IMMEDIATE Trial - Out of Hospital Administration of Glucose, Insulin and Potassium. (IMMEDIATE)

• ClinicalTrials.gov Identifier: NCT00091507
• Recruitment Status: Completed
• First Posted: September 13, 2004
• Results First Posted: January 30, 2013
• Last Update Posted: March 2, 2016
• Sponsor: Tufts Medical Center
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Tufts Medical Center

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Angina, Unstable; Cardiovascular Diseases; Heart Diseases; Coronary Disease; Myocardial Infarction; Heart Failure, Congestive	Drug: GIK; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 911 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care Trial
• Study Start Date: November 2006
• Actual Primary Completion Date: August 2011
• Actual Study Completion Date: August 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 -- GIK; GIK = glucose-insulin-potassium; In one-liter: Dextrose 30% + 80 mEq Potassium Chloride + 50 units Regular Insulin; infused at 1.5 ml/kg/hour for a total of 12 hours.	Drug: GIK; Intravenous solution, 1.5ml/kg/hour, continuous infusion for total of 12 hours.; Other Name: Glucose-Insulin Potassium
Placebo Comparator: 2 -- Placebo; Dextrose 5%, infused at 1.5 ml/kg/hour for total of 12 hours.	Drug: Placebo; Intravenous solution of Dextrose 5 percent at 1.5 ml/kg/hour for a total of 12 hours.; Other Name: Dextrose 5%

Outcome Measures

Primary Outcome Measures :

1. Progression of Acute Coronary Syndrome to Myocardial Infarction [ Time Frame: 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 Outcome Measures :

1. Cardiac Arrest [ Time Frame: 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.
2. Heart Failure or Death [ Time Frame: 30 days ]
   Outcome for all participants (composite of re-hospitalization for heart failure or death within 30 days)
3. Mortality [ Time Frame: 30 days ]
   Outcome for all participants (mortality at 30 days).
4. Cardiac Arrest or Acute Mortality [ Time Frame: Prehospital setting through hospitalization ]
   Outcome for all participants (composite of cardiac arrest or acute mortality)

Eligibility Criteria

• Ages Eligible for Study: 30 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Alaska

Anchorage Site

Anchorage, Alaska, United States, 99501

United States, Connecticut

New Haven Site

New Haven, Connecticut, United States, 06511

United States, Georgia

Macon Site

Macon, Georgia, United States, 31208

United States, Massachusetts

Brockton Site

Brockton, Massachusetts, United States, 02301

Concord Site

Concord, Massachusetts, United States, 01742

United States, Minnesota

St. Paul Site

St. Paul, Minnesota, United States, 55128

United States, New Mexico

Albuquerque Site

Albuquerque, New Mexico, United States, 87131

United States, Pennsylvania

Hershey Site

Hershey, Pennsylvania, United States, 17033

United States, South Dakota

Sioux Falls Site

Sioux Falls, South Dakota, United States, 57104

United States, Texas

Dallas Site

Dallas, Texas, United States, 75201

El Paso Site

El Paso, Texas, United States, 79905

United States, Washington

Bellingham Site

Bellingham, Washington, United States, 98225

United States, Wisconsin

Milwaukee Site

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Tufts Medical Center

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Study Chair: Harry Selker, MD, MSPH; Tufts Medical Center, Trial Coordinating Center
• Principal Investigator: Ralph D'Agostino, PhD; Tufts Medical Center, Data Coordinating Center
• Principal Investigator: James Udelson, MD; Tufts Medical Center, LV Core Lab

More Information

Publications of Results:

Selker HP, Beshansky JR, Sheehan PR, Massaro JM, Griffith JL, D'Agostino RB, Ruthazer R, Atkins JM, Sayah AJ, Levy MK, Richards ME, Aufderheide TP, Braude DA, Pirrallo RG, Doyle DD, Frascone RJ, Kosiak DJ, Leaming JM, Van Gelder CM, Walter GP, Wayne MA, Woolard RH, Opie LH, Rackley CE, Apstein CS, Udelson JE. Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: the IMMEDIATE randomized controlled trial. JAMA. 2012 May 9;307(18):1925-33. doi: 10.1001/jama.2012.426. Epub 2012 Mar 27.

Other Publications:

Selker HP, Beshansky JR, Ruthazer R, Sheehan PR, Sayah AJ, Atkins JM, Aufderheide TP, Pirrallo RG, D'Agostino RB, Massaro JM, Griffith JL. Emergency medical service predictive instrument-aided diagnosis and treatment of acute coronary syndromes and ST-segment elevation myocardial infarction in the IMMEDIATE trial. Prehosp Emerg Care. 2011 Apr-Jun;15(2):139-48. doi: 10.3109/10903127.2010.545478.

