Aortic Valve Stenosis
Conditions
Brief summary
The main objective of this study is to evaluate the feasibility and safety of the GEMINUS system in patients with severe symptomatic aortic stenosis. This is a prospective, open label, multicentre, single arm, first in human clinical study. Clinical follow up for all patients will be performed at 30 days, 6 months, 1, 2, 3, 4 and 5 years post-implantation
Interventions
DEVICEGEMINUS Transcatheter Aortic Valve Implantation system
Implantation of the GEMINUS Transcatheter Aortic Valve Implantation system
Sponsors
Valve Medical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years 2. Patient understands the implications of participating in the study and provides informed consent 3. Patient is willing to comply with specified follow-up evaluation 4. Severe aortic stenosis as per ACC/AHA 2020 guidelines (e.g. AVA ≤ 1.0 cm2 (or AVA index ≤ 0.6cm2/m2)\* AND PV ≥ 4 m/sec or mean gradient ≥ 40 mmHg)\*\* as determined by TTE/CT-TAVI \*May be larger with mixed AS/AR \*\*For low flow low gradient AS or paradoxical low flow severe AS must meet ACC/AHA guidelines (table 13 stages of AS in the guideline) 5. Cardiac Symptoms: ≥ NYHA Class II 6. Patient ≥ intermediate surgical risk as assessed by the heart team or ≥75 years old. 7. Aortic annulus diameter ≥22 mm and \< 29 mm, assessed by CT TAVI 8. Anatomically suitable for implantation of the GEMINUS device 9. Peripheral vessels (common femoral and iliac arteries) of acceptable size (minimal diameter \> 4mm), tortuosity, and calcification to accommodate the 12Fr catheter system. 10. Patients assessed by the heart team to be at high risk for access site related bleeding/vascular complications due to the caliber/ calcification/ atherosclerosis of the iliofemoral vessels.
Exclusion criteria
1. Patient not suitable for surgical bailout 2. Congenital uni/bi/quadricuspid valve, or noncalcified aortic valve. 3. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation ≥3+). 4. Active or recent (within 6 months) endocarditis. 5. Active systemic infections. 6. Recent MI (≤ 1 month). 7. Any therapeutic invasive cardiac procedure (except BAV) performed within 30 days of the index procedure. 8. Prosthetic heart valve in any position. 9. Severe (\> 3+) mitral, tricuspid or pulmonic regurgitation. 10. Blood dyscrasias as defined: leukopenia (WBC\<3000/mm3), acute anemia (Hb \<8mg%), thrombocytopenia (platelet count \<50,000 cells/mm3), history of bleeding diathesis or coagulopathy. 11. Untreated clinically significant coronary artery disease requiring revascularization. 12. Hemodynamic instability requiring inotropic support or mechanical support devices. 13. Hypertrophic cardiomyopathy with or without obstruction (HCM). 14. Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) \<20%. 15. Echocardiographic evidence of intracardiac mass, thrombus or vegetation. 16. Active peptic ulcer or upper GI bleeding within the prior 3 months. 17. Known hypersensitivity or contraindication to heparin, inability to tolerate antiplatelet therapy or sensitivity to contrast media (which cannot be adequately premedicated). 18. Recent (\<6 months) cerebrovascular accident (CVA) or transient ischemic attack (TIA). 19. Renal insufficiency (eGFR\<30 mL/min) and/or end stage renal disease requiring chronic dialysis. 20. Severe aortic disease, including abdominal aortic or thoracic aneurysm (lumen diameter \> 5cm), marked tortuosity, or severe aortic arch atheroma. 21. Life expectancy \< 12 months due to non-cardiac co-morbid conditions. 22. Currently participating in an investigational drug or another device study that has not reached its primary endpoint
