Contact information
Type
Scientific
Primary contact
Dr David Ansley
ORCID ID
Contact details
University of British Columbia
Department of Anesthesiology
Pharmacology and Therapeutics
Room 3300
3rd Floor JPP
910 West 10th Ave
Vancouver
V5Z 4E3
Canada
-
david.ansley@vch.ca
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00734383
Protocol/serial number
210938
Study information
Scientific title
Propofol cardioprotection during ischaemia-reperfusion to preserve myocardial function: an interventional randomised efficacy study
Acronym
PRO-TECT II
Study hypothesis
Elevated oxidant stress may occur during myocardial ischaemia-reperfusion, influencing release and action of tumour necrosis factor-alpha (TNF-a), which inhibits cardioprotective endothelial NOS (eNOS), enhances endothelin-1 (ET-1) formation, and promotes the conversion of nitric oxide to cardiotoxic peroxynitrite. These factors cause cardiac dysfunction. Effective antioxidant intervention during ischaemia-reperfusion will preserve myocardial function.
Ethics approval
University of British Columbia (UBC) Clinical Research Ethics Board, 22/09/2009, ref: H04-70456
Study design
Interventional treatment randomised double-blind (subject, investigator) placebo-controlled parallel assignment efficacy study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Cardioprotection for type II diabetics
Intervention
1. Experimental - propofol cardioprotection:
Ten minutes prior to initiation of CPB, we will stop delivery of isoflurane, inject 1 mg/kg intravenous (iv) and then continuously infuse propofol at 120 µg/kg/min iv until 15 minutes after release of the aortic cross clamp (reperfusion).
2. Experimental - volatile anaesthesia preconditioning:
Anaesthesia will be maintained using an inspired concentration of isoflurane between 0.5 - 2% before, during, and after CPB, without administration of propofol. For ten minutes prior to the initiation of CPB we will deliver Isoflurane 2.5% end tidal then resume maintenance anaesthesia as described.
Total duration of treatment and follow up is currently up to 30 days post-operatively at the current time.
Intervention type
Drug
Phase
Not Applicable
Drug names
Propofol
Primary outcome measure
Peri-operative plasma 15 f2t isoprostane, a biologically active marker of oxidative stress. Timeframe: 24 hours post-operation.
Secondary outcome measures
Biochemical outcomes:
1. Plasma total antioxidant concentration
2. Systemic and coronary sinus levels of troponin I, ET-1, TNF-a, and peroxynitrite formation in blood
3. Gene and protein expression of inducible NOS (iNOS) and eNOS
4. Protein expression of Akt and its activation
5. Evidence of superoxide formation in atrial tissue
Clinical outcomes:
6. Incidence rate of low cardiac output syndrome during the first 6 hours after surgery
7. Incidence rate of inotropic support or intra-aortic balloon counterpulsation required for greater than 30 minutes duration to treat low cardiac output syndrome
8. Intensive care unit and hospital lengths of stay
Overall trial start date
01/04/2007
Overall trial end date
31/03/2012
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Adult patients aged 18 - 80 years, either sex
2. Undergoing primary coronary artery bypass graft (CABG) surgery requiring cardiopulmonary bypass (CPB) at the Vancouver General Hospital
3. Require revascularisation of three or more coronary arteries with an anticipated aortic cross-clamp time of at least 60 minutes
4. Have a pre-operative systolic blood pressure above 90 mmHg in the absence of inotropic or mechanical support
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
144 (study recruitment completed)
Participant exclusion criteria
1. Type I diabetes mellitus (defined as an established history and diagnosis of diabetes mellitus requiring insulin therapy from the time of diagnosis)
2. Co-existing valvular heart disease (moderate to severe aortic stenosis or mitral regurgitation)
3. Acute or evolving myocardial infarction
4. History of hypersensitivity to propofol or any of its formulation components
5. Taking non-steroidal anti-inflammatory drugs, vitamin C, or vitamin E within five days of surgery
Recruitment start date
01/04/2007
Recruitment end date
31/03/2012
Locations
Countries of recruitment
Canada
Trial participating centre
University of British Columbia
Vancouver
V5Z 4E3
Canada
Sponsor information
Organisation
University of British Columbia (Canada)
Sponsor details
Office of Research Services
#102 - 6190 Agronomy Road
Vancouver
British Columbia
V6T 1Z3
Canada
Sponsor type
University/education
Website
Funders
Funder type
Research organisation
Funder name
Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: 210938)
Alternative name(s)
Instituts de Recherche en Santé du Canada, CIHR
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
Canada
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26721648