Severe Symptomatic Calcified Native Aortic Valve Stenosis
Conditions
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
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.
Interventions
DEVICECerebral 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.
DEVICETAVR
Sponsors
Claret Medical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
| Patients With Major Adverse Cardiac and Cerebrovascular Events (MACCE) at 30 Days | 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
| Measure | Time frame |
|---|---|
| Captured Debris Histopathology (Observational) | Post-procedure |
Countries
Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Safety Arm Safety Arm patients received TAVR and the Sentinel System. Patients enrolled in this arm of the study received safety follow-up at discharge, at 30 days and 90 days post-procedure; and neurological evaluation at baseline, discharge, 30 days and 90 days (only in the case of a stroke ≤ 30 days) post procedure. | 123 |
| Test Arm Test Arm patients received TAVR and the Sentinel System. Patients enrolled in this arm of the study underwent safety follow-up at discharge, at 30 and at 90 days post-procedure; MRI assessment for efficacy at baseline, 2-7 days and 30 days post-procedure; neurological evaluation at baseline, discharge, 30 days and 90 days (only in the case of a stroke ≤ 30 days) post procedure; neurocognitive evaluation at baseline, 2-7 days (optional), 30 days and 90 days post-procedure; Quality of Life assessment at baseline, 30 days and 90 days; and histopathological evaluation of debris captured in the Sentinel device filters. | 121 |
| Control Arm Control Arm patients received TAVR only. Patients enrolled in this arm of the study underwent safety follow-up at discharge, at 30 and at 90 days post-procedure; MRI assessment for efficacy at baseline, 2-7 days and 30 days post-procedure; neurological evaluation at baseline, discharge, 30 days and 90 days (only in the case of a stroke ≤ 30 days) post procedure; neurocognitive evaluation at baseline, 2-7 days (optional), 30 days and 90 days post-procedure; and Quality of Life assessment at baseline, 30 days and 90 days. | 119 |
| Total | 363 |
Baseline characteristics
| Characteristic | Test Arm | Total | Safety Arm | Control Arm |
|---|---|---|---|---|
| Age, Continuous | 82.0 years STANDARD_DEVIATION 7.95 | 82.3 years STANDARD_DEVIATION 8.31 | 81.5 years STANDARD_DEVIATION 8.98 | 83.4 years STANDARD_DEVIATION 7.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 118 Participants | 359 Participants | 123 Participants | 118 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| History of Atrial Fibrillation | 42 Participants | 115 Participants | 37 Participants | 36 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 10 Participants | 8 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 5 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) White | 115 Participants | 339 Participants | 109 Participants | 115 Participants |
| Region of Enrollment Germany | 26 participants | 74 participants | 25 participants | 23 participants |
| Region of Enrollment United States | 95 participants | 289 participants | 98 participants | 96 participants |
| Sex: Female, Male Female | 63 Participants | 189 Participants | 68 Participants | 58 Participants |
| Sex: Female, Male Male | 58 Participants | 174 Participants | 55 Participants | 61 Participants |
| STS PROM Score | 6.4 units on a scale STANDARD_DEVIATION 3.28 | 6.7 units on a scale STANDARD_DEVIATION 3.79 | 6.2 units on a scale STANDARD_DEVIATION 3.17 | 7.5 units on a scale STANDARD_DEVIATION 4.66 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 244 | 4 / 119 |
| other Total, other adverse events | 158 / 244 | 79 / 119 |
| serious Total, serious adverse events | 17 / 244 | 11 / 119 |
Outcome results
Primary
Patients With Major Adverse Cardiac and Cerebrovascular Events (MACCE) at 30 Days
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%.
Time frame: 30 Days Post-Procedure
Population: Safety Arm and Test Arm. ITT with imputation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Test Arm | Patients With Major Adverse Cardiac and Cerebrovascular Events (MACCE) at 30 Days | 18 Participants |
Primary
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.
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.
Time frame: Day 2-7 Post-Procedure
Population: ITT with Imputation. Test Arm compared to the Control Arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Test Arm | 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. | 109.1 mm3 |
| Control Arm | 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. | 174 mm3 |
Secondary
Captured Debris Histopathology (Observational)
Time frame: Post-procedure
Population: Only Test Arm patients had debris samples collected. Only samples with evaluable filters were used in the analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Test Arm | Captured Debris Histopathology (Observational) | Debris present | 104 Participants |
| Test Arm | Captured Debris Histopathology (Observational) | No debris present | 1 Participants |