Clinical trial NCT02214277: Cerebral Protection in Transcatheter Aortic Valve Replacement
Official title: Cerebral Protection in Transcatheter Aortic Valve Replacement - The SENTINEL Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Severe Symptomatic Calcified Native Aortic Valve Stenosis
Keywords: Embolic Protection
Edwards SAPIEN THV
Edwards SAPIEN XT
TAVR
Transfemoral
Transapical
Heart Valve Diseases
Heart Diseases
TAVI
Aortic Stenosis
Aortic Valve
Transcatheter Heart Valve
Lead sponsor: Claret Medical
Sponsor class: INDUSTRY
First posted: 2014-08-12
Enrollment: 363
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: Day 2-7 Post-Procedure
measure: Patients With Major Adverse Cardiac and Cerebrovascular Events (MACCE) at 30 Days
timeFrame: 30 Days Post-Procedure
Secondary outcomes:
measure: Captured Debris Histopathology (Observational)
timeFrame: Post-procedure
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Clearwater
country: United States
facility: Morton Plant Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: UT Houston / Memorial Hermann
state: Texas
city: Charlottesville
country: United States
facility: UVA Advanced Cardiac Valve Center
state: Virginia
city: Seattle
country: United States
facility: UW Medical Center
state: Washington
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig - Universitatsklinik
Study officials:
affiliation: Columbia University
name: Susheel Kodali, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Samir Kapadia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.