinase MB Isoenzyme (CKMB) elevated above the institution's upper limit of normal).
* In the judgment of the Investigator, the femoral vein cannot accommodate a 24 F catheter or presence of ipsilateral deep vein thrombosis (DVT).
* Ejection fraction \< 20%, and/or end-systolic dimension \> 60 mm as defined in Appendix A of the EVEREST II protocol.
* Mitral valve orifice area \< 4.0 cm2 as defined in Appendix A of the EVEREST II protocol.
* If leaflet flail is present:

  1. Flail Width: the width of the flail segment is greater than or equal to 15 mm, as defined in Section 4.3 and Appendix A, or
  2. Flail Gap: the flail gap is greater than or equal to 10 mm, as defined in Section 4.3 and Appendix A.
* If leaflet tethering is present:

  a). Coaptation Length: the vertical coaptation length is less than 2 mm, as defined in Section 4.3 and Appendix A.
* Leaflet anatomy which may preclude clip implantation, proper clip positioning on the leaflets or sufficient reduction in MR. This may include:
* Evidence of calcification in the grasping area of the A2 and/or P2 scallops
* Presence of a significant cleft of A2 or P2 scallops
* More than one anatomic criteria dimensionally near the exclusion limits
* Bileaflet flail or severe bileaflet prolapse
* Lack of both primary and secondary chordal support
* Hemodynamic instability defined as systolic pressure \< 90 mmHg without after load reduction or cardiogenic shock or the need for inotropic support or intra-aortic balloon pump.
* Need for emergent or urgent surgery for any reason.
* Prior mitral valve leaflet surgery or any currently implanted mechanical prosthetic mitral valve.
* Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
* Active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic diseased (i.e. noncompliant, perforated).
* History of bleeding diathesis or coagulopathy or subject will refuse blood transfusions.
* Active infections requiring current antibiotic therapy (if temporary illness, patients may enroll 2 weeks after discontinuation of antibiotics). Patients must be free from infection prior to treatment. Any required dental work should be completed a minimum of 3 weeks prior to treatment.
* Intravenous drug abuse or suspected inability to adhere to follow-up.
* Patients in whom transesophageal echocardiography (TEE) is contraindicated.
* A known hypersensitivity or contraindication to study or
* In the judgment of the Investigator, patients in whom the presence of a permanent pacemaker or pacing leads would interfere with placement of the test device or the placement of the test device would disrupt the leads.
* Currently participating in an investigational drug or another device study that has not completed the primary endpoint or that clinically interferes with the current study endpoints. \[Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials\].

Primary outcomes:
measure: Composite Functional and Structural Measures - Freedom From Death
timeFrame: 12 months
measure: Percentage of Participants With Freedom From Death and Mitral Regurgitation (MR) >2+
timeFrame: 12 months
measure: Number of Participants With Clinical Measures of Benefit-New York Heart Association (NYHA) Class
timeFrame: 30 days
measure: Number of Participants With New York Heart Association (NYHA) Class
timeFrame: 12 months
measure: Clinical Measures of Benefit-Quality of Life (QOL) as Measured by Short Form (SF) 36
timeFrame: 12 months
measure: Left Ventricular End Diastolic Volume (LVEDV)
timeFrame: 12 months
measure: Left Ventricular End Systolic Volume (LVESV)
timeFrame: 12 months
measure: Left Ventricular (LV) Function - Internal Dimension
timeFrame: 12 months
measure: Number of Patients With CHF Having Hospitalization During Discharge Through 12 Months
timeFrame: 12 months
measure: Number of CHF Events Leading to Hospitalizations During Discharge Through 12 Months
timeFrame: 12 months
measure: Left Ventricular End Diastolic Volume (LVEDV)
timeFrame: Discharge or 30 days
measure: Left Ventricular End Systolic Volume (LVESV)
timeFrame: Discharge or 30 days
measure: Left Ventricular (LV) Function - Internal Dimension
timeFrame: Discharge or 30 days
Secondary outcomes:
measure: Number of Participants Experiencing Major Adverse Events (MAE)
timeFrame: 30 days
measure: Number of Participants Experiencing Major Adverse Events
