EVEREST II Pivotal Study High Risk Registry (HRR)

NCT01940120 | Completed Results DMC

• 1 other identifier: 0401A
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 2

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).

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

Outcome Measures

Primary Outcomes (13)

• Composite Functional and Structural Measures - Freedom From Death

  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).

  12 months

• Percentage of Participants With Freedom From Death and Mitral Regurgitation (MR) >2+

  Kaplan-Meier estimated percentage of patients who are alive and have a mitral regurgitation severity grade of 2+ or less

  12 months

• Number of Participants With Clinical Measures of Benefit-New York Heart Association (NYHA) Class

  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.

  30 days

• Number of Participants With 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.

  12 months

• Clinical Measures of Benefit-Quality of Life (QOL) as Measured by Short Form (SF) 36

  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.

  12 months

• Left Ventricular End Diastolic Volume (LVEDV)

  Left Ventricular End Diastolic Volume (LVEDV) as determined by the core echocardiography laboratory from a transthoracic echocardiogram (TTE).

  12 months

• Left Ventricular End Systolic Volume (LVESV)

  Left Ventricular End Systolic Volume (LVESV) as determined by the core echocardiography laboratory from a transthoracic echocardiogram (TTE).

  12 months

• Left Ventricular (LV) Function - Internal Dimension

  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).

  12 months

• Number of Patients With CHF Having Hospitalization During Discharge Through 12 Months

  Number of patients with incidence of re-hospitalizations for CHF in the 12-months after the MitraClip implant procedure.

  12 months

• Number of CHF Events Leading to Hospitalizations During Discharge Through 12 Months

  Incidence of re-hospitalizations for CHF in the 12-months after the MitraClip implant procedure.

  12 months

• Left Ventricular End Diastolic Volume (LVEDV)

  Left Ventricular End Diastolic Volume (LVEDV) as determined by the core echocardiography laboratory from a transthoracic echocardiogram (TTE).

  Discharge or 30 days

• Left Ventricular End Systolic Volume (LVESV)

  Left Ventricular End Systolic Volume (LVESV) as determined by the core echocardiography laboratory from a transthoracic echocardiogram (TTE).

  Discharge or 30 days

• Left Ventricular (LV) Function - Internal Dimension

  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).

  Discharge or 30 days

Secondary Outcomes (138)

• Number of Participants Experiencing Major Adverse Events (MAE)

  30 days

• Number of Participants Experiencing Major Adverse Events

  12 months

• Procedural Freedom From In-hospital MAE

  30 Days

• Number of Participants Over 75 Years of Age With MAE

  30 days

• Number of Participants Over 75 Years of Age With MAE

  12 months

Study Arms (1)

High Risk Registry Arm

EXPERIMENTAL

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.

Device: Percutaneous mitral valve repair using MitraClip implant

Interventions

Percutaneous mitral valve repair using MitraClip implant DEVICE

Procedure/Surgery: Mitral valve repair or replacement surgery Repair or replacement of mitral valve

Also known as: MitraClip, MitraClip Implant

High Risk Registry Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Bileaflet flail or severe bileaflet prolapse
• Lack of both primary and secondary chordal support

Sponsors & Collaborators

• Abbott Medical Devices: lead

Study Sites (2)

Evanston Northwestern Healthcare 2650 Ridge Ave., Walgreen Bldg, 3rd Floor, Cardiology

Evanston, Illinois, 60201, United States

Location

The Care Group Heart Center 10590 N. Meridian, Ste. 300

Indianapolis, Indiana, 46290, United States

Location

Related Publications (3)

• 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.

  PMID: 30586701 DERIVED

• 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.

  PMID: 30077993 DERIVED

• 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.

  PMID: 25593120 DERIVED

Related Links

• Sponsor information

MeSH Terms

Conditions

Mitral Valve Insufficiency; Mitral Valve Prolapse; Coronary Artery Disease; Heart Failure; Myocardial Infarction

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Heart Valve Prolapse; Coronary Disease; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Results Point of Contact

• Title: Chithra Sangli
• Organization: Abbott Vascular Structural Heart (formerly Evalve, Inc.)

chithra.sangli@av.abbott.com

650-430-1329

Study Officials

• Ted Feldman, M.D.

  Endeavor Health

  PRINCIPAL INVESTIGATOR

• Donald G Glower Jr.,, M.D.

  Duke University Medical Center, Department of Surgery

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2013
• First Posted: September 12, 2013
• Study Start: February 1, 2007
• Primary Completion: March 1, 2008
• Study Completion: February 1, 2013
• Last Updated: November 7, 2018
• Results First Posted: January 16, 2017

Record last verified: 2018-11

Locations

US (2)