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

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ClinicalTrials.gov Identifier: NCT02591927
Recruitment Status : Not yet recruiting
First Posted : October 30, 2015
Last Update Posted : October 30, 2015
Sponsor:
Information provided by (Responsible Party):
Pier Giorgio Masci, Centre Hospitalier Universitaire Vaudois

Brief Summary:

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

Condition or disease Intervention/treatment Phase
Myocardial Infarction Drug: Glucose-Insulin-Potassium Drug: Glucose 5% Phase 3

Detailed 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 334 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Reappraisal of Glucose-insulin-potassium Therapy in Acute St-segment Elevation Myocardial Infarction by Pre-hospital Administration
Study Start Date : February 2016
Estimated Primary Completion Date : February 2019


Arm Intervention/treatment
Active Comparator: Glucose-Insulin-Potassium
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.
Drug: Glucose-Insulin-Potassium
Rackley's GIK formula by continuous I.V. infusion at 1.5 ml/Kg/hour for 12 hours (about 100 ml/hour for a 70 kg patient).
Other Name: GIK

Placebo Comparator: Glucose 5%
Glucose 5%
Drug: Glucose 5%
Glucose 5% (Placebo) by continuous I.V. infusion at 1.5ml/kg/hour for 12 hours (about 100 ml/hour for 70 Kg patient)
Other Name: Placebo




Primary Outcome Measures :
  1. Infarct size quantified by Late Gadolinium Enhancement using Cardiovascular Magnetic Resonance [ Time Frame: 12 to 72 hours after the acute event ]

Secondary Outcome Measures :
  1. The severity of ischemia/reperfusion injury (myocardial edema, microvascular obstruction and myocardial hemorrhage) [ Time Frame: 12 to 72 hours after the acute event ]
    The of ischemia/reperfusion injury will be assessed by multiparametric CMR

  2. Major Adverse Cardiovascular Events [ Time Frame: at 7-day, 30-day, 4-month and at 1-year follow-up ]
  3. Post-infarction Remodeling [ Time Frame: 4-month follow-up ]
    Adverse post-infarction remodeling is defined as increase of LV end-systolic volume more than 15% between the first CMR (12 to 72 hours after the acute event) and second CMR (4-month after the acute event)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02591927


Contacts
Contact: Pier-Giorgio Masci, MD 79-556-48-63 ext +41 pgmasci@gmail.com
Contact: Juerg Schwitter, MD 79-556-83-27 ext +41 jurg.schwitter@chuv.ch

Locations
Switzerland
Centre Hospitalier Universitaire Vaudois - CHUV Not yet recruiting
Lausanne, Vaud, Switzerland, 1011
Contact: PierGiorgio Masci, MD, PhD    79-556-48-63 ext +41    pgmasci@gmail.com   
Sponsors and Collaborators
Centre Hospitalier Universitaire Vaudois
Investigators
Principal Investigator: Pier-Giorgio Masci, MD Centre Hospitalier Universitaire Vaudois
Study Director: Juerg Schwitter, MD Centre Hospitalier Universitaire Vaudois
Study Chair: Pierre Vogt, MD Centre Hospitalier Universitaire Vadois
Study Chair: Eric Eeckhout, MD Centre Hospitalier Universitaire Vaudois
Study Chair: Juan-Fernando Iglesias Centre Hospitalier Universitaire Vaudois
Study Chair: Olivier Muller Centre Hospitalier Universitaire Vaudois
Study Chair: Olivier Hugli Centre Hospitalier Universitaire Vaudois
Study Chair: Fabrice Dami Centre Hospitalier Universitaire Vaudois
Study Chair: Pierre Monney Centre Hospitalier Universitaire Vaudois

Publications:
Responsible Party: Pier Giorgio Masci, Principal Investigator, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier: NCT02591927     History of Changes
Other Study ID Numbers: 32003B_159727
First Posted: October 30, 2015    Key Record Dates
Last Update Posted: October 30, 2015
Last Verified: October 2015

Keywords provided by Pier Giorgio Masci, Centre Hospitalier Universitaire Vaudois:
myocardial infarction
glucose-insulin-potassium

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
ST Elevation Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Insulin, Globin Zinc
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs