Cooling in Myocardial Infarction

NCT ID: NCT01777750

Last Updated: 2019-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2019-01-31

Brief Summary

The primary goal in the treatment of acute myocardial infarction is to reperfuse the ischemic myocardium to reduce infarct size. Animal data and human data suggest that whole-body cooling to temperatures below 35°C before revascularisation can additionally reduce infarct size and therefore improves outcome in these patients.

The purpose of the study is to determine if a combined cooling strategy started in the out-of-hospital arena is able to reduce infarct size in acute myocardial infarction.

Detailed Description

Background: Contemporary therapy in patients with an on-going ST-elevation myocardial infarction (STEMI) is to reperfuse the ischemic myocardium as soon as possible to reduce infarct size and associated complications. A recent pilot-study showed a significant reduction in infarct size by the induction of pre-reperfusion hypothermia.

Objectives: To demonstrate a reduction in infarct size/myocardium at risk (measured by magnet resonance imaging) in patients with ST-Elevation myocardial infarction by strategic temperature management with the use of external cooling pads in the out-of-hospital setting and the continuation with cold saline and central venous catheter cooling in hospital. In a parallel translational study, the molecular effects of rapid and early cooling on inflammatory processes at the culprit lesion site will be defined.

Methodology: Randomized, prospective, controlled trial Number of subjects: 120 patients (60 per group) Investigational medical device: EMCOOLS flex pad is an external cooling pad, that consists of multiple cooling cells filled with a patented cooling gel. EMCOOLS flex pad will be used in the out-of-hospital setting to initiate cooling. The Philips RTx Endovascular System™ is an endovascular thermal control system that circulates cooled saline through an indwelling central venous catheter in a closed-loop manner. It will be used in combination with 1-2 litres of intravenous cold saline to induce hypothermia below 35 degrees Celsius.

Duration: One hour after successful revascularization the cooling procedure will be stopped, subjects will be covered with a blanket and are allowed to passively re-warm. Clinical follow-up for 180 days.

Primary endpoint: Myocardial infarct size (as a percentage of myocardium at risk) assessed by cardiac MRI at 4±2 days. Influence of target temperature management on coronary macrophages and monocytes as well as impact on plasma levels of immune cell chemotaxis and activation.

Conditions

ST-elevation Myocardial Infarction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Pre- and perinterventional hypothermia

Cooling will be initiated by the application of cooling pads in the out-of-hospital setting followed by an infusion of 1000-2000ml of cold saline. In the cath lab a endovascular cooling catheter will be placed into the inferior vena cava via a femoral vein to achieve a core temperature of \<35°C prior to revascularization.

Group Type: ACTIVE_COMPARATOR

EMCOOLS flex pad; Philips Innercool RTx

Intervention Type: DEVICE

Surface cooling with EMCOOLS flex pads (out-of-hospital); Infusion of 1000ml to 2000ml of cold saline (out-of-hospital); central-venous cooling (Philips Inntercool RTx)

Standard treatment

Standard treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

EMCOOLS flex pad; Philips Innercool RTx

Surface cooling with EMCOOLS flex pads (out-of-hospital); Infusion of 1000ml to 2000ml of cold saline (out-of-hospital); central-venous cooling (Philips Inntercool RTx)

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Age between 18 and 75 years
• Immediate transfer to cath-lab is possible
• Anterior or inferior ST-segment myocardial infarction
• ST-Segment elevation of >0.2mV in 2 or more anatomically contiguous leads
• Duration of symptoms <6 hours

Exclusion Criteria

• Participation in another study
• Patients presenting with cardiac arrest/cardiogenic shock
• Tympanic temperature <35.0°C prior to enrolment
• Thrombolytic therapy
• Previous MI
• Previous PCI or coronary artery bypass graft
• Severe heart failure at presentation (defined as a New York Heart Association (NYHA) functional class III or IV), or Killip classes II through IV
• Clinical signs of active infection
• End-stage kidney disease or hepatic failure
• Recent stroke (within the past six months)
• Conditions that may be exacerbated by hypothermia, such as haematological dyscrasias, oral anticoagulant treatment with international normalized ratio >1.5, severe pulmonary disease
• Pregnancy
• Women of childbearing potential
• Allergy to meperidine, buspirone, magnesium, or polyvinyl chloride
• Use of a monoamine oxidase inhibitor such as selegiline in the previous 14 days
• absolute contraindications against MRI (PM, ICD, ferromagnetic implants)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Austrian Science Fund (FWF)

OTHER

Sponsor Role: collaborator

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Dr. Christoph Testori

Department of Emergency Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christoph Testori, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna, Dept. of Emergency Medicine

Locations

Medical University of Vienna

Vienna, , Austria

Countries

Austria

References

Mangold A, Ondracek AS, Hofbauer TM, Scherz T, Artner T, Panagiotides N, Beitzke D, Ruzicka G, Nistler S, Wohlschlager-Krenn E, Winker R, Quehenberger P, Traxler-Weidenauer D, Spannbauer A, Gyongyosi M, Testori C, Lang IM. Culprit site extracellular DNA and microvascular obstruction in ST-elevation myocardial infarction. Cardiovasc Res. 2022 Jun 29;118(8):2006-2017. doi: 10.1093/cvr/cvab217.

Reference Type: DERIVED

PMID: 34173822 (View on PubMed)

Testori C, Beitzke D, Mangold A, Sterz F, Loewe C, Weiser C, Scherz T, Herkner H, Lang I. Out-of-hospital initiation of hypothermia in ST-segment elevation myocardial infarction: a randomised trial. Heart. 2019 Apr;105(7):531-537. doi: 10.1136/heartjnl-2018-313705. Epub 2018 Oct 25.

Reference Type: DERIVED

PMID: 30361270 (View on PubMed)

Other Identifiers

KLI209

Identifier Type: -

Identifier Source: org_study_id