Clinical trial NCT03004599: Safety and Efficacy of SYM-SV/DS-002 in Patients With Severe Aortic Stenosis
Official title: Safety and Efficacy of SYM-SV/DS-002 in Patients With Severe Aortic Stenosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Severe Aortic Stenosis
Keywords: Valvular Heart Disease
Critical Aortic Stenosis
Severe Aortic Stenosis
High Risk
Aortic Valve Replacement
Cardiovascular Disease
Aortic Stenosis
Heart Valve Therapy
Transcatheter
Transfemoral
TAVI
TAVR
ACURATE neo™ Aortic Bioprosthesis
ACURATE TF™ Transfemoral Delivery System
Lead sponsor: Medico's Hirata Inc.
Sponsor class: OTHER
First posted: 2016-12-29
Enrollment: 11
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Safety and Efficacy of SYM-SV/DS-002 in Patients with Severe Aortic Stenosis

Detailed description: To evaluate the safety and efficacy of Transfemoral Transcatheter Aortic Valve Implantation using SYM-SV-002 Aortic Bioprosthesis and SYM-DS-002 Transfemoral Delivery System in patients presenting with symptomatic severe aortic stenosis and with difficulty to safely undergo conventional surgical aortic valve replacement (AVR)

Eligibility criteria: Inclusion Criteria:

1. At least one cardiologist and one cardiac surgeon agree that it is difficult for the patient to receive a surgical procedure due to medical factors such that the subject has various comorbidities and he/she is more likely to die or suffer from severe diseases than to have significant improvements by a surgical procedure.
2. Subject has senile degenerative aortic valve stenosis with:

   * mean gradient \> 40 mmHg, or maximum jet velocity greater than 4.0 m/sec by either resting or dobutamine stress echocardiogram, or simultaneous pressure recordings at cardiac catheterization
   * AND an initial aortic valve area of ≤ 0.8 cm2 (or aortic valve area index ≤ 0.5 cm2/m2) by resting echocardiogram or simultaneous pressure recordings at cardiac catheterization
3. Subject is symptomatic from his/her aortic valve stenosis (AS), as demonstrated by New York Heart Association (NYHA) Functional Class II or greater.
4. The subject has been informed of the nature of this trial, agrees to its provisions and has provided written informed consent as approved by the IRB of the respective clinical site.
5. The subject or the subject's legal representative agrees to visit the site where he/she receives index procedure for all required post-procedure follow-ups.

Exclusion Criteria:

1. Evidence of an acute myocardial infarction ≤ 30 days (The procedure day is counted as day 0.) before the implant procedure
2. Any percutaneous coronary or peripheral interventional procedures, including placements of bare metal stents are performed within 30 days prior to the implant procedure, or any drug eluting stents are placed within 6 months (One month is counted as 30 days.) prior to the implant procedure
3. Untreated clinically significant coronary artery disease (CAD) requiring revascularization
4. Blood dyscrasias as defined:

   leukopenia (WBC \< 1,000/mm3), thrombocytopenia (platelet count \<50,000 cells/mm3), history of bleeding diathesis or coagulopathy
5. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support
6. Need for emergency surgery for any reason
7. Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) \< 20% as measured by resting echocardiogram
8. Cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to the implant procedure (except mild TIA related to aortic stenosis)
9. End stage renal disease requiring chronic dialysis or serum creatinine \> 3.0 mg/dL
10. Active Gastrointestinal (GI) bleeding within 3 months prior to the implant procedure
11. A known hypersensitivity or contraindication to any of the following which cannot be adequately pre-medicated:

    * Aspirin
    * Heparin (HIT/HITTS)
    * Nitinol (titanium or nickel)
    * P2Y12 inhibitors (such as Ticlopidine etc.)
    * Contrast media
12. Ongoing sepsis, including active endocarditis
13. Subject refuses a blood transfusion
14. Life expectancy \< 12 months due to associated non-cardiac comorbid conditions
15. Other medical, social, or psychological conditions that in the opinion of a principal investigator or sub-investigator precludes the subject from appropriate consent
16. Severe dementia (unable to provide informed consent for the treatment/procedure, unable to live an independent life outside of a chronic care facility, or expected to be fundamentally unable to undergo rehabilitation after the procedure, or unable to come to the site for follow-up visits)
17. Currently participating in other trials of investigational drugs or other investigational devices
18. Native aortic annulus size \< 21 mm or \> 27 mm per the baseline diagnostic imaging
19. Pre-existing prosthetic heart valve and / or prosthetic ring in any position
20. Mixed aortic valve disease (aortic stenosis and predominant aortic regurgitation (3-4+))
21. Moderate to severe (3-4+) or severe (4+) mitral regurgitation or severe (4+) tricuspid regurgitation
22. Moderate to severe mitral stenosis
23. Hypertrophic obstructive cardiomyopathy
24. New or untreated echocardiographic evidence of intracardiac mass, thrombus or vegetation
25. Congenital bicuspid or unicuspid valve verified by echocardiograph
26. Extreme eccentric calcification of the native aortic valve
27. Transesophageal echocardiogram (TEE) is contraindicated.
28. Scheduled surgical or percutaneous procedure to be performed prior to 1-month visit post-implant procedure
29. Hepatic failure (Child C or more)
30. Aortic or peripheral condition NOT appropriate for transfemoral implant due to the size, disease and degree of calcification or tortuosity of the aorta or ilio-femoral arteries
31. Thoracic or abdominal aortic aneurysm
32. Woman who is pregnant, breastfeeding or willing to become pregnant

Primary outcomes:
measure: Survival rate
timeFrame: at 12 months post-procedure
Secondary outcomes:
measure: Occurrence rates of MACCE
timeFrame: at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
measure: Occurrence rates of individual MACCE components
timeFrame: at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
measure: Occurrence rates of Major Adverse Events (MAEs)
timeFrame: at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
measure: Occurrence rate of conduction disturbance requiring Permanent Pacemaker Implantation(PPI)
timeFrame: at 1 month, 6 month, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
measure: Change in NYHA class from baseline
timeFrame: at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
measure: Change in distance walked during 6-Minute Walk Test (6MWT) from baseline
timeFrame: at 1 month and 12 month post-procedure
measure: Change in QOL from baseline
timeFrame: at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
measure: Change in QOL from baseline
timeFrame: at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
measure: Echocardiographic assessment of valve performance
timeFrame: at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
measure: Echocardiographic assessment of valve performance
timeFrame: at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
measure: Echocardiographic assessment of valve performance
timeFrame: at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
measure: Echocardiographic assessment of valve performance
timeFrame: at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
measure: Device success
timeFrame: Number of days from admission to discharge (estimated to be at 7 days post-procedure on average)
measure: Procedural success
timeFrame: Number of days from admission to discharge (estimated to be at 7 days post-procedure on average)
measure: Occurrence rate of Prosthetic Valve Dysfunction (PVD)
timeFrame: at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
measure: Occurrence rate of clinical endpoints per VARC 2
timeFrame: at 1 month post-procedure
Other outcomes:
Locations:
city: Kitakyushu
country: Japan
facility: Kokura Memorial Hospital
state: Fukuoka
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Fuchu
country: Japan
facility: Sakakibara Heart Institute
state: Tokyo
city: Itabashi
country: Japan
facility: Teikyo University Hospital
state: Tokyo
city: Shinjuku
country: Japan
facility: Keio University Hospital
state: Tokyo
Study officials:
References: