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

NCT04962646 | Recruiting DMC

• 1 other identifier: 2021-02039
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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

Keywords

Aorta, Dissection, Stroke

Outcome Measures

Primary Outcomes (2)

• Number of ischemic lesions on magnetic resonance imaging (MRI)

  Number of ischemic lesions visualized using MRI

  MRI will be performed before postoperative day 7. When not possible due to medical considerations, MRI may be performed up to 30 days after surgery.

• Size of ischemic lesions on magnetic resonance imaging (MRI)

  Size of ischemic lesions visualized using MRI

  MRI will be performed before postoperative day 7. When not possible due to medical considerations, MRI may be performed up to 30 days after surgery.

Secondary Outcomes (26)

• Clinical neurological injury

  Up to postoperative day 7.

• Neurological function

  Postoperative day 4 or at discharge from the ICU.

• Neurological function

  Postoperative day 4 or at discharge from the ICU.

• Level of consciousness

  Postoperative day 4 or at discharge from the ICU.

• Levels of S100B.

  Preoperatively, 24 hours from start of surgery, postoperative day 4 and 3 months after surgery.

Study Arms (2)

Intervention

EXPERIMENTAL

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.

Procedure: Carbon dioxide flooding

Control

NO INTERVENTION

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.

Interventions

Carbon dioxide flooding 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.

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Region Skane: lead

Study Sites (1)

Skane University Hospital

Lund, Sweden

RECRUITING

Related Publications (1)

• 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.

  PMID: 37230515 DERIVED

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Igor Zindovic, MD. PhD

  Region Skåne, Skåne university hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Igor Zindovic, MD, PhD

CONTACT

+4646175288; igor.zindovic@med.lu.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, randomized, controlled, patient- and reviewer blinded interventional study.

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: July 15, 2021
• Study Start: January 1, 2022
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: April 11, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)