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

NCT ID: NCT00765908

Last Updated: 2008-10-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2009-10-31

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.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Angioplasty balloon

Intervention Type: DEVICE

90 second balloon inflation x 2

B

Control group. These patients will have a standard procedure with balloon inflations of 30 seconds or less as per standard.

Group Type: ACTIVE_COMPARATOR

Angioplasty balloon

Intervention Type: DEVICE

30 seconds or less balloon inflations x 2

Interventions

Angioplasty balloon

90 second balloon inflation x 2

Intervention Type: DEVICE

Angioplasty balloon

30 seconds or less balloon inflations x 2

Intervention Type: DEVICE

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Hospital for Sick Children

OTHER

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

University Health Network

Principal Investigators

Vladimir Dzavik, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Central Contacts

Vladimir Dzavik, MD

Role: CONTACT

Phone: 416-340-4800

Email: vlad.dzavik@uhn.on.ca

Other Identifiers

UHN 2008-1

Identifier Type: -

Identifier Source: org_study_id