INTERvention With Cerebral Embolic Protection in Transcatheter Aortic Valve Implantation (INTERCEPTavi) (INTERCEPTavi)
Primary Purpose
Stroke, Aortic Valve Stenosis, Silent Cerebral Infarct
Status
Recruiting
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
CO2 and saline flushing
Saline flushing
Sponsored by
About this trial
This is an interventional prevention trial for Stroke focused on measuring Stroke, Aortic Valve Stenosis, Silent Cerebral Infarct, Vascular Brain Injury, TAVI, Transcatheter aortic valve implantation, Transcranial doppler, Magnetic resonance imaging, CO2, Carbon dioxide
Eligibility Criteria
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
Sites / Locations
- Imperial College LondonRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Saline flushing
CO2 and saline flushing
Arm Description
TAVI valves will be prepared according to instruction for use(IFU) with saline flushing only.
TAVI valves will be flushed with CO2 and then saline as per IFU
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT05146037
First Posted
November 11, 2021
Last Updated
January 25, 2023
Sponsor
Imperial College London
Collaborators
Imperial College Healthcare NHS Trust
1. Study Identification
Unique Protocol Identification Number
NCT05146037
Brief Title
INTERvention With Cerebral Embolic Protection in Transcatheter Aortic Valve Implantation (INTERCEPTavi)
Acronym
INTERCEPTavi
Official Title
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'
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College London
Collaborators
Imperial College Healthcare NHS Trust
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Aortic Valve Stenosis, Silent Cerebral Infarct, Vascular Brain Injury
Keywords
Stroke, Aortic Valve Stenosis, Silent Cerebral Infarct, Vascular Brain Injury, TAVI, Transcatheter aortic valve implantation, Transcranial doppler, Magnetic resonance imaging, CO2, Carbon dioxide
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Patients will be randomised to CO2 and Saline flushing versus saline flushing only.
Masking
ParticipantOutcomes Assessor
Masking Description
Patients and outcome assessors will be blinded to intervention.
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Saline flushing
Arm Type
Active Comparator
Arm Description
TAVI valves will be prepared according to instruction for use(IFU) with saline flushing only.
Arm Title
CO2 and saline flushing
Arm Type
Experimental
Arm Description
TAVI valves will be flushed with CO2 and then saline as per IFU
Intervention Type
Other
Intervention Name(s)
CO2 and saline flushing
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Saline flushing
Intervention Description
TAVI valves will be flushed with saline only as per IFU.
Primary Outcome Measure Information:
Title
Number of participants suitable for recruitment for larger RCT
Description
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
Time Frame
Duration of study, approximately 15 months
Secondary Outcome Measure Information:
Title
Incidence of Vascular Brain Injury (VBI) on Diffusion Weighted-Magnetic Resonance Imaging (DW-MRI)
Description
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.
Time Frame
Post TAVI 1-7 days and 6-months post TAVI
Other Pre-specified Outcome Measures:
Title
Detection of periprocedural cerebral solid and gaseous emboli
Description
Document the overall rate of periprocedural cerebral solid and gaseous embolisation by transcranial doppler (TCD) monitoring during the TAVI procedure.
Time Frame
During TAVI procedure
Title
Neurological deficit
Description
Patients will undergo neurological assessment pre TAVI (baseline), post TAVI as inpatient, at 6-weeks and 6-months following TAVI.
Time Frame
6 Months
Title
Inflammatory biomarker assessing brain injury
Description
Serial measurement of pro-inflammatory biomarkers pre-operatively, at the end of procedure and 24 hours post-operatively as a marker of brain damage including S100B
Time Frame
24 hours post TAVI
Title
Neurocognitive decline
Description
Patients will undergo neurocognitive assessment pre TAVI (baseline), post TAVI as inpatient, at 6-weeks and 6-months following TAVI.
Time Frame
6 Months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Saud Ahmed Khawaja, MBBS
Phone
+44 203 313 1626
Email
Saud.khawaja@nhs.net
First Name & Middle Initial & Last Name or Official Title & Degree
Ghada Mikhail, MD
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ghada Mikhail
Organizational Affiliation
Imperial College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Imperial College London
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Saud Ahmed Khawaja, MBBS
Phone
+44 203 313 1626
Email
Saud.khawaja@nhs.net
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
27994872
Citation
Inci K, Koutouzi G, Chernoray V, Jeppsson A, Nilsson H, Falkenberg M. Air bubbles are released by thoracic endograft deployment: An in vitro experimental study. SAGE Open Med. 2016 Dec 7;4:2050312116682130. doi: 10.1177/2050312116682130. eCollection 2016.
Results Reference
background
PubMed Identifier
27798380
Citation
Rohlffs F, Tsilimparis N, Saleptsis V, Diener H, Debus ES, Kolbel T. Air Embolism During TEVAR: Carbon Dioxide Flushing Decreases the Amount of Gas Released from Thoracic Stent-Grafts During Deployment. J Endovasc Ther. 2017 Feb;24(1):84-88. doi: 10.1177/1526602816675621. Epub 2016 Oct 26.
Results Reference
background
PubMed Identifier
18222261
Citation
Martens S, Neumann K, Sodemann C, Deschka H, Wimmer-Greinecker G, Moritz A. Carbon dioxide field flooding reduces neurologic impairment after open heart surgery. Ann Thorac Surg. 2008 Feb;85(2):543-7. doi: 10.1016/j.athoracsur.2007.08.047.
Results Reference
background
PubMed Identifier
21371850
Citation
Bismuth J, Garami Z, Anaya-Ayala JE, Naoum JJ, El Sayed HF, Peden EK, Lumsden AB, Davies MG. Transcranial Doppler findings during thoracic endovascular aortic repair. J Vasc Surg. 2011 Aug;54(2):364-9. doi: 10.1016/j.jvs.2010.12.063. Epub 2011 Mar 3.
Results Reference
background
PubMed Identifier
29431856
Citation
Perera AH, Rudarakanchana N, Monzon L, Bicknell CD, Modarai B, Kirmi O, Athanasiou T, Hamady M, Gibbs RG. Cerebral embolization, silent cerebral infarction and neurocognitive decline after thoracic endovascular aortic repair. Br J Surg. 2018 Mar;105(4):366-378. doi: 10.1002/bjs.10718. Epub 2018 Feb 12.
Results Reference
background
Learn more about this trial
INTERvention With Cerebral Embolic Protection in Transcatheter Aortic Valve Implantation (INTERCEPTavi)
We'll reach out to this number within 24 hrs