Reappraisal of GIK in Acute STEMI by Pre-hospital Administration (REAGIK-STEMI)

Vaud University Hospital Center

Status and phase: Unknown; Phase 3

Conditions: Myocardial Infarction

Treatments: Drug: Glucose-Insulin-Potassium; Drug: Glucose 5%

Study type: Interventional

Funder types: Other

Identifiers

NCT02591927

32003B_159727

Details and patient eligibility

About

The purpose of this study is:

1. to assess whether pre-hospital glucose-insulin-potassium (GIK) administration in acute STEMI patients would reduce infarct size and ischemia/reperfusion damage using comprehensive tissue characterization by cardiovascular magnetic resonance (CMR) at an early post-infarction phase.
2. to explore the putative cardioprotective mechanisms of pre-hospital GIK administration

Full description

Background - After an acute ST-segment elevation myocardial infarction (STEMI), early and successful myocardial reperfusion with primary percutaneous coronary intervention (PCI) is the most effective strategy for reducing the infarct size and improving clinical outcome. The process of restoring blood flow to the ischemic myocardium, however, can induce injury per se, paradoxically increasing the extent of final infarction (i.e., reperfusion injury). Research has been focusing for years on a strategy to effectively counteract reperfusion injury and, thereby, reduce the final infarct size with salutary effects on clinical outcome. Robust experimental evidences support Glucose-Insulin-Potassium (GIK) as an effective cardioprotective agent being capable to metabolically protect the myocardium against ischemia and ischemia/reperfusion injury. These benefits are clearly related to the time that GIK is administered in the course of cardiac ischemia, with effectiveness increasing with early administration. However, clinical trials in the reperfusion era have lost the opportunity to translate the beneficial effects seen in the laboratory to the clinical setting, because of the unacceptably prolonged delay from the onset of ischemic symptoms to GIK administration. A properly-designed prospective trial with double-blinded randomization to placebo or GIK in the out-of-hospital setting would straightforwardly overcome this limitation, thereby providing convincing evidences in favor or disfavor of GIK treatment. Notable, GIK is an un-expensive compound, and upon the verification of its efficacy, GIK treatment would be ready for primetime clinical application with matchless cost/effectiveness profile.

Aims

1. to assess whether pre-hospital GIK administration in acute STEMI patients would reduce infarct size and ischemia/reperfusion damage using comprehensive tissue characterization by cardiovascular magnetic resonance (CMR) at an early post-infarction phase.
2. to explore the putative cardioprotective mechanisms of pre-hospital GIK administration

Methods - The investigators will conduct a single-center randomized, placebo-controlled, double-blinded trial for testing the efficacy of pre-hospital GIK administration in patients with acutely reperfused STEMI. The pre-specified primary end-point is the reduction of infarct size, as quantitated by late gadolinium enhancement CMR in the early post-infarction phase. Major secondary end-points are: 1) reduction of ischemia/reperfusion injury quantitated by CMR, and 2) investigation of the putative cardioprotective mechanisms ofGIK treatment in subjects with acute STEMI.

Outlook: The investigators study results, if positive, will persuade the scientific community to reconsider pre-hospital GIK treatment as adjunctive to primary PCI in acute STEMI patients and revitalize the field of metabolism-based cardioprotection. They will illustrate by which mechanisms cardioprotection is achieved in the clinical setting, prompting large prospective multicentre trials to test the efficacy of pre-hospital GIK administration on hard clinical end-points.

Enrollment: 334 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

1. Patients with the diagnosis of acute STEMI
2. age≥ 18
3. informed consent for study participation.

Exclusion Criteria evaluated during ambulance transport to primary PCI center:

1. end-stage renal failure requiring dialysis,
2. prior MI or coronary revascularization (PCI or CABG),
3. active malignances,
4. Pregnancy,
5. Hemodynamic instability (systolic blood pressure <100mmHg or significant pulmonary congestion defined as O2 saturation <90% on ambient air at pulso-oxymetry)

Exclusion Criteria evaluated after hospital admission at the primary PCI center (all patients will be re-evaluated for study continuation):

1. total ischemic time more than 8 hours (from symptoms onset to infarct-related artery mechanical re-opening)
2. evidence at diagnostic angiograms of TIMI flow-grade >1 of infarct-related artery or significant epicardial collaterals to the ischemic myocardium at risk (Rentrop flow-grade >1),
3. moderate-to-severe renal failure (estimated glomerular filtration rate < 30 ml/min/1.73 m2 by Cockcroft-Gault formula) and
4. urgent CABG.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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334 participants in 2 patient groups, including a placebo group

Glucose-Insulin-Potassium

Active Comparator group

Description:

Rackley's Glucose-Insulin-Potassium formula consisting of 30% glucose (300 mg/L), 50 units of regular insulin per liter and 80 mEqu of KCL per liter.

Treatment:

Drug: Glucose-Insulin-Potassium

Glucose 5%

Placebo Comparator group

Description:

Glucose 5%

Treatment:

Drug: Glucose 5%