Myocardial InfarctionPhase 3REAGIK-STEMINCT02591927
Reappraisal of GIK in Acute STEMI by Pre-hospital Administration
A Phase 3 study testing Glucose-Insulin-Potassium and Glucose 5% in people with Myocardial Infarction, run by Centre Hospitalier Universitaire Vaudois at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myocardial Infarction
- What is being tested?
- Glucose-Insulin-Potassium and Glucose 5%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 334 participants
- Where
- 1 siteSwitzerland
- Study dates
- Feb 2016to Feb 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with the diagnosis of acute STEMI
- age≥ 18
- informed consent for study participation.
- Exclusion Criteria evaluated during ambulance transport to primary PCI center:
- end-stage renal failure requiring dialysis,
- prior MI or coronary revascularization (PCI or CABG),
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- active malignances,
- Pregnancy,
- 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):
- total ischemic time more than 8 hours (from symptoms onset to infarct-related artery mechanical re-opening)
- 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),
- moderate-to-severe renal failure (estimated glomerular filtration rate < 30 ml/min/1.73 m2 by Cockcroft-Gault formula) and
- urgent CABG.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Centre Hospitalier Universitaire Vaudois - CHUV
Lausanne, Canton of Vaud, 1011
PierGiorgio Masci, MD, PhD, 79-556-48-63 ext. +41, pgmasci@gmail.com
About this study
Official title: Reappraisal of Glucose-insulin-potassium Therapy in Acute St-segment Elevation Myocardial Infarction by Pre-hospital Administration
The purpose of this study is:
- 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.
- to explore the putative cardioprotective mechanisms of pre-hospital GIK administration
Read the 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
- 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.
- 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.
- Conditions
- Myocardial Infarction
- Being tested
- Glucose-Insulin-Potassium, Glucose 5%
- Keywords
- myocardial infarction, glucose-insulin-potassium
- Medical subject headings
- Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glucose-Insulin-PotassiumDrug
Also called GIK
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).
Glucose 5%Drug
Also called Placebo
Glucose 5% (Placebo) by continuous I.V. infusion at 1.5ml/kg/hour for 12 hours (about 100 ml/hour for 70 Kg patient)
| Study group | Role | What they receive |
|---|---|---|
| Glucose-Insulin-Potassium | Active comparator | 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. Receives: Drug: Glucose-Insulin-Potassium |
| Glucose 5% | Placebo comparator | Glucose 5% Receives: Drug: Glucose 5% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infarct size quantified by Late Gadolinium Enhancement using Cardiovascular Magnetic Resonance
Measured: 12 to 72 hours after the acute event
Secondary outcomes (3)
The severity of ischemia/reperfusion injury (myocardial edema, microvascular obstruction and myocardial hemorrhage)
The of ischemia/reperfusion injury will be assessed by multiparametric CMR
Measured: 12 to 72 hours after the acute event
Major Adverse Cardiovascular Events
Measured: at 7-day, 30-day, 4-month and at 1-year follow-up
Post-infarction Remodeling
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)
Measured: 4-month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2015 (estimated)
- Study startFeb 2016
- Primary completionFeb 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Myocardial InfarctionStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire VaudoisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 334 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire Vaudois
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pier Giorgio Masci, Centre Hospitalier Universitaire Vaudois
- Investigators
- Pier-Giorgio Masci, MD, Principal investigator, Centre Hospitalier Universitaire VaudoisJuerg Schwitter, MD, Study director, Centre Hospitalier Universitaire VaudoisPierre Vogt, MD, Study chair, Centre Hospitalier Universitaire VadoisEric Eeckhout, MD, Study chair, Centre Hospitalier Universitaire VaudoisJuan-Fernando Iglesias, Study chair, Centre Hospitalier Universitaire VaudoisOlivier Muller, Study chair, Centre Hospitalier Universitaire VaudoisOlivier Hugli, Study chair, Centre Hospitalier Universitaire VaudoisFabrice Dami, Study chair, Centre Hospitalier Universitaire Vaudois
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02591927
- Sponsor's protocol ID
- 32003B_159727
- Acronym
- REAGIK-STEMI
- Status last verified
- Oct 2015
- First submitted
- 28 Oct 2015
- Last updated
- 30 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Grossman AN, Opie LH, Beshansky JR, Ingwall JS, Rackley CE, Selker HP. Glucose-insulin-potassium revived: current status in acute coronary syndromes and the energy-depleted heart. Circulation. 2013 Mar 5;127(9):1040-8. doi: 10.1161/CIRCULATIONAHA.112.130625. No abstract available.
