NCT04962646: CARTA

CARbon Dioxide Flooding to Reduce Postoperative Neurological Injury Following Surgery for Acute Type A Aortic Dissection

Recruiting now NA Last updated 11 April 2025

What this trial tests

NA trial testing Carbon dioxide flooding in D000784 in 80 participants. Currently enrolling.

Timeline

1 January 2022

Primary endpoint
30 June 2025

30 June 2025

Quick facts

Lead sponsor	Region Skane
Phase	NA
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	prevention
Enrollment	80
Start date	1 January 2022
Primary completion	30 June 2025
Estimated completion	30 June 2025
Sites	1 location across Sweden

Drugs / interventions tested

• Carbon dioxide flooding

Conditions studied

• D000784 — all drugs for D000784 →
• D020521 — all drugs for D020521 →

Sponsor

Region Skane — full company profile →

Who can join

18 and older, any sex, with D000784 or D020521. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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 5L/min 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.

Update November 2024.

The study has recruited 68/80 participants. We anticipate that remaining participants will be recruited by June 2025.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Global trends in research of acute type a aortic dissection: A bibliometric analysis from 2002 to 2022.
   Qi Z, Tang R, Wang QG, Zeng YF, et al · · 2023 · cited 2× · PMID 37501968 · DOI 10.1016/j.heliyon.2023.e17955
2. Carbon dioxide flooding to reduce postoperative neurological injury following surgery for acute type A aortic dissection: a prospective, randomised, blinded, controlled clinical trial, CARTA study protocol - objectives and design.
   Ede J, Teurneau-Hermansson K, Moseby-Knappe M, Ramgren B, et al · · 2023 · cited 1× · PMID 37230515 · DOI 10.1136/bmjopen-2022-063837