timeFrame: 12 months
measure: Procedural Freedom From In-hospital MAE
timeFrame: 30 Days
measure: Number of Participants Over 75 Years of Age With MAE
timeFrame: 30 days
measure: Number of Participants Over 75 Years of Age With MAE
timeFrame: 12 months
measure: Number of Participants Experiencing Major Vascular Complications
timeFrame: 30 days
measure: Number of Participants Experiencing Major Vascular Complications
timeFrame: 12 months
measure: Number of Participants With Major Bleeding Complications
timeFrame: 30 days
measure: Number of Participants With Major Bleeding Complications
timeFrame: 12 months
measure: Number of Participants With Non-cerebral Thromboembolism
timeFrame: 30 days
measure: Number of Participants With Non-cerebral Thromboembolism
timeFrame: 12 months
measure: Number of Participants With Thrombosis
timeFrame: 30 days
measure: Number of Participants With Thrombosis
timeFrame: 12 months
measure: Number of Participants With Hemolysis
timeFrame: 30 days
measure: Number of Participants With Hemolysis
timeFrame: 12 months
measure: Number of Participants With Dysrhythmias
timeFrame: 30 days
measure: Number of Participants With Dysrhythmias
timeFrame: 12 months
measure: Number of Participants With Endocarditis
timeFrame: 30 days
measure: Number of Participants With Endocarditis
timeFrame: 12 months
measure: Number of Participants With Atrial Septal Defect (ASD)
timeFrame: 30 days
measure: Number of Participants With Atrial Septal Defect (ASD)
timeFrame: 12 months
measure: Number of Participants With Mitral Valve Stenosis
timeFrame: 30 days
measure: Number of Participants With Mitral Valve Stenosis
timeFrame: 12 months
measure: Number of Participants With Mitral Valve Stenosis
timeFrame: 24 months
measure: Number of Participants With Mitral Valve Stenosis
timeFrame: 36 months
measure: Number of Participants With Mitral Valve Stenosis
timeFrame: 48 months
measure: Mitral Valve Area: By Planimetry
timeFrame: 30 days
measure: Mitral Valve Area: By Planimetry
timeFrame: 12 months
measure: Mitral Valve Area: By Planimetry
timeFrame: 24 months
measure: Mitral Valve Area: By Planimetry
timeFrame: 36 months
measure: Mitral Valve Area: By Planimetry
timeFrame: 48 months
measure: Mitral Valve Area: By Planimetry
timeFrame: 60 months
measure: Mitral Valve Area: By Pressure Half-time
timeFrame: 30 days
measure: Mitral Valve Area: By Pressure Half-time
timeFrame: 12 months
measure: Mitral Valve Area: By Pressure Half-time
timeFrame: 24 months
measure: Mitral Valve Area: By Pressure Half-time
timeFrame: 36 months
measure: Mitral Valve Area: By Pressure Half-time
timeFrame: 48 months
measure: Mitral Valve Area: By Pressure Half-time
timeFrame: 60 months
measure: Mitral Valve Area Index : By Planimetry
timeFrame: 30 days
measure: Mitral Valve Area Index : By Planimetry
timeFrame: 12 months
measure: Mitral Valve Area Index : By Planimetry
timeFrame: 24 months
measure: Mitral Valve Area Index : By Planimetry
timeFrame: 36 months
measure: Mitral Valve Area Index : By Planimetry
timeFrame: 48 months
measure: Mitral Valve Area Index : By Planimetry
timeFrame: 60 months
measure: Mitral Valve Area (MVA) Index: by Pressure-Half Time Formula
timeFrame: 30 days
measure: Mitral Valve Area Index : By Pressure Half-time Formula
timeFrame: 12 months
measure: Mitral Valve Area Index : By Pressure Half-time Formula
timeFrame: 24 months
measure: Mitral Valve Area Index : By Pressure Half-time Formula
timeFrame: 36 months
measure: Mitral Valve Area Index : By Pressure Half-time Formula
timeFrame: 48 months
measure: Mitral Valve Area Index : By Pressure Half-time Formula
timeFrame: 60 months
measure: Transvalvular Mitral Valve Gradient
timeFrame: 30 days
measure: Transvalvular Mitral Valve Gradient
timeFrame: 12 months
measure: Transvalvular Mitral Valve Gradient
timeFrame: 24 months
measure: Transvalvular Mitral Valve Gradient
timeFrame: 36 months
measure: Transvalvular Mitral Valve Gradient
timeFrame: 48 months
measure: Transvalvular Mitral Valve Gradient
timeFrame: 60 months
measure: Mitral Valve Index
timeFrame: 30 days
measure: Mitral Valve Index
timeFrame: 12 months
measure: Number of Participants With New Coumadin Use
timeFrame: 30 days
measure: Number of Participants With New Coumadin Use
timeFrame: 6 months
measure: Number of Participants With New Coumadin Use
