Coronary Artery DiseasePhase 1/2NCT00765908
Ischaemic Pre-Conditioning in Elective Percutaneous Coronary Intervention (PCI) Patients
A Phase 1/2 study testing Angioplasty balloon in people with Coronary Artery Disease, run by University Health Network, Toronto.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- Angioplasty balloon
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- Oct 2008to Oct 2009
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
No sites are listed yet.
About this study
Official title: 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.
Read the 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
- Being tested
- Angioplasty balloon
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Angioplasty balloonDevice
90 second balloon inflation x 2
Angioplasty balloonDevice
30 seconds or less balloon inflations x 2
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | 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. Receives: Device: Angioplasty balloon |
| B | Active comparator | Control group. These patients will have a standard procedure with balloon inflations of 30 seconds or less as per standard. Receives: Device: Angioplasty balloon |
What is being measured
The primary outcome is the main question the study is designed to answer.
Attenuation of infarct size and improved post-ischemia haemodynamic recovery in rat hearts.
Measured: immediate
Secondary outcomes (1)
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.
Measured: immediate
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2008 (estimated)
- Study startOct 2008
- Primary completionOct 2009 (estimated)
- Study completionOct 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- The Hospital for Sick Children
- Investigators
- Vladimir Dzavik, MD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00765908
- Sponsor's protocol ID
- UHN 2008-1
- Status last verified
- Aug 2008
- First submitted
- 1 Oct 2008
- Last updated
- 3 Oct 2008
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ischaemic Pre-Conditioning in Elective PCI Patients - Attenuation of Subsequent Ischaemia in a Validated Animal Model
- ClinicalTrials.gov ID
- NCT00765908
- Acronym / sponsor ID
- UHN 2008-1
- Conditions
- Coronary Artery Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- The Hospital for Sick Children
- Study start
- Oct 2008
- Primary completion
- Oct 2009 (estimated)
- Study completion
- Oct 2009 (estimated)
- First posted
- 3 Oct 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Device: Angioplasty balloonPatients 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. |
| B | Active comparator | Device: Angioplasty balloonControl group. These patients will have a standard procedure with balloon inflations of 30 seconds or less as per standard. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Angioplasty balloon90 second balloon inflation x 2 | Device | A |
| Angioplasty balloon30 seconds or less balloon inflations x 2 | Device | B |
Primary outcome
Attenuation of infarct size and improved post-ischemia haemodynamic recovery in rat hearts.
Time frame: immediate
1 secondary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2008.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vladimir Dzavik, MD principal investigator
University Health Network, Toronto
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Angioplasty balloon in people with Coronary Artery Disease, run by University Health Network, Toronto.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Oct 2008. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Vladimir Dzavik, MD (416-340-4800 ext. 6265, vlad.dzavik@uhn.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Attenuation of infarct size and improved post-ischemia haemodynamic recovery in rat hearts. (time frame: immediate). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2008.