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Clinical Trial
. 2012 May 9;307(18):1925-33.
doi: 10.1001/jama.2012.426. Epub 2012 Mar 27.

Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: the IMMEDIATE randomized controlled trial

Harry P Selker  1 , Joni R Beshansky, Patricia R Sheehan, Joseph M Massaro, John L Griffith, Ralph B D'Agostino, Robin Ruthazer, James M Atkins, Assaad J Sayah, Michael K Levy, Michael E Richards, Tom P Aufderheide, Darren A Braude, Ronald G Pirrallo, Delanor D Doyle, Ralph J Frascone, Donald J Kosiak, James M Leaming, Carin M Van Gelder, Gert-Paul Walter, Marvin A Wayne, Robert H Woolard, Lionel H Opie, Charles E Rackley, Carl S Apstein, James E Udelson
Affiliations
Clinical Trial

Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: the IMMEDIATE randomized controlled trial

Harry P Selker et al. JAMA. .

Abstract

Context: Laboratory studies suggest that in the setting of cardiac ischemia, immediate intravenous glucose-insulin-potassium (GIK) reduces ischemia-related arrhythmias and myocardial injury. Clinical trials have not consistently shown these benefits, possibly due to delayed administration.

Objective: To test out-of hospital emergency medical service (EMS) administration of GIK in the first hours of suspected acute coronary syndromes (ACS).

Design, setting, and participants: Randomized, placebo-controlled, double-blind effectiveness trial in 13 US cities (36 EMS agencies), from December 2006 through July 31, 2011, in which paramedics, aided by electrocardiograph (ECG)-based decision support, randomized 911 (871 enrolled) patients (mean age, 63.6 years; 71.0% men) with high probability of ACS.

Intervention: Intravenous GIK solution (n = 411) or identical-appearing 5% glucose placebo (n = 460) administered by paramedics in the out-of-hospital setting and continued for 12 hours.

Main outcome measures: The prespecified primary end point was progression of ACS to myocardial infarction (MI) within 24 hours, as assessed by biomarkers and ECG evidence. Prespecified secondary end points included survival at 30 days and a composite of prehospital or in-hospital cardiac arrest or in-hospital mortality, analyzed by intent-to-treat and by presentation with ST-segment elevation.

Results: There was no significant difference in the rate of progression to MI among patients who received GIK (n = 200; 48.7%) vs those who received placebo (n = 242; 52.6%) (odds ratio [OR], 0.88; 95% CI, 0.66-1.13; P = .28). Thirty-day mortality was 4.4% with GIK vs 6.1% with placebo (hazard ratio [HR], 0.72; 95% CI, 0.40-1.29; P = .27). The composite of cardiac arrest or in-hospital mortality occurred in 4.4% with GIK vs 8.7% with placebo (OR, 0.48; 95% CI, 0.27-0.85; P = .01). Among patients with ST-segment elevation (163 with GIK and 194 with placebo), progression to MI was 85.3% with GIK vs 88.7% with placebo (OR, 0.74; 95% CI, 0.40-1.38; P = .34); 30-day mortality was 4.9% with GIK vs 7.7% with placebo (HR, 0.63; 95% CI, 0.27-1.49; P = .29). The composite outcome of cardiac arrest or in-hospital mortality was 6.1% with GIK vs 14.4% with placebo (OR, 0.39; 95% CI, 0.18-0.82; P = .01). Serious adverse events occurred in 6.8% (n = 28) with GIK vs 8.9% (n = 41) with placebo (P = .26).

Conclusions: Among patients with suspected ACS, out-of-hospital administration of intravenous GIK, compared with glucose placebo, did not reduce progression to MI. Compared with placebo, GIK administration was not associated with improvement in 30-day survival but was associated with lower rates of the composite outcome of cardiac arrest or in-hospital mortality.

Trial registration: clinicaltrials.gov Identifier: NCT00091507.

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Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Selker, principal investigator, reported institutional receipt of grant funds and indirect payment for his work and travel expenses; the institution’s grant paid for honoraria to members of the scientific advisory committee, DSMB, and Harvard Clinical Research Institute for event adjudication and statistical analysis, Curlin Inc for intravenous pumps, and Philips Healthcare for ECG decision support software. Dr Selker also reported an expired patent for the TPI ECG software, but no royalties are received. Ms Beshansky, co-principal investigator, reported institutional and indirect receipt of grant support and support for travel expenses. Dr Massaro reported grant support provided to his institution and direct receipt of funds, in addition to support for travel. Drs D’Agostino and Atkins reported institutional grant support and support for travel expenses. Drs Braude, Doyle, Frascone, Griffith, Leaming, Richards, Udelson, and Woolard, Ms Ruthazer, and Ms Sheehan reported grant support (NIH, NHLBI) provided to their institution. Dr Kosiak reported institutional and direct receipt of funds in support for travel expenses and fees for data review and training. Dr Rackley reported direct receipt of funds for fees for participating on the IMMEDIATE Trial scientific advisory committee. Dr Opie reported consulting fees, support for travel, and fees for scientific advisory committee participation; direct payment for employment (salary) and grants pending (Medical Research Council); and institutional payment for travel (European Society of Cardiology Task Force) outside of the submitted work. Dr Pirrallo reported institutional grant support and support for travel expenses; and relevant but outside of the submitted work he reported direct payment for board membership in National Association of EMS Physicians. Dr Sayah reported institutional receipt of grant support and fees for participating in review activities. Dr Van Gelder reported institutional and direct receipt of grant funds and institutional receipt of funds for provision of equipment and administrative support. Dr Aufderheide reported institutional grant support, support for travel expenses, and provision for software and equipment; also reported as relevant but outside of the submitted work: board membership (volunteer at Citizen CPR Foundation and Take Heart America), consultant (funds to institution, Medtronic Inc), 5 pending emergency research grants (funds to institution, NHLBI, NINDS, Leducq Foundation, Medtronic Foundation); and volunteer member (BLS Subcommittee and Research Working Group, AHA). Dr Wayne reported grant support provided to his institution and direct receipt of funds; also reported, as relevant but outside of the submitted work: direct payment for employment as emergency medicine physician, EMS director, expert testimony, royalties (chest tube by Cook Critical Care), payment for development of educational presentations, and travel expenses for a nonprofit foundation administration. Dr Walter reported institutional receipt of funds for equipment, administrative support, paramedic training, and investigator effort; also reported, relevant but outside the submitted work: receipt of funds for employment as the medical director for the paramedic service at Emerson Hospital. Drs Levy and Apstein reported no conflicts of interest.

Figures

Figure
Figure
Screening and Enrollment of Participants in the IMMEDIATE Randomized Controlled Trial ACS indicates acute coronary syndromes; ECG, electrocardiogram; and ED, emergency department. aRandomized group included 18 participants (8 in glucose-insulin-potassium [GIK] group, 10 in placebo group) who did not meet eligibility requirements. bThe 871 enrollments occurred in 850 individual patients.
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