Top

Published in:

Open Access 01-12-2013 | Study protocol

The Nordic Aortic Valve Intervention (NOTION) trial comparing transcatheter versus surgical valve implantation: study protocol for a randomised controlled trial

Authors: Hans Gustav Thyregod, Lars Søndergaard, Nikolaj Ihlemann, Olaf Franzen, Lars Willy Andersen, Peter Bo Hansen, Peter Skov Olsen, Henrik Nissen, Per Winkel, Christian Gluud, Daniel Andreas Steinbrüchel

Published in: Trials | Issue 1/2013

Abstract

Background

Degenerative aortic valve (AV) stenosis is the most prevalent heart valve disease in the western world. Surgical aortic valve replacement (SAVR) has until recently been the standard of treatment for patients with severe AV stenosis. Whether transcatheter aortic valve implantation (TAVI) can be offered with improved safety and similar effectiveness in a population including low-risk patients has yet to be examined in a randomised setting.

Methods/Design

This randomised clinical trial will evaluate the benefits and risks of TAVI using the transarterial CoreValve System (Medtronic Inc., Minneapolis, MN, USA) (intervention group) compared with SAVR (control group) in patients with severe degenerative AV stenosis. Randomisation ratio is 1:1, enrolling a total of 280 patients aged 70 years or older without significant coronary artery disease and with a low, moderate, or high surgical risk profile. Trial outcomes include a primary composite outcome of myocardial infarction, stroke, or all-cause mortality within the first year after intervention (expected rates 5% for TAVI, 15% for SAVR). Exploratory safety outcomes include procedure complications, valve re-intervention, and cardiovascular death, as well as cardiac, cerebral, pulmonary, renal, and vascular complications. Exploratory efficacy outcomes include New York Heart Association functional status, quality of life, and valve prosthesis and cardiac performance. Enrolment began in December 2009, and 269 patients have been enrolled up to December 2012.

Discussion

The trial is designed to evaluate the performance of TAVI in comparison with SAVR. The trial results may influence the choice of treatment modality for patients with severe degenerative AV stenosis.

Trial registration

ClinicalTrials.gov: NCT01057173

Available only for authorised users

Iung B, Baron G, Butchart EG, Delahaye F, Gohlke-Bärwolf C, Levang OW, Tornos P, Vanoverschelde JL, Vermeer F, Boersma E, Ravaud P, Vahanian A: A prospective survey of patients with valvular heart disease in Europe: the Euro Heart Survey on Valvular Heart Disease. Eur Heart J. 2003, 24: 1231-1243. 10.1016/S0195-668X(03)00201-X.CrossRefPubMed

Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M: Burden of valvular heart diseases: a population-based study. Lancet. 2006, 368: 1005-1011. 10.1016/S0140-6736(06)69208-8.CrossRefPubMed

Ross J, Braunwald E: Aortic stenosis. Circulation. 1968, 38: 61-67.CrossRefPubMed

Vahanian A, Baumgartner H, Bax J, Butchart E, Dion R, Filippatos G, Flachskampf F, Hall R, Iung B, Kasprzak J, Nataf P, Tornos P, Torracca L, Wenink A, Task Force on the Management of Valvular Hearth Disease of the European Society of Cardiology ESC Committee for Practice Guidelines: Guidelines on the management of valvular heart disease: the task force on the management of valvular heart disease of the European Society of cardiology. Eur Heart J. 2007, 28: 230-268.PubMed

Vahanian A, Iung B: The new ESC/EACTS guidelines on the management of valvular heart disease. Arch Cardiovasc Dis. 2012, 105: 465-467. 10.1016/j.acvd.2012.09.001.CrossRefPubMed

Iung B, Cachier A, Baron G, Messika-Zeitoun D, Delahaye F, Tornos P, Gohlke-Bärwolf C, Boersma E, Ravaud P, Vahanian A: Decision-making in elderly patients with severe aortic stenosis: why are so many denied surgery?. Eur Heart J. 2005, 26: 2714-2720. 10.1093/eurheartj/ehi471.CrossRefPubMed

O'Brien SM, Shahian DM, Filardo G, Ferraris VA, Haan CK, Rich JB, Normand SL, DeLong ER, Shewan CM, Dokholyan RS, Peterson ED, Edwards FH, Anderson RP, Society of Thoracic Surgeons Quality Measurement Task Force: The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 2–isolated valve surgery. Ann Thorac Surg. 2009, 88: S23-S42. 10.1016/j.athoracsur.2009.05.056.CrossRefPubMed

Roques F, Nashef SA, Michel P: Risk factors for early mortality after valve surgery in Europe in the 1990s: lessons from the EuroSCORE pilot program. J Heart Valve Dis. 2001, 10: 572-577. discussion 577–578PubMed

Nashef SA, Roques F, Sharples LD, Nilsson J, Smith C, Goldstone AR, Lockowandt U: EuroSCORE II. Eur J Cardiothorac Surg. 2012, 41: 734-744. 10.1093/ejcts/ezs043. discussion 744–735CrossRefPubMed

10.

