Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001142224
Ethics application status
Approved
Date submitted
24/06/2018
Date registered
12/07/2018
Date last updated
12/07/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Can we reduce cerebral injury in patients undergoing combined aortic valve replacement and coronary artery bypass grafting?
Scientific title
Does Axillary Inflow Reduce Cerebral Injury in patients undergoing Combined Aortic Valve Replacement and Coronary Artery Bypass Grafting?
Secondary ID [1] 295159 0
Nil known
Universal Trial Number (UTN)
U1111-1215-5081
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cerebral injury 308272 0
Aortic valve disease 308273 0
Coronary artery disease 308274 0
Axillary cannulation 308275 0
aortic cannulation 308276 0
Condition category
Condition code
Surgery 307284 307284 0 0
Surgical techniques
Cardiovascular 307285 307285 0 0
Coronary heart disease
Stroke 307286 307286 0 0
Ischaemic
Cardiovascular 307287 307287 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cerebral injury is a debilitating complication of cardiac surgery occurring in up to 3-4% of patients undergoing combined aortic valve replacement (AVR) and coronary artery bypass grafting (CABG). Peri-operative stroke is often multifactorial and resulting from emboli from the heart-lung machine, cannulation site and cross-clamp site. Traditionally the distal ascending aorta is cannulated to provide arterial inflow from the heart lung machine for patients undergoing cardiac surgery. In patients with significant aortic atheroma, the risk of stroke may be minimised by reducing instrumentation of diseased aorta. Alternative cannulation sites that prevent cannulation of the aorta include: right axillary cannulation and common femoral cannulation. Right axillary cannulation is increasingly being used for major aortic surgery due to a improved neurological outcomes. It has not yet been shown if this benefit will extend to other aspects of cardiac surgery with a higher risk of stroke.

This study is a randomised control trail comparing cannulation strategy; with right axillary cannulation or central aortic cannulation for intermediate or high risk for cerebral injury after combined AVR + CABG.

Patients in the intervention arm will have arterial cannulation via the right axillary artery. Right axillary cannulation involves an approximately 5cm incision inferior to the right clavicle with dissection through pectorals major, pectorals minor is either retracted laterally or divided and the axillary artery is secured. The vessel is assess for suitability and is accessed either through direct cannulation with and appropriately sized arterial return cannula or an 8mm pre-clotted Dacron graft is anastomosed to the vessel in an end-to-side fashion through which perfusion is completed. The remainder of the procedure is unchanged regardless of cannulation strategy.

All procedures will be undertaken by a consultant cardiothoracic surgeon. Aortic valve replacement + coronary artery bypass surgery takes approximately 4-6 hours with central cannulation, axillary artery cannulation adds approximately 15-20 minutes to the operative time overall, with no additional cardiopulmonary bypass or cross-clamp time.
Intervention code [1] 301498 0
Treatment: Surgery
Comparator / control treatment
Control group patients receive the currently accepted cannulation strategy with cannulation of the distal ascending aorta. There is no difference in the remainder of the operation between cannulation strategies. Aortic valve replacement + coronary artery bypass surgery takes approximately 4-6 hours overall.
Control group
Active

