A Study of the Evalve® Cardiovascular Valve Repair (MitraClip®) System Endovascular Valve Edge-to-Edge REpair STudy (EVEREST II) EVEREST II High Risk Registry
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Abbott Medical Devices
- Enrollment
- 78
- Locations
- 4
- Primary Endpoint
- Left Ventricular (LV) Function - Internal Dimension
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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:
- •Porcelain aorta or mobile ascending aortic atheroma
- •Post-radiation mediastinum
- •Previous mediastinitis
- •Functional MR with EF<40
- •Over 75 years old with EF<40
- •Re-operation with patent grafts
- •Two or more prior chest surgeries
- •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:
- •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
- •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].
Arms & Interventions
High Risk Registry Arm
Includes patients with a predicted procedural mortality of 12% or higher. The high risk registry arm of the study is powered to show superiority of safety of treatment with the MitraClip compared to mitral valve surgery. The patients who are enrolled in this arm will undergo percutaneous mitral valve repair using MitraClip implant.
Intervention: Percutaneous mitral valve repair using MitraClip implant (Device)
Outcomes
Primary Outcomes
Left Ventricular (LV) Function - Internal Dimension
Time Frame: Discharge or 30 days
Left Ventricular Internal Dimension in diastole (LVIDd) and Left Ventricular Internal Dimension in systole (LVIDs) as determined by the core echocardiography laboratory from a transthoracic echocardiogram (TTE).
Left Ventricular End Diastolic Volume (LVEDV)
Time Frame: Discharge or 30 days
Left Ventricular End Diastolic Volume (LVEDV) as determined by the core echocardiography laboratory from a transthoracic echocardiogram (TTE).
Percentage of Participants With Freedom From Death and Mitral Regurgitation (MR) >2+
Time Frame: 12 months
Kaplan-Meier estimated percentage of patients who are alive and have a mitral regurgitation severity grade of 2+ or less
Number of Participants With Clinical Measures of Benefit-New York Heart Association (NYHA) Class
Time Frame: 30 days
The major effectiveness endpoint is an assessment of multiple functional and structural measures of benefit including New York Heart Association (NYHA) Class. Class I: Patients with cardiac disease but without resulting limitations of physical activity. Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain. Class III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea, or anginal pain. Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.
Clinical Measures of Benefit-Quality of Life (QOL) as Measured by Short Form (SF) 36
Time Frame: 12 months
Standardized quality of life surveys allow physicians to evaluate the effectiveness of different treatment methods and the physical and psychological benefits a patient is likely to receive from a particular treatment.In the EVEREST II HRR,the patients were asked to complete the SF-36 QOL survey at baseline, 30 days and 12 months. The physical \& mental function were assessed by the Physical Component Summary (PCS) score \& Mental Component Summary (MCS) score. The PCS \& MCS norms for 65-75 year olds are 44 and 52 respectively; and 31 \& 46 for congestive heart failure (CHF) patients respectively. Each scale from the SF-36 is an algebraic sum of responses for all items in that scale.For ease of analysis each scale is then transformed to a 0-100 scale using a formula that converts the lowest \& highest possible scores to 0 \& 100 respectively.The scoring of the SF-36 indicates that 0% in a domain represents the poorest possible QoL \& 100% indicates full QoL.
Composite Functional and Structural Measures - Freedom From Death
Time Frame: 12 months
Defined as all causes of death for the primary safety Major Adverse Event (MAE) Endpoint. Death is further divided into 2 categories: A. Cardiac death is defined as death due to any of the following: 1. Acute myocardial infarction. 2. Cardiac perforation/pericardial tamponade. 3. Arrhythmia or conduction abnormality. 4. Stroke within 30 days of the procedure or stroke suspected of being related to the procedure. 5. Death due to any complication of the procedure, including bleeding, vascular repair, transfusion reaction, or bypass surgery. 6. Any death for which a cardiac cause cannot be excluded. B. Non-cardiac death is defined as a death not due to cardiac causes (as defined above).
Number of Participants With New York Heart Association (NYHA) Class
Time Frame: 12 months
Class I: Patients with cardiac disease but without resulting limitations of physical activity. Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain. Class III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea, or anginal pain. Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.
Left Ventricular End Systolic Volume (LVESV)
Time Frame: Discharge or 30 days
Left Ventricular End Systolic Volume (LVESV) as determined by the core echocardiography laboratory from a transthoracic echocardiogram (TTE).
