COOL AMI EU Pivotal Trial to Assess Cooling as an Adjunctive Therapy to PCI In Patients With Acute MI (Phase A)

Study Overview
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Brief Summary
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The objective of this trial is to evaluate the safety and effectiveness of therapeutic hypothermia, using the ZOLL Proteus IVTM System, as an adjunctive therapy for patients presenting with acute anterior myocardial infarction (AMI) and undergoing percutaneous coronary intervention (PCI).

Detailed Description
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A multicenter, prospective, interventional, randomized-controlled trial. Randomization will be in a 1:1 ratio, Test Arm (PCI + Cooling) or Control Arm (PCI alone) in up to 468 randomized subjects (234 subjects in each arm). Endpoint: Relative reduction of 20% in mean anterior myocardial infarct size as determined by Cardiac Magnetic Resonance (cMR) imaging at 4-6 days post infarct in the Test Arm (cooling + PCI) relative to the Control Arm (PCI only).

Official Title
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COOL-AMI EU Pivotal Trial: A Multicenter, Prospective, Randomized-Controlled Trial to Assess the Safety and Effectiveness of Cooling As an Adjunctive Therapy to Percutaneous Intervention in Patients With Acute Myocardial Infarction

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Device: Intravascular permissive hypothermia as an adjunct to PCI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient is ≥ 18 years of age. The patient must have symptoms consistent with AMI (i.e. chest pain, arm pain, etc.) and unresponsive to nitroglycerin, with symptoms beginning greater than 30 minutes but less than 6 hours prior to presentation at hospital. Qualifying Infarct location: Roll-In subjects: Evidence of Acute Anterior or Inferior MI with ST-segment elevation of >= 0.2 mV in two or more anterior or inferior contiguous precordial leads. Randomized subjects: Evidence of Acute Anterior MI only with ST-segment elevation of >= 0.2 mV in two or more anterior contiguous precordial leads. The patient is eligible for PCI. The patient is willing to provide written informed consent to participate in this clinical trial. Exclusion Criteria: The patient has had a previous Myocardial Infarction. The patient is experiencing cardiogenic shock (systolic blood pressure [SBP] <80 mmHg and non-responsive to fluids, or SBP <100 mmHg with vasopressors, or requirement for an intra-aortic balloon pump [IABP]). The patient is presenting with resuscitated cardiac arrest, atrial fibrillation, or Killip risk stratification class II through IV. The patient has an aortic dissection or requires an immediate surgical or procedural intervention other than PCI. The patient has known history of Congestive Heart Failure (CHF), hepatic failure, end-stage kidney disease or severe renal failure (clearance < 30ml/min/1.73m²). The patient is febrile (temperature > 37.5 °C) or has experienced an infection with fever in the last 5 days. The patient has a known previous CABG. The patient has a known recent stroke within 90 days of admission. Cardio-pulmonary decompensation that has occurred en route to the hospital or, in the opinion of the physician, that is imminent or likely to occur following presentation to the clinical site. Contraindications to hypothermia, such as patients with known hematologic dyscrasias which affect thrombosis (e.g., cryoglobulinemia, sickle cell disease, serum cold agglutinins) or vasospastic disorders (such as Raynaud's or thromboangitis obliterans).The patient has a known hypersensitivity or contraindication to aspirin, heparin, or sensitivity to contrast media, which cannot be adequately pre-medicated. Any contraindication to cardiac MRI, or any implant in the upper body which may cause artifacts on cardiac MRI imaging. The patient has a known hypersensitivity or contraindication to aspirin, heparin, or sensitivity to contrast media, which cannot be adequately pre-medicated. The patient has a known history of bleeding diathesis, coagulopathy, cryoglobulinemia, sickle cell anemia, or will refuse blood transfusions. The patient has a height of <1.5 meters (4 feet 11 inches). The patient has a known hypersensitivity or contraindication to buspirone hydrochloride or Pethidine (Meperidine) and/or has been treated with a monoamine oxidase inhibitor in the past 14 days. Patient has a known history of severe hepatic or renal impairment, untreated hypothyroidism, Addison's disease, benign prostatic hypertrophy, or urethral stricture that in the opinion of the physician would be incompatible with Pethidine administration. The patient has an Inferior Vena Cava filter in place (IVC). The patient has a pre-MI life expectancy of <1 year due to underlying medical conditions or pre-existing co-morbidities. The patient has a known, unresolved history of drug use or alcohol dependency, or lacks the ability to comprehend or follow instructions. The patient is currently enrolled in another investigational drug or device trial. The patient is apprehensive about or unwilling to undergo the required MRI imaging at follow-up, has a documented or suspected diagnosis of claustrophobia, or has Gadolinium allergy, or is in permanent Atrial Fibrillation. The patient has received thrombolytic therapy en route to the hospital. The patient shows clinical evidence of spontaneous reperfusion as observed symptomatically and/ or from ECG findings (partial or complete ST resolution in ECG prior to informed consent and randomization). The patient is a vulnerable subject, for instance, a person in detention (i.e., prisoner or ward of the state). The patient is a female who is known to be pregnant.

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cooling + PCI<br>The subjects will be considered to be enrolled in the Test Arm of the trial when all inclusion and exclusion criteria have been met, the informed consent form has been signed, and randomization to the Test Arm of the trial to allow cooling with the Proteus IVTM System before and after PCI. | Device: Intravascular permissive hypothermia as an adjunct to PCI<br>* Cooling with ZOLL Proteus IVTM System before and after Percutaneous Coronary Intervention (PCI) -or- Standard of Care for PCI<br>|
| Other: PCI only<br>The subjects will be considered to be enrolled in the Control Arm of the trial when all inclusion and exclusion criteria have been met, the informed consent form has been signed, and randomization to the Control Arm of the trial to allow PCI only. | Device: Intravascular permissive hypothermia as an adjunct to PCI<br>* Cooling with ZOLL Proteus IVTM System before and after Percutaneous Coronary Intervention (PCI) -or- Standard of Care for PCI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Reduction of 20% in Mean Anterior Myocardial Infarct Size as Determined by Cardiac Magnetic Resonance (cMR) Imaging at 4-6 Days Post Infarct in the Test Arm (Cooling + PCI) Relative to the Control Arm (PCI Only). | The primary outcome is to compare the mean infarct size in the Test Arm (cooling + PCI) to the mean infarct size in the Control Arm (PCI only) at 4-6 days post infarct. | 4-6 Days | 
| Per-patient Rate of Composite Major Adverse Cardiac Events (MACE) in Randomized Subjects | The primary safety outcome is to compare the per-patient rate of composite Major Adverse Cardiac Events (MACE) in the Test Arm (cooling + PCI) to the Control Arm (PCI only) at 30-Day follow-up to determine non-inferiority to the Control. Composite MACE is defined as Cardiac Death (CD), All Myocardial Re-Infarction (All MI) and Clinically-Indicated Target Vessel Revascularization (CI-TVR). | 30 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypothermia, Acute Myocardial Infarction, AMI, PCI, Therapeutic Hypothermia