Transcatheter Aortic Valve Implantation Without Predilation (SIMPLIFy TAVI)

• ClinicalTrials.gov Identifier: NCT01539746
• Recruitment Status: Completed
• First Posted: February 27, 2012
• Last Update Posted: November 7, 2022
• Sponsor: University Hospital, Bonn
• Information provided by (Responsible Party): Georg Nickenig, University Hospital, Bonn

Tracking Information

• First Submitted Date: February 21, 2012
• First Posted Date: February 27, 2012
• Last Update Posted Date: November 7, 2022
• Actual Study Start Date: January 9, 2013
• Actual Primary Completion Date: November 22, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 24, 2012)

Primary composite efficacy endpoint [ Time Frame: 30 days after TAVI ]

Occurrence of all-cause mortality, stroke, non-fatal myocardial infarction, acute kidney injury, or pacemaker implantation at 30 days after TAVI.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 30, 2013)

• Cardiovascular & all-cause mortality [ Time Frame: 6 months, 12 months after TAVI ]
• Major/minor stroke [ Time Frame: 6 months, 12 months after TAVI ]
• Myocardial infarction [ Time Frame: 6 months, 12 months after TAVI ]
• conduction disturbances and pacemaker implantation rate [ Time Frame: 6 months, 12 months after TAVI ]
• Acute kidney injury [ Time Frame: 6 months, 12 months after TAVI ]
• Rate of postdilation [ Time Frame: 30 days, 6 months, 12 months after TAVI ]
• Transvalvular mean gradient as assessed by echocardiography [ Time Frame: 30 days, 6 months, 12 months after TAVI ]
• Re-hospitalization for symptoms of cardiac/valve-related decompensation [ Time Frame: 30 days, 6 months, 12 months after TAVI ]
• Severity of periprosthetic aortic regurgitation (AR) as assessed by echocardiography, angiography, and hemodynamic measurements (AR index) [ Time Frame: 30 days, 6 months, 12 months after TAVI ]
• Life-threatening/major/minor bleeding [ Time Frame: 30 days, 6 months, 12 months after TAVI ]
• Vascular access complications [ Time Frame: 30 days, 6 months, 12 months after TAVI ]
• Repeat procedure for valve-related dysfunction (surgical or interventional therapy) [ Time Frame: 30 days, 6 months, 12 months after TAVI ]

Original Secondary Outcome Measures (submitted: February 24, 2012)

• Cardiovascular & all-cause mortality [ Time Frame: 30 days, 6 months, 12 months after TAVI ]
• Major/minor stroke [ Time Frame: 30 days, 6 months, 12 months after TAVI ]
• Myocardial infarction [ Time Frame: 30 days, 6 months, 12 months after TAVI ]
• Conduction disturbances and pacemaker rate [ Time Frame: 30 days, 6 months, 12 months after TAVI ]
• Acute kidney injury [ Time Frame: 30 days, 6 months, 12 months after TAVI ]
• Rate of postdilation [ Time Frame: 30 days, 6 months, 12 months after TAVI ]
• Transvalvular mean gradient as assessed by echocardiography [ Time Frame: 30 days, 6 months, 12 months after TAVI ]
• Re-hospitalization for symptoms of cardiac/valve-related decompensation [ Time Frame: 30 days, 6 months, 12 months after TAVI ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Transcatheter Aortic Valve Implantation Without Predilation
• Official Title: Use of the Self-Expanding Medtronic CoreValve Prosthesis Without Predilation in Patients With Severely IMPaired Left-VentrIcular Ejection Fraction for TAVI Trial - The SIMPLIFy TAVI Trial
• Brief Summary: The purpose of this study is to demonstrate that the avoidance of balloon valvuloplasty for predilation of the native aortic valve is associated with a reduction of the composite primary endpoint in TAVI patients with severely impaired left-ventricular ejection fraction (LVEF ≤35%).

