ACURATE NEO/TF Transcatheter Heart Valves and Non-inferiority Versus Medtronic CoreValve Systems

Overview

A Multicenter, prospective, non-randomized, non-inferiority trial evaluating the safety and clinical efficacy of the next-generation, self-expandable Boston Scientific ACURATE NEO/TF Transcatheter Heart Valves, implanted in patients with severe aortic stenosis. A comparison with the Medtronic EVOLUT R/EVOLUT PRO systems from DIRECT trial.

Full Title of Study: “Evaluation of Safety and Clinical Efficacy of Boston Scientific ACURATE NEO/TF Transcatheter Heart Valves and Comparison With Medtronic EVOLUT R/ PRO Systems in All Comers Undergoing TAVR”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: March 20, 2021

Detailed Description

The aim of this study is to evaluate the 30 day clinical and echo outcomes of Boston Scientific ACURATE NEO/TF TAVR and to compare them with outcomes in patients from the DIRECT trial treated with the Evolut TAVR system (Evolut R and Evolut PRO), aiming in showing non-inferiority of the ACURATE NEO/TF device. Primary endpoint will be device success rate as defined by the VARC-2 criteria. Secondary endpoints involve the composite endpoint of early safety at 30 days, according to the VARC-2 definitions, specifically all cause mortality, cardiovascular mortality, stroke-TIA, acute kidney injury, conduction disturbances-arrhythmias, life-threatening or disabling bleeding, myocardial infarction, major vascular complication, valve related dysfunction requiring repeat procedure (BAV,TAVR,SAVR) as well as the echocardiographic outcomes and valve performance as designated by the VARC-2 definitions at 30 days.

Study type: Observational, non-inferiority trial

Estimated Enrollment: 80 patients

Allocation: Non – randomized, all comers

Primary Purpose: Treatment

Observational Model: Case-Control

Condition or disease: Aortic valve stenosis

Intervention/Treatment: Device: Boston Scientific ACURATE neoTM transfemoral TAVI system

Time Perspective: Prospective

Participating centers: Henry Dunant Hospital (Athens, Greece), Hippokration Hospital (Athens, Greece), Silesian Center for Heart Diseases (Zabrze, Poland), Athens Naval Hospital (Athens, Greece). It is possible that the number of the participating center may change.

Methods: Based on an anticipated incidence proportion of 90% for the primary composite endpoint of device success at 30 days, the total required sample size amounts to 80 patients. Patients treated with the Boston Scientific ACURATE NEO/TF system will be prospectively. All patients will be followed for at least 30 days. Event rates will be presented by Kaplan-Meier curves. On the basis of previous observations regarding TAVR success rate by VARC 2 definitions (DIRECT study), the study design uses a predefined non-inferiority margin of Δ = 15% for the primary endpoint of device success rate at 30 days. The primary hypothesis is non-inferiority of ACURATE NEO/TF TAVR versus Evolut R and Evolut-Pro TAVR (based on the results of the DIRECT trial) for the primary endpoint at 30 days. The non-inferiority assumption will be tested at a one-sided significance level with a type I error rate (a=0.05). Non-inferiority will be met if the lower bound of the one-sided 95% confidence interval (CI) of the primary weighted difference of proportions endpoint (weighted average test-control) is over -15%. Pre-specified subgroup analyses will be conducted by using the appropriate interaction tests contrasting categories of mean gradient, aortic valve area (AVA) and left ventricular ejection fraction (>50% vs 50%).

Interventions

  • Device: Transcatheter Aortic Valve Implantation with ACURATE NEO/TF
    • Transcatheter implantation of the heart valve device ACURATE NEO/TF in patients suffering from severe aortic stenosis and are candidates for this operation
  • Device: Transcatheter Aortic Valve Implantation with Medtronic Evolut R/Pro
    • Transcatheter implantation of the heart valve device Medtronic Evolut R/Pro in patients suffering from severe aortic stenosis and are candidates for this operation

Arms, Groups and Cohorts

  • Other: Patients treated with Medtronic Evolut R/Pro
    • TAVI patients treated with Medtronic Evolut R – Evolut PRO Transcatheter Heart Valves, participated in the DIRECT trial
  • Active Comparator: Patients treated with Acurate NEO/TF
    • TAVI patients treated with Symetis Acurate NEO/TF Transcatheter Heart Valve recruited prospectively.

