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

NCT00670228 | Terminated Phase 3 Results DMC

• 1 other identifier: LANTU_L_01687
• Study Type: interventional
• Target: 34
• Locations: 5 countries
• Sites: 5

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).

Conditions

AMI

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Left Ventricular (LV) Function Evaluated by Cardiac Magnetic Resonance Imaging (MRI)

  At Day 3

• Occurrence of the Major Adverse Cardiovascular Events (MACE)

  At Day 60

• Biomarkers of Inflammation Measurement: CRP (C-Reactive Protein)

  At Day 60

Study Arms (2)

Intensive Insulin Therapy (IIT)

ACTIVE COMPARATOR

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); Drug: Insulin Glulisine (Apidra)

Standard Glycemic Care (SGC)

ACTIVE COMPARATOR

In SGC arm subjects assigned to "standard of care" received subcutaneous regular insulin per sliding scale.

Drug: Standard Therapy

Interventions

Insulin Glargine (LANTUS) DRUG

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

Intensive Insulin Therapy (IIT)

Insulin Glulisine (Apidra) DRUG

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.

Intensive Insulin Therapy (IIT)

Standard Therapy DRUG

Standard insulin therapy titrated to blood sugar control

Also known as: multiple insulins per hospital protocol

Standard Glycemic Care (SGC)

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanofi: lead

Study Sites (5)

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, United States

Location

Sanofi-Aventis Administrative Office

Buenos Aires, Argentina

Location

Sanofi-Aventis Administrative Office

São Paulo, Brazil

Location

Sanofi-Aventis Administrative Office

Laval, Canada

Location

Sanofi-Aventis Administrative Office

Col. Coyoacan, Mexico

Location

MeSH Terms

Interventions

Insulin Glargine; insulin glulisine; Standard of Care

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed. Only descriptive statistics were presented for primary and key secondary efficacy endpoints. The analysis focused on a review of safety Adverse Events (AEs) data.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: sanofi-aventis

GV-contact-us@sanofi-aventis.com

Study Officials

• Clinical Study Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 29, 2008
• First Posted: May 1, 2008
• Study Start: April 1, 2008
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: February 11, 2011
• Results First Posted: February 11, 2011

Record last verified: 2011-01

Locations

US (1); ME (1); AR (1); BR (1); CA (1)