Clinical trial NCT01539746: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Aortic Stenosis
Left Ventricular Function Systolic Dysfunction
High-risk Patients
Transcatheter Aortic Valve Implantation
Keywords: Aortic stenosis
Transcatheter aortic valve implantation
TAVI
Predilation
Balloon valvuloplasty
BAV
CoreValve
Lead sponsor: University Hospital, Bonn
Sponsor class: OTHER
First posted: 2012-02-27
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Primary composite efficacy endpoint
timeFrame: 30 days after TAVI
Secondary outcomes:
measure: Cardiovascular & all-cause mortality
timeFrame: 6 months, 12 months after TAVI
measure: Major/minor stroke
timeFrame: 6 months, 12 months after TAVI
measure: Myocardial infarction
timeFrame: 6 months, 12 months after TAVI
measure: conduction disturbances and pacemaker implantation rate
timeFrame: 6 months, 12 months after TAVI
measure: Acute kidney injury
timeFrame: 6 months, 12 months after TAVI
measure: Rate of postdilation
timeFrame: 30 days, 6 months, 12 months after TAVI
measure: Transvalvular mean gradient as assessed by echocardiography
timeFrame: 30 days, 6 months, 12 months after TAVI
measure: Re-hospitalization for symptoms of cardiac/valve-related decompensation
timeFrame: 30 days, 6 months, 12 months after TAVI
measure: Severity of periprosthetic aortic regurgitation (AR) as assessed by echocardiography, angiography, and hemodynamic measurements (AR index)
timeFrame: 30 days, 6 months, 12 months after TAVI
measure: Life-threatening/major/minor bleeding
timeFrame: 30 days, 6 months, 12 months after TAVI
measure: Vascular access complications
timeFrame: 30 days, 6 months, 12 months after TAVI
measure: Repeat procedure for valve-related dysfunction (surgical or interventional therapy)
timeFrame: 30 days, 6 months, 12 months after TAVI
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: Department of Medicine II - Cardiology, University Hospital Bonn
city: Düsseldorf
country: Germany
facility: Department of Cardiology, University Hospital Düsseldorf
city: Essen
country: Germany
facility: West German Heart Center, University Hospital Essen
city: Heidelberg
country: Germany
facility: Department of Medicine III - Cardiology, University Hospital Heidelberg
city: Trier
country: Germany
facility: Department of Cardiology, Hospital Barmherzige Brüder Trier
city: Tübingen
country: Germany
facility: Department of Medicine III - Cardiology, University Hospital Tübingen
Study officials:
affiliation: Department of Medicine II, University Hospital Bonn
name: Georg Nickenig, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Medicine II, University Hospital Bonn
name: Jan-Malte Sinning, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.