|Basic and clinical research by our team and others suggests intravenous glucose, insulin, and potassium (GIK) metabolic myocardial support reduces ischemia-induced arrhythmias, progression from unstable angina pectoris (UAP) to acute myocardial infarction (AMI), 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 acute coronary syndromes (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. Thus, we propose the IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care) Trial, a randomized placebo-controlled 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), and its use in prehospital EMS.
Our primary hypothesis is that early GIK will be associated with fewer patients having biomarker and ECG evidence of AMI. This is consistent with reduced progression of threatened AMI to completed AMI. Major secondary hypotheses posit GIK will lead to improved survival at 30 days and at 1 year, reduce pre/in-hospital cardiac arrest and limiting MI size reducing the propensity for HF. Other hypotheses address the mechanisms of these effects.
Inclusion of 880 patients (excluding AMI Killip class >2) should provide >90% statistical power to detect 20.4% reductions in primary endpoints and major secondary endpoints. A 300-subject Biological Mechanism Cohort assessed for LV function, ventricular arrhythmia markers, and biochemical tests, will provide >80% power for clinically relevant differences between GIK and placebo.
If the 30-50% reduction in acute mortality rates in prior GIK trials and reductions in HF are confirmed, this inexpensive treatment could substantially reduce the most common causes of death and hospitalization in the US.