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

NCT ID: NCT04962646

Last Updated: 2025-04-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-01
• Study Completion Date: 2025-06-30

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 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.

Conditions

D000784; D020521

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Intervention

Once the thoracic cavity os opened during surgery, carbon dioxide flooding using a diffusor will be instigated with a flow of 5L/min. The flooding will be terminated once the aorta and the heart have no open contact with surrounding air.

Group Type: EXPERIMENTAL

Carbon dioxide flooding

Intervention Type: PROCEDURE

Once the thoracic cavity is opened a flow of carbon dioxide of 5L/min will be initiated into the surgical wound and proceed until there is no connection between the cardiac or aortic cavity and surrounding air.

Control

No intervention. No sham will be used as the staff performing the surgery would have been able to detect the lack of carbon dioxide in the surgical wound.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Carbon dioxide flooding

Once the thoracic cavity is opened a flow of carbon dioxide of 5L/min will be initiated into the surgical wound and proceed until there is no connection between the cardiac or aortic cavity and surrounding air.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Verified acute type A aortic dissection.
• Patient accepted for surgical repair.

Exclusion Criteria

• New-onset neurological symptoms defined as focal neurological symptoms or altered state of consciousness at time of inclusion.
• History of stroke with permanent neurological deficiency.
• Previous cardiac surgery.
• Surgery performed with cross clamping of the aorta without open distal anastomosis or open inspection of the distal aorta.
• Presence of implants or devices not compatible with Magnetic Resonance Imaging.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Region Skane

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Igor Zindovic, MD. PhD

Role: PRINCIPAL_INVESTIGATOR

Region Skåne, Skåne university hospital

Locations

Skane University Hospital

Lund, , Sweden

Site Status: RECRUITING

Countries

Sweden

Central Contacts

Igor Zindovic, MD, PhD

Role: CONTACT

igor.zindovic@med.lu.se

+4646175288

Facility Contacts

Igor Zindovic, MD, PhD

Role: primary

Igor.zindovic@med.lu.se

0046702202051

Jacob Ede

Role: backup

Jacob.ede@med.lu.se

004646171000

References

Ede J, Teurneau-Hermansson K, Moseby-Knappe M, Ramgren B, Bjursten H, Ederoth P, Larsson M, Mattsson-Carlgren N, Sjogren J, Wierup P, Nozohoor S, Zindovic I. 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. BMJ Open. 2023 May 25;13(5):e063837. doi: 10.1136/bmjopen-2022-063837.

Reference Type: DERIVED

PMID: 37230515 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2021-02039

Identifier Type: -

Identifier Source: org_study_id