EUROpean Intracoronary Cooling Evaluation in Patients With ST-elevation Myocardial Infarction.

NCT ID: NCT03447834

Last Updated: 2022-07-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-01
• Study Completion Date: 2023-06-30

Brief Summary

In acute myocardial infarction, early restoration of epicardial and myocardial blood flow is of paramount importance to limit infarction size and create optimum conditions for favourable long-term outcome. Currently, restoration of epicardial blood flow is preferably and effectively obtained by primary percutaneous coronary intervention (PPCI). After opening the occluded artery, however, the reperfusion process itself causes damage to the myocardium, the so called "reperfusion injury". The phenomenon of reperfusion injury is incompletely understood and currently there is no established therapy for preventing it. Contributory factors are intramyocardial edema with compression of the microvasculature, oxidative stress, calcium overload, mitochondrial transition pore opening, micro embolization, neutrophil plugging and hyper contracture. This results in myocardial stunning, reperfusion arrhythmias and ongoing myocardial necrosis. There is general agreement that a large part of the cell death caused by myocardial reperfusion injury occurs during the first few minutes of reperfusion, and that early treatment is required to prevent it.

Myocardial hypothermia may attenuate the pathological mechanisms mentioned above. However, limited data are available on the beneficial effects of hypothermia to protect the myocardium from reperfusion damage. In animals, several studies demonstrated a protective effect of hypothermia on the infarction area. This effect was only noted when hypothermia was established before reperfusion. Hypothermia is therefore thought to attenuate several damaging acute reperfusion processes such as oxidative stress, release of cytokines and development of interstitial or cellular edema. Furthermore, it has been shown that induced hypothermia resulted in increased ATP-preservation in the ischemic myocardium compared to normothermia. The intracoronary use of hypothermia by infused cold saline in pigs was demonstrated to be safe by Otake et al. In their study, saline of 4°C was used without complications (such as vasospasm, hemodynamic instability or bradycardia) and it even attenuated ventricular arrhythmia significantly.

Studies in humans, however, have not been able to confirm this effect, which is believed to be mainly due to the fact that the therapeutic temperature could not reached before reperfusion in the majority of patients or not achieved at all. Furthermore, in these studies it was intended to induce total body hypothermia, which in turn may lead to systemic reactions such as shivering and enhanced adrenergic state often requiring sedatives, which may necessitate artificial ventilation.

In fact, up to now any attempt to achieve therapeutic myocardial hypothermia in humans with myocardial infarction, is fundamentally limited because of four reasons:

1. Inability to cool the myocardium timely, i.e. before reperfusion

2. Inability to cool the diseased myocardium selectively

3. Inability to achieve an adequate decrease of temperature quick enough

4. Inability to achieve an adequate decrease of temperature large enough

Consequently, every attempt to achieve effective hypothermia in ST-segment myocardial infarction in humans has been severely hampered and was inadequate. In the last two years, the investigators have developed a methodology overcoming all of the limitations mentioned above. At first, the investigators have tested that methodology in isolated beating pig hearts with coronary artery occlusion and next, the investigators have tested the safety and feasibility of this methodology in humans.

Therefore, the time has come to perform a proof-of-principle study in humans, which is the subject of this protocol.

Conditions

Acute Myocardial Infarction; Reperfusion Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Selective intracoronary hypothermia + PPCI

Patients will be eligible for this study if they are admitted for acute anterior wall ST-elevation myocardial infarction with total ST-segment deviation of at least 5 mm. If the patient has TIMI grade flow 0 or 1, the experimental arm will be treated by selective intracoronary hypothermia just before and after reperfusion, in addition to routine PPCI.

Group Type: EXPERIMENTAL

Selective intracoronary hypothermia + PPCI

Intervention Type: OTHER

Selective intracoronary hypothermia is a new technique, recently tested for safety and feasibility in the SINTAMI trial. The procedure starts by advancing a guidewire beyond the occlusion in the culprit artery, followed by an OTWB that is inflated at the location of the occlusion, at a low pressure (4 atm), to prevent reperfusion. After that, a pressure/temperature wire will be advanced along the inflated OTWB and is placed in the distal coronary artery. Then the guidewire is removed and the lumen is used for infusion of saline. During the 'occlusion phase', saline at room temperature is infused for 10 minutes with distal coronary temperature 6-8°C below body temperature. After that, the balloon of the OTWB is deflated. Simultaneously, infusion is started with saline of 4°C, the so called 'reperfusion phase'. This is continued for 10 more minutes. After that, the OTWB can be retracted and the procedure can continue not different from routine PPCI.