Outcomes
Primary outcome [1] 306245 0
To determine if any difference in radiological evident cerebral injury post-AVR + CABG dependant on cannulation strategy. Radiological evidence of cerebral injury is assessed by MRI brain. The number of emboli, distribution of emboli and a volumetric assessment of cerebral embolic load is collected in every patient. Pre-existing disease is excluded with a pre-operative MRI brain that is performed within 7 days of the operation. To minimise data heterogeneity, all MRI brains are performed on the same 3T MRI scanner in the one institution, all images are interpreted by a consultant neuro-radiologist. (Pre-op MRI sequences: Sag t1, Ax DWI, Ax T2 Flair, Ax SWI, Cor T2, TOF MRA - Post-op MRI sequences: Ax DWI, Ax SWI, Ax T2 Flair). The radiologist is blinded as to cannulation strategy. Any difference in number, volume or distribution of emboli is deemed clinically significant.
Timepoint [1] 306245 0
7 days post-cardiac surgery
Primary outcome [2] 306246 0
To determine if there is any difference in clinically relevant cerebral injury between cannulation strategy for patients undergoing combined AVR+CABG. All patients will be reviewed by a consultant neurologist and have clinical and quantitative assessment of evidence of stroke using the National Institute of Health Stroke Score (NIHSS) performed on Day 7 post-operatively (or day of discharge if before day 7). All patients are reviewed by a consultant neurologist with NIHSS assessed within 7 days of the operation. The neurologist is blinded to the cannulation strategy. The patient is also followed up at 3 months post-operatively to determine the presence of any permanent neurological deficit. Any difference in NIHSS between groups is deemed clinically significant.
Timepoint [2] 306246 0
Primary outcome day 7 post-operatively to assess early neurological deficit. Review at 3 months post-operatively to assess permanent neurological dysfunction
Primary outcome [3] 306247 0
All cause mortality post-operatively.
Timepoint [3] 306247 0
3 months
Secondary outcome [1] 347985 0
Any difference in wound complications between groups assessed by requirement for antibiotics, re-operation or prolonged hospitalisation as a result of wound infection, wound haematoma or wound dehiscence.
Timepoint [1] 347985 0
7 days
Secondary outcome [2] 347986 0
Any difference in renal dysfunction between intervention or control group. Presence and degree of renal dysfunction is assessed using the serum creatinine criteria of the Acute Kidney Injury Network staging system, accordingly the requirement of any renal replacement therapy is included as stage 3 acute kidney injury regardless of indication.
Timepoint [2] 347986 0
Duration of hospital admission
Secondary outcome [3] 347987 0
Any difference in intubation time post-operatively. Intubation time expressed in hours from the time the patient arrived in the intensive care unit post-operatively until extubation.
Timepoint [3] 347987 0
7 days post-op

Eligibility
Key inclusion criteria
All patients undergoing AVR+CABG at Royal North Shore Hospital including emergency surgery
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with previous history of stroke
Patients not agreeable/ineligible for MRI brain (e.g claustrophobia, non-compatible implantable devices)
Patients with significant right subclavian stenosis
Patients with pre-existing brachial plexus palsy
Patients unable to complete 3 month follow-up
Patients unable to provide their own consent

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sequentially numbered, sealed opaque envelopes with envelopes be filled by an individual not related to the study
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Pilot study to determine feasibility, safety and if any trend towards difference is apparent which could lead to larger multi-centred study to determine true difference

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
27/06/2018
Date of last participant enrolment
Anticipated
30/06/2020
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 11121 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 22937 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 299749 0
Hospital
Name [1] 299749 0
Royal North Shore Hospital
Country [1] 299749 0
Australia
Primary sponsor type
Hospital
Name
Departent of cardiothoracic Surgery, Royal North Shore Hospital
Address
Department of Cardiothoracic Surgery
Royal North Shore Hospital
Reserve Road
St Leonard's
NSW 2065
Country
Australia
Secondary sponsor category [1] 299088 0
Individual
Name [1] 299088 0
Levi Bassin
Address [1] 299088 0
Department of Cardiothoracic Surgery
Royal North Shore Hospital
Reserve Road
St Leonard's
NSW 2065
Country [1] 299088 0
Australia
Secondary sponsor category [2] 299246 0
Individual
Name [2] 299246 0
Campbell Flynn
Address [2] 299246 0
Department of Cardiothoracic Surgery
Royal North Shore Hospital
Reserve Road
St Leonard's
NSW 2065
Country [2] 299246 0
Australia
Secondary sponsor category [3] 299247 0
Individual
Name [3] 299247 0
John Brereton
Address [3] 299247 0
Department of Cardiothoracic Surgery
Royal North Shore Hospital
Reserve Road
St Leonard's
NSW 2065
Country [3] 299247 0
Australia
Other collaborator category [1] 280193 0
Individual
Name [1] 280193 0
David Marshman
Address [1] 280193 0
Department of Cardiothoracic Surgery
Royal North Shore Hospital
Reserve Road
St Leonard's
NSW 2065
Country [1] 280193 0
Australia
Other collaborator category [2] 280194 0
Individual
Name [2] 280194 0
Manu Mathur
Address [2] 280194 0
Department of Cardiothoracic Surgery
Royal North Shore Hospital
Reserve Road
St Leonard's
NSW 2065
Country [2] 280194 0
Australia
Other collaborator category [3] 280195 0
Individual
Name [3] 280195 0
Peter Brady
Address [3] 280195 0
Department of Cardiothoracic Surgery
Royal North Shore Hospital
Reserve Road
St Leonard's
NSW 2065
Country [3] 280195 0
Australia
Other collaborator category [4] 280196 0
Individual
Name [4] 280196 0
Michael Harden
Address [4] 280196 0
Department of Cardiothoracic Surgery
Royal North Shore Hospital
Reserve Road
St Leonard's
NSW 2065
Country [4] 280196 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300639 0
Northern Sydney Health District Human Research Ethics Committee
Ethics committee address [1] 300639 0
Kolling Building, Level 13
Royal North Shore Hospital
St Leonard's
NSW 2065
Ethics committee country [1] 300639 0
Date submitted for ethics approval [1] 300639 0
Approval date [1] 300639 0
25/05/2018
Ethics approval number [1] 300639 0
RESP/15/238

