Acute Coronary Syndromes, Hyperglycemia, Myocardial Infarction
Conditions
Keywords
hyperglycemia, acute coronary syndromes, myocardial infarction
Brief summary
The purpose of this study is to determine the efficacy of intravenous Exenatide therapy in hyperglycemic patients admitted to the coronary intensive care unit.
Detailed description
Diabetic patients with acute myocardial infarction (MI) have particularly poor outcomes. Clinical practice guidelines from the American College of Cardiology/American Heart Association for the treatment of patients with acute coronary syndromes call for treatment to achieve preprandial glucose \<110 mg/dL, a maximum daily target \<180 mg/dL, and a post-discharge hemoglobin A1c \<7%. Initiation of aggressive insulin therapy is also warranted to achieve blood glucose \<150 mg/dL during days 0-3 and 80-110 mg/dL when possible thereafter. To date, no studies have been conducted assessing the efficacy of intravenous exenatide administration on achieving glucose lowering in hyperglycemic coronary ICU patients.
Interventions
DRUGExenatide
0.05 µg/min bolus of open-label exenatide followed by a constant infusion of 0.025 µg/min for 24-48 hours
Sponsors
Amylin Pharmaceuticals, LLC.
Saint Luke's Health System
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Admission to coronary ICU * Admission blood glucose 140-299 mg/dL * Primary cardiovascular diagnosis by attending physician * Under primary care of cardiology service * Age \> 18 years old * Ventilator independent * Able to provide informed consent
Exclusion criteria
* Admission blood glucose \< 140 or \> 300 mg/dL * Ventilator dependent * Unconscious sedation * Type 1 diabetes * Known pregnancy * Admitted to coronary ICU for right heart cath to measure hemodynamics prior to transplant * Post transplant procedure * Currently enrolled in another clinical trial * Unable to provide informed consent * Creatinine clearance \< 30 mL/min * On insulin treatment except for monotherapy with long-acting basal insulin (e.g., insulin glargine \[Lantus®\] or detemir \[Levemir®\]) * Gastroparesis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Glucose Values From Steady State Through 48 Hours or Until Discharge. | 1-48 hours | Time to steady state was defined as the time from the initiation of drug infusion to first glucose value that is ≤140 mg/dl. Median glucose values were then calculated for each patient from the start of steady state through 48 hours or until discharge. |
| Time to Steady State | Start of infusion through 48 hours or until discharge | Time to steady state was defined as the time from the initiation of drug infusion (Exenatide or Insulin) to first glucose value that is ≤140 mg/dl. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Hypoglycemia and Severe Hypoglycemia | 1-48 hours | Total number of patients having at least one hypoglycemic episode (blood glucose less than 70 mg/dl), including episodes classified as severe (blood glucose less than 50 mg/dl) |
| Serious Adverse Events (Death, Non-fatal Myocardial Infarction, and Non-fatal Stroke Through 30 Days) | 30 days | — |
Countries
United States
Participant flow
Recruitment details
Recruitment start: October 2008 Enrollment complete: June 2010 Recruitment location: Coronary Intensive Care Unit at Saint Luke's Hospital of Kansas City All eligible patients providing informed consent were assigned to a single group: exenatide infusion
Pre-assignment details
All glucose lowering medications were discontinued prior to infusion of exenatide to study the relation between exenatide and blood glucose.
Participants by arm
| Arm | Count |
|---|---|
| Exenatide Patients were treated with a 0.05 μg/min bolus of intravenous exenatide for 30 minutes,followed by a fixed dose infusion (0.025 μg/min) for a maximum duration of 48 hours. Blood glucose values were measured hourly following commencement of infusion. | 40 |
| Moderate In September 2009, the intensive glucose control protocol in ACS patients was modified to reflect emerging data on glucose management in the ICU. From this point forward, patients with an admission blood glucose \>180 mg/dL received intravenous insulin infusion to achieve a target blood glucose 100-140 mg/dL. | 71 |
| Intensive In 2008, the Mid America Heart and Vascular Institute implemented an intensive glucose control protocol using IV insulin in critically ill hyperglycemic patients hospitalized with ACS. All patients admitted with blood glucose ≥140 mg/dL received intravenous insulin infusion to achieve a target blood glucose 90-120 mg/dL. The efficacy of this protocol has been studied compared to ACS patients with admission blood glucose \>140 mg/dL admitted prior to protocol implementation. | 84 |
| Total | 195 |
Baseline characteristics
| Characteristic | Total | Exenatide | Moderate | Intensive |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 88 Participants | 19 Participants | 30 Participants | 39 Participants |
| Age, Categorical Between 18 and 65 years | 107 Participants | 21 Participants | 41 Participants | 45 Participants |
| Age, Continuous | 64.18 years STANDARD_DEVIATION 12.5 | 65 years STANDARD_DEVIATION 11.9 | 64 years STANDARD_DEVIATION 11.5 | 64 years STANDARD_DEVIATION 13.7 |
| Region of Enrollment United States | 195 participants | 40 participants | 71 participants | 84 participants |
| Sex: Female, Male Female | 65 Participants | 7 Participants | 26 Participants | 32 Participants |
| Sex: Female, Male Male | 130 Participants | 33 Participants | 45 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 40 |
| serious Total, serious adverse events | 4 / 40 |
Outcome results
Primary
Median Glucose Values From Steady State Through 48 Hours or Until Discharge.
