Intervention With Cerebral Embolic Protection in TEVAR: Gaseous Protection

Study Overview
=================
Brief Summary
-----------------
Vascular brain infarction (VBI) occurs in 67% of patients undergoing TEVAR. Overt stroke occurs in 13% of these patients and 88% of patients suffer from neurocognitive impairment. Cerebral air embolisation during the stent-graft deployment phase of TEVAR may be a cause of VBI. Standard treatment to de-air stent-grafts is through the use of a saline flush. This study aims to investigate whether carbon-dioxide or saline is the better fluid to de-air TEVAR stent-grafts prior to insertion in to the patient and compare VBI rate in the carbon-dioxide group and saline group.

Detailed Description
-----------------
Thoracic endovascular aortic repair (TEVAR) is the re-lining of the thoracic aorta to prevent life threatening haemorrhage and death from rupture. This involves a small cut in the femoral artery in the groin and under imaging guidance, the insertion of wires and a stent into the thoracic aorta. Prior to insertion into the patient, stents are flushed with saline to remove air and prevent air reaching the brain that can cause a form of brain injury known as vascular brain infarction (VBI). However, our preliminary clinical data suggests that saline flushing is not effective at de-airing stent-grafts used in TEVAR. Carbon-dioxide has been used extensively in cardiac surgery to displace air from the chest cavity to prevent peri-procedural cerebral air embolisation. We hypothesise that flushing the stent-grafts with carbon-dioxide may be better at removing air from the stent-grafts than saline flush. Patients undergoing TEVAR will be approached to participate in this study. After written consent is obtained, participants will be randomised to undergo (TEVAR) with carbon dioxide or saline flushing of stent-grafts. Pre-operatively, participants will undergo extensive neurocognitive testing, and a baseline blood test. Intra-operatively, participants will undergo continuous transcranial doppler monitoring (TCD) of the middle cerebral artery (MCA) to look for cerebral air embolisation at stent-graft deployment phase of TEVAR. Blood testing pre-op, immediately post op, and 24 hours post op will be taken to measure for biomarkers of brain injury. Post-operatively, participants will undergo another diffusion-weighted brain MRI within 72 hours post-procedure, stroke and delirium assessment at day 1, 3 and day 7 +/- day of discharge, and at 6-weeks and 6-month follow-up.

Official Title
-----------------
Carbon-Dioxide Flushing Versus Saline Flushing in Thoracic Endovascular Aortic Repair to Reduce Neurological Injury: A Pilot Randomised Controlled Trial

Conditions
-----------------
Stroke, Silent Cerebral Infarction, Neurocognitive Dysfunction, Vascular Brain Injury

Intervention / Treatment
-----------------
* Other: CO2 flushing
* Other: Saline flushing


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All participants suitable for TEVAR with capacity to consent Exclusion Criteria: Participants who lack capacity to consent Contraindications to MRI such as pacemaker Pregnant participants Participants who do not wish to participate Participants <18yrs

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 randomisation
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: carbon-dioxide<br>Flushing of stent-grafts in TEVAR with carbon-dioxide | Other: CO2 flushing<br>* As above<br>|
| Active Comparator: Saline<br>Flushing of stent-grafts with saline | Other: Saline flushing<br>* As above<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment | The number of patients recruited into the trial will be collected | 36 months | 
| Retention | The proportion of patients undergoing follow-up assessments will be collected | 36 months | 
| Study design for full randomised controlled trial | The proportion of patients who are eligible for the trial will be collected | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number, size and location of new ischaemic lesions on post-operative diffusion-weighted MRI scans | Using DW-MRI at <72 hours post operatively (day 1-7), and also 6 months post operatively, we will assess for new ischaemic lesions | 36 months | 
| Number of gaseous and solid intra-operative transcranial doppler microembolic signals by phase of TEVAR | At all London units, transcranial doppler insonation of the middle cerebral artery will be carried out during the procedure, and analysed offline at a later date to evaluate gaseous or solid emboli during TEVAR | Duration of surgery, 36 months collection | 
| Number of participants with stroke or delirium as an inpatient | Patients will undergo stroke and delirium assessment. | These will be carried out within 48 hours of patients' return to level 1 care. 36 months collection | 
| Serial biomarker blood tests | Blood samples will be taken preoperatively, at the end of the procedure and 24 hours late. These will be analysed for a biomarker of neuroglial injury, S100B | 36 months | 
| Risk factor assessment | Data such as stent type will be collected. | 36 months | 
| Neurological assessment, delirium assessment and quality of life testing | Patients will undergo a baseline neurocognitive, delirium and quality of life testing. These will be repeated as an outpatient to measure change post operatively. | Pre-op, first outpatient assessment (approximately 6 weeks), 6 months. 36 months collection | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Stroke, Silent cerebral infarction, Carbon dioxide, Thoracic endovascular aortic repair, TEVAR, DW-MRI, Vascular brain infarction