The ReTAVI Prospective Observational Registry

Aortic Valve Stenosis Clinical Trial

Official title:

Evaluation of Clinical Outcomes of Patients Undergoing a Redo-TAVI Procedure; a Multicenter Prospective Observational Registry

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05601453
• Other study ID #: ReTAVI Registry
• Status: Recruiting
• Start date: September 5, 2023
• Est. completion date: December 2026

Study information

• Verified date: April 2024
• Source: Institut für Pharmakologie und Präventive Medizin
• Contact: Claudia Lüske, PhD
• Phone: 044718503324
• Email: claudia.lueske[@]ippmed.de
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Patients with severe aortic stenosis (sAS) treated with transcatheter aortic valve implantation (TAVI) (increasingly younger & lower risk pts) are experiencing SVD of the index THV and thus developing an indication for a redo-TAVI procedure.

The evidence on redo-TAVI (where a transcatheter heart valve [THV] is implanted into another THV) is limited, with initial data showing acceptable safety as well efficacy in highly selected and limited populations.

Aim is to evaluate short- and long-term data on patients undergoing transcatheter redo-TAVI procedures with THVs for failure of a previously implanted THV and to determine VARC-3 defined efficacy and safety at 30 days and functional outcome at 1 year.

Description:

Between 1.4 and 2.8% of all patients undergoing transcatheter heart valve (THV) implantation require a second THV implanted into the previously implanted THV because of clinically significant aortic regurgitation [1-3]. 90% of THV-in-THV implants were considered successful although the mortality in the redo-TAVI group was higher at similar STS risks as in those with a successful first implant.

Redo-TAVI may also be a promising treatment strategy in degenerated THVs, but there is insufficient knowledge which strategy and valve design may result in the best outcomes [4]. Evidence so far reported is based on case reports and small case series, but not on a prospective, multicenter documentation.

Currently, ~ 5% of THV are implanted in degenerated surgical bioprosthetic valves. With the expanded use of THV for treatment of lower risk patients with severe aortic stenosis (sAS), it is estimated that the number of patients requiring re-treatment for THV failure is likely to rise within the next years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 2026
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Consecutive patients fulfilling the following criteria:

1. Consenting adult patient (=18 years)

2. Procedural success of the first TAVI

3. TAVI device failure of the index THV, irrespective of SVD severity

4. Intention to treat the patient with a redo-TAVI procedure (SAPIEN family THV)

5. The Local Heart Team and the Case Review Board consider the patient suitable and indicated for elective redo-TAVI

6. Patient is scheduled to undergo a 30 Day and 12 Months follow-up (both visits taking place in the hospital)

Exclusion Criteria:

1. Patients without signed informed consent / data protection statement (according to requirements of local IRB/IEC)

2. Life expectancy below 12 months

3. Patients with largely incomplete data with respect to the aims of the project

4. Pregnant women at the time of the redo-TAVI

Note: For all patients included a defined core data set will be collected prospectively. All patients being in accordance with above stated inclusion and exclusion criteria and receiving a balloon-expandable transcatheter aortic valve will be included in the extended documentation.

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Structural Valve Degeneration

Intervention

Procedure:
• Elective redo transcatheter aortic valve implantation (redo-TAVI)
Elective redo-TAVI procedure with the intention to treat the patient with a SAPIEN family valve implantation (currently the only registered medical devices for redo-TAVI use)

