Clinical trial NCT05909748: FIH Study of the GEMINUS TAVI System in Patients With Severe Symptomatic Aortic Stenosis
Official title: First in Human Study of the GEMINUS Transcatheter Aortic Valve Implantation System in Patients With Severe Symptomatic Aortic Stenosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aortic Valve Stenosis
Lead sponsor: Valve Medical
Sponsor class: INDUSTRY
First posted: 2023-06-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Technical success (at exit from procedure room)
timeFrame: immediately after procedure
Secondary outcomes:
measure: Device success composite endpoint
timeFrame: 30 days
measure: Early safety composite endpoint (VARC 3)
timeFrame: 30 days
measure: Early safety composite endpoint (Modified VARC)
timeFrame: 30 days
measure: Clinical efficacy composite endpoint
timeFrame: 1, 2, 3, 4, 5 years
measure: All-cause mortality
timeFrame: 30 days, 6 months, 1, 2, 3, 4, 5 years
measure: Disabling stroke
timeFrame: 6 months, 2, 3, 4, 5 years
measure: Any stroke
timeFrame: 30 days, 6 months, 1, 2, 3, 4, 5 years
measure: Peri-procedural MI (per ARC-2)
timeFrame: within 2 days after procedure
measure: Repeat hospitalization for procedure or valve related cause
timeFrame: 30 days, 6 months, 1, 2, 3, 4, 5 years
measure: Repeat aortic valve intervention
timeFrame: 30 days, 6 months, 1, 2, 3, 4, 5 years
measure: AKI (Stage 3 or 4)
timeFrame: 30 days
measure: Bleeding ≥ VARC-3 type 2
timeFrame: 30 days, 6 months, 1, 2, 3, 4, 5 years
measure: Bleeding ≥ Modified VARC type 3
timeFrame: 30 days, 6 months, 1, 2, 3, 4, 5 years
measure: KCCQ- Kansas City Cardiomyopathy Questionnaire
timeFrame: 6 months, 1 year
measure: Hemodynamic valve performance: Mean pressure gradient
timeFrame: pre-discharge, 30 days, 6 months, 1, 2, 3, 4, 5 years
measure: Hemodynamic valve performance: peak velocity
timeFrame: pre-discharge, 30 days, 6 months, 1, 2, 3, 4, 5 years
measure: Hemodynamic valve performance: aortic valve area
timeFrame: pre-discharge, 30 days, 6 months, 1, 2, 3, 4, 5 years
measure: Hemodynamic valve performance: aortic regurgitation
timeFrame: pre-discharge, 30 days, 6 months, 1, 2, 3, 4, 5 years
measure: Freedom from new permanent pacemaker due to procedure-related conduction abnormalities
timeFrame: 30 days
Other outcomes:
Locations:
city: Petah tikva
country: Israel
facility: Rabin Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasly Medical Center
Study officials:
affiliation: Rabin Medical Center
name: Ran Kornowski, Prof.
role: PRINCIPAL_INVESTIGATOR
References: