Effect of Lantus and Apidra in Patients With Acute ST Elevation Myocardial Infarction

Study Overview
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Brief Summary
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Primary objective: To demonstrate that in hyperglycemic subjects with anterior STEMI (ST Elevation Myocardial Infarction) undergoing Percutaneous Coronary Intervention (PCI), tight glycemic control using insulin glulisine and insulin glargine, i.e. Intensive Insulin Therapy (IIT), results in reducing infarct size at day 60 versus (vs) Standard Glycemic Care (SGC). Secondary objectives: To demonstrate that tight glycemic control using insulin glulisine and insulin glargine reduces markers of inflammation and improves Left Ventricular (LV) function and Cardio-Vascular (CV) outcomes from baseline values, in hyperglycemic subjects with STEMI undergoing Percutaneous Coronary Intervention (PCI).

Official Title
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A Multi-center, Phase 3b, Stratified, Randomized, Open-label Clinical Trial to Evaluate the Efficacy of Intensive Apidra®/Lantus® Therapy vs Sliding Scale Insulin on Infarct Size in Hyperglycemic Subjects With Anterior STEMI (ST Elevation Myocardial Infarction) Undergoing PCI (Percutaneous Coronary Intervention)

Conditions
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AMI

Intervention / Treatment
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* Drug: Insulin Glargine (LANTUS)
* Drug: Insulin Glulisine (Apidra)
* Drug: Standard Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women = or > 35 years of age presenting to the hospital with hyperglycemia (plasma glucose >140 mg/dL) and Primary Anterior wall ST-Elevation Myocardial Infarction (AW STEMI) No history of illicit drug abuse in past year A minimum of 30 minutes but < or = 6 hours of continuous pain/symptoms immediately prior to presentation Subjects who will undergo primary percutaneous coronary intervention (PCI) At least 2 contiguous precordial leads demonstrating at least 2 mm of ST-segment elevation consistent with anterior wall MI Signed informed consent and HIPAA documentation (US only) prior to participation in the study Subjects ability and willingness to adhere to and be compliant with study protocol Exclusion Criteria: A prior history of Myocardial Infarction (MI) Subjects who have received any thrombolytic therapy during the current hospital admission Severe Heart Failure or cardiogenic shock (Killip class 3 or 4) by history or present at the time of screening Subjects with a plasma glucose >400 mg/dL or diabetic ketoacidosis (DKA) History of Type 1 diabetes Active bleeding Active malignancy, chronic or other medical conditions likely to result in death over the next one year Recent hypotension requiring inotropic support in the past 30 days Participation in another clinical research study in the past 30 days Pregnant or lactating women (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraception method) Unwilling to give informed consent Subjects directly involved in the conduct of the study Known hypersensitivity to insulin glargine or glulisine Contraindication to MRI: a)Intracranial aneurysm clips (Unless the investigator is certain that it is made of non-ferromagnetic material such as titanium)b)Intra-orbital metal fragments c)Any electrically, magnetically or mechanically activated implants (including cardiac pacemakers, biostimulators, neurostimulators, cochlear implants, and hearing aids) d)Warning about Gadolinium-based contrast agents (GBCAs) Exposure to GBCAs increases the risk for nephrogenic systemic fibrosis (NSF). Therefore the following subjects should be excluded from the trial based on a history and/or laboratory tests: acute or chronic severe renal insufficiency (glomerular filtration rate <30 mL/min/1.73m2), as calculated by the MDRD (Modification of diet in Renal Disease) equation, or acute renal insufficiency of any severity Subjects with blood pressure > or = to 200/110 mmHg at time of randomization Subjects with a high degree of non-transient AV (Atrio-Ventricular) block The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 35 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 |
| --- | --- |
| Active Comparator: Intensive Insulin Therapy (IIT)<br>In IIT arm, subjects received intravenous (IV) insulin glulisine and subcutaneous (sc) insulin glargine to maintain a Blood Glucose (BG) concentration between 90-130 mg/dL. | Drug: Insulin Glargine (LANTUS)<br>* Subcutaneous insulin glargine was initiated 90 prior to the insulin glulisine infusion discontinuation (i.e. 48 hours after randomization) and titrated as per physician preference to maintain the plasma glucose between 90-130 mg/dL<br>Drug: Insulin Glulisine (Apidra)<br>* Prior PCI, subjects received a single IV bolus of insulin glulisine. The dose was 0.025 U/kg based upon patient reported weight. Then IV insulin glulisine infusion was started within one hour of the IV insulin glulisine bolus and administered at a minimum rate of 2 U/h for 48 hours. The infusion was titrated in order to achieve and maintain the plasma glucose between 90 and 130 mg/dL.<br>|
| Active Comparator: Standard Glycemic Care (SGC)<br>In SGC arm subjects assigned to standard of care received subcutaneous regular insulin per sliding scale. | Drug: Standard Therapy<br>* Standard insulin therapy titrated to blood sugar control<br>* Other names: multiple insulins per hospital protocol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infarct Size Absolute Change From Baseline at Day 60 | Infarct size is measured by cardiac Magnetic Resonance Imaging (MRI) as the percentage of Left Ventricular (LV) mass. | From baseline at Day 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular (LV) Function Evaluated by Cardiac Magnetic Resonance Imaging (MRI) | Due to study early termination and the limited number of randomized subjects, descriptive statistics for the Day 3 Ejection Fraction were selected for presentation instead of for Day 60 as initially planned. | At Day 3 | 
| Occurrence of the Major Adverse Cardiovascular Events (MACE) | MACE: Cardiac death, New onset or worsening congestive heart failure (>24 h post-admission) event evaluating using New York Heart Association (NYHA) Class II or greater Non-fatal Myocardial Infarction, Severe arrhythmia, Stroke/TIA (Transient Ischemic Attack), Cardiogenic shock, Catheterization/revascularization, Unstable angina leading to hospitalisation | At Day 60 | 
| Biomarkers of Inflammation Measurement: CRP (C-Reactive Protein) |  | At Day 60 |