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. 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. Am Heart J. 2012 Mar;163(3):315-22. doi: 10.1016/j.ahj.2012.02.002.

Ellis KL, Zhou Y, Rodriguez-Murillo L, Beshansky JR, Ainehsazan E, Selker HP, Huggins GS, Cupples LA, Peter I. Common variants associated with changes in levels of circulating free fatty acids after administration of glucose-insulin-potassium (GIK) therapy in the IMMEDIATE trial. Pharmacogenomics J. 2017 Jan;17(1):76-83. doi: 10.1038/tpj.2015.84. Epub 2015 Dec 8.

Ellis KL, Zhou Y, Beshansky JR, Ainehsazan E, Selker HP, Cupples LA, Huggins GS, Peter I. Genetic modifiers of response to glucose-insulin-potassium (GIK) infusion in acute coronary syndromes and associations with clinical outcomes in the IMMEDIATE trial. Pharmacogenomics J. 2015 Dec;15(6):488-95. doi: 10.1038/tpj.2015.10. Epub 2015 Mar 17.

Alkofide H, Huggins GS, Beshansky JR, Ruthazer R, Peter I, Ray M, Mukherjee JT, Selker HP. C-Reactive protein reactions to glucose-insulin-potassium infusion and relations to infarct size in patients with acute coronary syndromes. BMC Cardiovasc Disord. 2015 Dec 3;15:163. doi: 10.1186/s12872-015-0153-7.

Alkofide H, Huggins GS, Ruthazer R, Beshansky JR, Selker HP. Serum adiponectin levels in patients with acute coronary syndromes: Serial changes and relation to infarct size. Diab Vasc Dis Res. 2015 Nov;12(6):411-9. doi: 10.1177/1479164115592638. Epub 2015 Jul 20.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Selker HP, Udelson JE, Massaro JM, Ruthazer R, D'Agostino RB, Griffith JL, Sheehan PR, Desvigne-Nickens P, Rosenberg Y, Tian X, Vickery EM, Atkins JM, Aufderheide TP, Sayah AJ, Pirrallo RG, Levy MK, Richards ME, Braude DA, Doyle DD, Frascone RJ, Kosiak DJ, Leaming JM, Van Gelder CM, Walter GP, Wayne MA, Woolard RH, Beshansky JR. One-year outcomes of out-of-hospital administration of intravenous glucose, insulin, and potassium (GIK) in patients with suspected acute coronary syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care] Trial). Am J Cardiol. 2014 May 15;113(10):1599-605. doi: 10.1016/j.amjcard.2014.02.010. Epub 2014 Mar 1.

Beshansky JR, Sheehan PR, Klima KJ, Hadar N, Vickery EM, Selker HP. A community consultation survey to evaluate support for and success of the IMMEDIATE trial. Clin Trials. 2014 Apr;11(2):178-86. doi: 10.1177/1740774514526476.

Sullivan AL, Beshansky JR, Ruthazer R, Murman DH, Mader TJ, Selker HP. Factors associated with longer time to treatment for patients with suspected acute coronary syndromes: a cohort study. Circ Cardiovasc Qual Outcomes. 2014 Jan;7(1):86-94. doi: 10.1161/CIRCOUTCOMES.113.000396. Epub 2014 Jan 14.

• Responsible Party: Tufts Medical Center
• ClinicalTrials.gov Identifier: NCT00091507
• Other Study ID Numbers: 165; U01HL077826 ( U.S. NIH Grant/Contract ); U01HL077823 ( U.S. NIH Grant/Contract ); U01HL077822 ( U.S. NIH Grant/Contract ); U01HL077821 ( U.S. NIH Grant/Contract )
• First Posted: September 13, 2004
• Results First Posted: January 30, 2013
• Last Update Posted: March 2, 2016
• Last Verified: February 2016

Keywords provided by Tufts Medical Center:

Acute Coronary Syndrome

Additional relevant MeSH terms:

Heart Failure; Cardiovascular Diseases; Myocardial Infarction; Heart Diseases; Coronary Disease; Angina, Unstable; Infarction; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Vascular Diseases; Angina Pectoris; Chest Pain; Pain; Neurologic Manifestations; Insulin; Hypoglycemic Agents; Physiological Effects of Drugs