Carbon Dioxide Surgical Field Flooding and Aortic No-touch Off-pump Coronary Artery Bypass Grafting to Reduce Neurological Injuries After Surgical Coronary Revascularization (CANON): a Randomised, Controlled, Investigator and Patient Blinded Single Center Superiority Trial With Three Parallel Arms. (CANON)

The objective of this study is to investigate the value of employing the aortic no-touch off-pump coronary artery bypass technique and the practice of carbon dioxide surgical field flooding for the prevention of type 1 and 2 neurological injuries following surgical coronary revascularization.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Stroke; Postoperative Delirium; Postoperative Cognitive Dysfunction; Coronary Artery Bypass Surgery; Neurological Injury; Off-Pump Coronary Artery Bypass
• Intervention / Treatment: Procedure: aortic no-touch OPCABG; Procedure: OPCABG with partial clamp applying carbon dioxide; Procedure: OPCABG with partial clamp

Detailed Description

Neurological injuries remain a major concern following coronary artery bypass grafting (CABG) that offset survival benefit of CABG over percutaneous coronary interventions. Among numerous efforts to combat this issue, is off-pump CABG (OPCABG) that obviates the need for extracorporeal circulation and is associated with improved outcomes. The objective of this study is to examine whether the neuroprotective effect of OPCABG can be further pronounced by the use of two state-of-the-art operating techniques.

In this randomised, controlled, investigator and patient blinded single center superiority trial with three parallel arms a total of 360 patients will be recruited. They will be allocated in a 1:1:1 ratio to two treatment and one control arms. Treatment arms undergoing either aortic no-touch OPCABG or OPCABG with a partial clamp applying carbon dioxide surgical field flooding will be compared against control arm undergoing OPCABG. The primary endpoint will be the appearance of new lesions on control brain magnetic resonance imaging 3 days after surgery. Secondary endpoints will include the prevalence of new focal neurological deficits in the first 7 days after surgery, the occurrence of postoperative cognitive dysfunction at either 1 week or 3 months after surgery and the incidence of delirium in the first 7 days after surgery. Data will be analysed on intention-to-treat principles and a per protocol basis.

• Study Type: Interventional
• Enrollment (Actual): 192
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Kujawsko-Pomorskie
    • Bydgoszcz, Kujawsko-Pomorskie, Poland, 85-001
      • Department of Cardiac Surgery, Dr Antoni Jurasz Memorial University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• elective and/or urgent coronary artery bypass

Exclusion Criteria:

• emergent and salvage setting
• score below age- and education-adjusted cut-off scores in mini mental state examination
• score above 8 on the subscales of hospital anxiety and depression scale
• neurologic deficit of any etiology
• previous psychiatric illness
• use of tranquilizers or antipsychotics
• alcohol or drug abuse
• history of cardiac surgery
• left ventricular ejection fraction less than 30%
• extracranial carotid artery stenosis of more than 70%
• body mass index of more than 35 kg/m2
• any contraindication for magnetic resonance imaging (e.g., magnetic resonance imaging - incompatible implantable device and claustrophobia)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: aortic no-touch OPCABG	Procedure: aortic no-touch OPCABG; (Study arm 1) In this intervention only the internal mammary artery grafts will be used (i.e. left internal mammary artery graft, right internal mammary artery graft, or a Y-graft that uses right internal mammary artery graft anastomosed onto left internal mammary artery graft to allow for a wide territory of myocardial revascularization). However, in the rare event that the aforementioned approach is insufficient to reach all target vessels, a reversed (great) saphenous vein graft may be used to extend the left internal mammary artery graft or the right internal mammary artery graft.
Experimental: OPCABG with partial clamp applying carbon dioxide	Procedure: OPCABG with partial clamp applying carbon dioxide; (Study arm 2) In this intervention chest cavity will be insufflated with carbon dioxide at a flow above 5 l/min during the entire surgical procedure.
Active Comparator: OPCABG with partial clamp	Procedure: OPCABG with partial clamp; (Study arm 3) This is the control arm undergoing "traditional" OPCABG with partial clamp.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New lesions on control brain magnetic resonance imaging.	Appearance of new lesions on control brain magnetic resonance imaging 3 days after surgery.	3 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New focal neurological deficits.	Prevalence of new focal neurological deficits in the first 7 days after surgery.	7 days after surgery
Occurence of postoperative cognitive dysfunction	Occurrence of postoperative cognitive dysfunction at either 1 week or 3 months after surgery	1 week or 3 months after surgery
Incidence of delirium	Incidence of delirium in the first 7 days after surgery.	7 days after surgery

Collaborators and Investigators

• Sponsor: Collegium Medicum w Bydgoszczy
• Investigators: Principal Investigator: Krzysztof Szwed, M.D. Ph.D., Department of Clinical Neuropsychology, Nicolaus Copernicus University, Collegium Medicum, Poland; Study Chair: Alina Borkowska, Professor, Department of Clinical Neuropsychology, Nicolaus Copernicus University, Collegium Medicum, Poland

Publications and helpful links

General Publications

• Krzysztof S, Wojciech P, Zbigniew S, Mariusz K, Remigiusz T, Damian P, Magdalena S, Marta T, Lech A, Alina B. CArbon dioxide surgical field flooding and aortic NO-touch off-pump coronary artery bypass grafting to reduce Neurological injuries after surgical coronary revascularisation (CANON): protocol for a randomised, controlled, investigator and patient blinded single-centre superiority trial with three parallel arms. BMJ Open. 2017 Jul 10;7(7):e016785. doi: 10.1136/bmjopen-2017-016785.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2017
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): July 1, 2018

Study Registration Dates

• First Submitted: February 28, 2017
• First Submitted That Met QC Criteria: March 3, 2017
• First Posted (Actual): March 9, 2017

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: February 3, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Stroke; Coronary Artery Disease; Bypass surgery; Coronary Artery Bypass Grafting; Coronary Artery Bypass Surgery; Brain Injuries; Neurological Injury; Postoperative Cognitive Dysfunction; Postoperative Delirium; Beating Heart Coronary Artery Bypass; Off-Pump Coronary Artery Bypass
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Postoperative Complications; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Cognition Disorders; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Delirium; Wounds and Injuries; Cognitive Dysfunction; Postoperative Cognitive Complications; Trauma, Nervous System
• Other Study ID Numbers: KB 60/2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The data that support the findings of this study are available from the corresponding author upon reasonable request.
• IPD Sharing Time Frame: Available without time limits.
• IPD Sharing Access Criteria: The data that support the findings of this study are available from the corresponding author upon reasonable request.
• IPD Sharing Supporting Information Type: Study Protocol; Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No