Angina, Unstable, Cardiovascular Diseases, Coronary Disease, Heart Diseases, Heart Failure, Congestive, Myocardial Infarction
Conditions
Keywords
Acute Coronary Syndrome
Brief summary
The purpose of this study is to test the impact of pharmacological myocardial metabolic support, in the form of intravenous (IV) glucose, insulin and potassium (GIK), for the treatment of patients with threatened or established acute myocardial infarction (AMI).
Detailed description
BACKGROUND: Basic and clinical research suggests intravenous GIK metabolic myocardial support reduces ischemia-induced arrhythmias, progression from unstable angina pectoris (UAP) to acute myocardial infarction (AMI), myocardial infarction (MI) size, and mortality. Also, for ST elevation MI (STEMI), GIK may prolong time of benefit of coronary reperfusion. These effects should reduce short- and long-term mortality from ACS, including AMI and UAP, and the propensity for heart failure (HF). These benefits are related to the earliness of ACS, when both risk and opportunity to save lives are highest. DESIGN NARRATIVE: This is a randomized, placebo-controlled, double-blinded, multicenter clinical trial of IMMEDIATE GIK as early as possible in ACS in the prehospital emergency medical service (EMS) setting. Distinct from prior and ongoing GIK trials, this will test GIK for all ACS rather than only for AMI or STEMI in prehospital EMS. The primary hypothesis is that early GIK will prevent or reduce the size of acute myocardial infarction. Major secondary hypotheses posit GIK will reduce mortality (30 days and 1 year), reduce pre- or in-hospital cardiac arrest and the propensity for heart failure. Other hypotheses address mechanisms of these effects.
Interventions
DRUGGIK
Intravenous solution, 1.5ml/kg/hour, continuous infusion for total of 12 hours.
DRUGPlacebo
Intravenous solution of Dextrose 5 percent at 1.5 ml/kg/hour for a total of 12 hours.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Tufts Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Symptoms of threatened or established AMI including but not limited to: 1. Chest pain, discomfort, or tightness 2. Arm or shoulder pain 3. Jaw pain 4. Epigastric discomfort 5. Shortness of breath * 12-lead electrocardiogram (ECG) with two or more contiguous leads with ST elevation greater than 1 mm, ST depression greater than 0.5 mm, T wave inversion or other T wave abnormalities (hyperacute T waves), or left bundle branch block (not known to be old). Identification aided by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI)and thrombolytic predictive instrument (TPI) decision support software (ACI-TIPI \>= 75% and TPI detection of suspected STEMI).
Exclusion criteria
* End-stage kidney failure requiring dialysis * Rales present more than halfway up the back * Unable to comply with the requirements of the study * Incarcerated * Known to be pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression of Acute Coronary Syndrome to Myocardial Infarction | 24 hours | Outcome for all participants during the first 24 hours of hospitalization; evidence of myocardial infarction is determined by ECG and biomarker results. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac Arrest | 1 to 18 hours (From prehospital setting through hospitalization.) | Outcome for all participants who had a cardiac arrest from initial contact in the prehospital setting through their subsequent hospitalization. |
| Heart Failure or Death | 30 days | Outcome for all participants (composite of re-hospitalization for heart failure or death within 30 days) |
| Mortality | 30 days | Outcome for all participants (mortality at 30 days). |
| Cardiac Arrest or Acute Mortality | Prehospital setting through hospitalization | Outcome for all participants (composite of cardiac arrest or acute mortality) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GIK -- GIK = glucose-insulin-potassium | 432 |
| Placebo Dextrose 5% | 479 |
| Total | 911 |
Baseline characteristics
| Characteristic | GIK -- | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 63.9 years STANDARD_DEVIATION 13.9 | 63.3 years STANDARD_DEVIATION 14.1 | 63.6 years STANDARD_DEVIATION 14 |
| Region of Enrollment United States | 432 participants | 479 participants | 911 participants |
| Sex: Female, Male Female | 119 Participants | 146 Participants | 265 Participants |
| Sex: Female, Male Male | 313 Participants | 333 Participants | 646 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 295 / 411 | 199 / 460 |
| serious Total, serious adverse events | 28 / 411 | 41 / 460 |
Outcome results
Primary
Progression of Acute Coronary Syndrome to Myocardial Infarction
Outcome for all participants during the first 24 hours of hospitalization; evidence of myocardial infarction is determined by ECG and biomarker results.
Time frame: 24 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GIK -- | Progression of Acute Coronary Syndrome to Myocardial Infarction | 200 participants |
| Placebo | Progression of Acute Coronary Syndrome to Myocardial Infarction | 242 participants |
p-value: 0.2895% CI: [0.66, 1.13]Regression, Logistic
Secondary
Cardiac Arrest
Outcome for all participants who had a cardiac arrest from initial contact in the prehospital setting through their subsequent hospitalization.
Time frame: 1 to 18 hours (From prehospital setting through hospitalization.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GIK -- | Cardiac Arrest | 15 participants |
| Placebo | Cardiac Arrest | 29 participants |
p-value: 0.0895% CI: [0.3, 1.07]Regression, Logistic
Secondary
Cardiac Arrest or Acute Mortality
Outcome for all participants (composite of cardiac arrest or acute mortality)
Time frame: Prehospital setting through hospitalization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GIK -- | Cardiac Arrest or Acute Mortality | 18 participants |
| Placebo | Cardiac Arrest or Acute Mortality | 40 participants |
p-value: 0.0195% CI: [0.27, 0.85]Regression, Logistic
Secondary
Heart Failure or Death
Outcome for all participants (composite of re-hospitalization for heart failure or death within 30 days)
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GIK -- | Heart Failure or Death | 23 participants |
| Placebo | Heart Failure or Death | 35 participants |
p-value: 0.2495% CI: [0.43, 1.23]Regression, Logistic
Secondary
Mortality
Outcome for all participants (mortality at 30 days).
Time frame: 30 days
Population: 30 day mortality.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GIK -- | Mortality | 18 participants |
| Placebo | Mortality | 28 participants |
p-value: 0.2795% CI: [0.4, 1.29]Regression, Logistic