INTERvention With Cerebral Embolic Protection in Transcatheter Aortic Valve Implantation (INTERCEPTavi)

Study Overview
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Brief Summary
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The study aims to evaluate the processes of a pilot single-centre randomised controlled trial (RCT) of carbon-dioxide flushing of transcatheter aortic valves (TAVI-CO2) versus standard saline flushing of valves (TAVI-S) and assess potential neuroprotection through a number of neurological endpoints for planning of a full-sized RCT

Detailed Description
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Aortic stenosis (AS) is one of the most common valve diseases and is increasing worldwide due to an ageing population. Transcatheter Aortic Valve Replacement (TAVI) is a keyhole procedure that can be done through the groin to replace the narrowed aortic valve with a new valve, avoiding the need for cardiac surgery.Improved device design and greater operator experience has improved TAVI outcomes. It has become the standard treatment option in patients who are at high risk for cardiac surgery and is now being used increasingly in lower risk patients. Cerebrovascular accidents in TAVI patients remain a significant risk with a reported 3 - 5 % risk. Furthermore, these patients have neurovascular injury that is not clinically identifiable. Covert brain injury has been identified to occur in many surgical and cardiovascular catheter-based interventions such as TAVI and can cause vascular brain injury (VBI). TAVI valves are manufactured in room air conditions and retain air. Studies in TEVAR (Thoracic Endovascular Aortic Repair) stent grafts have shown release of air when they are deployed in the aorta. In vitro testing of TAVI valves has shown release of air when they are deployed. Carbon-dioxide (CO2) is 1.5 times denser than air and can displace it. It is 25 times more soluble in blood than air and does not lead to bubble formation. Hence CO2 bubble are unlikely to result in significant damage. CO2 has been used in cardiac surgery with beneficial effects. It has shown to reduce peri-procedural cerebral air embolisation and post operative cognitive dysfunction. This study aims to look at the neuroprotective benefits of flushing TAVI valves with CO2 and saline versus saline only by reducing air embolisation. Patients undergoing TAVI will be approached to participate in this study. After consent is obtained, patients will undergo baseline MRI, neurological and neurocognitive testing pre-TAVI. Patient will be randomised to saline only or CO2 and saline flushing of their valves. During their TAVI procedure, they will have transcranial doppler (TCD) monitoring of their middle cerebral artery (MCA) bilaterally to record cerebral embolisation. Patients will also have biomarker testing pre-TAVI, post-TAVI and 24 hours following TAVI. They will have DW-MRI brain between day 1-7 following their TAVI to look for vascular brain injury. Thus MRI will be repeated at 6-months following their TAVI. Patients will also have neurological and neurocognitive testing during their inpatient admission, at 6-weeks and 6-months outpatients.

Official Title
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INTERvention With Cerebral Embolic Protection in Transcatheter Aortic Valve Implantation (INTERCEPTavi): 'Carbon-Dioxide Flushing Versus Saline Flushing of Transcatheter Aortic Valves: A Single-centre Randomised Controlled Trial'

Conditions
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Stroke, Aortic Valve Stenosis, Silent Cerebral Infarct, Vascular Brain Injury

Intervention / Treatment
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* Other: CO2 and saline flushing
* Other: Saline flushing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients between the ages of 18 and 100 years undergoing transcatheter aortic valve implantation (TAVI) for aortic stenosis under local anaesthetic. Exclusion Criteria: Patients that lack capacity to provide informed consent Patients that have had a stroke within 12 months Patients aged less than 18 years of age Patients that are pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomised to CO2 and Saline flushing versus saline flushing only.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Saline flushing<br>TAVI valves will be prepared according to instruction for use(IFU) with saline flushing only. | Other: Saline flushing<br>* TAVI valves will be flushed with saline only as per IFU.<br>|
| Experimental: CO2 and saline flushing<br>TAVI valves will be flushed with CO2 and then saline as per IFU | Other: CO2 and saline flushing<br>* TAVI valves will be prepared by flushing with CO2 to displace any retained air during manufacturing and preparation. The valves will then be flushed with saline as per IFU.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants suitable for recruitment for larger RCT | Conduct an evaluation of the processes described in this pilot RCT for a full-scale RCT including: Screening, Recruitment and Randomisation Retention in follow-up assessments Study design for a full RCT and identification of important stratification variables Refine sample size calculation for a full RCT | Duration of study, approximately 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Vascular Brain Injury (VBI) on Diffusion Weighted-Magnetic Resonance Imaging (DW-MRI) | Assessment of the incidence of DW-MRI detected VBI lesions following TAVI procedure. Patients will have MRI following their TAVI within 1-7 days and then at 6-months post TAVI. | Post TAVI 1-7 days and 6-months post TAVI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Aortic Valve Stenosis, Silent Cerebral Infarct, Vascular Brain Injury, TAVI, Transcatheter aortic valve implantation, Transcranial doppler, Magnetic resonance imaging, CO2, Carbon dioxide