Clinical Trial Outcome Measures

Primary Measures

  • Device success
    • Time Frame: 30 days
    • ACURATE NEO/TF device implantation success rates, as designated by the VARC-2 criteria

Secondary Measures

  • All cause Mortality
    • Time Frame: 30 days
    • Death teates during the hospitalization of the patient, as designated by the VARC-2 criteria
  • All stroke
    • Time Frame: 30 days
    • Cerebrovascular accident rates during and after the hospitalization of the patient, as designated by the VARC-2 criteria
  • New pacemaker implantation
    • Time Frame: 30 days
    • New pacemaker implantation rates during and after the hospitalization of the patient, as designated by the VARC-2 criteria
  • Vascular complications
    • Time Frame: 30 days
    • Vascular complications rates during and after the hospitalization of the patient, as designated by the VARC-2 criteria
  • Μyocardial infarction
    • Time Frame: 30 days
    • Μyocardial infarction rates during and after the hospitalization of the patient. Valve related dysfunction requiring repeat procedure rates
  • Valve related dysfunction
    • Time Frame: 30 days
    • Valve related dysfunction rates requiring repeat procedure rates (BAV, TAVI or SAVR
  • Echocardiographic endpoint
    • Time Frame: 30 days
    • Echocardiographic endpoint (4) [Time Frame: Post-procedurally]. Intended valve performance: No prosthesis mismatch, mean aortic valve gradient <20 mmHg or peak velocity <3 m/s, without moderate or severe prosthetic valve aortic regurgitation.
  • Post-dilatation
    • Time Frame: 30 days
    • Post-dilatation rates

Participating in This Clinical Trial

Inclusion Criteria

  • Patient with severe symptomatic aortic stenosis defined by a mean aortic gradient > 40 mmHg or peak jet velocity > 4.0 m/s or an aortic valve area (AVA) < 1cm2 or AVA indexed to body surface area (BSA) of <0.6 cm2/m2
  • Patient is symptomatic (heart failure with New York Heart Association (NYHA) Functional Class > I, angina or syncope)
  • Patients are considered at high risk for mortality with conventional surgical aortic valve replacement as assessed by a Heart Team consisting of a cardiologist and surgeon or as confirmed by a logistic EuroSCORE I > 20% and / or STS score > 8% OR
  • Over 80 years old OR
  • Over 65 years old with 1 or 2 (but not more than two) from the following criteria:

Liver cirrhosis (Class A or B). Pulmonary insufficiency: VMS<1 liter. Previous heart surgery (CABG, vascular surgery). Porcelain aorta. Pulmonary artery systolic pressure >60 mmHg and high risk for heart surgery. Relapsing pulmonary embolism. Right ventricular insufficiency. Thoracic wall injuries that contraindicate an open heart surgery. History of radiation therapy of the mediastinum. Connective tissue disease that contraindicates an open heart surgery. Frailty/cachexia.

  • Aortic valve diameter of ≥20mm and ≤2 9mm as measured by echo.
  • Ascending aorta diameter ≤ 43 mm at the sinotubular junction.
  • Arterial aorto-iliac-femoral axis suitable for transfemoral access as assessed by conventional angiography and/or multi-detector computed tomographic angiography (access vessel diameter ≥ 6mm)
  • Patient understands the purpose, the potential risks as well as benefits of the trial and is willing to participate in all parts of the follow-up
  • Patient has given written consent to participate in the trial

Exclusion Criteria

  • A known hypersensitivity or contraindication to any of the following which cannot be adequately pre-medicated: aspirin or heparin and bivalirudin, ticlodipine and clopidogrel, nitinol (titanium or nickel), contrast media
  • Ongoing sepsis, including active endocarditis.
  • Any percutaneous coronary or peripheral interventional procedure with a bare metal or drug eluting stent performed within 30 days prior to Heart Team assessment.
  • Echocardiographic evidence of LV or LA thrombus.
  • Mitral or tricuspid valve insufficiency (> grade II).
  • Previous aortic valve replacement (mechanical or bioprosthetic).
  • Recent (within 6 months of Heart Team assessment) cerebrovascular accident (CVA) or transient ischemic attack (TIA).
  • Patients with:

Femoral, iliac or aortic vascular disease (stenosis etc) that precludes the insertion of a transcatheter sheath.

OR Symptomatic carotid or vertebral artery disease (> 70% stenosis).