Andersen HR, Knudsen LL, Hasenkam JM: Transluminal implantation of artificial heart valves. Description of a new expandable aortic valve and initial results with implantation by catheter technique in closed chest pigs. Eur Heart J. 1992, 13: 704-708.PubMed

11.

Cribier A, Eltchaninoff H, Bash A, Borenstein N, Tron C, Bauer F, Derumeaux G, Anselme F, Laborde F, Leon MB: Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: first human case description. Circulation. 2002, 106: 3006-3008. 10.1161/01.CIR.0000047200.36165.B8.CrossRefPubMed

12.

Cribier A, Eltchaninoff H, Tron C, Bauer F, Agatiello C, Sebagh L, Bash A, Nusimovici D, Litzler PY, Bessou JP, Leon MB: Early experience with percutaneous transcatheter implantation of heart valve prosthesis for the treatment of end-stage inoperable patients with calcific aortic stenosis. J Am Coll Cardiol. 2004, 43: 698-703. 10.1016/j.jacc.2003.11.026.CrossRefPubMed

13.

Grube E, Laborde JC, Gerckens U, Felderhoff T, Sauren B, Buellesfeld L, Mueller R, Menichelli M, Schmidt T, Zickmann B, Iversen S, Stone GW: Percutaneous implantation of the CoreValve self-expanding valve prosthesis in high-risk patients with aortic valve disease: the Siegburg first-in-man study. Circulation. 2006, 114: 1616-1624. 10.1161/CIRCULATIONAHA.106.639450.CrossRefPubMed

14.

Kahlert P, Knipp SC, Schlamann M, Thielmann M, Al-Rashid F, Weber M, Johansson U, Wendt D, Jakob HG, Forsting M, Sack S, Erbel R, Eggebrecht H: Silent and apparent cerebral ischemia after percutaneous transfemoral aortic valve implantation: a diffusion-weighted magnetic resonance imaging study. Circulation. 2010, 121: 870-878. 10.1161/CIRCULATIONAHA.109.855866.CrossRefPubMed

15.

Gilard M, Eltchaninoff H, Iung B, Donzeau-Gouge P, Chevreul K, Fajadet J, Leprince P, Leguerrier A, Lievre M, Prat A, Teiger E, Lefevre T, Himbert D, Tchetche D, Carrié D, Albat B, Cribier A, Rioufol G, Sudre A, Blanchard D, Collet F, Dos Santos P, Meneveau N, Tirouvanziam A, Caussin C, Guyon P, Boschat J, Le Breton H, Collart F, Houel R: Registry of transcatheter aortic-valve implantation in high-risk patients. N Engl J Med. 2012, 366: 1705-1715. 10.1056/NEJMoa1114705.CrossRefPubMed

16.

Webb J, Cribier A: Percutaneous transarterial aortic valve implantation: what do we know?. Eur Heart J. 2011, 32: 140-147. 10.1093/eurheartj/ehq453.CrossRefPubMed

17.

Tzikas A, van Dalen BM, Van Mieghem NM, Gutierrez-Chico JL, Nuis RJ, Kauer F, Schultz C, Serruys PW, de Jaegere PP, Geleijnse ML: Frequency of conduction abnormalities after transcatheter aortic valve implantation with the Medtronic-CoreValve and the effect on left ventricular ejection fraction. Am J Cardiol. 2011, 107: 285-289. 10.1016/j.amjcard.2010.09.015.CrossRefPubMed

18.

Olsen LK, Engstrøm T, Wachtell K, Kristensen T, Hassager C, Ihlemann N, Møller JE, Andersen LW, Olsen PS, Søndergaard L: Percutaneous aortic valve replacement – initial experience and results. Ugeskr Laeger. 2009, 171: 1289-1293.PubMed

19.

Moat NE, Ludman P, de Belder MA, Bridgewater B, Cunningham AD, Young CP, Thomas M, Kovac J, Spyt T, MacCarthy PA, Wendler O, Hildick-Smith D, Davies SW, Trivedi U, Blackman DJ, Levy RD, Brecker SJ, Baumbach A, Daniel T, Gray H, Mullen MJ: Long-term outcomes after transcatheter aortic valve implantation in high-risk patients with severe aortic stenosis: The U.K. TAVI (United Kingdom Transcatheter Aortic Valve Implantation) registry. J Am Coll Cardiol. 2011, 58: 2130-2138. 10.1016/j.jacc.2011.08.050.CrossRefPubMed

20.

