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

Phase 3

Terminated

Conditions: AMI

Interventions: Drug: Insulin Glargine (LANTUS)
Drug: Standard Therapy
Drug: Insulin Glulisine (Apidra)

Registration Number: NCT00670228

Lead Sponsor: Sanofi

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 34

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intensive Insulin Therapy (IIT)	Insulin Glargine (LANTUS)	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.
Intensive Insulin Therapy (IIT)	Insulin Glulisine (Apidra)	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.
Standard Glycemic Care (SGC)	Standard Therapy	In SGC arm subjects assigned to "standard of care" received subcutaneous regular insulin per sliding scale.

Primary Outcome Measures

Name	Time	Method
Infarct Size Absolute Change From Baseline at Day 60	From baseline at Day 60	Infarct size is measured by cardiac Magnetic Resonance Imaging (MRI) as the percentage of Left Ventricular (LV) mass.

Secondary Outcome Measures

Name	Time	Method
Left Ventricular (LV) Function Evaluated by Cardiac Magnetic Resonance Imaging (MRI)	At Day 3	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.
Occurrence of the Major Adverse Cardiovascular Events (MACE)	At Day 60	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
Biomarkers of Inflammation Measurement: CRP (C-Reactive Protein)	At Day 60