  • The patient has a bleeding diathesis, coagulopathy or denies blood transfusion.
  • Estimated life expectancy of less than 12 months due to associated non-cardiac co-morbid conditions.
  • Creatinine clearance < 20 ml/min.
  • Active gastritis or gastrointestinal ulcer.
  • Pregnancy.
  • Severe left ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20%.
  • Unicuspid or bicuspid aortic valve.
  • Mixed aortic valve disease (aortic stenosis and aortic regurgitation> 2+).
  • Liver failure (Child-Pugh class C).
  • Severe dementia (resulting in either inability to provide informed consent for the study/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits).
  • Extreme aortic valve calcification and calcific asymmetry (if semiquantively measured: grade 4, Agatston score: grade 4 AgS>5000 AU).
  • Aortic valve area of < 0.4 cm2.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • National and Kapodistrian University of Athens
  • Collaborator
    • Naval Hospital, Athens
  • Provider of Information About this Clinical Study
    • Principal Investigator: Konstantinos Toutouzas, Professor – National and Kapodistrian University of Athens
  • Overall Official(s)
    • Konstantinos P Toutouzas, Professor, Study Director, Professor of Cardiology
  • Overall Contact(s)
    • Leonidas A Koliastasis, 6974270752, lkoliastasis@gmail.com

References

Arora S, Strassle PD, Ramm CJ, Rhodes JA, Vaidya SR, Caranasos TG, Vavalle JP. Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Lower Surgical Risk Scores: A Systematic Review and Meta-Analysis of Early Outcomes. Heart Lung Circ. 2017 Aug;26(8):840-845. doi: 10.1016/j.hlc.2016.12.003. Epub 2017 Jan 24. Review.

Adams HSL, Ashokkumar S, Newcomb A, MacIsaac AI, Whitbourn RJ, Palmer S. Contemporary review of severe aortic stenosis. Intern Med J. 2019 Mar;49(3):297-305. doi: 10.1111/imj.14071. Review.

Saikrishnan N, Kumar G, Sawaya FJ, Lerakis S, Yoganathan AP. Accurate assessment of aortic stenosis: a review of diagnostic modalities and hemodynamics. Circulation. 2014 Jan 14;129(2):244-53. doi: 10.1161/CIRCULATIONAHA.113.002310. Review. Erratum in: Circulation. 2014 Oct 7;130(15):e136.

4. Piérard L. Transcatheter aortic valve implantation: indications. E-Journal of Cardiology Practice [Internet]. 2016 5 May 2019 [cited 2019 5 May 2019]; Volume 14 Available from: https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-14/transcatheter-aortic-valve-implantation-indications

Möllmann H, Diemert P, Grube E, Baldus S, Kempfert J, Abizaid A. Symetis ACURATE TF™ aortic bioprosthesis. EuroIntervention. 2013 Sep 10;9 Suppl:S107-10. doi: 10.4244/EIJV9SSA22.

Manoharan G, Walton AS, Brecker SJ, Pasupati S, Blackman DJ, Qiao H, Meredith IT. Treatment of Symptomatic Severe Aortic Stenosis With a Novel Resheathable Supra-Annular Self-Expanding Transcatheter Aortic Valve System. JACC Cardiovasc Interv. 2015 Aug 24;8(10):1359-67. doi: 10.1016/j.jcin.2015.05.015.

Forrest JK, Mangi AA, Popma JJ, Khabbaz K, Reardon MJ, Kleiman NS, Yakubov SJ, Watson D, Kodali S, George I, Tadros P, Zorn GL 3rd, Brown J, Kipperman R, Saul S, Qiao H, Oh JK, Williams MR. Early Outcomes With the Evolut PRO Repositionable Self-Expanding Transcatheter Aortic Valve With Pericardial Wrap. JACC Cardiovasc Interv. 2018 Jan 22;11(2):160-168. doi: 10.1016/j.jcin.2017.10.014.

Toutouzas K, Benetos G, Voudris V, Drakopoulou M, Stathogiannis K, Latsios G, Synetos A, Antonopoulos A, Kosmas E, Iakovou I, Katsimagklis G, Mastrokostopoulos A, Moraitis S, Zeniou V, Danenberg H, Vavuranakis M, Tousoulis D. Pre-Dilatation Versus No Pre-Dilatation for Implantation of a Self-Expanding Valve in All Comers Undergoing TAVR: The DIRECT Trial. JACC Cardiovasc Interv. 2019 Apr 22;12(8):767-777. doi: 10.1016/j.jcin.2019.02.005. Epub 2019 Mar 27.

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