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

October 2, 2008 updated by: University Health Network, Toronto

Ischaemic Pre-Conditioning in Elective PCI Patients - Attenuation of Subsequent Ischaemia in a Validated Animal Model

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Device: Angioplasty balloon
30 seconds or less balloon inflations 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
90 second balloon inflation x 2
Device: Angioplasty balloon
30 seconds or less balloon inflations x 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Attenuation of infarct size and improved post-ischemia haemodynamic recovery in rat hearts.
Time Frame: immediate
immediate

Secondary Outcome Measures

Outcome Measure
Time Frame
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
immediate

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Collaborators

The Hospital for Sick Children

Investigators

  • Principal Investigator: Vladimir Dzavik, MD, University Health Network, Toronto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (Anticipated)

October 1, 2009

Study Completion (Anticipated)

October 1, 2009

Study Registration Dates

First Submitted

October 1, 2008

First Submitted That Met QC Criteria

October 2, 2008

First Posted (Estimate)

October 3, 2008

Study Record Updates

Last Update Posted (Estimate)

October 3, 2008

Last Update Submitted That Met QC Criteria

October 2, 2008

Last Verified

August 1, 2008

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UHN 2008-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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