Cerebral Protection in Transcatheter Aortic Valve Replacement

• ClinicalTrials.gov Identifier: NCT02214277
• Recruitment Status: Completed
• First Posted: August 12, 2014
• Results First Posted: May 11, 2018
• Last Update Posted: May 11, 2018
• Sponsor: Claret Medical
• Information provided by (Responsible Party): Claret Medical

Study Description

Brief Summary:

The Sentinel System will be a safe and effective method for capturing and removing embolic material (thrombus/debris) during transcatheter aortic valve replacement in order to reduce the ischemic burden in the cerebral anterior circulation.

Condition or disease	Intervention/treatment	Phase
Severe Symptomatic Calcified Native Aortic Valve Stenosis	Device: Cerebral Protection System-The SENTINEL System with TAVR; Device: TAVR	Not Applicable

Detailed Description:

The Sentinel™ Cerebral Protection System is indicated for use as an embolic capture and retrieval system intended to reduce the ischemic burden in the cerebral anterior circulation while performing transcatheter aortic valve replacement.

The objective of this study is to assess the safety and efficacy of the Claret Medical Sentinel Cerebral Protection System used for embolic protection during Transcatheter Aortic Valve Replacement (TAVR) compared to TAVR standard of care (without embolic protection).

The study population is comprised of subjects with severe symptomatic calcified native aortic valve stenosis who meet the commercially approved indications for TAVR with the Edwards SAPIEN THV or SAPIEN XT and comply with the inclusion/exclusion criteria.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 363 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Cerebral Protection in Transcatheter Aortic Valve Replacement - The SENTINEL Study
• Study Start Date: September 2014
• Actual Primary Completion Date: March 2016
• Actual Study Completion Date: June 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Test Arm	Device: Cerebral Protection System-The SENTINEL System with TAVR; Claret Medical Sentinel Cerebral Protection System is intended for use as an embolic protection system to contain and remove embolic material (thrombus/debris) that may enter the carotid arteries.; Other Names: Cerebral Protection System: The SENTINEL System; TAVR Device: Edwards SAPIEN THV or Edwards SAPIEN XT
Active Comparator: Control Arm	Device: TAVR; Other Name: TAVR: Edwards SAPIEN THV or Edwards SAPIEN XT
Safety Arm	Device: Cerebral Protection System-The SENTINEL System with TAVR; Claret Medical Sentinel Cerebral Protection System is intended for use as an embolic protection system to contain and remove embolic material (thrombus/debris) that may enter the carotid arteries.; Other Names: Cerebral Protection System: The SENTINEL System; TAVR Device: Edwards SAPIEN THV or Edwards SAPIEN XT

Outcome Measures

Primary Outcome Measures :

1. Reduction in Median Total New Lesion Volume in Protected Territories Between Test and Control Arms as Assessed by DW-MRI at Day 2-7 Post-procedure. [ Time Frame: Day 2-7 Post-Procedure ]
   Total new lesion volume is defined as the sum of all diffusion-positive new cerebral lesions in post-TAVR DW-MRI relative to the pre-TAVR DW-MRI scans. Protected territories are defined as brain territories uniquely perfused by the vessels protected by the Sentinel System, namely the left and right carotid arteries, and the right vertebral artery.
2. Patients With Major Adverse Cardiac and Cerebrovascular Events (MACCE) at 30 Days [ Time Frame: 30 Days Post-Procedure ]
   Primary Safety Endpoint: MACCE (all death, all stroke, and acute kidney injury class 3 within 72 hours or discharge, whatever occurs first) at 30 days compared to a historical performance goal of 18.3%.