Locations

Country	Name	City	State
Austria	LKH-University Hospital and Medical University of Graz	Graz
Austria	Kepler University Clinic Linz	Linz
Austria	University Hospital St. Pölten	St. Pölten
Austria	Medical University of Vienna	Vienna
Canada	Trillium Health Partners Mississauga Hospital	Mississauga
Canada	McGill University Health Centre	Montréal
Canada	Institut Universitaire de Cardiologie et de Pneumologie	Québec
Canada	Toronto General Hospital	Toronto
Canada	St. Paul's Hospital, Vancouver	Vancouver
France	Centre Hospitalier Universitaire de Bordeaux	Bordeaux
France	Centre Hospitalier Universitaire de Clermont-Ferrand	Clermont-Ferrand
France	Centre Hospitalier Universitaire de Lille	Lille
France	Hospices Civils de Lyon	Lyon
France	Hôpitaux Universitaires de Marseille Timone	Marseille
France	Jacques Cartier Private Hospital, Massy	Massy
France	Centre Hospitalier Universitaire de Nantes	Nantes
France	Hôpital Bichat-Claude-Bernard	Paris
France	Hôpital Européen Georges-Pompidou	Paris
France	Centre hospitalier universitaire de Rennes	Rennes
France	Centre Hospitalier Universitaire de Rouen	Roubaix
France	Clinique de la Porte de Paris (CCN)	Saint-Denis
France	Centre Hospitalier Universitaire de Toulouse	Toulouse
Germany	University Heart Center Freiburg Bad Krozingen	Bad Krozingen
Germany	Heart and Diabetes Center North Rhine-Westphalia	Bad Oeynhausen
Germany	German Heart Center of Charité Berlin	Berlin
Germany	BG University Hospital Bergmannsheil gGmbH	Bochum
Germany	University Hospital of Duesseldorf	Duesseldorf
Germany	Elisabeth Hospital, Essen	Essen
Germany	MHH Hannover Medical School	Hannover
Germany	German Heart Centre Munich	Munich
Germany	Robert-Bosch-Hospital, Stuttgart	Stuttgart
Germany	University Hospital Ulm	Ulm
Israel	Tel Aviv Medical Center	Tel Aviv
Italy	AOU Ospedali Riuniti Ancona, Umberto I, G. M. Lancisi, G. Salesi	Ancona
Italy	IRCCS Azienda Ospedaliero Universitaria di Bologna	Bologna
Italy	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia	Brescia
Italy	Careggi Hospital	Florence
Italy	IRCCS Ospedale Galeazzi Sant'Ambrogio	Milan
Italy	Azienda Ospedale-Università Padova (AOUP)	Padua
Italy	Azienda Ospedaliero-Universitaria Pisana	Pisa
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Italy	Policlinici universitari | Sapienza Università di Roma	Roma
Italy	Università degli Studi di Trieste	Trieste
Italy	Ospedale San Bortolo di Vicenza	Vicenza
Netherlands	St. Antonius Ziekenhuis, Nieuwegein	Nieuwegein
Poland	Medical University of Bialystok	Bialystok
Poland	University Clinical Centre of Gdansk	Gdansk
Poland	Medical University of Silesia	Katowice
Poland	University Hospital of Kraków	Kraków
Poland	Institute of Cardiology Warsaw	Warsaw
Poland	Medical University of Warsaw	Warsaw
Poland	Wroclaw Medical University	Wroclaw
Portugal	Hospital de Santa Cruz, Carnaxide-Lisabon	Carnaxide
Portugal	Centro Hospitalar Vila Nova de Gaia / Espinho	Vila Nova De Gaia
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital University Germans Trias i Pujol	Barcelona
Spain	Hospital Universitario de León	León
Spain	Hospital Clinico Universitario San Carlos	Madrid
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Hospital Álvaro Cunqueiro, Vigo	Vigo
Switzerland	University Hospital of Basel	Basel
Switzerland	Hôpitaux universitaires de Genève	Geneva
Switzerland	Centre hospitalier universitaire vaudois et Université de Lausanne	Lausanne
United Kingdom	Royal Papworth Hospital, Cambridge	Cambridge
United Kingdom	Harefield Hospital	Harefield

Sponsors (2)

Lead Sponsor	Collaborator
Institut für Pharmakologie und Präventive Medizin	Edwards Lifesciences

Countries where clinical trial is conducted

Austria,  Canada,  France,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Portugal,  Spain,  Switzerland,  United Kingdom, 

References & Publications (9)

Deeb GM, Chetcuti SJ, Reardon MJ, Patel HJ, Grossman PM, Schreiber T, Forrest JK, Bajwa TK, O'Hair DP, Petrossian G, Robinson N, Katz S, Hartman A, Dauerman HL, Schmoker J, Khabbaz K, Watson DR, Yakubov SJ, Oh JK, Li S, Kleiman NS, Adams DH, Popma JJ. 1-Year Results in Patients Undergoing Transcatheter Aortic Valve Replacement With Failed Surgical Bioprostheses. JACC Cardiovasc Interv. 2017 May 22;10(10):1034-1044. doi: 10.1016/j.jcin.2017.03.018. — View Citation