Detailed Description

Transcatheter aortic valve implantation (TAVI) has evolved as an alternative to surgical aortic valve replacement (SAVR) with now more than 50,000 implantations in patients with symptomatic severe aortic stenosis, who were considered to be at very high or prohibitive operative risk. Before deployment of transcatheter heart valves (THV), current medical practice requires right-ventricular rapid burst pacing (>180 bpm) with induction of a functional cardiac arrest for up to 30 seconds for balloon aortic valvuloplasty (BAV). This step is thought to be necessary to predilate the native aortic valve and to facilitate an accurate positioning of the THV. However, BAV has been shown to have numerous detrimental effects: i) the functional cardiac arrest induced by rapid pacing for BAV leads to transient coronary, cerebral, and renal ischemia. ii) In patients with impaired left ventricular ejection fraction, prolonged cardiac depression after rapid pacing is observed and may result in hemodynamic failure and systemic inflammatory response syndrome (SIRS), which are both associated with a high peri-procedural mortality. iii) BAV has been identified as a major source of embolization of thrombotic and valvular material and increases the risk for coronary obstruction with subsequent myocardial infarction and stroke. iv) the local trauma in the left-ventricular outflow tract caused by BAV contributes to conduction disturbances with the need for permanent pacemaker implantation after TAVI.

A non-randomized pilot study by Grube et al. (JACC Interventions 2011) has recently shown that TAVI without BAV is feasible and safe, since self-expanding THV are able to "dilate" the stenosed aortic valve through the radial forces of the self-expanding nitinol frame, in which the prosthesis is mounted. According to the mentioned study, omitting BAV allows the delivery of the THV in a controlled fashion without hemodynamic compromise of the patient.

Patients with LVEF≤35% will be randomized (like the flip of a coin) to TAVI without BAV (experimental group) or TAVI with BAV for predilation (control group).

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Aortic Stenosis
• Left Ventricular Function Systolic Dysfunction
• High-risk Patients
• Transcatheter Aortic Valve Implantation

Intervention

• Procedure: TAVI without BAV
  Avoidance of balloon valvuloplasty (BAV) of the native aortic valve before valve deployment
• Procedure: TAVI standard procedure
  TAVI standard procedure including BAV before valve deployment

Study Arms

• Experimental: TAVI without predilation
  Intervention: Procedure: TAVI without BAV
• Active Comparator: Standard TAVI procedure
  Intervention: Procedure: TAVI standard procedure

Publications *

• Grube E, Naber C, Abizaid A, Sousa E, Mendiz O, Lemos P, Kalil Filho R, Mangione J, Buellesfeld L. Feasibility of transcatheter aortic valve implantation without balloon pre-dilation: a pilot study. JACC Cardiovasc Interv. 2011 Jul;4(7):751-7. doi: 10.1016/j.jcin.2011.03.015.
• 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. J Am Coll Cardiol. 2011 Jan 18;57(3):253-69. doi: 10.1016/j.jacc.2010.12.005. Epub 2011 Jan 7.
• 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.
• Sinning JM, Scheer AC, Adenauer V, Ghanem A, Hammerstingl C, Schueler R, Muller C, Vasa-Nicotera M, Grube E, Nickenig G, Werner N. Systemic inflammatory response syndrome predicts increased mortality in patients after transcatheter aortic valve implantation. Eur Heart J. 2012 Jun;33(12):1459-68. doi: 10.1093/eurheartj/ehs002. Epub 2012 Jan 26.
• Nuis RJ, Van Mieghem NM, Schultz CJ, Tzikas A, Van der Boon RM, Maugenest AM, Cheng J, Piazza N, van Domburg RT, Serruys PW, de Jaegere PP. Timing and potential mechanisms of new conduction abnormalities during the implantation of the Medtronic CoreValve System in patients with aortic stenosis. Eur Heart J. 2011 Aug;32(16):2067-74. doi: 10.1093/eurheartj/ehr110. Epub 2011 May 28.
• Kahlert P, Erbel R. Transcatheter aortic valve implantation in the era after commercialization: quo vadis in the real world? Circulation. 2011 Jan 25;123(3):239-41. doi: 10.1161/CIRCULATIONAHA.110.004713. Epub 2011 Jan 10. No abstract available.
• Ghanem A, Muller A, Nahle CP, Kocurek J, Werner N, Hammerstingl C, Schild HH, Schwab JO, Mellert F, Fimmers R, Nickenig G, Thomas D. Risk and fate of cerebral embolism after transfemoral aortic valve implantation: a prospective pilot study with diffusion-weighted magnetic resonance imaging. J Am Coll Cardiol. 2010 Apr 6;55(14):1427-32. doi: 10.1016/j.jacc.2009.12.026. Epub 2010 Feb 24.
• Drews T, Pasic M, Buz S, Unbehaun A, Dreysse S, Kukucka M, Mladenow A, Hetzer R. Transcranial Doppler sound detection of cerebral microembolism during transapical aortic valve implantation. Thorac Cardiovasc Surg. 2011 Jun;59(4):237-42. doi: 10.1055/s-0030-1250495. Epub 2011 Mar 25.
• Sinning JM, Ghanem A, Steinhauser H, Adenauer V, Hammerstingl C, Nickenig G, Werner N. Renal function as predictor of mortality in patients after percutaneous transcatheter aortic valve implantation. JACC Cardiovasc Interv. 2010 Nov;3(11):1141-9. doi: 10.1016/j.jcin.2010.09.009.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 24, 2012): 110
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: November 22, 2019
• Actual Primary Completion Date: November 22, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• LVEF ≤35%
• Aortic valve stenosis with an aortic valve area <1 cm2 (<0,6 cm3/m2)
• Males or females at least 18 years of age
• Logistic EuroSCORE ≥15% and age ≥75 years or if age <75 years: logistic EuroSCORE ≥20% and/or a significant contraindication for open heart surgery (e.g., porcelain aorta or severe COPD)
• Signed informed consent

Exclusion Criteria:

• Patients with a device regulating the heart rhythm by pacing (e.g. pacemaker, resynchronization device, implanted defibrillator)
• Patients with a pre-existing class I or class II indication for new pacemaker implantation according to the 2007 ESC guidelines
• Lack of written informed consent, severe mental disorder, drug/alcohol addiction
• Life expectancy < 1 year
• Hypersensitivity or contraindication to acetyl salicyl acid, heparin, ticlopidine, clopidogrel, nitinol or sensitivity to contrast media that cannot be adequately premedicated
• Recent myocardial infarction (STEMI within the last 3 months)
• Left ventricular or atrial thrombus by echocardiography
• Uncontrolled atrial fibrillation
• Mitral or tricuspidal valvular insufficiency (> grade II)
• Previous aortic valve replacement with mechanical valve
• Evolutive or recent cerebrovascular event (within the last 3 months)
• Vascular conditions that make insertion and endovascular access to the aortic valve impossible
• Symptomatic carotid or vertebral arterial narrowing (>70%) disease
• Abdominal or thoracic aortic aneurysm in the path of the delivery system
• Bleeding diathesis or coagulopathy or patient refusing blood transfusion
• Active gastritis or peptic ulcer disease
• Severely impaired renal function, GFR < 30 ml/min
• Participation in another drug or device study that would jeopardize the appropriate analysis of end-points of this study.
• High probability of non-adherence to the follow-up requirements (due to social, psychological or medical reasons)
• Pregnancy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT01539746
• Other Study ID Numbers: SIMPLIFy TAVI Trial
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Georg Nickenig, University Hospital, Bonn
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital, Bonn
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Georg Nickenig, MD; Department of Medicine II, University Hospital Bonn
• Study Director: Jan-Malte Sinning, MD; Department of Medicine II, University Hospital Bonn

• PRS Account: University Hospital, Bonn
• Verification Date: November 2022