Safety and Efficacy of SYM-SV/DS-002 in Patients With Severe Aortic Stenosis

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

Study Overview

• Status: Terminated
• Conditions: Severe Aortic Stenosis
• Intervention / Treatment: Device: SYM-SV-002 Aortic Bioprosthesis and SYM-DS-002 Transfemoral Delivery System

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)

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Japan
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 802-8555
      • Kokura Memorial Hospital
  • Osaka
    • Suita, Osaka, Japan, 565-0871
      • Osaka University Hospital
  • Tokyo
    • Fuchu, Tokyo, Japan, 183-0003
      • Sakakibara Heart Institute
    • Itabashi, Tokyo, Japan, 173-8606
      • Teikyo University Hospital
    • Shinjuku, Tokyo, Japan, 160-8582
      • Keio University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Transcatheter Aortic Valve Implantation (TAVI)	Device: SYM-SV-002 Aortic Bioprosthesis and SYM-DS-002 Transfemoral Delivery System; Transcatheter Aortic Valve Implantation via Transfemoral Approach; Other Names: ACURATE neo™ Aortic Bioprosthesis; ACURATE TF™ Transfemoral Delivery System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Survival rate	at 12 months post-procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence rates of MACCE	MACCE is defined as a composite of: All Cause Mortality; Myocardial infarction (MI); All Stroke; Reintervention	at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
Occurrence rates of individual MACCE components	Individual MACCE components include: All Cause Mortality; Myocardial infarction (MI); All Stroke; Reintervention	at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
Occurrence rates of Major Adverse Events (MAEs)	MAEs include: MACCE; Acute Kidney Injury (AKI); Cardiac Tamponade; Prosthetic Valve Dysfunction (PVD); Cardiogenic Shock; Prosthetic Valve Endocarditis; Life-Threatening, Disabling or Major Bleeding; Major Vascular Complications; Cardiac Perforation; Device Migration/Valve Embolism	at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
Occurrence rate of conduction disturbance requiring Permanent Pacemaker Implantation(PPI)		at 1 month, 6 month, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
Change in NYHA class from baseline		at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
Change in distance walked during 6-Minute Walk Test (6MWT) from baseline		at 1 month and 12 month post-procedure
Change in QOL from baseline	Kansas City Cardiomyopathy Questionnaire (KCCQ)	at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
Change in QOL from baseline	SF-36	at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
Echocardiographic assessment of valve performance	Effective Orifice Area Index (EOAI)	at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
Echocardiographic assessment of valve performance	Mean gradient	at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
Echocardiographic assessment of valve performance	Degree of Aortic valve Regurgitation (AR) (Transvalvular and Paravalvular)	at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
Echocardiographic assessment of valve performance	Left ventricular ejection fraction (LVEF)	at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
Device success	Device success is defined as that all of the following are achieved: Successful vascular access; Successful delivery and deployment of the device; Successful retrieval of the delivery system; Correct position of the device in the proper anatomical location (placement in the aortic annulus with no impedance on device function); Intended performance of the prosthetic heart valve is confirmed by echocardiography (defined as below):; No Patient-Prosthesis Mismatch (PPM) (EOAI >0.85cm2/m2); And mean aortic valve gradient < 20 mmHg or peak velocity < 3 m/sec,; And no moderate or severe prosthetic valve regurgitation; Only one valve implanted in the proper anatomical location	Number of days from admission to discharge (estimated to be at 7 days post-procedure on average)
Procedural success	Procedural success is defined as that all of the following are achieved: Achievement of the device success; Absence of in-hospital MACCE	Number of days from admission to discharge (estimated to be at 7 days post-procedure on average)
Occurrence rate of Prosthetic Valve Dysfunction (PVD)	Prosthetic Valve Dysfunction (PVD) is defined as: Aortic regurgitation (AR) reported as moderate or severe by echocardiography assessments; Significant aortic stenosis (AS) which meets one or more of the following by echocardiography assessments:; Peak velocity > 4 m/s; Mean gradient > 35 mmHg; Effective Orifice Area (EOA) < 0.8 cm2; TVIV1／TVIV2 < 0.25	at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years and 5 years post-procedure
Occurrence rate of clinical endpoints per VARC 2	Mortality; Stroke; Myocardial infarction (MI); Bleeding complications; Acute kidney injury (AKI); Vascular complications; Conduction disturbances and arrhythmia; Other TAVI-related complications	at 1 month post-procedure

Collaborators and Investigators

• Sponsor: Medico's Hirata Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: December 9, 2016
• First Submitted That Met QC Criteria: December 22, 2016
• First Posted (Estimate): December 29, 2016

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: November 1, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Cardiovascular Disease; Aortic Stenosis; Aortic Valve Replacement; TAVI; Transfemoral; Transcatheter; TAVR; Valvular Heart Disease; High Risk; Severe Aortic Stenosis; Critical Aortic Stenosis; Heart Valve Therapy; ACURATE neo™ Aortic Bioprosthesis; ACURATE TF™ Transfemoral Delivery System
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: MH-P-002