Efficacy of Endovascular Catheter Cooling Combined With Cold Saline for the Treatment of Acute Myocardial Infarction

Study Overview
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Brief Summary
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The purpose of this study is to determine whether treatment of patients suffering from ST-elevation myocardial infarction (STEMI) with 1-2 liters of cold saline and central venous catheter cooling with Philips InnerCool RTx Endovascular System prior to percutaneous coronary intervention (PCI) result in a reduction in infarct size.

Detailed Description
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Acute myocardial infarction (AMI) is the leading cause of mortality in the western world today. Although reperfusion of the ischemic myocardium is a prerequisite for myocardial salvage, it has been described that the reperfusion in itself may cause additional damage to the myocardium (reperfusion injury). In the safety & feasibility trial RAPID MI-ICE we demonstrated that treatment of patients suffering from STEMI with 1-2 liters of cold saline and central venous catheter cooling with Philips InnerCool RTx Endovascular System prior to PCI was feasible, safe and resulted in a 38% reduction in infarct size/myocardium at risk. The aim of the present study is to confirm this finding in a larger multicenter trial. The study is a randomized, controlled, evaluator blinded, multicenter trial enrolling 120 patients at ten sites.

Official Title
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Rapid Endovascular Catheter Core Cooling Combined With Cold Saline as an Adjunct to Percutaneous Coronary Intervention For the Treatment of Acute Myocardial Infarction

Conditions
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Myocardial Infarction, Myocardial Reperfusion Injury, Anterior Wall Myocardial Infarction, Inferior Wall Myocardial Infarction

Intervention / Treatment
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* Procedure: Cooling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical symptoms and signs of myocardial infarction and have a 12-lead ECG providing evidence of an ongoing acute myocardial infarction, involving a large area of myocardium, as defined by the following ECG criteria. The ECG changes should be present upon arrival to the cath lab: Anterior infarct: ST-segment elevation >0.2mV measured 0.08 sec after the J point in 2 or more anatomically contiguous precordial leads, V1 through V4; and/or >0.2mV in lead V5 V6. Inferior infarct: ST elevation >0.2mV measured 0.08 sec after the J point in 2 or more anatomically contiguous inferior leads, coupled with ST depression in 2 contiguous anterior leads for a total ST deviation (inferior ST elevation plus anterior ST depression) of >0.8mV. Present to the study PCI lab within six (6) hours of the onset of acute cardiac ischemic signs or symptoms (such as chest pain or pressure, arm or jaw pain, dyspnea, nausea/vomiting, or syncope). Be a candidate for PCI and have PCI planned as the immediate intervention. Be willing and able to comply with study procedures, including returning for the MRI scan at 4 ±2 days and be available for additional follow up Subject understands study procedures and agrees to participate in the study by giving written informed consent. Be in Killips Class I. Exclusion Criteria: Age less than eighteen (<18) years of age Age greater than or equal to eighty (80) years of age Are pregnant. Having an aortic dissection History of a prior large myocardial infarct or an infarct in the same segment that is currently affected. Acute administration of a thrombolytic agent for the qualifying MI Clinical suspicion of a non-thrombotic (e.g., pericarditis, vasospasm, takotsubo, illicit drug use) cause for ST-segment elevation as determined by the investigator If (during the screening process) the determination is made by site-study personnel that initiation of cooling prior to diagnostic coronary angiography is technically not feasible for any reason (should the patient be randomized to the Hypothermia Arm), the prospective subject should not be enrolled. Known risk for heparin induced thrombocytopenia (HIT) Require an immediate surgical or procedural intervention other than PCI (e.g. CABG) Present in cardiogenic shock or with end-stage cardiomyopathy Have undergone at least ten (10) minutes of cardiopulmonary resuscitation (CPR) prior to presentation to the PCI facility History of surgical coronary artery revascularization (e.g. CABG) Active bleeding, coagulopathy, or other contraindication to the placement of a heparin-coated 14F central venous catheter via a 14F femoral venous introducer sheath (e.g., known history of heparin induced thrombocytopenia, or IVC filter) Contraindications to hypothermia Personal or familial history of malignant hyperthermia Known end-stage renal disease (ESRD; e.g., on dialysis, or status-post renal transplant), known severe hepatic failure (e.g., cirrhosis, or acute hepatitis), or any other contraindication to receiving meperidine (such as use of MAO inhibitors within previous 14 days, history of seizures, history of hypersensitivity to meperidine, etc.). Serious concurrant medical condition likely to result in death during the next 12 months. Any other acute or chronic condition which the Investigator believes will unacceptably increase the risk of study participation or interfere with study procedures and assessments. Contraindication to MRI (e.g., cardiac pacemaker, ICD, nerve stimulator, brain aneurysm clips, cochlear implants, claustrophobia) Deemed unsuitable by the investigators to participate in the study. Active or recent (within 1 month prior to study enrollment) participation in another investigational clinical research study. Enrollment in or planned to be enrolled in another study of AMI therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hypothermia treatment<br>1-2 liters of cold saline and central venous catheter cooling with Philips InnerCool RTx Endovascular System prior to PCI | Procedure: Cooling<br>* 1-2 liters of cold saline and central venous catheter cooling with Philips InnerCool RTx Endovascular System prior to PCI<br>* Other names: Hypothermia;|
| No Intervention: Standard treatment<br>Standard treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial infarct size (as a percentage of myocardium at risk) assessed by cardiac MRI. |  | At 4±2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial infarct size (as a percentage of myocardium at risk) both assessed by cardiac MRI at 4±2 days in the patients who are cooled and achieve a target temperature of < 35 C prior to PCI. |  | At 4±2 days | 
| Myocardial infarct size (as a percentage of myocardium at risk) both assessed by cardiac MRI at 4±2 days in patients with an occluded and non-occluded IRA before PCI. |  | At 4±2 days | 
| Myocardial infarct size (as a percentage of myocardium at risk) both assessed by cardiac MRI at 4±2 days in the per protocol population who are cooled according to protocol and meet inclusion criteria. |  | At 4±2 days | 
| Myocardial infarct size (as a percentage of myocardium at risk) both assessed by cardiac MRI at 4±2 days in patients with anterior or inferior myocardial infarctions separately. |  | At 4±2 days | 
| The effect of the hypothermia protocol on the incidence of death. |  | 45±15 days and 6 months. | 
| Plasma level of high sensitivity Troponin T AUC through 48 hours and peak plasma level of high sensitivity Troponin T within 48 hours after AMI. |  | 48 hours | 
| ST-segment resolution 1.5 hour after opening the IRA. |  | 1.5 hours | 
| Coronary blood flow and coronary angiography at the index event estimated by TIMI coronary flow and coronary perfusion grading. |  | 2 hours | 
| Plasma NT-proBNP levels at day 4±2. |  | Day 4±2. | 
| Incidence of death at 1, 2, 3, 4 and 5 years. |  | 5 years | 
| Myocardial infarct size (as a percentage of myocardium at risk) assessed by cardiac MRI at 6±1 months. |  | 6 months | 
| Incidence of heart failure within 45±15 days. |  | 6 months | 
| Incidence of pulmonary oedema. |  | 1 week | 
| Incidence of infections |  | 1 week | 
| Incidence of bleedings |  | 1 week | 
| The effect of the hypothermia protocol on the incidence of recurrent MI. |  | 6 months | 
| The effect of the hypothermia protocol on the incidence of emergent stent revascularisation. |  | 6 months | 
| The effect of the hypothermia protocol on the incidence of any hospitalisation. |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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STEMI, primary PCI, Hypothermia, Endovascular cooling, Cardiac MRI