Ischaemic Pre-Conditioning in Elective Percutaneous Coronary Intervention (PCI) Patients
Primary Purpose
Coronary Artery Disease
Status
Unknown status
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Angioplasty balloon
Angioplasty balloon
Sponsored by
About this trial
This is an interventional basic science trial for Coronary Artery Disease
Eligibility Criteria
Inclusion Criteria:
- Ability to give written informed consent.
- All patients who are listed for elective PCI of at least one major epicardial artery.
- Patients ≥ 18 years and ≤80 years of age.
Exclusion Criteria:
- Any patient who has experienced chest pain within the preceding 24 hrs
- Any patient who exhibits haemodynamic instability (systolic BP <90mmHg, pulmonary oedema);
- Any patient with electrophysiologic instability (arrythmias eg rapid AF) or an abnormal baseline electrocardiogram (ECG) (e.g., significant ST segment depression, left bundle-branch block) which precludes analysis of the ST segment shift during PCI
- Patients unable to give informed consent
- Previous inclusion in this or any other clinical trial within one month prior to inclusion.
- Diabetes
- Uncontrolled hypertension (BP>180/110).
- Anaemia (Hb <10g/l).
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
A
B
Arm Description
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.
Control group. These patients will have a standard procedure with balloon inflations of 30 seconds or less as per standard.
Outcomes
Primary Outcome Measures
Attenuation of infarct size and improved post-ischemia haemodynamic recovery in rat hearts.
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT00765908
First Posted
October 1, 2008
Last Updated
October 2, 2008
Sponsor
University Health Network, Toronto
Collaborators
The Hospital for Sick Children
1. Study Identification
Unique Protocol Identification Number
NCT00765908
Brief Title
Ischaemic Pre-Conditioning in Elective Percutaneous Coronary Intervention (PCI) Patients
Official Title
Ischaemic Pre-Conditioning in Elective PCI Patients - Attenuation of Subsequent Ischaemia in a Validated Animal Model
Study Type
Interventional
2. Study Status
Record Verification Date
August 2008
Overall Recruitment Status
Unknown status
Study Start Date
October 2008 (undefined)
Primary Completion Date
October 2009 (Anticipated)
Study Completion Date
October 2009 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
University Health Network, Toronto
Collaborators
The Hospital for Sick Children
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study aims to assess the potential for ischaemic peri-conditioning (IP) in elective percutaneous coronary intervention (PCI) patients to attenuate ischaemia in an animal model of myocardial infarct.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Experimental
Arm Description
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.
Arm Title
B
Arm Type
Active Comparator
Arm Description
Control group. These patients will have a standard procedure with balloon inflations of 30 seconds or less as per standard.
Intervention Type
Device
Intervention Name(s)
Angioplasty balloon
Intervention Description
90 second balloon inflation x 2
Intervention Type
Device
Intervention Name(s)
Angioplasty balloon
Intervention Description
30 seconds or less balloon inflations x 2
Primary Outcome Measure Information:
Title
Attenuation of infarct size and improved post-ischemia haemodynamic recovery in rat hearts.
Time Frame
immediate
Secondary Outcome Measure Information:
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Ability to give written informed consent.
All patients who are listed for elective PCI of at least one major epicardial artery.
Patients ≥ 18 years and ≤80 years of age.
Exclusion Criteria:
Any patient who has experienced chest pain within the preceding 24 hrs
Any patient who exhibits haemodynamic instability (systolic BP <90mmHg, pulmonary oedema);
Any patient with electrophysiologic instability (arrythmias eg rapid AF) or an abnormal baseline electrocardiogram (ECG) (e.g., significant ST segment depression, left bundle-branch block) which precludes analysis of the ST segment shift during PCI
Patients unable to give informed consent
Previous inclusion in this or any other clinical trial within one month prior to inclusion.
Diabetes
Uncontrolled hypertension (BP>180/110).
Anaemia (Hb <10g/l).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vladimir Dzavik, MD
Phone
416-340-4800
Ext
6265
Email
vlad.dzavik@uhn.on.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vladimir Dzavik, MD
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Ischaemic Pre-Conditioning in Elective Percutaneous Coronary Intervention (PCI) Patients
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