Clinical trial NCT01777750: Cooling in Myocardial Infarction
Official title: Strategic Target Temperature Management in Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: ST-elevation Myocardial Infarction
Keywords: Myocardial Infarction
Myocardial Reperfusion Injury
Reperfusion Injury
Anterior Wall Myocardial Infarction
Inferior Wall Myocardial Infarction
Pathologic Processes
Myocardial Ischemia
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
Collaborators: name: Austrian Science Fund (FWF)
First posted: 2013-01-29
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Infarct size (as percentage of myocardium at risk) assessed by cardiac MRI
timeFrame: Day 4±2
Secondary outcomes:
measure: Incidence of major adverse cardiac events
timeFrame: 6 months
measure: Immune cell activation
timeFrame: 4±2 days
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
Study officials:
affiliation: Medical University of Vienna, Dept. of Emergency Medicine
name: Christoph Testori, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.