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

Primary Purpose

AMI

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Insulin Glargine (LANTUS)
Insulin Glulisine (Apidra)
Standard Therapy
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for AMI

Eligibility Criteria

35 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Intensive Insulin Therapy (IIT)

Standard Glycemic Care (SGC)

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
April 29, 2008
Last Updated
January 14, 2011
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT00670228
Brief Title
Effect of Lantus and Apidra in Patients With Acute ST Elevation Myocardial Infarction
Acronym
INTENSIVE
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2011
Overall Recruitment Status
Terminated
Why Stopped
Due to Negative feasibility assessment of recruiting the planned number of subjects within the study timelines
Study Start Date
April 2008 (undefined)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
November 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Sanofi

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AMI

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intensive Insulin Therapy (IIT)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Standard Glycemic Care (SGC)
Arm Type
Active Comparator
Arm Description
In SGC arm subjects assigned to "standard of care" received subcutaneous regular insulin per sliding scale.
Intervention Type
Drug
Intervention Name(s)
Insulin Glargine (LANTUS)
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Insulin Glulisine (Apidra)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Standard Therapy
Other Intervention Name(s)
multiple insulins per hospital protocol
Intervention Description
Standard insulin therapy titrated to blood sugar control
Primary Outcome Measure Information:
Title
Infarct Size Absolute Change From Baseline at Day 60
Description
Infarct size is measured by cardiac Magnetic Resonance Imaging (MRI) as the percentage of Left Ventricular (LV) mass.
Time Frame
From baseline at Day 60
Secondary Outcome Measure Information:
Title
Left Ventricular (LV) Function Evaluated by Cardiac Magnetic Resonance Imaging (MRI)
Description
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.
Time Frame
At Day 3
Title
Occurrence of the Major Adverse Cardiovascular Events (MACE)
Description
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
Time Frame
At Day 60
Title
Biomarkers of Inflammation Measurement: CRP (C-Reactive Protein)
Time Frame
At Day 60

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Study Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Sanofi-Aventis Administrative Office
City
Bridgewater
State/Province
New Jersey
Country
United States
Facility Name
Sanofi-Aventis Administrative Office
City
Buenos Aires
Country
Argentina
Facility Name
Sanofi-Aventis Administrative Office
City
Sao Paulo
Country
Brazil
Facility Name
Sanofi-Aventis Administrative Office
City
Laval
Country
Canada
Facility Name
Sanofi-Aventis Administrative Office
City
Col. Coyoacan
Country
Mexico

12. IPD Sharing Statement

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

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