PubMed 23459576Selker HP, Beshansky JR, Sheehan PR, Massaro JM, Griffith JL, D'Agostino RB, Ruthazer R, Atkins JM, Sayah AJ, Levy MK, Richards ME, Aufderheide TP, Braude DA, Pirrallo RG, Doyle DD, Frascone RJ, Kosiak DJ, Leaming JM, Van Gelder CM, Walter GP, Wayne MA, Woolard RH, Opie LH, Rackley CE, Apstein CS, Udelson JE. Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: the IMMEDIATE randomized controlled trial. JAMA. 2012 May 9;307(18):1925-33. doi: 10.1001/jama.2012.426. Epub 2012 Mar 27.
PubMed 22452807
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reappraisal of Glucose-insulin-potassium Therapy in Acute St-segment Elevation Myocardial Infarction by Pre-hospital Administration
- ClinicalTrials.gov ID
- NCT02591927
- Acronym / sponsor ID
- REAGIK-STEMI / 32003B_159727
- Conditions
- Myocardial Infarction
- Keywords
- myocardial infarction, glucose-insulin-potassium
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 334 participants (estimated)
- Lead sponsor
- Centre Hospitalier Universitaire VaudoisUniversity, hospital or other
- Study start
- Feb 2016
- Primary completion
- Feb 2019 (estimated)
- First posted
- 30 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is:
- 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.
- to explore the putative cardioprotective mechanisms of pre-hospital GIK administration
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
- 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.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Glucose-Insulin-Potassium | Active comparator | Drug: Glucose-Insulin-PotassiumRackley'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. |
| Glucose 5% | Placebo comparator | Drug: Glucose 5%Glucose 5% |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients with the diagnosis of acute STEMI
- age≥ 18
- informed consent for study participation.
- end-stage renal failure requiring dialysis,
- prior MI or coronary revascularization (PCI or CABG),
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Glucose-Insulin-PotassiumAlso: GIKRackley'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). | Drug | Glucose-Insulin-Potassium |
| Glucose 5%Also: PlaceboGlucose 5% (Placebo) by continuous I.V. infusion at 1.5ml/kg/hour for 12 hours (about 100 ml/hour for 70 Kg patient) | Drug | Glucose 5% |
Primary outcome
Infarct size quantified by Late Gadolinium Enhancement using Cardiovascular Magnetic Resonance
Time frame: 12 to 72 hours after the acute event
3 secondary outcomes
The severity of ischemia/reperfusion injury (myocardial edema, microvascular obstruction and myocardial hemorrhage)
Time frame: 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
Post-infarction Remodeling
Time frame: 4-month follow-up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2015.
- Background: PubMed 23459576Grossman AN, Opie LH, Beshansky JR, Ingwall JS, Rackley CE, Selker HP. Glucose-insulin-potassium revived: current status in acute coronary syndromes and the energy-depleted heart. Circulation. 2013 Mar 5;127(9):1040-8. doi: 10.1161/CIRCULATIONAHA.112.130625. No abstract available.
- Background: PubMed 22452807Selker HP, Beshansky JR, Sheehan PR, Massaro JM, Griffith JL, D'Agostino RB, Ruthazer R, Atkins JM, Sayah AJ, Levy MK, Richards ME, Aufderheide TP, Braude DA, Pirrallo RG, Doyle DD, Frascone RJ, Kosiak DJ, Leaming JM, Van Gelder CM, Walter GP, Wayne MA, Woolard RH, Opie LH, Rackley CE, Apstein CS, Udelson JE. Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: the IMMEDIATE randomized controlled trial. JAMA. 2012 May 9;307(18):1925-33. doi: 10.1001/jama.2012.426. Epub 2012 Mar 27.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pier-Giorgio Masci, MD principal investigator
Centre Hospitalier Universitaire Vaudois
Juerg Schwitter, MD study director
Centre Hospitalier Universitaire Vaudois
Pierre Vogt, MD study chair
Centre Hospitalier Universitaire Vadois
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Glucose-Insulin-Potassium and Glucose 5% in people with Myocardial Infarction, run by Centre Hospitalier Universitaire Vaudois at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Pier-Giorgio Masci, MD (79-556-48-63 ext. +41, pgmasci@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Infarct size quantified by Late Gadolinium Enhancement using Cardiovascular Magnetic Resonance (time frame: 12 to 72 hours after the acute event). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02591927, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2015.