Hypothermia as an Adjunctive Therapy to Percutaneous Intervention in Patients With Acute Myocardial Infarction

Not Applicable

• Conditions: Hypothermia, Induced; Rewarming; Myocardial Infarction; Percutaneous Cornonary Intervention
• Interventions: Device: Proteus® Cooling System; Procedure: Primary Percutaneous Coronary Intervention

• Registration Number: NCT02664194
• Lead Sponsor: University of Sao Paulo General Hospital

Brief Summary

To evaluate and improve the safety and efficacy of hypothermia as an adjunctive therapy to percutaneous coronary intervention in patients with acute myocardial infarction.

Detailed Description

Single-center, prospective, randomized, controlled clinical study involving at least 70 patients with up to 10 roll-in patients (for training purposes).

Male and female adults presenting with acute myocardial infarction may be eligible for this research study. To qualify, patients must go to the Emergency Room within up to 6 hours of onset of chest pain, present with anterior or inferior acute myocardial infarction with elevation of the ST segment greater than 1mm in 2 or more contiguous leads in the anterior or inferior wall and be eligible for the performance of a percutaneous intervention procedure.

The intervention will be intravascular hypothermia using Proteus System® as an adjunctive method to percutaneous coronary intervention, adjunct hypothermia methods and parameters.

During the randomization phase, at least 70 patients who meet the eligibility criteria will be randomly assigned to the 03 hour hypothermia group (percutaneous coronary intervention + cooling), to the 01 hour hypothermia group (percutaneous coronary intervention + cooling) or to the control group (percutaneous coronary intervention only) in a 1:1:1 ratio.

All patients receiving PCI + Cooling will also be randomized to groups A and B. Group A will receive 1 liter of chilled normal saline (4°C) prior to PCI/reperfusion, and Group B will not receive chilled normal saline (4°C), prior to PCI.

All patients included in the randomization phase will be included in the statistical analysis.

Approximately 10 Roll-in patients may be enrolled at the center (for training purpose), with anterior or inferior wall infarcts.

The primary endpoint will be reduction of the infarct size (%LV), studied with cardiac magnetic resonance imaging (cMR) using late gadolinium enhancement 5 days after the AMI, and 30 days after the infarction.

The secundary endpoints will be

* incidence of major adverse cardiac events (MACE) or death within 30 days;

* resolution of the ST segment elevation after PCI;

* ejection fraction determined by cMR after 30 days.

* evaluation of adverse events potentially related to hypothermia and/or endovascular cooling within 30 days.

* Differences in plaquelet aggregation during cooling and rewarming.

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-01-18
• Study First Submitted QC: 2016-01-25
• Study First Posted: 2016-01-26
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-04
• Last Update Posted: 2018-05-11
• Primary Completion: 2019-01
• Study Completion: 2019-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• Patient aged > 18 years.
• The patient must have symptoms consistent with an acute myocardial infarction (chest pain, that is, pain in the arm, etc.) that do not improve with nitroglycerin, with an onset of symptoms greater than 30 minutes but less than six hours before admission to the emergency room.
• Roll-In Patients: Anterior or Inferior MI with ST-segment elevation of > 1mm in two or more contiguous anterior precordial or inferior leads.
• Randomized Patients: Anterior wall AMI with elevation of ST segment > 1mm in two or more anterior precordial contiguous leads.
• Patient must be eligible for PCI.
• The patient or the patient's legal guardian agrees to and is willing to sign the informed consent form to participate in the clinical study (for countries where appropriate).

