Ischaemic Pre-Conditioning in Elective Percutaneous Coronary Intervention (PCI) Patients
Recruitment status was Not yet recruiting
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Basic Science
|Official Title:||Ischaemic Pre-Conditioning in Elective PCI Patients - Attenuation of Subsequent Ischaemia in a Validated Animal Model|
- Attenuation of infarct size and improved post-ischemia haemodynamic recovery in rat hearts. [ Time Frame: immediate ] [ Designated as safety issue: No ]
- Clinical endpoints: (i) induction of IP, defined as a minimum 33% reduction in magnitude of ST segment deviation in the territory of the affected artery between the first and second balloon inflation. (ii) Reduction in CK rise post procedure. [ Time Frame: immediate ] [ Designated as safety issue: No ]
|Study Start Date:||October 2008|
|Estimated Study Completion Date:||October 2009|
|Estimated Primary Completion Date:||October 2009 (Final data collection date for primary outcome measure)|
Patients undergoing elective PCI will be randomised to 90 second balloon inflations rather than the standard less than 30 second inflations in order to induce peri-ischaemic conditioning.
Device: Angioplasty balloon
90 second balloon inflation x 2
Active Comparator: B
Control group. These patients will have a standard procedure with balloon inflations of 30 seconds or less as per standard.
Device: Angioplasty balloon
30 seconds or less balloon inflations x 2
Ischaemic preconditioning (IPC) was first described in a canine model by Murray et al in 1986. By deliberately inducing brief periods of myocardial ischaemia and reperfusion by intermittent occlusion of a coronary artery, the ability of the heart to withstand a subsequent, more prolonged episode of myocardial ischaemia was enhanced, to the extent that infarct size was reduced. This ubiquitous endogenous form of cardioprotection has been observed in many different species and is capable of limiting ischaemia-reperfusion in non-cardiac organs such as the brain, liver, gut, bladder and skin. It has been demonstrated to improve long term clinical outcomes in patients undergoing elective percutaneous coronary intervention (PCI)and to improve distal myocardial perfusion and mitigate infarct size in patients undergoing primary PCI . Despite extensive investigations into the cellular and molecular basis of IP, the precise mechanism(s) whereby myocytes develop tolerance to potentially fatal ischemia is unclear. There are also unanswered questions regarding the necessary frequency and duration of transient ischaemia needed to invoke the protection. Less than 60 seconds has been shown to be too short in some studies, whereas there is clearly an upper limit (above 10 minutes in most tissues) whereupon the preconditioning stimulus itself may have detrimental effects. Nonetheless, previous studies of IP in the heart have shown that a factor is released during IP, which can be transferred to protect another heart . Furthermore, preliminary data by our group suggests that 3 or 4 cycles of 5 minutes of transient limb ischaemia and 5 minutes of reperfusion (remote ischemic preconditioning, rIPC) leads to the release of a circulating cardioprotective factor(s) into the blood stream, which reduces cardiac damage in experimental animals, and patients undergoing cardiac surgery.
The proposed study will test whether these humoral factors are released from the heart, into the bloodstream, by patients undergoing PCI. The Langendorff method, in which a perfused rat heart is isolated ex vivo, is a well validated technique which has been used widely in studies of IP. It allows us to measure directly several cardiac physiological parameters, as well as the myocardial infarct size after prolonged ischaemia. We have previously shown that serum from healthy adults undergoing rIPC can be dialysed to produce a crystalloid perfusate. When this is used in the Langendorff preparation myocardial infarction size is reduced. We will employ the same method to examine the possible release, and any dose response to a pre-conditioning stimulus (coronary angioplasty balloon inflation) of varying duration in adults undergoing elective PCI.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00765908
|Contact: Vladimir Dzavik, MD||416-340-4800 ext firstname.lastname@example.org|
|Principal Investigator:||Vladimir Dzavik, MD||University Health Network, Toronto|