Phase II Clinical Trial to Evaluate the Benefits of Postconditioning in ST-Elevation Myocardial Infarction (STEMI)

Study Overview
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Brief Summary
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This study will evaluate change in heart muscle function from baseline to three months and twelve months in participants who present with a heart attack and a completely occluded coronary artery. These subjects will be randomized to receive standard Percutaneous transluminal coronary angioplasty (PTCA)/Stenting to open the artery or routine PTCA/Stenting plus post conditioning. Post conditioning commences immediately upon reperfusion using four cycles of thirty second inflations with a standard angioplasty balloon followed by a thirty seconds of reperfusion. The investigators hypothesize that Postconditioning reduces the size of the heart attack when utilized with successful primary Angioplasty/stent.

Detailed Description
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Single center study involving 140 patients randomized to Post Conditioning + Percutaneous coronary intervention (PCI) versus routine PCI during their ST-Elevation Myocardial Infarction (STEMI, Heart Attack) presentation. The Post Conditioning protocol consists of performing four, 30-second PTCA (Angioplasty) balloon occlusions followed by 30-seconds of reperfusion over a total of 4 minutes. The first balloon inflation occurs immediately after an angioplasty guidewire is placed through the obstruction in the artery. Following this protocol the vessel is stented as part of the usual practice for treatment of STEMI. No other treatment differences will occur between the two groups and all patients will receive the usual post-STEMI care. Patients in both groups will receive a cardiac MRI 3-5 days following their STEMI for measurement of heart attack size and heart muscle function, among other measures. Patients will undergo collection of blood for creatine kinase (CK)-MB and troponin I every 8 hours for 24 hours following PCI. All patients will be followed by phone follow-up visits to review history and major adverse cardiac event (MACE) (death, recurrent STEMI, repeat revascularization, arrhythmias, implantable cardioverter-defibrillator (ICD) placement and hospitalization for congestive heart failure (CHF)). All patients will be required to take P2Y12 inhibitors and aspirin for the duration of the trial. All patients will be treated with angiotensin-converting enzyme inhibitor (ACE-I), beta blockers and statins.

Official Title
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Phase II Clinical Trial to Evaluate the Benefits of Postconditioning in STEMI

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Procedure: Post Conditioning + Primary PCI
* Procedure: Standard Primary PCI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years old, < 80 years old Able to give informed consent Able to undergo cMRl (cardiac magnetic resonance imaging ST-segment elevation infarction with 100% occlusion of a major epicardial vessel (> 2.5 mm) No angiographic evidence of collateral flow distal to occluded artery Ischemic duration between 1.0 and 6 hours Thrombolysis in myocardial infarction (TIMI) 3 Flow following PCI Exclusion Criteria: Visible collateral blood flow to the distal vasculature of the occluded vessel Previous Coronary Artery Bypass Graft surgery Previous q-wave myocardial infarction in the same territory Inability to give informed consent Inability to undergo cMRl Life expectancy less than one year History of Non-compliance or alcohol or drug addiction Patients with cardiogenic shock, cardiac arrest, hypothermia on presentation Chronic dialysis or significant renal insufficiency (Creatinine Clearance < 35 mI/mm/i .73 m2) TIMI Flow > 0 on presentation Ischemic Time > 6 hours or < 1.0 hours Presence of significant valvular heart disease (>mod Aortic Stenosis, >2+ Mitral Regurgitation) Known Left Ventricular systolic dysfunction (Left Ventricular Ejection Fraction < 50% prior to STEMI)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Post conditioning + PCI<br> | Procedure: Post Conditioning + Primary PCI<br>* Four, 30-second PTCA balloon occlusions followed by 30-seconds of reperfusion over a total of 4 minutes, in addition to Percutaneous Coronary Intervention as clinically indicated.<br>|
| Active Comparator: Standard PCI<br> | Procedure: Standard Primary PCI<br>* Routine Percutaneous Coronary Intervention as clinically indicated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infarct Size on Baseline Cardiac Magnetic Resonance Imaging (cMRI) | Infarct size was quantified by delayed, contrast-enhanced MRI | Day 3-5 post-PCI | 
| Myocardial Salvage Index (MSI) on Baseline cMRI | The myocardial salvage index (MSI) was calculated using the formula: MSI = (AAR - Infarct size) / AAR X 100 % where quantitative estimation of myocardium at risk (AAR) was measured as the hyperintense region on T2- weighted imaging. Measurements were performed using the QMass software package (Medis mc, Raleigh NC) by a single investigator who was blinded to treatment. The endocardial and epicardial borders were manually identified and the regions of interest (edema or scar) were automated as 2 standard deviations above the mean density of the myocardium. | Day 3-5 post-PCI | 
| Micro Vascular Obstruction (MVO) on Baseline cMRI | High T1 imaging was utilized for the determination of the presence or absence of MVO. | Day 3-5 post-PCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Left Ventricular Ejection Fraction |  | baseline | 
| Infarct Size by Peak Troponin |  | over first 72 hour post PCI | 
| Infarct Size by Peak Creatine Kinase (CK) |  | over first 72 hours post PCI | 
| Left Ventricular Remodeling (Left Ventricular End Diastolic Volume - LVEDV) as Measured by cMRl | LVEDV was defined as the volume of blood in the left ventricle at end load or filling in diastole or the amount of blood in the ventricles just before systole. | baseline | 
| Left Ventricular Remodeling (Left Ventricular End Systolic Volume - LVESV) as Measured by cMRl | LVESV was defined as the volume of blood in the left ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. | baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myocardial Infarction, STEMI, Post Conditioning, Primary Percutaneous Coronary Intervention