Exclusion Criteria

• The patient had a previous myocardial infarction.
• The patient is experiencing cardiogenic shock (systolic blood pressure (SBP) < 80 mmHg and not responsive to fluids, or SBP < 100 mmHg with vasopressors, or in need of an intra-aortic balloon - IAB).
• The patient is presenting with resuscitated cardiac arrest, atrial fibrillation or Killip risk Stratification class II through IV.
• The patient has aortic dissection or requires an immediate surgical or procedural intervention other than PCI.
• The patient has known Congestive Heart Failure (CHF), hepatic failure, end-stage kidney disease or sever renal failure (clearance < 30 ml/min/1.73m2 .
• The patient is febrile (temperature > 37.5 °) or has experienced an infection with fever in the last 5 days.
• The patient has known previous CABG.
• The patient has known recent stroke within 90 days of admission.
• Cardiopulmonsary 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 9e.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 [agents], which cannot be adequately pre-medicated.
• The patient has a known history of bleeding diathesis, coagulopathy, cryoglobulinemia or sickle cell anemia, or will refuse blood transfusion.
• The patient is < 1.5 m (4 feet 11 inches) tall.
• The patient has a known hypersensitivity to buspirone hydrochloride or meperidine and/or was treated with a monoamine oxidase inhibitor in the last 14 days.
• The patient has a known history of severe hepatic or renal failure, untreated hypothyroidism, Addison's disease, benign prostatic hypertrophy or urethral stricture, that in the opinion of the physician, would be incompatible with the administration of pethidine/meperidine.
• The patient has an Inferior Vena Cava filter in place (IVC).
• The patient has a pre-MI life expectancy < 1 year due to underlying medical conditions or pre-existing morbidities.
• The patient has a known, unresolved history of drug use or alcohol dependency, or is not able to comprehend or follow the instructions.
• The patient is currently enrolled in another investigational drug or device trial that has not completed the primary endpoint. (Note: For the purpose of this protocol, patients involved in extended follow-up trials for products that were investigational but are currently commercially available are not considered enrolled in an investigational 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 before randomization) upon admission
• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
03 Hours Hypothermia Group - Proteus® Cooling System	Proteus® Cooling System	03 hours of intravascular hypothermia as an adjunctive method to primary percutaneous coronary intervention, adjunct hypothermia methods and parameters using Proteus® Cooling System.
Control Group	Primary Percutaneous Coronary Intervention	Primary percutaneous coronary intervention only
03 Hours Hypothermia Group - Proteus® Cooling System	Primary Percutaneous Coronary Intervention	03 hours of intravascular hypothermia as an adjunctive method to primary percutaneous coronary intervention, adjunct hypothermia methods and parameters using Proteus® Cooling System.
01 Hour Hypothermia Group - Proteus® Cooling System	Proteus® Cooling System	01 hour of intravascular hypothermia as an adjunctive method to primary percutaneous coronary intervention, adjunct hypothermia methods and parameters using Proteus® Cooling System.
01 Hour Hypothermia Group - Proteus® Cooling System	Primary Percutaneous Coronary Intervention	01 hour of intravascular hypothermia as an adjunctive method to primary percutaneous coronary intervention, adjunct hypothermia methods and parameters using Proteus® Cooling System.

Primary Outcome Measures

Name	Time	Method
Infarct size	30 days after STEMI	Reduction of the infarct size (%LV), studied with cardiac magnetic resonance imaging(cMR) using late gadolinium enhancement 5 days after the AMI, and 30 days after the infarction.
Ejection fraction	30 days after STEMI	ejection fraction (%) as determined cardiac resonance imaging (cMR) at 30 days after randomization.
MACE	30 days after STEMI	Incidence up to 30 days after randomization of major adverse cardiac events (MACE), defined as: death related to cardiac complications, recurrent AMI or need for revascularization of the target vessel.

Secondary Outcome Measures

Name	Time	Method
ST Segment Elevation	3 hours after STEMI	Resolution of the ST segment elevation (milimiters) after PCI.
Cardiac enzymes	30 days after STEMI	Serial evaluation of cardiac enzymes (Troponin I - ng/mL) in order to provide a secondary measure of cell injury
Composite of adverse events	30 days after STEMI	Composite of adverse events, defined as: 1. All-cause mortality; 2. Recurrent AMI; 3. Need for revascularization of the target vessel; 4. Cerebral vascular accident; 5. Cardiogenic shock; 6. Pulmonary embolism; 7. Ventricular fibrillation; 8. Vascular complications requiring surgery; 9. Bleeding requiring transfusion of 2 or more units of red blood cell concentrate
Device complications	30 days after STEMI	Complications potentially related to the implantation or to the use of the ZOLL System (hematoma, venous puncture, vascular complications requiring surgery, bleeding, surgical wound infection, systemic infection, deep venous thrombosis, pulmonary embolism by tomography)
Cooling complications	30 days after STEMI	Potential complications related to cooling (thermal discomfort, myocardial ischemia, coagulopathy, arrhythmias, hypotension and pulmonary edema).
All cause mortality	30 days after STEMI	All cause mortality
Anterior MI	30 days after STEMI	Patients with elevation of the ST segment greater than 1mm in 2 or more contiguous leads in the anterior wall (v1 to v6)
03 hours versus 01 hour cooling	30 days after STEMI	Comparison of three hours of cooling versus one hour of cooling regarding infarct size (%LV) as determined by study with cardiac magnetic resonance

Trial Locations

Locations (1)

InCor - Instituto do Coracao - HCFMUSP; 🇧🇷 Sao Paulo, SP, Brazil