PRO-TECT II: Propofol cardioprotection for type II diabetics

ISRCTN	ISRCTN70879185
DOI	https://doi.org/10.1186/ISRCTN70879185
ClinicalTrials.gov (NCT)	NCT00734383
Protocol serial number	210938
Sponsor	University of British Columbia (Canada)
Funder	Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: 210938)

Submission date: 05/03/2010
Registration date: 11/03/2010
Last edited: 04/01/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr David Ansley
Scientific

University of British Columbia
Department of Anesthesiology, Pharmacology and Therapeutics
Room 3300, 3rd Floor JPP
910 West 10th Ave
Vancouver
V5Z 4E3
Canada

Email	david.ansley@vch.ca

Study information

Primary study design	Interventional
Study design	Interventional treatment randomised double-blind (subject, investigator) placebo-controlled parallel assignment efficacy study
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Propofol cardioprotection during ischaemia-reperfusion to preserve myocardial function: an interventional randomised efficacy study
Study acronym	PRO-TECT II
Study objectives	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(s)	University of British Columbia (UBC) Clinical Research Ethics Board, 22/09/2009, ref: H04-70456
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Propofol
Primary outcome measure(s)	Peri-operative plasma 15 f2t isoprostane, a biologically active marker of oxidative stress. Timeframe: 24 hours post-operation.
Key secondary outcome measure(s)	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
Completion date	31/03/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	80 Years
Sex	All
Target sample size at registration	144
Key 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
Key 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
Date of first enrolment	01/04/2007
Date of final enrolment	31/03/2012

Locations

Countries of recruitment

Canada

Study participating centre

University of British Columbia

Vancouver
V5Z 4E3
Canada

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/04/2016		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

As of 20/12/2011, target number of participants have been modified to study recruitment completed.
Previous target number of participants: 144