FIH Study of the GEMINUS TAVI System in Patients With Severe Symptomatic Aortic Stenosis

Study Overview
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Brief Summary
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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

Official Title
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First in Human Study of the GEMINUS Transcatheter Aortic Valve Implantation System in Patients With Severe Symptomatic Aortic Stenosis

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Device: GEMINUS Transcatheter Aortic Valve Implantation system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Patient understands the implications of participating in the study and provides informed consent Patient is willing to comply with specified follow-up evaluation 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) Cardiac Symptoms: ≥ NYHA Class II Patient ≥ intermediate surgical risk as assessed by the heart team or ≥75 years old. Aortic annulus diameter ≥22 mm and < 29 mm, assessed by CT TAVI Anatomically suitable for implantation of the GEMINUS device Peripheral vessels (common femoral and iliac arteries) of acceptable size (minimal diameter > 4mm), tortuosity, and calcification to accommodate the 12Fr catheter system. 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: Patient not suitable for surgical bailout Congenital uni/bi/quadricuspid valve, or noncalcified aortic valve. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation ≥3+). Active or recent (within 6 months) endocarditis. Active systemic infections. Recent MI (≤ 1 month). Any therapeutic invasive cardiac procedure (except BAV) performed within 30 days of the index procedure. Prosthetic heart valve in any position. Severe (> 3+) mitral, tricuspid or pulmonic regurgitation. 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. Untreated clinically significant coronary artery disease requiring revascularization. Hemodynamic instability requiring inotropic support or mechanical support devices. Hypertrophic cardiomyopathy with or without obstruction (HCM). Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) <20%. Echocardiographic evidence of intracardiac mass, thrombus or vegetation. Active peptic ulcer or upper GI bleeding within the prior 3 months. Known hypersensitivity or contraindication to heparin, inability to tolerate antiplatelet therapy or sensitivity to contrast media (which cannot be adequately premedicated). Recent (<6 months) cerebrovascular accident (CVA) or transient ischemic attack (TIA). Renal insufficiency (eGFR<30 mL/min) and/or end stage renal disease requiring chronic dialysis. Severe aortic disease, including abdominal aortic or thoracic aneurysm (lumen diameter > 5cm), marked tortuosity, or severe aortic arch atheroma. Life expectancy < 12 months due to non-cardiac co-morbid conditions. Currently participating in an investigational drug or another device study that has not reached its primary endpoint

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GEMINUS Transcatheter Aortic Valve Implantation system<br>Clinical follow up for all patients will be performed at 30 days, 6 months, 1, 2, 3, 4 and 5 years post-implantation | Device: GEMINUS Transcatheter Aortic Valve Implantation system<br>* Implantation of the GEMINUS Transcatheter Aortic Valve Implantation system<br>* Other names: GEMINUS TAVI system;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Technical success (at exit from procedure room) | 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 | immediately after procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device success composite endpoint | 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) | 30 days | 
| Early safety composite endpoint (VARC 3) | 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 | 30 days | 
| Early safety composite endpoint (Modified VARC) | 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 | 30 days | 
| Clinical efficacy composite endpoint | 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) | 1, 2, 3, 4, 5 years | 
| All-cause mortality | All-cause mortality | 30 days, 6 months, 1, 2, 3, 4, 5 years | 
| Disabling stroke | Disabling stroke | 6 months, 2, 3, 4, 5 years | 
| Any stroke | Any stroke | 30 days, 6 months, 1, 2, 3, 4, 5 years | 
| Peri-procedural MI (per ARC-2) | Peri-procedural MI (per ARC-2). | within 2 days after procedure | 
| Repeat hospitalization for procedure or valve related cause | Repeat hospitalization for procedure or valve related cause | 30 days, 6 months, 1, 2, 3, 4, 5 years | 
| Repeat aortic valve intervention | Repeat aortic valve intervention | 30 days, 6 months, 1, 2, 3, 4, 5 years | 
| AKI (Stage 3 or 4) | AKI (Stage 3 or 4) | 30 days | 
| Bleeding ≥ VARC-3 type 2 | Bleeding ≥ VARC-3 type 2 | 30 days, 6 months, 1, 2, 3, 4, 5 years | 
| Bleeding ≥ Modified VARC type 3 | Bleeding ≥ Modified VARC type 3 | 30 days, 6 months, 1, 2, 3, 4, 5 years | 
| KCCQ | KCCQ | 6 months, 1 year | 
| Hemodynamic valve performance: Mean pressure gradient | Hemodynamic valve performance: Mean pressure gradient | pre-discharge, 30 days, 6 months, 1, 2, 3, 4, 5 years | 
| Hemodynamic valve performance: peak velocity | Hemodynamic valve performance: peak velocity | pre-discharge, 30 days, 6 months, 1, 2, 3, 4, 5 years | 
| Hemodynamic valve performance: aortic valve area | Hemodynamic valve performance: aortic valve area | pre-discharge, 30 days, 6 months, 1, 2, 3, 4, 5 years | 
| Hemodynamic valve performance: aortic regurgitation | Hemodynamic valve performance: aortic regurgitation | pre-discharge, 30 days, 6 months, 1, 2, 3, 4, 5 years | 
| Freedom from new permanent pacemaker due to procedure-related conduction abnormalities | Freedom from new permanent pacemaker due to procedure-related conduction abnormalities | 30 days |