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

Cardiovascular Diseases Clinical Trial

— IMMEDIATE  

Official title:

Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00091507
• Other study ID #: 165
• Secondary ID: U01HL077826U01HL
• Status: Completed
• Phase: Phase 3
• First received: September 9, 2004
• Last updated: February 3, 2016
• Start date: November 2006
• Est. completion date: August 2012

Study information

• Verified date: February 2016
• Source: Tufts Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 911
• Est. completion date: August 2012
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Angina, Unstable
• Cardiovascular Diseases
• Coronary Artery Disease
• Coronary Disease
• Heart Diseases
• Heart Failure
• Heart Failure, Congestive
• Myocardial Infarction

Intervention

Drug:
• GIK
Intravenous solution, 1.5ml/kg/hour, continuous infusion for total of 12 hours.
• Placebo
Intravenous solution of Dextrose 5 percent at 1.5 ml/kg/hour for a total of 12 hours.

Locations

Country	Name	City	State
United States	Albuquerque Site	Albuquerque	New Mexico
United States	Anchorage Site	Anchorage	Alaska
United States	Bellingham Site	Bellingham	Washington
United States	Brockton Site	Brockton	Massachusetts
United States	Concord Site	Concord	Massachusetts
United States	Dallas Site	Dallas	Texas
United States	El Paso Site	El Paso	Texas
United States	Hershey Site	Hershey	Pennsylvania
United States	Macon Site	Macon	Georgia
United States	Milwaukee Site	Milwaukee	Wisconsin
United States	New Haven Site	New Haven	Connecticut
United States	Sioux Falls Site	Sioux Falls	South Dakota
United States	St. Paul Site	St. Paul	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Tufts Medical Center	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. — View Citation

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. 2015 Dec 8. doi: 10.1038/tpj.2015.84. [Epub ahead of print] — View Citation

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. — View Citation

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. — View Citation

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, W — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression of Acute Coronary Syndrome to Myocardial Infarction	Outcome for all participants during the first 24 hours of hospitalization; evidence of myocardial infarction is determined by ECG and biomarker results.	24 hours	No
Secondary	Cardiac Arrest	Outcome for all participants who had a cardiac arrest from initial contact in the prehospital setting through their subsequent hospitalization.	1 to 18 hours (From prehospital setting through hospitalization.)	No
Secondary	Heart Failure or Death	Outcome for all participants (composite of re-hospitalization for heart failure or death within 30 days)	30 days	No
Secondary	Mortality	Outcome for all participants (mortality at 30 days).	30 days	No
Secondary	Cardiac Arrest or Acute Mortality	Outcome for all participants (composite of cardiac arrest or acute mortality)	Prehospital setting through hospitalization	No