Grube E, Schuler G, Buellesfeld L, Gerckens U, Linke A, Wenaweser P, Sauren B, Mohr FW, Walther T, Zickmann B, Iversen S, Felderhoff T, Cartier R, Bonan R: Percutaneous aortic valve replacement for severe aortic stenosis in high-risk patients using the second- and current third-generation self-expanding CoreValve prosthesis: device success and 30-day clinical outcome. J Am Coll Cardiol. 2007, 50: 69-76. 10.1016/j.jacc.2007.04.047.CrossRefPubMed

21.

Hammerstingl C, Nickenig G, Grube E: Treatment of a degenerative stenosed CoreValve® aortic bioprosthesis by transcatheter valve-in-valve insertion. Catheter Cardiovasc Interv. 2012, 79: 748-755. 10.1002/ccd.23228.CrossRefPubMed

22.

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, 363: 1597-1607. 10.1056/NEJMoa1008232.CrossRefPubMed

23.

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, 364: 2187-2198. 10.1056/NEJMoa1103510.CrossRefPubMed

24.

Makkar RR, Fontana GP, Jilaihawi H, Kapadia S, Pichard AD, Douglas PS, Thourani VH, Babaliaros VC, Webb JG, Herrmann HC, Bavaria JE, Kodali S, Brown DL, Bowers B, Dewey TM, Svensson LG, Tuzcu M, Moses JW, Williams MR, Siegel RJ, Akin JJ, Anderson WN, Pocock S, Smith CR, Leon MB, PARTNER Trial Investigators: Transcatheter aortic-valve replacement for inoperable severe aortic stenosis. N Engl J Med. 2012, 366: 1696-1704. 10.1056/NEJMoa1202277.CrossRefPubMed

25.

Kodali SK, Williams MR, Smith CR, Svensson LG, Webb JG, Makkar RR, Fontana GP, Dewey TM, Thourani VH, Pichard AD, Fischbein M, Szeto WY, Lim S, Greason KL, Teirstein PS, Malaisrie SC, Douglas PS, Hahn RT, Whisenant B, Zajarias A, Wang D, Akin JJ, Anderson WN, Leon MB, PARTNER Trial Investigators: Two-year outcomes after transcatheter or surgical aortic-valve replacement. N Engl J Med. 2012, 366: 1686-1695. 10.1056/NEJMoa1200384.CrossRefPubMed

26.

Nielsen HH, Klaaborg KE, Nissen H, Terp K, Mortensen PE, Kjeldsen BJ, Jakobsen CJ, Andersen HR, Egeblad H, Krusell LR, Thuesen L, Hjortdal VE: A prospective, randomised trial of transapical transcatheter aortic valve implantation vs. surgical aortic valve replacement in operable elderly patients with aortic stenosis: the STACCATO trial. EuroIntervention. 2012, 8: 383-389. 10.4244/EIJV8I3A58.CrossRefPubMed

27.

Vahanian A, Alfieri OR, Al-Attar N, Antunes MJ, Bax J, Cormier B, Cribier A, De Jaegere P, Fournial G, Kappetein AP, Kovac J, Ludgate S, Maisano F, Moat N, Mohr FW, Nataf P, Pierard L, Pomar JL, Schofer J, Tornos P, Tuzcu M, van Hout B, von Segesser LK, Walther T: Transcatheter valve implantation for patients with aortic stenosis: a position statement from the European Association of Cardio-Thoracic Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration with the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur J Cardiothorac Surg. 2008, 34: 1-8. 10.1016/j.ejcts.2008.04.039.CrossRefPubMed

28.

Andersen TF, Madsen M, Jørgensen J, Mellemkjoer L, Olsen JH: The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan Med Bull. 1999, 46: 263-268.PubMed

29.

Pedersen CB, Gøtzsche H, Møller JO, Mortensen PB: The Danish Civil Registration System. A cohort of eight million persons. Dan Med Bull. 2006, 53: 441-449.PubMed

30.

Helweg-Larsen K: The Danish register of causes of death. Scand J Public Health. 2011, 39: 26-29.CrossRefPubMed

31.