Standard PPCI

The control group will receive routine PPCI.

Group Type: OTHER

Standard PPCI

Intervention Type: OTHER

PPCI per routine

Interventions

Selective intracoronary hypothermia + PPCI

Selective intracoronary hypothermia is a new technique, recently tested for safety and feasibility in the SINTAMI trial. The procedure starts by advancing a guidewire beyond the occlusion in the culprit artery, followed by an OTWB that is inflated at the location of the occlusion, at a low pressure (4 atm), to prevent reperfusion. After that, a pressure/temperature wire will be advanced along the inflated OTWB and is placed in the distal coronary artery. Then the guidewire is removed and the lumen is used for infusion of saline. During the 'occlusion phase', saline at room temperature is infused for 10 minutes with distal coronary temperature 6-8°C below body temperature. After that, the balloon of the OTWB is deflated. Simultaneously, infusion is started with saline of 4°C, the so called 'reperfusion phase'. This is continued for 10 more minutes. After that, the OTWB can be retracted and the procedure can continue not different from routine PPCI.

Intervention Type: OTHER

Standard PPCI

PPCI per routine

Intervention Type: OTHER

Other Intervention Names

Selective intracoronary hypothermia

Eligibility Criteria

Inclusion Criteria

• Acute anterior wall ST-elevation myocardial infarction
• Total ST-segment deviation of at least 5 mm
• Presenting within 6 hours after onset of complaints
• TIMI 0 or 1 flow in the LAD
• Hemodynamically stable and in an acceptable clinical condition
• Able to give informed consent

Exclusion Criteria

• Age <18 year or >80 year
• Cardiogenic shock or hemodynamically unstable patients
• Patients with previous myocardial infarction in the culprit artery of with previous bypass surgery
• Very tortuous or calcified coronary arteries
• Complex or long-lasting primary PCI expected
• Severe concomitant disease or conditions with a life expectancy of less than one year
• Inability to understand and give informed consent
• Known contra-indication for MRI
• Pregnancy
• Severe conduction disturbances necessitating implantation of temporary pacemaker

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abbott

INDUSTRY

Sponsor Role: collaborator

Golden Jubilee National Hospital

OTHER_GOV

Sponsor Role: collaborator

Onze Lieve Vrouwziekenhuis Aalst

OTHER

Sponsor Role: collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role: collaborator

Örebro University, Sweden

OTHER

Sponsor Role: collaborator

Skane University Hospital

OTHER

Sponsor Role: collaborator

University of Belgrade

OTHER

Sponsor Role: collaborator

Mid and South Essex NHS Foundation Trust

OTHER

Sponsor Role: collaborator

Catharina Ziekenhuis Eindhoven

OTHER

Sponsor Role: lead

Responsible Party

Nico Pijls

N.H.J Pijls, MD, PhD, Professor of Cardiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Catharina hospital

Eindhoven, North Brabant, Netherlands

Countries

Netherlands

References

El Farissi M, Pijls NHJ, Good R, Engstrom T, Keeble TR, Beleslin B, De Bruyne B, Frobert O, Erlinge D, Teeuwen K, Eerdekens R, Demandt JPA, Mangion K, Lonborg J, Setz-Pels W, Karamasis G, Wijnbergen I, Vlaar PJ, de Vos A, Brueren GR, Oldroyd K, Berry C, Tonino PAL, Van't Veer M, Otterspoor LC. A randomised trial of selective intracoronary hypothermia during primary PCI. EuroIntervention. 2024 Jun 17;20(12):e740-e749. doi: 10.4244/EIJ-D-23-01042.

Reference Type: DERIVED

PMID: 38887884 (View on PubMed)

El Farissi M, Good R, Engstrom T, Oldroyd KG, Karamasis GV, Vlaar PJ, Lonborg JT, Teeuwen K, Keeble TR, Mangion K, De Bruyne B, Frobert O, De Vos A, Zwart B, Snijder RJR, Brueren GRG, Palmers PJ, Wijnbergen IF, Berry C, Tonino PAL, Otterspoor LC, Pijls NHJ. Safety of Selective Intracoronary Hypothermia During Primary Percutaneous Coronary Intervention in Patients With Anterior STEMI. JACC Cardiovasc Interv. 2021 Sep 27;14(18):2047-2055. doi: 10.1016/j.jcin.2021.06.009. Epub 2021 Aug 25.

Reference Type: DERIVED

PMID: 34454860 (View on PubMed)

Other Identifiers

EURO-ICE

Identifier Type: -

Identifier Source: org_study_id