timeFrame: 12 months
measure: Number of Participants Discharged to a Nursing Home or Skilled Nursing Facility or Hospital
timeFrame: 30 Days
measure: Post-procedure Length of Hospital Stay
timeFrame: Length of Hospital Stay, assessed at 30 days
measure: Post-procedure Intensive Care Unit (ICU)/ Critical Care Unit (CCU) Time
timeFrame: Length of ICU/CCU stay, assessed at 30 Days
measure: Number of Participants With Successful Clip Implant
timeFrame: 30 Days
measure: Number of Participants With High Risk Procedural Success
timeFrame: 30 days
measure: Number of Participants With MR Severity
timeFrame: Discharge or 30 days
measure: Number of Participants With MR Severity
timeFrame: 12 months
measure: Number of Participants With MR Severity
timeFrame: 24 months
measure: Number of Participants With MR Severity
timeFrame: 36 months
measure: Number of Participants With MR Severity
timeFrame: 48 months
measure: Number of Participants With MR Severity
timeFrame: 60 months
measure: Number of Participants With Treatment Durability
timeFrame: 12 months
measure: Number of Participants With Treatment Durability
timeFrame: 24 months
measure: Number of Participants With Clinical Durability
timeFrame: 12 months
measure: Number of Participants With Clinical Durability
timeFrame: 24 months
measure: Number of Participants With Composite Functional and Structural Measures - Clinical Measures of Benefit-New York Heart Association (NYHA) Class
timeFrame: 24 months
measure: Number of Participants With Composite Functional and Structural Measures - Clinical Measures of Benefit-New York Heart Association (NYHA) Class
timeFrame: 36 months
measure: Number of Participants With Composite Functional and Structural Measures - Clinical Measures of Benefit-New York Heart Association (NYHA) Class
timeFrame: 48 months
measure: Number of Participants With New York Heart Association (NYHA) Class
timeFrame: 60 months
measure: Left Ventricular End-diastolic Volume (LVEDV).
timeFrame: 24 months
measure: Left Ventricular End-diastolic Volume (LVEDV).
timeFrame: 36 months
measure: Left Ventricular End-diastolic Volume (LVEDV).
timeFrame: 48 months
measure: Left Ventricular End-diastolic Volume (LVEDV).
timeFrame: 60 months
measure: Left Ventricular End-systolic Volume (LVESV).
timeFrame: 24 months
measure: Left Ventricular End-systolic Volume (LVESV).
timeFrame: 36 months
measure: Left Ventricular End-systolic Volume (LVESV).
timeFrame: 48 months
measure: Left Ventricular End-systolic Volume (LVESV).
timeFrame: 60 months
measure: Left Ventricular Measurement: Left Ventricular Internal Dimension Diastole (LVIDd), Left Ventricular Internal Dimension Systole (LVIDs)
timeFrame: 24 months
measure: Left Ventricular Measurement: Left Ventricular Internal Dimension Diastole (LVIDd), Left Ventricular Internal Dimension Systole (LVIDs)
timeFrame: 36 months
measure: Left Ventricular Measurement: Left Ventricular Internal Dimension Diastole (LVIDd), Left Ventricular Internal Dimension Systole (LVIDs)
timeFrame: 48 months
measure: Left Ventricular Measurement: Left Ventricular Internal Dimension Diastole (LVIDd), Left Ventricular Internal Dimension Systole (LVIDs)
timeFrame: 60 months
measure: Number of Days Re-hospitalized for CHF
timeFrame: 12 months
measure: Number of Hospital Re-Admissions for Congestive Heart Failure (CHF)
timeFrame: 12 months
measure: Regurgitant Volume
timeFrame: 30 days
measure: Regurgitant Volume
timeFrame: 12 months
measure: Regurgitant Volume
timeFrame: 24 months
measure: Regurgitant Fraction (RF)
timeFrame: 30 days
measure: Regurgitant Fraction
timeFrame: 12 months
measure: Regurgitant Fraction
timeFrame: 24 months
measure: Cardiac Output (CO)
timeFrame: 30 Days
measure: Cardiac Output
timeFrame: 12 months
measure: Cardiac Output
timeFrame: 24 months
measure: Cardiac Index
timeFrame: 30 Days
measure: Cardiac Index
timeFrame: 12 months
measure: Cardiac Index
timeFrame: 24 months
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: Discharge or 30 days
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: 12 months
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: 24 months
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: 36 months
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: 48 months
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: 60 months
measure: Percentage of Participants With Freedom From Mitral Valve Surgery
timeFrame: Baseline
measure: Percentage of Participants With Freedom From Mitral Valve Surgery
timeFrame: 12 months
measure: Percentage of Participants With Freedom From Mitral Valve Surgery
timeFrame: 24 months
measure: Percentage of Participants With Freedom From Mitral Valve Surgery
timeFrame: 36 months
measure: Percentage of Participants With Freedom From Mitral Valve Surgery
timeFrame: 48 months
measure: Percentage of Participants With Freedom From Mitral Valve Surgery
timeFrame: 60 months
measure: Number of Participants With Mitral Valve Repair Success
timeFrame: 12 months
measure: Number of Participants With Mitral Valve Repair Success
timeFrame: 24 months
measure: Composite Functional and Structural Measures - Percentage of Participants With Freedom From Death
timeFrame: 24 months
measure: Percentage of Participants With Composite Functional and Structural Measures - Freedom From Death and MR >2+
timeFrame: 24 months
measure: Number of Participants With Device Embolization or Single Leaflet Device Attachment
timeFrame: 0 to 12 months
measure: Number of Participants With Device Embolization or Single Leaflet Device Attachment
timeFrame: 24 months
measure: Number of Participants With Device Embolization or Single Leaflet Device Attachment
timeFrame: 48 months
measure: Number of Participants With Device Embolization or Single Leaflet Device Attachment
timeFrame: 36 months
measure: Number of Participants With Device Embolization or Single Leaflet Device Attachment
timeFrame: 60 months
measure: Number of Participants With Mitral Valve Surgery Post-MitraClip Procedure
timeFrame: 60 months
measure: Number of Participants With Second MitraClip Device Implanted
timeFrame: 0 to 5 years
measure: Percentage of Participants With Freedom From All-Cause Mortality and Mitral Valve Surgery
timeFrame: 12 months
measure: Percentage of Participants With Freedom From All-Cause Mortality and Mitral Valve Surgery
timeFrame: 24 months
measure: Percentage of Participants With Freedom From All-Cause Mortality and Mitral Valve Surgery
timeFrame: 36 months
measure: Percentage of Participants With Freedom From All-Cause Mortality and Mitral Valve Surgery
timeFrame: 48 months
measure: Percentage of Participants With Freedom From All-Cause Mortality and Mitral Valve Surgery
timeFrame: 60 months
measure: Number of Participants With Mitral Valve Replacement
timeFrame: 12 months
measure: Number of Participants With Mitral Valve Replacement
timeFrame: 24 months
measure: Number of Participants With Mitral Valve Replacement
timeFrame: 36 months
measure: Number of Participants With Mitral Valve Replacement
timeFrame: 48 months
Other outcomes:
Locations:
city: Evanston
country: United States
facility: Evanston Northwestern Healthcare 2650 Ridge Ave., Walgreen Bldg, 3rd Floor, Cardiology
state: Illinois
city: Indianapolis
country: United States
facility: The Care Group Heart Center 10590 N. Meridian, Ste. 300
state: Indiana
Study officials:
affiliation: Endeavor Health
name: Ted Feldman, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University Medical Center, Department of Surgery
name: Donald G Glower Jr.,, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ailawadi G, Lim DS, Mack MJ, Trento A, Kar S, Grayburn PA, Glower DD, Wang A, Foster E, Qasim A, Weissman NJ, Ellis J, Crosson L, Fan F, Kron IL, Pearson PJ, Feldman T; EVEREST II Investigators. One-Year Outcomes After MitraClip for Functional Mitral Regurgitation. Circulation. 2019 Jan 2;139(1):37-47. doi: 10.1161/CIRCULATIONAHA.117.031733.
citation: Kar S, Feldman T, Qasim A, Trento A, Kapadia S, Pedersen W, Lim DS, Kipperman R, Smalling RW, Bajwa T, Hermann HC, Hermiller JB, Lasala JM, Reisman M, Glower D, Mauri L, Whitlow P; EVEREST II Investigators. Five-year outcomes of transcatheter reduction of significant mitral regurgitation in high-surgical-risk patients. Heart. 2019 Nov;105(21):1622-1628. doi: 10.1136/heartjnl-2017-312605. Epub 2018 Aug 4.
citation: Wang A, Sangli C, Lim S, Ailawadi G, Kar S, Herrmann HC, Grayburn P, Foster E, Weissman NJ, Glower D, Feldman T. Evaluation of renal function before and after percutaneous mitral valve repair. Circ Cardiovasc Interv. 2015 Jan;8(1):e001349. doi: 10.1161/CIRCINTERVENTIONS.113.001349.