Kamioka N, Caughron H, Corrigan F, Block P, Babaliaros V. Supra-annular valve strategy for an early degenerated transcatheter balloon-expandable heart valve. Catheter Cardiovasc Interv. 2018 Dec 1;92(7):1458-1460. doi: 10.1002/ccd.27506. Epub 2018 Jan 23. — View Citation

Kopp-Schneider A, Wiesenfarth M, Witt R, Edelmann D, Witt O, Abel U. Monitoring futility and efficacy in phase II trials with Bayesian posterior distributions-A calibration approach. Biom J. 2019 May;61(3):488-502. doi: 10.1002/bimj.201700209. Epub 2018 Sep 2. — View Citation

Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Brown DL, Block PC, Guyton RA, Pichard AD, Bavaria JE, Herrmann HC, Douglas PS, Petersen JL, Akin JJ, Anderson WN, Wang D, Pocock S; PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010 Oct 21;363(17):1597-607. doi: 10.1056/NEJMoa1008232. Epub 2010 Sep 22. — View Citation

Smith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Williams M, Dewey T, Kapadia S, Babaliaros V, Thourani VH, Corso P, Pichard AD, Bavaria JE, Herrmann HC, Akin JJ, Anderson WN, Wang D, Pocock SJ; PARTNER Trial Investigators. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011 Jun 9;364(23):2187-98. doi: 10.1056/NEJMoa1103510. Epub 2011 Jun 5. — View Citation

Tarantini G, Delgado V, de Backer O, Sathananthan J, Treede H, Saia F, Blackman D, Parma R. Redo-Transcatheter Aortic Valve Implantation Using the SAPIEN 3/Ultra Transcatheter Heart Valves-Expert Consensus on Procedural Planning and Techniques. Am J Cardiol. 2023 Apr 1;192:228-244. doi: 10.1016/j.amjcard.2023.01.010. Epub 2023 Jan 27. — View Citation

Toggweiler S, Wood DA, Rodes-Cabau J, Kapadia S, Willson AB, Ye J, Cheung A, Leipsic J, Binder RK, Gurvitch R, Freeman M, Thompson CR, Svensson LG, Dumont E, Tuzcu EM, Webb JG. Transcatheter valve-in-valve implantation for failed balloon-expandable transcatheter aortic valves. JACC Cardiovasc Interv. 2012 May;5(5):571-577. doi: 10.1016/j.jcin.2012.03.008. — View Citation

VARC-3 WRITING COMMITTEE; Genereux P, Piazza N, Alu MC, Nazif T, Hahn RT, Pibarot P, Bax JJ, Leipsic JA, Blanke P, Blackstone EH, Finn MT, Kapadia S, Linke A, Mack MJ, Makkar R, Mehran R, Popma JJ, Reardon M, Rodes-Cabau J, Van Mieghem NM, Webb JG, Cohen DJ, Leon MB. Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research. Eur Heart J. 2021 May 14;42(19):1825-1857. doi: 10.1093/eurheartj/ehaa799. — View Citation

