|Title||IMMEDIATE-2 (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care) Trial|
|Study Description||1,600 participants with symptoms consistent with ACS will be identified by emergency medical system (EMS) paramedics in the field prior to transport to the receiving hospital or by emergency department (ED) staff upon presentation. All 1,600 participants will be randomized to receive a 12-hour IV infusion of either GIK or placebo. Data for this cohort will be collected for two years following treatment. The first 900 consenting participants also will be enrolled in an FDA Accelerated Approval Path Cohort with an additional 30-day data collection point.|
|Objectives||Primary Objective: The purpose of this study is to test the impact of pharmacological myocardial metabolic support by intravenous (IV) glucose, insulin and potassium (GIK) for the treatment of patients with acute coronary syndromes (ACS), including acute myocardial infarction (AMI) and unstable angina pectoris (UAP).|
|Primary Endpoints||For Short Term Outcome Group (Accelerated Approval): The combination of the incidence of all-cause 30-day mortality, in-hospital cardiac arrest, and infarct size prior to discharge from the index hospitalization [H1]. Infarct size based on resting Tc99m-sestamibi imaging studies will be determined in a central core laboratory, using standardized quantitative techniques, blinded to group assignment. Treatments will be compared on this composite end point using the Finkelstein-Schoenfeld approach. (Note: Cardiac arrest includes the following rhythms: ventricular fibrillation or ventricular tachycardia, requiring defibrillation or cardioversion, asystole, or pulseless electrical activity, and will be referred to from here on as cardiac arrest.) (Study Hypothesis 1) For the Long-Term Clinical Follow-Up Cohort: The combination of all-cause mortality, or hospitalization for heart failure over a two-year follow up period, or in-hospital cardiac arrest. (Study Hypothesis 6 ). Regulatory endpoint: Composite of 30-day all-cause mortality or in-hospital cardiac arrest.|
|Study Population||1,600 participants, of whom 900 will be enrolled in the Accelerated Approval Cohort. Patients 30 years old and older with symptoms suggestive of ACS who have 12-lead ECG performed will be screened by EMS paramedics or by ED personnel for eligibility. Patients who have end stage renal failure requiring dialysis and those presenting with Killip Class 3 or 4 AMIs will not be eligible for enrollment (Killip Class 3: heart failure [HF] with rales at least half-way up the lung fields; Killip Class 4: HF with cardiogenic shock and a systolic BP less than 90 mm Hg).|
|Description of Sites/Facilities Enrolling Participants||Clinical Sites will be Emergency Medical Services (EMS) systems and their receiving hospitals Emergency departments (EDs). Sites will be a mix of academic medical centers and community hospitals, geographically spread across the US in urban and rural areas.|
|Description of Study Intervention||IV Glucose-insulin-potassium (GIK) 30% dextrose mixed with 80 potassium chloride, and 50 units regular insulin per one liter, given at 1.5 ml/kg/hour.|
|Study Duration||60 months in total (52 months from when the study opens to enrollment until completion of data analyses).|
The sample of 900 randomized participants is projected to result in 800 participants with ACS and thereby should provide 95% power to detect a significant beneficial effect of GIK over placebo using the Finkelstein-Schoenfeld approach under the following assumptions:
a. 30-day all-cause mortality rate is 6% for placebo and 4.5% for GIK.
b. Cardiac arrest rate is 3% for placebo and 1.5% for GIK.
c. Infarct size is 8% of left ventricle for placebo and 4% for GIK.
The entire 1,600 participants should provide over 90% power to detect an event ratio of 0.70 in the MITT group for the composite long-term clinical outcome of all-cause mortality or hospitalization for heart failure over a two year follow-up period, or in-hospital cardiac arrest. Details of the power analysis are included in the analysis plan.
|Primary Analytical Group||Modified intent-to-treat (MITT) analysis, defined as all those randomized and started on study drug and maintained on treatment after full evaluation for ACS in the ED. Approximately 80% of the ITT group will be included in the MITT.|
|Secondary Analytical Group||ST elevation analysis defined as those in the ITT Group who present with ST elevation.|
|Safety Analytical Group||Intention-to-treat (ITT) analysis, defined as including all those randomized and started on study drug and who gave written informed consent.|