Time to steady state was defined as the time from the initiation of drug infusion to first glucose value that is ≤140 mg/dl. Median glucose values were then calculated for each patient from the start of steady state through 48 hours or until discharge.
Time frame: 1-48 hours
Population: Intention to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exenatide | Median Glucose Values From Steady State Through 48 Hours or Until Discharge. | 132 mg/dL |
| Moderate | Median Glucose Values From Steady State Through 48 Hours or Until Discharge. | 127 mg/dL |
| Intensive | Median Glucose Values From Steady State Through 48 Hours or Until Discharge. | 105 mg/dL |
Comparison: Median Glucose Values (mg/dl) after steady state were evaluated across the three groups (Exenatide,Moderate and Intensive) with a Kruskal-Wallis test.p-value: <0.001Kruskal-Wallis
Comparison: Median Glucose Values (mg/dl) after steady state were evaluated between the Exenatide and Intensive study groups using a Wilcoxon Rank Sum tests.p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: Median Glucose Values (mg/dl) after steady state were evaluated between the Exenatide and Moderate study groups using a Wilcoxon Rank Sum tests.p-value: 0.15Wilcoxon (Mann-Whitney)
Primary
Time to Steady State
Time to steady state was defined as the time from the initiation of drug infusion (Exenatide or Insulin) to first glucose value that is ≤140 mg/dl.
Time frame: Start of infusion through 48 hours or until discharge
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exenatide | Time to Steady State | 2.0 hours |
| Moderate | Time to Steady State | 12.0 hours |
| Intensive | Time to Steady State | 3.0 hours |
Comparison: Median Time (Hrs) to steady state was evaluated across the three groups (exenatide, moderate and intensive) with a Kruskal-Wallis test.p-value: <0.001Kruskal-Wallis
Comparison: Median time (hours) to steady state were evaluated between the Exenatide and Intensive study groups using a Wilcoxon Rank Sum tests.p-value: 0.8Wilcoxon (Mann-Whitney)
Comparison: Median time (hours) to steady state were evaluated between the Exenatide and Moderate study groups using a Wilcoxon Rank Sum tests.p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Rates of Hypoglycemia and Severe Hypoglycemia
Total number of patients having at least one hypoglycemic episode (blood glucose less than 70 mg/dl), including episodes classified as severe (blood glucose less than 50 mg/dl)
Time frame: 1-48 hours
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exenatide | Rates of Hypoglycemia and Severe Hypoglycemia | Patients with at least one hypoglycemic episode | 4 participants |
| Exenatide | Rates of Hypoglycemia and Severe Hypoglycemia | Patients with at least one severe episode | 0 participants |
| Moderate | Rates of Hypoglycemia and Severe Hypoglycemia | Patients with at least one hypoglycemic episode | 14 participants |
| Moderate | Rates of Hypoglycemia and Severe Hypoglycemia | Patients with at least one severe episode | 2 participants |
| Intensive | Rates of Hypoglycemia and Severe Hypoglycemia | Patients with at least one hypoglycemic episode | 22 participants |
| Intensive | Rates of Hypoglycemia and Severe Hypoglycemia | Patients with at least one severe episode | 1 participants |
Secondary
Serious Adverse Events (Death, Non-fatal Myocardial Infarction, and Non-fatal Stroke Through 30 Days)
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide | Serious Adverse Events (Death, Non-fatal Myocardial Infarction, and Non-fatal Stroke Through 30 Days) | 4 participants |