The Aortic Surgery Cerebral Protection Evaluation (ACE) Randomized CardioLink-3 Trial

Sponsor

Unity Health Toronto (Other)

Overall Status

Completed

CT.gov ID

NCT02554032

Collaborator

London Health Sciences Centre (Other)

110

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The ACE trial is a multicentre, randomized controlled trial comparing axillary vs. innominate artery cannulation for established antegrade cerebral perfusion in patients having aortic surgery (thoracic and aortic arch) requiring deep hypothermic circulatory arrest using a non-inferiority trial design.

Condition or Disease	Intervention/Treatment	Phase
Aortic Aneurysm, Thoracic	Procedure: Axillary artery cannulation Procedure: Innominate artery cannulation	N/A

Detailed Description

Surgery on the thoracic aorta often requires a brief period of deep hypothermic circulatory arrest (DHCA). The most feared complication of aortic surgery is neurological injury, which can range from mild cognitive impairment to more severe injuries such as stroke. Due to the significant morbidity and mortality associated with post-operative stroke and neurological dysfunction, cerebral protection techniques have evolved extensively. A recommended approach to cerebral protection during DHCA is to deliver blood to the brain in an antegrade fashion via the arterial system, so called antegrade cerebral perfusion (ACP). Axillary artery cannulation, a form of ACP, has become the preferred method of neuroprotection for aortic operations requiring DHCA. However, axillary artery cannulation requires more surgical time and presents potential complications such as brachial plexus injury, seromas, and limb ischemia. The present study aims to determine whether a less common alternative strategy, innominate artery cannulation, offers similar neuroprotection compared to axillary artery cannulation and reduces operative times. A total of 110 patients undergoing elective aortic surgery will be randomly assigned to one of the two strategies. The primary outcome will be the number of patients with new ischemic lesions found on post-operative diffusion weighted MRI (DW-MRI) and total operative time.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

110 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

A Randomized Controlled Trial of Axillary vs. Innominate Artery Cannulation for Antegrade Cerebral Protection in Aortic Surgery: The ACE Randomized Trial

Study Start Date :

Jun 1, 2015

Actual Primary Completion Date :

Jul 1, 2018

Actual Study Completion Date :

Jul 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Axillary artery cannulation Axillary artery cannulation for antegrade cerebral perfusion	Procedure: Axillary artery cannulation The right axillary artery will be exposed via an infraclavicular incision and a Dacron graft sewn to it in an end to side fashion after 5000 units of IV heparin. Following median sternotomy and full systemic heparinization, CPB will be initiated and the patient cooled. The base of the innominate artery will be clamped, and antegrade cerebral perfusion will be provided via the axillary artery. Following completion of the distal open aortic anastomosis, the clamp on the innominate artery will be removed, CPB via the aorta will be resumed and the patient will be rewarmed. After completion of surgery and weaning from CPB, the axillary artery graft will then be removed, the artery repaired and the skin will be closed.
Active Comparator: Innominate artery cannulation Innominate artery cannulation for antegrade cerebral perfusion	Procedure: Innominate artery cannulation After median sternotomy, systemic heparinization, cannulation of the ascending aorta and right atrium, CPB and systemic cooling will be initiated. The ascending aorta, proximal arch and the base of the innominate artery will be mobilized. Purse-string sutures are placed on the anterior wall of the proximal innominate artery and a pediatric venous cannula inserted using a J wire and sequential dilatation. Circulatory arrest with ACP is provided by clamping the base of the innominate artery and connecting the afferent limb of the CPB circuit to the innominate cannula. Once the distal aortic anastomosis is completed, ACP is discontinued, and full CPB via the aortic graft is resumed. Rewarming and the remaining surgery are then completed.

Arm

Intervention/Treatment

Active Comparator: Axillary artery cannulation

Axillary artery cannulation for antegrade cerebral perfusion

Procedure: Axillary artery cannulation

The right axillary artery will be exposed via an infraclavicular incision and a Dacron graft sewn to it in an end to side fashion after 5000 units of IV heparin. Following median sternotomy and full systemic heparinization, CPB will be initiated and the patient cooled. The base of the innominate artery will be clamped, and antegrade cerebral perfusion will be provided via the axillary artery. Following completion of the distal open aortic anastomosis, the clamp on the innominate artery will be removed, CPB via the aorta will be resumed and the patient will be rewarmed. After completion of surgery and weaning from CPB, the axillary artery graft will then be removed, the artery repaired and the skin will be closed.

Active Comparator: Innominate artery cannulation

Innominate artery cannulation for antegrade cerebral perfusion

Procedure: Innominate artery cannulation

After median sternotomy, systemic heparinization, cannulation of the ascending aorta and right atrium, CPB and systemic cooling will be initiated. The ascending aorta, proximal arch and the base of the innominate artery will be mobilized. Purse-string sutures are placed on the anterior wall of the proximal innominate artery and a pediatric venous cannula inserted using a J wire and sequential dilatation. Circulatory arrest with ACP is provided by clamping the base of the innominate artery and connecting the afferent limb of the CPB circuit to the innominate cannula. Once the distal aortic anastomosis is completed, ACP is discontinued, and full CPB via the aortic graft is resumed. Rewarming and the remaining surgery are then completed.

Outcome Measures

Primary Outcome Measures

new severe ischemic lesions [Post-operative day 4]
The primary safety endpoint of this trial is the proportion of patients with new severe ischemic lesions found on post-operative DW-MRI compared with pre-operative MRI.
Total operative time [Intra-operative]
The primary efficacy endpoint of this trial is the difference in total operative time between the innominate artery cannulation group and the axillary artery cannulation group.

Secondary Outcome Measures

all-cause mortality [30-day]
Stroke or TIA (transient ischemic attack) [30-day]
Neurocognitive dysfunction [Post-operative day 4]
Montreal Cognitive Assessment (MOCA) and Mini-Mental State Examination (MMSE)
Number of new ischemic lesions [Post-operative day 4]
assessed by DW-MRI
Volume of new ischemic lesions [Post-operative day 4]
assessed by DW-MRI
Intracerebral hemorrhage [Post-operative day 4]
assessed by DW-MRI
S100B and Neuron Specific Enolase [24 hours post-op]
Post-operative serum level of circulating biomarkers of neuronal injury
Post-operative sepsis, delirium, seizure, encephalopathy, atrial fibrillation, post-operative myocardial infarction, re-operation [30-day]
Seroma, brachial plexus injury, reduced arm mobility and pain, arm ischemia [30-day]

Other Outcome Measures

Cerebral oximetry desaturation [intra-operative]
CPB (cardiopulmonary bypass) time [intra-operative]
Deep hypothermic circulatory arrest time [intra-operative]
Antegrade cerebral perfusion time [intra-operative]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years.
Elective aortic arch operation.
Planned open distal anastamosis with deep hypothermic circulatory arrest.

Exclusion Criteria:

Patients undergoing surgery for aortic dissection or urgent/emergent operation.
Patients undergoing surgery for total aortic arch replacement.
Patients who are unable to undergo MRI scan (such as due to claustrophobia).
Use of an investigational drug or device at the time of enrolment
Participation in another clinical trial which interferes with performance of the study procedures or assessment of the outcomes