Leon MB, Piazza N, Nikolsky E, Blackstone EH, Cutlip DE, Kappetein AP, Krucoff MW, Mack M, Mehran R, Miller C, Morel MA, Petersen J, Popma JJ, Takkenberg JJ, Vahanian A, van Es GA, Vranckx P, Webb JG, Windecker S, Serruys PW: Standardized endpoint definitions for transcatheter aortic valve implantation clinical trials: a consensus report from the Valve Academic Research Consortium. Eur Heart J. 2011, 32: 205-217. 10.1093/eurheartj/ehq406.CrossRefPubMed

32.

Kappetein AP, Head SJ, Généreux P, Piazza N, van Mieghem NM, Blackstone EH, Brott TG, Cohen DJ, Cutlip DE, van Es GA, Hahn RT, Kirtane AJ, Krucoff MW, Kodali S, Mack MJ, Mehran R, Rodés-Cabau J, Vranckx P, Webb JG, Windecker S, Serruys PW, Leon MB: Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document (VARC-2). Eur J Cardiothorac Surg. 2012, 42: S45-S60. 10.1093/ejcts/ezs533.CrossRefPubMed

33.

Dvir D, Webb J, Brecker S, Bleiziffer S, Hildick-Smith D, Colombo A, Descoutures F, Hengstenberg C, Moat NE, Bekeredjian R, Napodano M, Testa L, Lefevre T, Guetta V, Nissen H, Hernández JM, Roy D, Teles RC, Segev A, Dumonteil N, Fiorina C, Gotzmann M, Tchetche D, Abdel-Wahab M, De Marco F, Baumbach A, Laborde JC, Kornowski R: Transcatheter aortic valve replacement for degenerative bioprosthetic surgical valves: results from the global valve-in-valve registry. Circulation. 2012, 126: 2335-2344. 10.1161/CIRCULATIONAHA.112.104505.CrossRefPubMed

34.

Thyregod HG, Lund JT, Engstrøm T, Steinbrüchel DA: Transcatheter aortic valve prosthesis surgically replaced 4 months after implantation. Eur J Cardiothorac Surg. 2010, 37: 494-496.PubMed

35.

Ussia GP, Scarabelli M, Mulè M, Barbanti M, Sarkar K, Cammalleri V, Immè S, Aruta P, Pistritto AM, Gulino S, Deste W, Capodanno D, Tamburino C: Dual antiplatelet therapy versus aspirin alone in patients undergoing transcatheter aortic valve implantation. Am J Cardiol. 2011, 108: 1772-1776. 10.1016/j.amjcard.2011.07.049.CrossRefPubMed

36.

Wood L, Egger M, Gluud LL, Schulz KF, Jüni P, Altman DG, Gluud C, Martin RM, Wood AJ, Sterne JA: Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study. BMJ. 2008, 336: 601-605. 10.1136/bmj.39465.451748.AD.CrossRefPubMedPubMedCentral

37.

Savovic J, Jones HE, Altman DG, Altman DG, Harris RJ, Jüni P, Pildal J, Als-Nielsen B, Balk EM, Gluud C, Gluud LL, Ioannidis JP, Schulz KF, Beynon R, Welton NJ, Wood L, Moher D, Deeks JJ, Sterne JA: Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Ann Intern Med. 2012, 157: 429-438.CrossRefPubMed

Title: The Nordic Aortic Valve Intervention (NOTION) trial comparing transcatheter versus surgical valve implantation: study protocol for a randomised controlled trial
Authors: Hans Gustav Thyregod
Lars Søndergaard
Nikolaj Ihlemann
Olaf Franzen
Lars Willy Andersen
Peter Bo Hansen
Peter Skov Olsen
Henrik Nissen
Per Winkel
Christian Gluud
Daniel Andreas Steinbrüchel
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Trials / Issue 1/2013
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/1745-6215-14-11

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The Nordic Aortic Valve Intervention (NOTION) trial comparing transcatheter versus surgical valve implantation: study protocol for a randomised controlled trial

Abstract

Background

Methods/Design

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods/Design

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2013

It’s plain and simple: transparency is good for science and in the public interest

Feasibility of omega-3 fatty acid supplementation as an adjunct therapy for people with chronic obstructive pulmonary disease: study protocol for a randomized controlled trial

Electroacupuncture for chemotherapy-induced peripheral neuropathy: study protocol for a pilot multicentre randomized, patient-assessor-blinded, controlled trial

Morning light therapy for juvenile depression and severe mood dysregulation: study protocol for a randomized controlled trial

Ondansetron and simvastatin added to treatment as usual in patients with schizophrenia: study protocol for a randomized controlled trial

The impact of supported telemetric monitoring in people with type 2 diabetes: study protocol for a randomised controlled trial