Summary
Brief summary
Stroke is a potential devastating complication of cardiac surgery occurring in up to 3-4% of patients undergoing combined aortic valve replacement (AVR) and coronary artery bypass grafting (CABG). Peri-operative stroke is often multifactorial and resulting from debris from the heart-lung machine and the sites of heart-lung machine into the blood-stream. Traditionally the first part of the main blood vessel leaving the heart (the aorta) punctured to provide oxygen-rich blood inflow from the heart lung machine for patients undergoing heart surgery. In patients with significant aortic atheroma, the risk of stroke may be minimised by reducing manipulation of diseased aorta. Alternative cannulation sites that do not require a puncture of the aorta include: right axillary cannulation (right arm artery) and common femoral cannulation (upper leg artery). Right axillary cannulation is increasingly being used for major aortic surgery due to a proven reduction in stroke. It has not yet been shown if this benefit will extend to other aspects of cardiac surgery that have a higher risk of stroke.

This study comparing cannulation strategy to determine if there is a reduction in stroke. Patients undergoing combined aortic valve replacement + coronary artery bypass surgery, who are deemed intermediate or high risk of stroke are randomly assigned to receive either right axillary cannulation or central aortic cannulation

Patients in the intervention arm will have arterial cannulation via the right axillary artery. Right axillary cannulation involves an approximately 5cm incision below the right collar bone to get access to the artery used for inflow to the heart-lung machine. The vessel is assessed for suitability to ensure it is suitable for use and if so they are connected to the heart-lung machine via this artery.

Patients in the control arm will be have the arterial inflow from the heart lung machine via the aorta as is conventionally done.

The remainder of the procedure is unchanged regardless of cannulation strategy.

In order to determine a difference in stroke the participant will have an MRI scan of the brain and an assessment performed in the hospital prior to the operation, this will also be repeated within seven days after the operation. The participant will also be required to follow up with a neurologist 3 months after the operation in addition to the routine post-operative review with the cardiothoracic surgeon.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84302 0
Dr Levi Bassin
Address 84302 0
Department of Cardiothoracic Surgery
Royal North Shore Hospital
Reserve Road
St Leonard's
NSW 2065
Country 84302 0
Australia
Phone 84302 0
+61 2 9926 7111
Fax 84302 0
Email 84302 0
admin@levibassin.com
Contact person for public queries
Name 84303 0
Dr Campbell Flynn
Address 84303 0
Department of Cardiothoracic Surgery
Royal North Shore Hospital
Reserve Road
St Leonard's
NSW 2065
Country 84303 0
Australia
Phone 84303 0
+61 2 9926 7111
Fax 84303 0
Email 84303 0
campbellf@doctors.org.uk
Contact person for scientific queries
Name 84304 0
Dr Campbell Flynn
Address 84304 0
Department of Cardiothoracic Surgery
Royal North Shore Hospital
Reserve Road
St Leonard's
NSW 2065
Country 84304 0
Australia
Phone 84304 0
+61 2 9926 7111
Fax 84304 0
Email 84304 0
campbellf@doctors.org.uk

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.