Ischaemic Pre-Conditioning in Elective Percutaneous Coronary Intervention (PCI) Patients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2008 by University Health Network, Toronto.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
The Hospital for Sick Children
Information provided by:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00765908
First received: October 1, 2008
Last updated: October 2, 2008
Last verified: August 2008
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Device: Angioplasty balloon
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Attenuation of infarct size and improved post-ischemia haemodynamic recovery in rat hearts. [ Time Frame: immediate ] [ Designated as safety issue: No ]

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. [ Time Frame: immediate ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
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)
Arms Assigned Interventions
Experimental: A
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00765908

Contacts
Contact: Vladimir Dzavik, MD 416-340-4800 ext 6265 vlad.dzavik@uhn.on.ca

Sponsors and Collaborators
University Health Network, Toronto
The Hospital for Sick Children
Investigators
Principal Investigator: Vladimir Dzavik, MD University Health Network, Toronto
  More Information

No publications provided

Responsible Party: Dr Vladimir Dzavik, University Health Network
ClinicalTrials.gov Identifier: NCT00765908     History of Changes
Other Study ID Numbers: UHN 2008-1
Study First Received: October 1, 2008
Last Updated: October 2, 2008
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on September 16, 2014