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

Phase 1

Completed

Conditions: Acute Myocardial Infarction

Interventions: Procedure: Post Conditioning + Primary PCI
Procedure: Standard Primary PCI

Registration Number: NCT01324453

Lead Sponsor: Minneapolis Heart Institute Foundation

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 103

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Post conditioning + PCI	Post Conditioning + Primary PCI	-
Standard PCI	Standard Primary PCI	-

Primary Outcome Measures

Name	Time	Method
Myocardial Salvage Index (MSI) on Baseline cMRI	Day 3-5 post-PCI	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.
Infarct Size on Baseline Cardiac Magnetic Resonance Imaging (cMRI)	Day 3-5 post-PCI	Infarct size was quantified by delayed, contrast-enhanced MRI
Micro Vascular Obstruction (MVO) on Baseline cMRI	Day 3-5 post-PCI	High T1 imaging was utilized for the determination of the presence or absence of MVO.

Secondary Outcome Measures

Name	Time	Method
Global Left Ventricular Ejection Fraction	baseline
Infarct Size by Peak Creatine Kinase (CK)	over first 72 hours post PCI
Left Ventricular Remodeling (Left Ventricular End Systolic Volume - LVESV) as Measured by cMRl	baseline	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.
Infarct Size by Peak Troponin	over first 72 hour post PCI
Left Ventricular Remodeling (Left Ventricular End Diastolic Volume - LVEDV) as Measured by cMRl	baseline	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.