Secondary Outcome Measures :

1. Captured Debris Histopathology (Observational) [ Time Frame: Post-procedure ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Approved indications for commercially available Edwards SAPIEN Transcatheter Heart Valve, model 9000TFX or SAPIEN XT, model 9300TFX meeting one of the three sub-criteria below:

   SAPIEN

   1. transfemoral delivery in subjects with severe symptomatic calcified native aortic valve stenosis without severe aortic insufficiency and with ejection fraction >20% who have been examined by a heart team including an experienced cardiac surgeon and a cardiologist and found to either be:

      1. inoperable and in whom existing co-morbidities would not preclude the expected benefit from correction of the aortic stenosis; or
      2. be operative candidates for aortic valve replacement but who have a Society of Thoracic Surgeons predicted operative risk score >8% or are judged by the heart team to be at a 15% risk of mortality for surgical aortic valve replacement.

      or

   2. transapical delivery in subjects with severe symptomatic calcified native aortic valve stenosis without severe aortic insufficiency and with ejection fraction > 20% who have been examined by a heart team including an experienced cardiac surgeon and a cardiologist and found to be operative candidates for aortic valve replacement but who have a Society of Thoracic Surgeons operative risk score 8% or are judged by the heart team to be at a 15% risk of mortality for surgical aortic valve replacement.

      SAPIEN XT (Transfemoral or Transapical only)

   3. in patients with symptomatic heart disease due to severe native calcific aortic stenosis (aortic valve area ≤ 1.0 cm2 or aortic valve area index ≤ 0.6 cm2/m2, a mean aortic valve gradient of ≥ 40 mmHg, or a peak aortic-jet velocity of ≥ 4.0 m/s), and with native anatomy appropriate for the 23, 26, or 29 mm valve system, who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., Society of Thoracic Surgeons operative risk score ≥8% or at a ≥15% risk of mortality at 30 days).
2. Compatible left common carotid artery (6.5 - 10 mm) and brachiocephalic artery (9 - 15 mm) diameters without significant stenosis (> 70%) as determined by Multi-Slice Computed Tomography (MSCT) scan or equivalent imaging modality
3. The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visit
4. The subject or the subject's legal representative has been informed of the nature of the trial, agrees to its provisions and has provided written informed consent as approved by the IRB of the respective clinical site

Exclusion Criteria:

General

1. Vasculature in the right extremity precluding 6Fr sheath radial or brachial access
2. Inadequate circulation to the right extremity as evidenced by signs of artery occlusion (modified Allen's test) or absence of radial/brachial pulse
3. Hemodialysis shunt, graft, or arterio-venous fistula involving the upper extremity vasculature
4. Evidence of an acute myocardial infarction ≤ 1 month before the intended treatment
5. Aortic valve is a congenital unicuspid or bicuspid valve; or is non-calcified
6. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation >3+)
7. Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 30 days of the index procedure (unless part of planned strategy for treatment of concomitant coronary artery disease)
8. Pre-existing prosthetic heart valve in any position, prosthetic ring, or severe (greater than 3+) mitral insufficiency
9. Blood dyscrasias as defined: Leukopenia, acute anemia, thrombocytopenia, history of bleeding diathesis or coagulopathy
10. Hemodynamic instability requiring inotropic support or mechanical heart assistance.
11. Need for emergency surgery for any reason
12. Hypertrophic cardiomyopathy with or without obstruction
13. Severe ventricular dysfunction with LVEF ≤20%
14. Echocardiographic evidence of intracardiac or aortic mass, thrombus, or vegetation
15. Symptomatic or asymptomatic severe occlusive carotid disease requiring concomitant CEA/stenting
16. Subject has undergone carotid stenting or carotid endarterectomy within the previous 6 weeks
17. Active peptic ulcer or upper GI bleeding within the prior 3 months
18. A known hypersensitivity or contraindication to aspirin, heparin, ticlopidine, or clopidogrel, or sensitivity to contrast media, which cannot be adequately pre-medicated
19. Recent (within 6 months) CVA or a TIA
20. Renal insufficiency (creatinine > 3.0 mg/dL or GFR < 30) and/or renal replacement therapy at the time of screening
21. Life expectancy < 12 months due to non-cardiac co-morbid conditions
22. Subjects in whom anti-platelet and/or anticoagulant therapy is contraindicated, or who will refuse transfusion
23. Subjects who have active bacterial endocarditis or other active infections
24. Currently participating in an investigational drug or another device study
25. Subjects who have a planned treatment with any other investigational device or procedure during the study follow-up period (90 days)
26. Subject with planned concomitant surgical or transcatheter ablation for Atrial Fibrillation during the study follow-up period (90 days)

