title: Study design for the Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care (IMMEDIATE) Trial: A double-blind randomized controlled trial of intravenous glucose, insulin, and potassium for acute coronary syndromes in emergency medical services.
abstract: BACKGROUND
  Experimental studies suggest that metabolic myocardial support by intravenous (IV) glucose, insulin, and potassium (GIK) reduces ischemia-induced arrhythmias, cardiac arrest, mortality, progression from unstable angina pectoris to acute myocardial infarction (AMI), and myocardial infarction size. However, trials of hospital administration of IV GIK to patients with ST-elevation myocardial infarction (STEMI) have generally not shown favorable effects possibly because of the GIK intervention taking place many hours after ischemic symptom onset. A trial of GIK used in the very first hours of ischemia has been needed, consistent with the timing of benefit seen in experimental studies.
  
  
  OBJECTIVE
  The IMMEDIATE Trial tested whether, if given very early, GIK could have the impact seen in experimental studies. Accordingly, distinct from prior trials, IMMEDIATE tested the impact of GIK (1) in patients with acute coronary syndromes (ACS), rather than only AMI or STEMI, and (2) administered in prehospital emergency medical service settings, rather than later, in hospitals, after emergency department evaluation.
  
  
  METHODS
  The IMMEDIATE Trial was an emergency medical service-based randomized placebo-controlled clinical effectiveness trial conducted in 13 cities across the United States that enrolled 911 participants. Eligible were patients 30 years or older for whom a paramedic performed a 12-lead electrocardiogram to evaluate chest pain or other symptoms suggestive of ACS for whom electrocardiograph-based acute cardiac ischemia time-insensitive predictive instrument indicated a ≥75% probability of ACS, and/or the thrombolytic predictive instrument indicated the presence of a STEMI, or if local criteria for STEMI notification of receiving hospitals were met. Prehospital IV GIK or placebo was started immediately. Prespecified were the primary end point of progression of ACS to infarction and, as major secondary end points, the composite of cardiac arrest or in-hospital mortality, 30-day mortality, and the composite of cardiac arrest, 30-day mortality, or hospitalization for heart failure. Analyses were planned on an intent-to-treat basis, on a modified intent-to-treat group who were confirmed in emergency departments to have ACS, and for participants presenting with STEMI.
  
  
  CONCLUSIONS
  The IMMEDIATE Trial tested whether GIK, when administered as early as possible in the course of ACS by paramedics using acute cardiac ischemia time-insensitive predictive instrument and thrombolytic predictive instrument decision support, would reduce progression to AMI, mortality, cardiac arrest, and heart failure. It also tested whether it would provide clinical and pathophysiologic information on GIK's biological mechanisms.
authors.affiliation: Center for Cardiovascular Health Services Research, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA. hselker@tuftsmedicalcenter.org
authors.forename: Harry P
authors.initials: HP
authors.lastname: Selker
authors.forename: Joni R
authors.initials: JR
authors.lastname: Beshansky
authors.forename: John L
authors.initials: JL
authors.lastname: Griffith
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.forename: James E
authors.initials: JE
authors.lastname: Udelson
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Rashba
authors.forename: Robin
authors.initials: R
authors.lastname: Ruthazer
authors.forename: Patricia R
authors.initials: PR
authors.lastname: Sheehan
authors.forename: Patrice
authors.initials: P
authors.lastname: Desvigne-Nickens
authors.forename: Yves D
authors.initials: YD
authors.lastname: Rosenberg
authors.forename: James M
authors.initials: JM
authors.lastname: Atkins
authors.forename: Assaad J
authors.initials: AJ
authors.lastname: Sayah
authors.forename: Tom P
authors.initials: TP
authors.lastname: Aufderheide
authors.forename: Charles E
authors.initials: CE
authors.lastname: Rackley
authors.forename: Lionel H
authors.initials: LH
authors.lastname: Opie
authors.forename: Costas T
authors.initials: CT
authors.lastname: Lambrew
authors.forename: Leonard A
authors.initials: LA
authors.lastname: Cobb
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Macleod
authors.forename: Joanne S
authors.initials: JS
authors.lastname: Ingwall
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Zalenski
authors.forename: Carl S
authors.initials: CS
authors.lastname: Apstein
mesh_terms: D054058:Acute Coronary Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D002314:Cardioplegic Solutions; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D004632:Emergency Medical Services / Q000379:methods*; D005500:Follow-Up Studies; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000008:administration & dosage; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D002314:Cardioplegic Solutions; D007328:Insulin; C030396:glucose-insulin-potassium cardioplegic solution; D005947:Glucose; D011188:Potassium