Clinical trial NCT00334373: Post Conditioning in PCI for Acute ST Elevation Myocardial Infarction
Official title: Post Conditioning in PCI for Acute ST Elevation Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myocardial Infarction
Keywords: Myocardial infarction
Magnetic Resonance Imaging
Coronary Angioplasty
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Foothills Interventional Cardiology Research Group
First posted: 2006-06-07
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to compare post-conditioning to standard angioplasty (50/50 chance) in patients who present with an acute heart attack and are taken directly for an angioplasty procedure. Post conditioning is a procedure that involves balloon inflation followed by deflation in a series of cycles that appears to show (based on early data) that it can decrease the amount of damage to the heart muscle as compared to standard angioplasty procedures.

Hypothesis: For Subjects undergoing direct PCI for STEMI, post conditioning with cycles of balloon inflation/deflation within the first minute following the re-establishment of coronary blood blow, will decrease the amount of irreversible myocardial damage assessed by delayed enhancement contrast CMR.

Detailed description: In patients who suffer a myocardial infarction, the blood flow usually ceases due to plaque rupture leading to thrombus formation and vessel occlusion. The resultant entity is known as ST Elevation segment myocardial infarction (STEMI) and is a significant health issue in industrialized countries. There are over 50,000 STEMI's every year in Canada and up to 10% of these patients die in hospital and another 10% die within the first year after their heart attack. The more common problem however is not death, but irreparable damage to the left ventricle leading to LV dysfunction and subsequent heart failure and arrythmias. Re-establishing blood flow promptly by administering plasminogen activators (lytics) or mechanically by performing angioplasty is possible and has lowered the mortality rate dramatically.

Although reperfusion is necessary, it gives rise to an entity known as ischemia-reperfusion where acutely re-establishing blood flow and oxygen levels of the heart has detrimental effects. Clinically this is manifested as no-reflow that causes subsequent damage to the left ventricle and decreases the beneficial affect of early reperfusion by PCI. The ischemia-reperfusion effect sets off a molecular cascade of events involving unfavorable interaction between neutrophils, platelets and endothelium, that is fairly well identified. Efforts to pharmacologically block this effect have not proven to be particularly effective.

Post conditioning follows from a concept of pre-conditioning in animals that showed a decrease in myocardial infarct size. Pre-conditioning is not useful as it requires to be performed prior to the development of ischemia/injury. Post conditioning in preliminary studies with animals and one small study in humans have shown promising results for decrease in infarct size. Post conditioning is a procedure of gradual conditioning in which the artery is opened and closed in cycles with inflation/deflation of the culprit artery followed immediately by standard PCI and placement of stent.

Eligibility criteria: Inclusion Criteria:

* 18 years and over
* ST elevation of \>/= 2mm in 3 consecutive anterior leads or \>/= to 2 mm in leads II, III and AVF with total 8 mm ST shift (ST depression of 1 mm in ant or lat leads)

Exclusion Criteria:

* Cardiogenic shock or severe heart failure
* Inability to undergo CMR (metallic objects or claustrophobia)
* Previous MI
* TIMI 2-3 flow in target artery
* Collaterals to infarct related artery \> Rentrop grade 1
* Inability to undertake successful PCI at time of angio
* Significant LM disease or requiring CABG during hospital stay
* Inability to proceed with post conditioning within 1 minute of establishing blood flow in culprit artery

Primary outcomes:
measure: Infarct size as measured by: salvage index = total area at risk - infarct size/total area at risk
timeFrame: 3-5 days post MI
Secondary outcomes:
measure: Corrected TIMI frame count (cTFC)
timeFrame: Immediately post PCI
measure: Myocardial blush score
timeFrame: Immediately post PCI
measure: CK release (under the curve)
timeFrame: 1st 48 hours post MI
measure: ST segment resolution by 48 hrs compared with admission
timeFrame: 1st 48 hours post MI
measure: MRI infarct size
timeFrame: 3-5 days and 6 months
measure: MRI maximal transmural extent of irreversible injury
timeFrame: 3-5 days and 6 months
measure: CMR regional end-systolic wall stress
timeFrame: 3-5 days and 6 months
measure: CMR Myocardial perfusion
timeFrame: 3-5 days and 6 months
measure: CMR Myocardial oxygenation
timeFrame: 3-5 days and 6 months
measure: Peripheral endothelial function testing (brachial u/s and pulse arterial tonometry) in hospital
timeFrame: 3-5 days post MI
measure: CMR quantification of volume of no-reflow
timeFrame: 3-5 days and 6 months
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
Study officials:
affiliation: University of Calgary, sub-investigator
name: Mouhieddin Traboulsi, MD
role: STUDY_DIRECTOR
affiliation: Sub-investigator, Stephenson CMR Centre, FMC; 1403-29th St NW, Calgary; T2N 2T9
name: Matthias Friedrich, MD
role: STUDY_CHAIR
References: