Impact of Predilatation Between Self-expanding Valves (DIRECTII)

Impact of Balloon Predilatation Between Self-expanding Valves in All Comers Undergoing TAVI

A Multicenter, prospective, non-randomized, 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 and the impact of predilatation in comparison with the Medtronic CoreValve EvolutT R/PRO systems from the DIRECT trial.

Study Overview

• Status: Completed
• Conditions: Aortic Stenosis
• Intervention / Treatment: Device: Transcatheter Aortic Valve Implantation with Medtronic CoreValve /Evolut R/Pro; Device: Transcatheter Aortic Valve Implantation with ACURATE NEO/TF

Detailed Description

The aim of the present prospective, multicenter, non-randomized trial is to compare the device success rate and the in-hospital and 30-day safety and echocardiographic clinical outcomes between TAVI with and without predilatation in all comers undergoing implantation of self-expanding valves. 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, acute kidney injury, life-threatening or disabling bleeding, major vascular complication, as well as the echocardiographic outcomes and valve performance as designated by the VARC-2 definitions at 30 days. VARC-1 and VARC-3 device success rates will be estimated as well.

Study type: Observational

Estimated Enrollment: 75 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: 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: Patients treated with the Boston Scientific ACURATE NEO/TF system will be prospectively. All patients will be followed for at least 30 days.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 11527
    • Hippocration Hospital First Department of Cardiology, University of Athens, Medical School

Participation Criteria

Eligibility Criteria

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

Description

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 EuroSCORE II ≥ 7% 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 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 (Agatston score: grade 4 AgS>5000 AU).
• Aortic valve area of < 0.4 cm2.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients treated with Medtronic CoreValve/ Evolut R/Pro; TAVI patients treated with Medtronic CoreValve /Evolut R - Evolut PRO Transcatheter Heart Valves, participated in the DIRECT trial	Device: Transcatheter Aortic Valve Implantation with Medtronic CoreValve /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; Other Names: Medtronic CoreValve /Evolut R/Pro
Active Comparator: Patients treated with ACURATE neo/TF; TAVI patients treated with ACURATE neo/TF Transcatheter Heart Valve recruited prospectively.	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; Other Names: Boston Scientific ACURATE neo/TF

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause Mortality	Death teates during the hospitalization of the patient, as designated by the VARC-2 criteria	30 days
All stroke	Cerebrovascular accident rates during and after the hospitalization of the patient, as designated by the VARC-2 criteria	30 days
New pacemaker implantation	New pacemaker implantation rates during and after the hospitalization of the patient, as designated by the VARC-2 criteria	30 days
Major Vascular complications	Vascular complications rates during and after the hospitalization of the patient, as designated by the VARC-2 criteria	30 days
Echocardiographic endpoint	Echocardiographic endpoint (Post TAVI aortic valve area in cm2)	30 days
Post-dilatation	Post-dilatation rates	30 days
Major Bleeding	Major bleeding during and after the hospitalization of the patient, as designated by the VARC-2 criteria	30 days
Acute kidney injury stage 2 or 3	AKI stage 2 or 3 during and after the hospitalization of the patient, as designated by the VARC-2 criteria	30 days
Device success	ACURATE NEO/TF device implantation success rates, as designated by the VARC-1 and VARC-3 criteria	30 days

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens
• Collaborators: University General Hospital of Heraklion; Naval Hospital, Athens; Silesian Centre for Heart Diseases; Interbalkan Medical Center, Thessaloniki, Greece
• Investigators: Study Director: Konstantinos P Toutouzas, Professor, Professor of Cardiology

Publications and helpful links

General Publications

• 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.
• 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.
• 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. No abstract available. 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
• Mollmann 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. No abstract available.
• 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):1359-1367. 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.
• Pagnesi M, Kim WK, Conradi L, Barbanti M, Stefanini GG, Zeus T, Pilgrim T, Schofer J, Zweiker D, Testa L, Taramasso M, Hildick-Smith D, Abizaid A, Wolf A, Van Mieghem NM, Sedaghat A, Wohrle J, Khogali S, Van der Heyden JAS, Webb JG, Estevez-Loureiro R, Mylotte D, MacCarthy P, Brugaletta S, Hamm CW, Bhadra OD, Schafer U, Costa G, Tamburino C, Cannata F, Reimers B, Veulemans V, Asami M, Windecker S, Eitan A, Schmidt A, Bianchi G, Bedogni F, Saccocci M, Maisano F, Alsanjari O, Siqueira D, Jensen CJ, Naber CK, Ziviello F, Sinning JM, Seeger J, Rottbauer W, Brouwer J, Alenezi A, Wood DA, Tzalamouras V, Regueiro A, Colombo A, Latib A. Transcatheter Aortic Valve Replacement With Next-Generation Self-Expanding Devices: A Multicenter, Retrospective, Propensity-Matched Comparison of Evolut PRO Versus Acurate neo Transcatheter Heart Valves. JACC Cardiovasc Interv. 2019 Mar 11;12(5):433-443. doi: 10.1016/j.jcin.2018.11.036.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2019
• Primary Completion (Actual): April 1, 2021
• Study Completion (Actual): July 20, 2022

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: November 6, 2019
• First Posted (Actual): November 8, 2019

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: valve; TAVI; Aortic stenosis; TAVR; DIRECT; ACURATE; transcatheter
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: DIRECT II

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No