Oxygenation of the Cerebrum and Cooling During Transcatheter Aortic Valve Implantation (TAVI) Procedures - Part II

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to assess the possible neuroprotective effects of cooling (targeted cooling of the brain to 33°C) during Transcatheter Aortic Valve Implantation (TAVI) procedures. From start of anesthesia, until final valve implantation, local cooling (by the RhinoChill device) will be applied to the brain. Effect of cooling on cerebral oxygenation, by cerebral oxygen saturation monitoring (NIRS ForeSight technology) during the TAVI procedure will be continuously assessed during native valve manipulation and during final valve deployment (=primary endpoint of he study). As secondary endpoints, neuropsychological testing performed before and after TAVI procedure will assess the effects of the use of cooling during the TAVI procedure. Neuron-specific enolase (NSE) and S100-beta will be analyzed during and up to 72hrs after TAVI to compare the cerebral ischemic damage between cooled and non-cooled patients. And finally, diffusion-weighted MRI of the brain will be performed 5 days before and 5-7 days after TAVI to compare the number and total amount of cerebral ischemic insults between cooled and non-cooled patients. The hypothesis behind this study is that by local cooling of the brain during manipulation of the calcified aorta and aortic valve, the brain might be protected from cerebral ischemic insults.

Conditions
-----------------
Aortic Valve Stenosis, Stroke

Intervention / Treatment
-----------------
* Device: targeted brain cooling (33°C) by RhinoChill device
* Device: Placebo - current clinical practice, no cooling


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: pts scheduled for transcatheter aortic valve implantation Exclusion Criteria: pts with pacemaker already implanted pts with recent stroke or Transient Ischemic Attacks (TIA) (6months) pts with extreme claustrophobia for MRI brain examination
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: targeted brain cooling<br>In these 15 pts, targeted brain cooling (tympanic temperature of 33°C) will be applied during the TAVI intervention by the use of the RhinoChill device (Benechill Inc, San Diego cA) | Device: targeted brain cooling (33°C) by RhinoChill device<br>* targeted brain cooling by Rhinochill device to 33°C tympanic temperature during TAVI procedure. After valve implantation, slow rewarming until 35.5°C<br>|
| Placebo Comparator: no use of targeted brain cooling<br>In these 15 pts, no cooling techniques will be applied and current clinical practice as to maintenance of normothermia will be followed during these TAVI interventions | Device: Placebo - current clinical practice, no cooling<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in cerebral oxygen saturation during periods of rapid ventricular pacing and valve implantation | changes in cerebral oxygen saturation during periods of rapid ventricular pacing (RVP) and valve implantation; changes in cerebral oxygen saturation compared to baseline values (of 10min) before periods of RVP (Area Under the Curve will be analysed and compared between cooled end non-cooled patients | during TAVI procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| composite outcome measure : MRI of the brain before and after TAVI; NSE before and after TAVI; S100-B before and after TAVI; neuropsychological testing before and after TAVI |  | one year |