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Technical success (at exit from procedure room) | immediately after procedure | Technical success (at exit from procedure room) composite endpoint: Freedom from mortality, Successful access, delivery of the device, and retrieval of the delivery System, Correct positioning of a single prosthetic heart valve into the proper anatomical location, Freedom from surgery or intervention related to the device or to a major vascular or access-related, or cardiac structural complication |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Device success composite endpoint | 30 days | Device success composite endpoint: Technical success; Freedom from mortality; Freedom from surgery or intervention related to the device or to a major vascular or access-related or cardiac structural complication; Intended performance of the valve (mean gradient \<20 mmHg, peak velocity \<3 m/s, Doppler velocity index ≥0.25, and less than moderate aortic regurgitation) |
| Early safety composite endpoint (VARC 3) | 30 days | Early safety composite endpoint: Freedom from all-cause mortality; Freedom from all stroke; Freedom from ≥ VARC-3 type 2 bleeding; Freedom from major vascular, access-related, or cardiac structural complication; Freedom from acute kidney injury stage 3 or 4; Freedom from moderate or severe aortic regurgitation; Freedom from new permanent pacemaker due to procedure-related conduction abnormalities; Freedom from surgery or intervention related to the device |
| Early safety composite endpoint (Modified VARC) | 30 days | Early safety composite endpoint: Freedom from all-cause mortality; Freedom from all stroke; Freedom from ≥ Modified VARC type 3 bleeding; Freedom from major vascular, access-related, or cardiac structural complication; Freedom from acute kidney injury stage 3 or 4; Freedom from moderate or severe aortic regurgitation; Freedom from new permanent pacemaker due to procedure-related conduction abnormalities; Freedom from surgery or intervention related to the device |
| Clinical efficacy composite endpoint | 1, 2, 3, 4, 5 years | Clinical efficacy composite endpoint: Freedom from all-cause mortality; Freedom from all stroke; Freedom from hospitalization for procedure- or valve-related causes; Freedom from KCCQ Overall Summary Score \<45 or decline from baseline of \>10 point (i.e. Unfavourable Outcome) |
| All-cause mortality | 30 days, 6 months, 1, 2, 3, 4, 5 years | All-cause mortality |
| Disabling stroke | 6 months, 2, 3, 4, 5 years | Disabling stroke |
| Any stroke | 30 days, 6 months, 1, 2, 3, 4, 5 years | Any stroke |
| Peri-procedural MI (per ARC-2) | within 2 days after procedure | Peri-procedural MI (per ARC-2). |
| Repeat hospitalization for procedure or valve related cause | 30 days, 6 months, 1, 2, 3, 4, 5 years | Repeat hospitalization for procedure or valve related cause |
| Repeat aortic valve intervention | 30 days, 6 months, 1, 2, 3, 4, 5 years | Repeat aortic valve intervention |
| AKI (Stage 3 or 4) | 30 days | AKI (Stage 3 or 4) |
| Bleeding ≥ VARC-3 type 2 | 30 days, 6 months, 1, 2, 3, 4, 5 years | Bleeding ≥ VARC-3 type 2 |
| Bleeding ≥ Modified VARC type 3 | 30 days, 6 months, 1, 2, 3, 4, 5 years | Bleeding ≥ Modified VARC type 3 |
| KCCQ- Kansas City Cardiomyopathy Questionnaire | 6 months, 1 year | Kansas City Cardiomyopathy Questionnaire, 0-5 (none- extremily) |
| Hemodynamic valve performance: Mean pressure gradient | pre-discharge, 30 days, 6 months, 1, 2, 3, 4, 5 years | Hemodynamic valve performance: Mean pressure gradient |
| Hemodynamic valve performance: peak velocity | pre-discharge, 30 days, 6 months, 1, 2, 3, 4, 5 years | Hemodynamic valve performance: peak velocity |
| Hemodynamic valve performance: aortic valve area | pre-discharge, 30 days, 6 months, 1, 2, 3, 4, 5 years | Hemodynamic valve performance: aortic valve area |
| Hemodynamic valve performance: aortic regurgitation | pre-discharge, 30 days, 6 months, 1, 2, 3, 4, 5 years | Hemodynamic valve performance: aortic regurgitation |
| Freedom from new permanent pacemaker due to procedure-related conduction abnormalities | 30 days | Freedom from new permanent pacemaker due to procedure-related conduction abnormalities |
Countries
Israel
Contacts
CONTACTBrenda Koltun Reuven
PRINCIPAL_INVESTIGATORRan Kornowski, Prof.
Rabin Medical Center
Outcome results
None listed