Ignite Creation Date:
2024-05-06 @ 4:21 PM
Last Modification Date:
2024-10-26 @ 2:09 PM
Study NCT ID:
NCT04962646
Status:
RECRUITING
Last Update Posted:
2023-11-13
First Post:
2021-06-09
Brief Title:
CARbon Dioxide Flooding to Reduce Postoperative Neurological Injury Following Surgery for Acute Type A Aortic Dissection
Sponsor:
Region Skane
Organization:
Region Skane
Study Overview
Official Title:
CARbon Dioxide Flooding to Reduce Postoperative Neurological Injury Following Surgery for Acute Type A Aortic Dissection - A Prospective Randomized Blinded Controlled Clinical Trial
Status:
RECRUITING
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CARTA
Brief Summary:
Aortic dissection is a life-threatening condition and a consequence of a tear of the innermost of the three aortic layers- the intima When a tear occurs blood surges through the tear and causes the flow of blood between the aortic layers causing a false lumen This causes a weakening of the aortic wall and hinders the blood from reaching its target organs and life saving emergent surgery is performed as routine
Approximately 20 of patients undergoing acute type a aortic dissection ATAAD surgery suffer from postoperative neurological injuries and It has been demonstrated that neurological injuries account for 10-15 of in-hospital deaths
In association with other cardiac procedures where the left side of the heart is opened and air may be trapped within the arterial circulation carbon dioxide flooding is used to displace open air from the surgical wound In comparison to air carbon dioxide is significantly more soluble in blood and may therefore decrease the risk of air embolism In cardiac surgery carbon dioxide flooding has been demonstrated to reduce levels of biomarkers of cerebral injury but carbon dioxide is not routinely employed in ATAAD surgery and has not been studied in association with these procedures
The hypothesis is that carbon dioxide flooding reduces cerebral air embolism and the aim of this project is to evaluate whether carbon dioxide flooding may reduce neurological injuries following ATAAD surgery
This is a prospective randomized controlled patient- and reviewer blinded interventional study Patients will be randomized to undergo surgery with carbon-dioxide flooding at 5Lmin to the open chest cavity or conventional surgery without carbon dioxide flooding Remaining aspects of the procedure will be identical
The patient external statistician and the reviewer analyzing the primary endpoints will be blinded for the randomization arms
The study will assess the following endpoints
Primary outcomes Presence number and volume of ischaemic lesions observed using magnetic resonance imaging MRI after ATAAD surgery
Secondary outcomes Clinical signs of neurological injury Levels of biomarkers of neurological injury S100B neuron specific enolase NSE neurofilament protein NFL Glial fibrillary acid protein GFAP Ubiquitin carboxyl-terminal hydrolase L1 UCH-L1 and Tau-protein TAU before and after surgery Quality of life postoperative recovery and neurological function after ATAAD surgery Primary outcomes in relation to retrograde cerebral perfusion
Start of inclusion is anticipated to start Jan 1st 2022 The writing of a manuscript describing the study methods and study objectives is expected to be started in 2021 and the final manuscript is expected to be written during 2025
An interim analysis of the primary endpoints and the safety arm will be performed after 40 patients have been randomized An external statistician together with the principle investigator will hereafter decide for the study to be continued or terminated due to harms futility or superiority
The safety arm will include intraoperative mortality in-hospital mortality re-operation for bleeding stroke myocardial infarction or other thromboembolic events
Update August 2023
Interim analyses were performed after 40 study participants had been included Results from the interim analyses raised important questions which need to be assessed by a Data Safety and Monitoring Board DSMB Since there are no documented harmful effects of the intervention a DSMB was not appointed before initiation of the trial The study was suspended on Aug 18th 2023
A DSMB will be appointed analyze the interim analyses collect necessary additional information and make a recommendation to the PI whether the study is may proceed or is to be terminated prematurely
Update September 2023
The DSMB has reviewed the interim analyses and additional study data The DSMB concluded that there was no reason to terminate the study and have recommended for the study to proceed Recruitment was re-initiated on September 5th 2023
Approximately 20 of patients undergoing acute type a aortic dissection ATAAD surgery suffer from postoperative neurological injuries and It has been demonstrated that neurological injuries account for 10-15 of in-hospital deaths
In association with other cardiac procedures where the left side of the heart is opened and air may be trapped within the arterial circulation carbon dioxide flooding is used to displace open air from the surgical wound In comparison to air carbon dioxide is significantly more soluble in blood and may therefore decrease the risk of air embolism In cardiac surgery carbon dioxide flooding has been demonstrated to reduce levels of biomarkers of cerebral injury but carbon dioxide is not routinely employed in ATAAD surgery and has not been studied in association with these procedures
The hypothesis is that carbon dioxide flooding reduces cerebral air embolism and the aim of this project is to evaluate whether carbon dioxide flooding may reduce neurological injuries following ATAAD surgery
This is a prospective randomized controlled patient- and reviewer blinded interventional study Patients will be randomized to undergo surgery with carbon-dioxide flooding at 5Lmin to the open chest cavity or conventional surgery without carbon dioxide flooding Remaining aspects of the procedure will be identical
The patient external statistician and the reviewer analyzing the primary endpoints will be blinded for the randomization arms
The study will assess the following endpoints
Primary outcomes Presence number and volume of ischaemic lesions observed using magnetic resonance imaging MRI after ATAAD surgery
Secondary outcomes Clinical signs of neurological injury Levels of biomarkers of neurological injury S100B neuron specific enolase NSE neurofilament protein NFL Glial fibrillary acid protein GFAP Ubiquitin carboxyl-terminal hydrolase L1 UCH-L1 and Tau-protein TAU before and after surgery Quality of life postoperative recovery and neurological function after ATAAD surgery Primary outcomes in relation to retrograde cerebral perfusion
Start of inclusion is anticipated to start Jan 1st 2022 The writing of a manuscript describing the study methods and study objectives is expected to be started in 2021 and the final manuscript is expected to be written during 2025
An interim analysis of the primary endpoints and the safety arm will be performed after 40 patients have been randomized An external statistician together with the principle investigator will hereafter decide for the study to be continued or terminated due to harms futility or superiority
The safety arm will include intraoperative mortality in-hospital mortality re-operation for bleeding stroke myocardial infarction or other thromboembolic events
Update August 2023
Interim analyses were performed after 40 study participants had been included Results from the interim analyses raised important questions which need to be assessed by a Data Safety and Monitoring Board DSMB Since there are no documented harmful effects of the intervention a DSMB was not appointed before initiation of the trial The study was suspended on Aug 18th 2023
A DSMB will be appointed analyze the interim analyses collect necessary additional information and make a recommendation to the PI whether the study is may proceed or is to be terminated prematurely
Update September 2023
The DSMB has reviewed the interim analyses and additional study data The DSMB concluded that there was no reason to terminate the study and have recommended for the study to proceed Recruitment was re-initiated on September 5th 2023
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None