TAVI in Intermediate Risk Septuagenarians With Risk Factors Not Captured by the Traditional Surgical Risk Scores

Single arm, observational trial of Transcatheter Aortic Valve Implantation (TAVI) with the Medtronic Evolut R and Evolut Pro The primary objective of this trial is to evaluate device success of TAVI with the Evolut R and Evolut Pro systems in septuagenarians with risk factors for adverse surgical outcomes not captured by the traditional risk scores and therefore of intermediate surgical risk.

Study Overview

• Status: Recruiting
• Conditions: Transcatheter Aortic Valve Replacement
• Intervention / Treatment: Device: Transcatheter Aortic Valve Implantation (TAVI)

Detailed Description

The purpose of this study is to investigate the safety and efficacy of transcatheter aortic valve implantation (TAVI) in septuagenarians with severe, symptomatic Aortic Stenosis (AS) and risk factors for adverse surgical outcomes not captured by the traditional risk scores and therefore of intermediate surgical risk.

The primary objective of this trial is to evaluate device success of TAVI with the Evolut R and Evolut Pro systems in septuagenarians with risk factors for adverse surgical outcomes not captured by the traditional risk scores and therefore of intermediate surgical risk.

The secondary objective is to assess early safety (at 30 days) and clinical efficacy (after 30 days) of the TAVI procedure.

Exploratory objective: comparative health economics in septuagenarians with symptomatic severe aortic stenosis and intermediate surgical risk treated with Transcatheter Aortic Valve Implantation (TAVI) vs Surgical Aortic Valve Replacement (SAVR) (matched historic cohort)

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

• Study Contact: Name: Dimitris Tousoulis, Prof; Phone Number: +302132088099; Email: tousoulis@med.uoa.gr
• Study Contact Backup: Name: Konstantinos Toutouzas, Prof; Phone Number: +302132088099; Email: ktoutouz@med.uoa.gr

Study Locations

• Greece
  • Athens, Greece, 17674
    • Not yet recruiting
    • Onassis Cardiac Surgery Center
    • Contact: Vassilios Voudris, MD
  • Athens, Greece, 11527
    • Not yet recruiting
    • Cardiology Department, Hippokration Hospital
    • Contact: Dimitris Syrseloudis, MD
  • Athens, Greece, 11527
    • Recruiting
    • First Department of Cardiology, National & Kapodistrian University of Athens
    • Contact: Konstantinos Toutouzas, Prof; Phone Number: +302132088099; Email: ktoutouz@med.uoa.gr
  • Heraklion, Greece, 71110
    • Not yet recruiting
    • University Hospital of Heraklion
    • Contact: Fragkiskos Parthenakis, Prof
  • Ioannina, Greece, 45500
    • Not yet recruiting
    • University Hospital of Ioannina
    • Contact: Lampros Michalis, Prof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients 75-79 years old who have symptomatic severe aortic stenosis at intermediate surgical risk defined by a Society of Thoracic Surgeons (STS) mortality risk of >=4% and <=8%, will be presented to the Heart Team for inclusion in the trial.

Patients will have risk factors not captured by traditional risk scores

Description

Inclusion Criteria:

1. Age 75-79
2. Subject must have Society of Thoracic Surgeons (STS) score >=4% and <=8%

3. Subject must have at least one from the risk factors presented below:

   i. Severely atherosclerotic or porcelain aorta ii. Internal Mammary Artery (IMA) or other conduit(s) crossing midline and/or adherent to posterior table of sternum iii. Pre-existing mechanical valve in any other position iv. Severe right ventricular dysfunction v. Hostile chest (abnormal chest wall anatomy due to severe kyphoscoliosis or other skeletal abnormalities, evidence of severe radiation damage, history of multiple recurrent pleural effusions causing internal adhesions) vi. Severe liver disease/cirrhosis vii. Frailty viii. Malignancy with life expectancy that exceeds 24 months ix. Renal replacement therapy with creatinine levels >200mmol/L or 2.26 mg/dl

4. Heart team consisting of at least one interventional cardiologist and one cardiac surgeon agree on indication and treatment proposal, based on their clinical judgment (including anatomy assessment, risk factors, etc)
5. Critical aortic valve area defined as an initial aortic valve area of <=1cm2 or aortic valve index <0.6cm2/m2

6. In presence of normal left ventricular function:

   1. Mean gradient >40mmHg OR Vmax>4m/sec OR
   2. In presence of low flow, low gradient severe AS, a dobutamine stress echo must be conducted that demonstrates presence of contractile reserve defined as follows >=20% increase in stroke volume and mean gradient >40mmHg
7. Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by New York Heart Association (NYHA) Functional Class II or greater
8. The subject is suitable for direct TAVI not preceded by balloon valvuloplasty according to the judgment of the treating physicians
9. The subject and the treating physician agree that the subject will return for all required post procedure follow-up visits.

Exclusion Criteria:

1. Hypersensitivity or contraindication to aspirin, heparin, clopidogrel, coumadin, nitinol, or sensitivity to contrast media which cannot be adequately pre-medicated;
2. Blood dyscrasias as defined: leukopenia (WBC<1000/mm3), thrombocytopenia (platelet count <50.000cells/mm3), history of bleeding diathesis or coagulopathy;
3. Ongoing sepsis, including active endocarditis
4. Any condition considered a contraindication to extracorporeal assistance;
5. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within six weeks prior treatment
6. Cardiogenic shock manifested by low cardiac output, vasopressor dependence or mechanical hemodynamic support;
7. Recent (within 6 months) cerebrovascular accident (CVA) or transient ischemic attack (TIA)
8. Active gastrointestinal (GI) bleeding within the past 3 months
9. Subject refuses a blood transfusion;
10. Severe dementia (resulting in either inability to provide informed consent for the trial/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits);
11. Multivessel coronary artery disease with a Syntax score >22
12. Estimated life expectancy of less than 24 months due to associated non-cardiac comorbid conditions
13. Other medical, social, or psychological conditions that in the opinion of the investigator precludes the subject from appropriate consentor adherence to the protocol required follow-up exams;
14. Currently participating in an investigational drug or another device trial (excluding registries)
15. Evidence of an acute myocardial infarction <=30 days before the index procedure
16. Need for emergency surgery for any reason

17. Uncontrolled atrial fibrillation

    Anatomical Exclusion Criteria:

18. Native aortic annulus size <18mm or >30mm per the baseline diagnostic imaging;
19. Mixed aortic valve disease [aortic stenosis and aortic regurgitation with predominant aortic regurgitation (3-4+]
20. Severe mitral or severe tricuspid regurgitation
21. Severe mitral stenosis;
22. Hypertrophic obstructive cardiomyopathy
23. Echocardiographic or Multislice Computed Tomography (MSCT) evidence of intracardiac mass, thrombus or vegetation
24. Anatomy of the aortic root and ascending aorta not suitable for TAVI with Evolut R or Evolut Pro system (aortic root angulation >70 degrees for femoral and left subclavian access or >30 degrees for right subclavian access)
25. Congenital bicuspid or unicuspid valve verified by echocardiography Vascular Exclusion Criteria
26. Transarterial access not able to accommodate an 16 French sheath

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device success (VARC-2 criteria)	Absence of procedural mortality; Correct positioning of the prosthetic heart valve into the proper anatomical location; Intended performance of the prosthetic heart valve (mean aortic valve gradient<20mmHg or peak velocity < 3m/s, and no moderate or severe prosthetic valve regurgitation) as assessed with 24h post implantation and pre-discharge echocardiogram	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of All-cause mortality	Early Safety	30 days
Rate of All stroke (disabling and non-disabling)	Early Safety	30 days
Rate of Life-threatening bleeding	Early Safety	30 days
Rate of Acute Kidney Injury-Stage 2 or 3 (including renal replacement therapy)	Early Safety	30 days
Rate of Coronary artery obstruction requiring intervention	Early Safety	30 days
Rate of Major vascular complication	Early Safety	30 days
Rate of Valve-related dysfunction requiring repeat procedure (BAV, TAVI or SAVR)	Early Safety	30 days
Rate of New pacemaker implantation	Early Safety	30 days
Rate of All-cause mortality	Clinical Efficacy	after 30 days and up to 2 years
Rate of All stroke (disabling and non-disabling)	Clinical Efficacy	after 30 days and up to 2 years
Rate of Hospitalizations for valve-related symptoms or worsening congestive heart failure NYHA class III or IV	Clinical Efficacy	after 30 days and up to 2 years
Rate of Valve related dysfunction	Mean aortic valve gradient >=20mmHg, Effective orifice area (EOA)<=0.9-1.1cm2, and/or Dimensionless Valve Index (DVI)<0.35 m/s and/or moderate or severe prosthetic valve regurgitation	after 30 days and up to 2 years

Collaborators and Investigators

• Sponsor: University of Athens
• Investigators: Principal Investigator: Dimitris Tousoulis, Prof, First Department of Cardiology, University of Athens

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): March 30, 2025

Study Registration Dates

• First Submitted: August 10, 2020
• First Submitted That Met QC Criteria: August 17, 2020
• First Posted (Actual): August 19, 2020

Study Record Updates

• Last Update Posted (Actual): August 19, 2020
• Last Update Submitted That Met QC Criteria: August 17, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: aortic stenosis; TAVI; Evolut R; Evolut Pro
• Other Study ID Numbers: 088891/2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No