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Reappraisal of glucose-insulin-potassium therapy in acute st-segment elevation myocardial infarction by pre-hospital administration (reagik-stemi)

English title Reappraisal of glucose-insulin-potassium therapy in acute st-segment elevation myocardial infarction by pre-hospital administration (reagik-stemi)
Applicant Eeckhout Eric
Number 159727
Funding scheme Project funding (Div. I-III)
Research institution Service de Cardiologie Département de Médecine CHUV
Institution of higher education University of Lausanne - LA
Main discipline Clinical Cardiovascular Research
Start/End 01.06.2015 - 31.05.2019
Approved amount 456'204.00
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All Disciplines (2)

Discipline
Clinical Cardiovascular Research
Pathophysiology

Keywords (3)

myocardial infarction; Magnetic resonance imaging; glucose-insulin-potassium

Lay Summary (French)

Lead
La maladie cardiaque ischémique représente l'une des principales causes de morbidité et de mortalité dans le monde. Bien que les récents progrès de la médecine ont permis de réduire la mortalité de l'infarctus aigu du myocarde, un nombre significatif de patients continuent d’avoir un mauvais pronostic en raison d’un risque élevé de développer une insuffisance cardiaque ou des arythmies mortelles. La meilleure stratégie serait de trouver des thérapies pour réduire la taille de l'infarctus.
Lay summary

Titre du projet de recherche

Evaluation de l’administration pré-hospitalière de glucose-insuline-potassium (GIK) dans l’infarctus aigu du myocarde avec élévation du segment ST

 

Lead

La maladie cardiaque ischémique représente l'une des principales causes de morbidité et de mortalité dans le monde. Bien que les récents progrès de la médecine ont permis de réduire la mortalité de l'infarctus aigu du myocarde, un nombre significatif de patients continuent d’avoir un mauvais pronostic en raison d’un risque élevé de développer une insuffisance cardiaque ou des arythmies mortelles. La meilleure stratégie serait de trouver des thérapies pour réduire la taille de l'infarctus.

 

Contenu et objectifs du travail de recherche

Notre étude vise à évaluer l'efficacité de l'administration d'une solution contenant du glucose, de l'insuline et du potassium (GIK) chez les patients atteints d’un infarctus aigu du myocarde. L'étude prévoit d'administrer la solution GIK pendant le transport des patients en ambulance vers l'hôpital afin de minimiser le délai entre l'apparition des symptômes et l'administration de la solution GIK. L’efficacité de la GIK sera évaluée grâce à la résonance magnétique du cœur pendant l’hospitalisation des patients. Cette méthodique d’imagerie avancée permet de mesurer avec précision la taille de l’infarctus et donc de tester l’efficacité de la GIK de manière précise et non invasive.

 

Contexte scientifique et social du projet de recherche

Le projet relève de la recherche clinique. Si les résultats de notre étude confirment l'efficacité de la GIK dans la réduction de taille de l'infarctus, ce traitement pourrait être évalué dans des études internationales impliquant plusieurs centres afin de tester l'efficacité de la GIK à améliorer le pronostic des patients atteints d’un infarctus aigu du myocarde.

 

Mots-clés

Infarctus aigu, glucose-insuline-potassium

 

Direct link to Lay Summary Last update: 05.11.2015

Responsible applicant and co-applicants

Employees

Project partner

Collaboration

Group / person Country
Types of collaboration
Ecole politechnique Fédérale Zurich (S. Kozerke, PhD) Switzerland (Europe)
- Research Infrastructure
Hospital Monzino, Milan, Italy (G-L. Pontone, MD) Italy (Europe)
- Research Infrastructure
Centre d'imagerie biomédicale, CIBM (M. Bach Cuadra, PhD) Switzerland (Europe)
- Research Infrastructure
Hôpital Yverdon-les-Bains (P. Jolivet, MD) Switzerland (Europe)
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
22nd Annual Scientific Meeting of the SCMR, Bellevue, USA, 2019 Poster A Novel Clustering Approach Applied to T1 Mapping Time Series To Identify Microvascular Obstruction in Patients With Sub-Acute ST-Elevation Myocardial Infarction 08.02.2019 Bellevue, WA, USA, United States of America Najdenovska Elena;


Associated projects

Number Title Start Funding scheme
173129 A Paradigm Shift in Magnetic Resonance Imaging of the Heart: 5D Imaging - Sample Now and Ask Questions Later 01.06.2017 Project funding (Div. I-III)

Abstract

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 its safety has been abundantly proven also in the out-hospital setting. Thus, upon the verification of its efficacy, GIK treatment would be ready for primetime clinical application with matchless cost/effectiveness profile. However, pharmaceutical companies do not promote research on GIK therapy because of the lack of economic interests, and thus financial sources of independent scientific foundation are definitively warranted. 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 administrationMethods - We will conduct a 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 of pre-hospital GIK treatment in subjects with acute STEMI. Outlook: Our 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.
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