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

October 29, 2015 updated by: Pier Giorgio Masci, Centre Hospitalier Universitaire Vaudois

Reappraisal of Glucose-insulin-potassium Therapy in Acute St-segment Elevation Myocardial Infarction by Pre-hospital Administration

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Enrollment (Anticipated)

334

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Pier-Giorgio Masci, MD
  • Phone Number: +41 79-556-48-63
  • Email: pgmasci@gmail.com

Study Contact Backup

Study Locations

  • Switzerland
    • Vaud
      • Lausanne, Vaud, Switzerland, 1011
        • Centre hospitalier universitaire vaudois - CHUV
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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 Names:
  • GIK
Placebo Comparator: 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 Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Infarct size quantified by Late Gadolinium Enhancement using Cardiovascular Magnetic Resonance
Time Frame: 12 to 72 hours after the acute event
12 to 72 hours after the acute event

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
12 to 72 hours after the acute event
Major Adverse Cardiovascular Events
Time Frame: at 7-day, 30-day, 4-month and at 1-year follow-up
at 7-day, 30-day, 4-month and at 1-year follow-up
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)
4-month follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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 and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2016

Primary Completion (Anticipated)

February 1, 2019

Study Registration Dates

First Submitted

October 28, 2015

First Submitted That Met QC Criteria

October 29, 2015

First Posted (Estimate)

October 30, 2015

Study Record Updates

Last Update Posted (Estimate)

October 30, 2015

Last Update Submitted That Met QC Criteria

October 29, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 32003B_159727

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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