Number of Patients With CHF Having Hospitalization During Discharge Through 12 Months
Time Frame: 12 months
Number of patients with incidence of re-hospitalizations for CHF in the 12-months after the MitraClip implant procedure.
Number of CHF Events Leading to Hospitalizations During Discharge Through 12 Months
Time Frame: 12 months
Incidence of re-hospitalizations for CHF in the 12-months after the MitraClip implant procedure.
Secondary Outcomes
- Procedural Freedom From In-hospital MAE(30 Days)
- Number of Participants Experiencing Major Adverse Events(12 months)
- Number of Participants Over 75 Years of Age With MAE(12 months)
- Number of Participants Experiencing Major Adverse Events (MAE)(30 days)
- Number of Participants Experiencing Major Vascular Complications(12 months)
- Number of Participants With Atrial Septal Defect (ASD)(12 months)
- Number of Participants With New Coumadin Use(12 months)
- Number of Participants Discharged to a Nursing Home or Skilled Nursing Facility or Hospital(30 Days)
- Number of Participants With Successful Clip Implant(30 Days)
- Number of Participants With MR Severity(60 months)
- Number of Participants With Treatment Durability(24 months)
- Number of Participants With Major Bleeding Complications(12 months)
- Mitral Valve Area: By Pressure Half-time(60 months)
- Mitral Valve Area (MVA) Index: by Pressure-Half Time Formula(30 days)
- Mitral Valve Index(12 months)
- Number of Participants With High Risk Procedural Success(30 days)
- Number of Participants With Composite Functional and Structural Measures - Clinical Measures of Benefit-New York Heart Association (NYHA) Class(48 months)
- Number of Participants With New York Heart Association (NYHA) Class(60 months)
- Regurgitant Volume(24 months)
- Number of Participants With Mitral Valve Surgery Post-MitraClip Procedure(60 months)
- Number of Participants With Non-cerebral Thromboembolism(12 months)
- Number of Participants With Thrombosis(12 months)
- Number of Participants With Dysrhythmias(12 months)
- Post-procedure Intensive Care Unit (ICU)/ Critical Care Unit (CCU) Time(Length of ICU/CCU stay, assessed at 30 Days)
- Left Ventricular Measurement: Left Ventricular Internal Dimension Diastole (LVIDd), Left Ventricular Internal Dimension Systole (LVIDs)(60 months)
- Number of Hospital Re-Admissions for Congestive Heart Failure (CHF)(12 months)
- Regurgitant Fraction (RF)(30 days)
- Cardiac Output(24 months)
- Number of Participants With Device Embolization or Single Leaflet Device Attachment(60 months)
- Number of Participants With Hemolysis(12 months)
- Mitral Valve Area Index : By Planimetry(60 months)
- Number of Participants With Endocarditis(12 months)
- Number of Participants With Mitral Valve Stenosis(48 months)
- Mitral Valve Area: By Planimetry(60 months)
- Mitral Valve Area Index : By Pressure Half-time Formula(60 months)
- Transvalvular Mitral Valve Gradient(60 months)
- Post-procedure Length of Hospital Stay(Length of Hospital Stay, assessed at 30 days)
- Number of Participants With Clinical Durability(24 months)
- Left Ventricular End-diastolic Volume (LVEDV).(60 months)
- Left Ventricular End-systolic Volume (LVESV).(60 months)
- Number of Days Re-hospitalized for CHF(12 months)
- Regurgitant Fraction(24 months)
- Percentage of Participants With Freedom From Mitral Valve Surgery(60 months)
- Number of Participants With Mitral Valve Repair Success(24 months)
- Percentage of Participants With Composite Functional and Structural Measures - Freedom From Death and MR >2+(24 months)
- Cardiac Output (CO)(30 Days)
- Cardiac Index(24 months)
- Left Ventricular Ejection Fraction (LVEF)(60 months)
- Composite Functional and Structural Measures - Percentage of Participants With Freedom From Death(24 months)
- Number of Participants With Second MitraClip Device Implanted(0 to 5 years)
- Percentage of Participants With Freedom From All-Cause Mortality and Mitral Valve Surgery(60 months)
- Number of Participants With Mitral Valve Replacement(48 months)