27. Any subject with a balloon valvuloplasty (BAV) within 30 days of the procedure

    Neurologic

28. Subject had active major psychiatric disease
29. Subject has severe visual, auditory, or learning impairment and who are unable to comprehend English and therefore unable to be consented for the study

30. Subjects with neurodegenerative or other progressive neurological disease or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities

    Angiographic

31. Excessive tortuosity in the right radial/brachial/subclavian artery preventing Sentinel System access and insertion

32. Subject whose brachiocephalic or left carotid artery reveals significant stenosis, calcification, ectasia, dissection, or aneurysm at the ostium or within 3 cm of the ostium

    Magnetic Resonance Imaging

33. Subject Body Mass Index (BMI) precluding imaging in scanner
34. Contraindications to MRI (subjects with any implantable temporary or permanent pacemaker or defibrillator, metal implants in field of view, metallic fragments, clips, or devices in the brain or eye before TAVR procedure)
35. Planned implantation of a pacemaker or defibrillator implantation after TAVR
36. Claustrophobia
37. Known allergy to gadolinium or contrast agent

Contacts and Locations

Locations

United States, California

Cedars-Sinai Medical Center

Los Angeles, California, United States

United States, District of Columbia

Washington Hospital Center

Washington, District of Columbia, United States

United States, Florida

Morton Plant Hospital

Clearwater, Florida, United States

United States, Georgia

Emory University Hospital

Atlanta, Georgia, United States

United States, Michigan

Henry Ford Hospital

Detroit, Michigan, United States

United States, Missouri

Barnes-Jewish Hospital

Saint Louis, Missouri, United States

United States, New York

Columbia University Medical Center

New York, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Weill Cornell Medical Center

New York, New York, United States

United States, Ohio

Cleveland Clinic Foundation

Cleveland, Ohio, United States

United States, Pennsylvania

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

United States, Texas

UT Houston / Memorial Hermann

Houston, Texas, United States

United States, Virginia

UVA Advanced Cardiac Valve Center

Charlottesville, Virginia, United States

United States, Washington

UW Medical Center

Seattle, Washington, United States

Germany

Herzzentrum Leipzig - Universitatsklinik

Leipzig, Germany, 04289

Sponsors and Collaborators

Claret Medical

Investigators

• Principal Investigator: Susheel Kodali, MD; Columbia University
• Principal Investigator: Samir Kapadia, MD; The Cleveland Clinic

More Information

Additional Information:

Related Info 

Publications of Results:

Kapadia SR, Kodali S, Makkar R, Mehran R, Lazar RM, Zivadinov R, Dwyer MG, Jilaihawi H, Virmani R, Anwaruddin S, Thourani VH, Nazif T, Mangner N, Woitek F, Krishnaswamy A, Mick S, Chakravarty T, Nakamura M, McCabe JM, Satler L, Zajarias A, Szeto WY, Svensson L, Alu MC, White RM, Kraemer C, Parhizgar A, Leon MB, Linke A; SENTINEL Trial Investigators. Protection Against Cerebral Embolism During Transcatheter Aortic Valve Replacement. J Am Coll Cardiol. 2017 Jan 31;69(4):367-377. doi: 10.1016/j.jacc.2016.10.023. Epub 2016 Nov 1.

• Responsible Party: Claret Medical
• ClinicalTrials.gov Identifier: NCT02214277
• Other Study ID Numbers: CP-10836
• First Posted: August 12, 2014
• Results First Posted: May 11, 2018
• Last Update Posted: May 11, 2018
• Last Verified: April 2018

Keywords provided by Claret Medical:

Embolic Protection; Edwards SAPIEN THV; Edwards SAPIEN XT; TAVR; Transfemoral; Transapical; Heart Valve Diseases; Heart Diseases; TAVI; Aortic Stenosis; Aortic Valve; Transcatheter Heart Valve

Additional relevant MeSH terms:

Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction