EVEREST II Pivotal Study High Risk Registry (HRR)

Abbott

Status: Completed

Conditions: Mitral Valve Regurgitation; Mitral Valve Insufficiency; Mitral Insufficiency; Mitral Regurgitation; Mitral Valve Incompetence

Treatments: Device: Percutaneous mitral valve repair using MitraClip implant

Study type: Interventional

Funder types: Industry

Identifiers

NCT01940120

0401A

Details and patient eligibility

About

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).

Full 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.

Enrollment: 78 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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].

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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78 participants in 1 patient group

High Risk Registry Arm

Experimental group

Description:

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.

Treatment:

Device: Percutaneous mitral valve repair using MitraClip implant