Webb JG, Mack MJ, White JM, Dvir D, Blanke P, Herrmann HC, Leipsic J, Kodali SK, Makkar R, Miller DC, Pibarot P, Pichard A, Satler LF, Svensson L, Alu MC, Suri RM, Leon MB. Transcatheter Aortic Valve Implantation Within Degenerated Aortic Surgical Bioprostheses: PARTNER 2 Valve-in-Valve Registry. J Am Coll Cardiol. 2017 May 9;69(18):2253-2262. doi: 10.1016/j.jacc.2017.02.057. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Compliance with recommendation	It will be assessed and percentages determined whether participatin centers follow the published recommendation (itemized, compliance being voluntary).	12 months
Other	Impact of alterations to published recommendations	The impact of potential alterations to the protocol on the procedural outcomes will be elucidated and descriptively described.	12 months
Other	Discretionary longer-term follow-up	Discretionary longer-term follow-up in terms of durability of the second aortic THV: Subclinical transcatheter heart valve thrombosis; Clinically symptomatic transcatheter heart valve thrombosis; All-cause mortality, stroke, and cardiovascular hospitalization; Stage II or III structural valve degeneration according to VARC 3 definitions; For the definition of transcatheter cardiac valve thrombosis, please refer to Outcome 5.; Number and percentage of subjects with above specified criteria with up to 5 years follow-up, along with individual component of the success, will be presented.	up to 5 years
Other	Exploratory objectives	Further, not predefined research questions will be explored based on the dataset such as: Hemodynamic outcome of the intervention; Applicability of VARC-3 criteria for the redo-TAVI situation; Coronary artery obstruction due to valve implantation; Coronary artery cannulation (in particular in case of risk plane above ostia); Early and late THV failure predictors (after TAVI and redo-TAVI procedures); CT findings related to THV failure (SVD)	12 months
Primary	Efficacy: VARC-3 defined device success at 30 days	Determine VARC-3 defined device success at 30 days; Technical success; Freedom from mortality; Freedom from surgery or intervention related to the device or 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); (Different definitions, in addition to the predefined such as the consideration of higher gradients than 20 mmHg, will be explored); These events will be adjudicated. Number and percentage of subjects with device success at 30 days as per VARC-3 definition, along with individual component of the success, will be presented.	30 days
Primary	Technical success: Technical success (at exit from procedure room)	Technical success at exit from procedure room defined as: 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 (excluding pacemaker) or to a major vascular or access-related, or cardiac structural complication; Number and percentage of subjects with technical success at exit from procedure room, along with individual component of the success, will be presented.	end of intervention
Primary	Safety: VARC-3 defined early safety at 30 days	Determine VARC-3 defined early safety at 30 days: Freedom from all-cause mortality; Freedom from all Stroke; Freedom from all VARC type 2-4 bleeding; Freedom from all major vascular, access-related, or cardiac structural complication; Freedom from all acute kidney injury stage III/IV; Freedom from all moderate/severe aortic regurgitation; Freedom from all new permanent pacemaker implantations due to procedure-related conduction abnormalities; Freedom from all surgery/intervention related to the device; These events will be adjudicated. Number and percentage of subjects with early safety at 30 days as per VARC-3 definition, along with individual component of the success, will be presented.	30 days
Primary	Procedural Outcomes (30 days)	Procedural outcomes at 30 days, defined as: Clinical and anatomical predictors of technical success (type of SVD [stenosis vs. regurgitation], valve size, implant depth, redo-TAVI balloon dilation, CT and echo-derived variables, etc.); Rate of central and paravalvular regurgitation; Valve performance, including residual mean gradient; Risk and predictors of coronary obstruction; Number and percentage of subjects with above specified outcomes at 30 days , along with individual component of the success, will be presented.	30 days
Primary	Durability of the second aortic THV (30 days)	Determine the durability of the second aortic THV: Subclinical transcatheter heart valve thrombosis at thirty days (when it becomes apparent, but no systematic screening); Endocarditis; Definition of transcatheter heart valve thrombosis Clinical sequelae of a thromboembolic event (e.g. stroke, TIA, retinal occlusion, other evidence of systemic thromboembolism) or worsening valve stenosis/ regurgitation (e.g. signs of heart failure, syncope) and; Haemodynamic valve deterioration Stage 2 or 3 or; Confirmatory imaging (CT evidence of HALT† or TEE findings) In the absence of clinical sequelae, both; Haemodynamic valve deterioration Stage 3 and; Confirmatory imaging (CT evidence of HALT or TEE findings); Number and percentage of subjects with above specified criteria at 3 months, along with individual component of the success, will be presented.	30 days
Primary	Durability of the second aortic THV (3 months)	Determine the durability of the second aortic THV: Subclinical transcatheter heart valve thrombosis at three months (if data obtained, when it becomes apparent, but no systematic screening); Clinical transcatheter heart valve thrombosis at three months (if data obtained); Endocarditis; For the definition of transcatheter cardiac valve thrombosis, please refer to Outcome 5.; Number and percentage of subjects with above specified criteria at 3 months, along with individual component of the success, will be presented.	3 months
Primary	Durability of the second aortic THV (12 months)	Determine the durability of the second aortic THV: Subclinical transcatheter heart valve thrombosis at twelve months (when it becomes apparent, but no systematic screening); Clinical transcatheter heart valve thrombosis at twelve months; All-cause mortality, stroke, myocardial infarction, and cardiovascular hospitalization at twelve months; Stage II or III structural valve degeneration according to VARC 3 definitions at twelve months (stage I may be documented); Endocarditis; For the definition of transcatheter cardiac valve thrombosis, please refer to Outcome 5. Number and percentage of subjects with above specified criteria at 12 months , along with individual component of the success, will be presented.	12 months