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

Harry P. Selker, Joni R. Beshansky, John L. Griffith, Ralph B. D'Agostino, Joseph M. Massaro, James E. Udelson, Eric J. Rashba, Robin Ruthazer, Patricia R. Sheehan, Patrice Desvigne-Nickens, Yves D. Rosenberg, James M Atkins, Assaad J. Sayah, Tom P. Aufderheide, Charles E. Rackley, Lionel H. Opie, Costas T. Lambrew, Leonard A. Cobb, Bruce A. MacLeod, Joanne S. IngwallRobert J. Zalenski, Carl S. Apstein

Research output: Contribution to journalArticle

20 Citations (Scopus)

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. Design: The IMMEDIATE Trial was an emergency medical service-based randomized placebo-controlled clinical effectiveness trial conducted in13 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)315-322
Number of pages8
JournalAmerican Heart Journal
Volume163
Issue number3
DOIs
StatePublished - Mar 2012

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Emergency Medical Services
Acute Coronary Syndrome
Potassium
Randomized Controlled Trials
Insulin
Glucose
Ischemia
Heart Arrest
Myocardial Infarction
Allied Health Personnel
Heart Failure
Mortality
Hospital Emergency Service
Electrocardiography
Therapeutics
Placebos
Hospital Administration
Induced Heart Arrest
Unstable Angina
Controlled Clinical Trials

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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. / Selker, Harry P.; Beshansky, Joni R.; Griffith, John L.; D'Agostino, Ralph B.; Massaro, Joseph M.; Udelson, James E.; Rashba, Eric J.; Ruthazer, Robin; Sheehan, Patricia R.; Desvigne-Nickens, Patrice; Rosenberg, Yves D.; Atkins, James M; Sayah, Assaad J.; Aufderheide, Tom P.; Rackley, Charles E.; Opie, Lionel H.; Lambrew, Costas T.; Cobb, Leonard A.; MacLeod, Bruce A.; Ingwall, Joanne S.; Zalenski, Robert J.; Apstein, Carl S.

In: American Heart Journal, Vol. 163, No. 3, 03.2012, p. 315-322.

Research output: Contribution to journalArticle

Selker, HP, Beshansky, JR, Griffith, JL, D'Agostino, RB, Massaro, JM, Udelson, JE, Rashba, EJ, Ruthazer, R, Sheehan, PR, Desvigne-Nickens, P, Rosenberg, YD, Atkins, JM, Sayah, AJ, Aufderheide, TP, Rackley, CE, Opie, LH, Lambrew, CT, Cobb, LA, MacLeod, BA, Ingwall, JS, Zalenski, RJ & Apstein, CS 2012, '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', American Heart Journal, vol. 163, no. 3, pp. 315-322. https://doi.org/10.1016/j.ahj.2012.02.002
Selker, Harry P. ; Beshansky, Joni R. ; Griffith, John L. ; D'Agostino, Ralph B. ; Massaro, Joseph M. ; Udelson, James E. ; Rashba, Eric J. ; Ruthazer, Robin ; Sheehan, Patricia R. ; Desvigne-Nickens, Patrice ; Rosenberg, Yves D. ; Atkins, James M ; Sayah, Assaad J. ; Aufderheide, Tom P. ; Rackley, Charles E. ; Opie, Lionel H. ; Lambrew, Costas T. ; Cobb, Leonard A. ; MacLeod, Bruce A. ; Ingwall, Joanne S. ; Zalenski, Robert J. ; Apstein, Carl S. / 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. In: American Heart Journal. 2012 ; Vol. 163, No. 3. pp. 315-322.
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T1 - Study design for the immediate myocardial metabolic enhancement during initial assessment and treatment in emergency care (IMMEDIATE) trial

T2 - A double-blind randomized controlled trial of intravenous glucose, insulin, and potassium for acute coronary syndromes in emergency medical services

AU - Selker, Harry P.

AU - Beshansky, Joni R.

AU - Griffith, John L.

AU - D'Agostino, Ralph B.

AU - Massaro, Joseph M.

AU - Udelson, James E.

AU - Rashba, Eric J.

AU - Ruthazer, Robin

AU - Sheehan, Patricia R.

AU - Desvigne-Nickens, Patrice

AU - Rosenberg, Yves D.

AU - Atkins, James M

AU - Sayah, Assaad J.

AU - Aufderheide, Tom P.

AU - Rackley, Charles E.

AU - Opie, Lionel H.

AU - Lambrew, Costas T.

AU - Cobb, Leonard A.

AU - MacLeod, Bruce A.

AU - Ingwall, Joanne S.

AU - Zalenski, Robert J.

AU - Apstein, Carl S.

PY - 2012/3

Y1 - 2012/3

N2 - 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. Design: The IMMEDIATE Trial was an emergency medical service-based randomized placebo-controlled clinical effectiveness trial conducted in13 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. Conclusion: 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.

AB - 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. Design: The IMMEDIATE Trial was an emergency medical service-based randomized placebo-controlled clinical effectiveness trial conducted in13 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. Conclusion: 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.

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