Acute Myocardial Infarction
Conditions
Keywords
Hypothermia, Acute Myocardial Infarction, AMI, PCI, Therapeutic Hypothermia
Brief summary
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
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).
Interventions
DEVICEIntravascular permissive hypothermia as an adjunct to PCI
Cooling with ZOLL Proteus IVTM System before and after Percutaneous Coronary Intervention (PCI) -or- Standard of Care for PCI
Sponsors
ZOLL Circulation, Inc., USA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The patient is ≥ 18 years of age. 2. 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. 3. Qualifying Infarct location: 1. 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. 2. Randomized subjects: Evidence of Acute Anterior MI only with ST-segment elevation of \>= 0.2 mV in two or more anterior contiguous precordial leads. 4. The patient is eligible for PCI. 5. The patient is willing to provide written informed consent to participate in this clinical trial.
Exclusion criteria
1. The patient has had a previous Myocardial Infarction. 2. 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 \[IABP\]). 3. The patient is presenting with resuscitated cardiac arrest, atrial fibrillation, or Killip risk stratification class II through IV. 4. The patient has an aortic dissection or requires an immediate surgical or procedural intervention other than PCI. 5. 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). 6. The patient is febrile (temperature \> 37.5 °C) or has experienced an infection with fever in the last 5 days. 7. The patient has a known previous CABG. 8. The patient has a known recent stroke within 90 days of admission. 9. 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. 10. 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. 11. Any contraindication to cardiac MRI, or any implant in the upper body which may cause artifacts on cardiac MRI imaging. 12. The patient has a known hypersensitivity or contraindication to aspirin, heparin, or sensitivity to contrast media, which cannot be adequately pre-medicated. 13. The patient has a known history of bleeding diathesis, coagulopathy, cryoglobulinemia, sickle cell anemia, or will refuse blood transfusions. 14. The patient has a height of \<1.5 meters (4 feet 11 inches). 15. 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. 16. 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. 17. The patient has an Inferior Vena Cava filter in place (IVC). 18. The patient has a pre-MI life expectancy of \<1 year due to underlying medical conditions or pre-existing co-morbidities. 19. The patient has a known, unresolved history of drug use or alcohol dependency, or lacks the ability to comprehend or follow instructions. 20. The patient is currently enrolled in another investigational drug or device trial. 21. 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. 22. The patient has received thrombolytic therapy en route to the hospital. 23. 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). 24. The patient is a vulnerable subject, for instance, a person in detention (i.e., prisoner or ward of the state). 25. The patient is a female who is known to be pregnant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). | 4-6 Days | 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. |
| Per-patient Rate of Composite Major Adverse Cardiac Events (MACE) in Randomized Subjects | 30 Days | 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). |
Countries
Slovenia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cooling + PCI 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.
Intravascular permissive hypothermia as an adjunct to PCI: Cooling with ZOLL Proteus IVTM System before and after Percutaneous Coronary Intervention (PCI) -or- Standard of Care for PCI | 58 |
| PCI Only 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.
Intravascular permissive hypothermia as an adjunct to PCI: Cooling with ZOLL Proteus IVTM System before and after Percutaneous Coronary Intervention (PCI) -or- Standard of Care for PCI | 53 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Bone Fracture | 1 | 0 |
| Overall Study | Death | 5 | 0 |
| Overall Study | Diagnosis of Takotsubo Cardiomyopathy | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Cooling + PCI | Total | PCI Only |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 39 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 72 Participants | 31 Participants |
| Age, Continuous | 58.4 years STANDARD_DEVIATION 10.7 | 59.6 years STANDARD_DEVIATION 10.9 | 61.0 years STANDARD_DEVIATION 11 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 57 Participants | 109 Participants | 52 Participants |
| Region of Enrollment Bosnia and Herzegovina | 5 participants | 9 participants | 4 participants |
| Region of Enrollment Estonia | 11 participants | 22 participants | 11 participants |
| Region of Enrollment Hungary | 17 participants | 32 participants | 15 participants |
| Region of Enrollment Serbia | 19 participants | 35 participants | 16 participants |
| Region of Enrollment Slovakia | 5 participants | 9 participants | 4 participants |
| Region of Enrollment Slovenia | 0 participants | 1 participants | 1 participants |
| Region of Enrollment United Kingdom | 1 participants | 3 participants | 2 participants |
| Sex: Female, Male Female | 15 Participants | 29 Participants | 14 Participants |
| Sex: Female, Male Male | 43 Participants | 82 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 58 | 0 / 53 |
| other Total, other adverse events | 45 / 58 | 22 / 53 |
| serious Total, serious adverse events | 18 / 58 | 4 / 53 |
Outcome results
Primary
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).
Time frame: 30 Days
Population: Per-protocol population. 16 Test Arm subjects were excluded from the analysis due to not meeting eligibility criteria, having a repeat MI before 4-6 day cMRI, or did not follow cooling per protocol.~4 Control Arm subjects were excluded from the analysis population due to not meeting eligibility criteria or having a repeat MI before 4-6 day cMRI.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cooling + PCI | Per-patient Rate of Composite Major Adverse Cardiac Events (MACE) in Randomized Subjects | Cardiac Death and Myocardial re-infarction and clinically-indicated target vessel revascularization | 1 Participants |
| Cooling + PCI | Per-patient Rate of Composite Major Adverse Cardiac Events (MACE) in Randomized Subjects | Cardiac Death | 1 Participants |
| Cooling + PCI | Per-patient Rate of Composite Major Adverse Cardiac Events (MACE) in Randomized Subjects | No MACE Event | 40 Participants |
| PCI Only | Per-patient Rate of Composite Major Adverse Cardiac Events (MACE) in Randomized Subjects | Cardiac Death and Myocardial re-infarction and clinically-indicated target vessel revascularization | 0 Participants |
| PCI Only | Per-patient Rate of Composite Major Adverse Cardiac Events (MACE) in Randomized Subjects | No MACE Event | 49 Participants |
| PCI Only | Per-patient Rate of Composite Major Adverse Cardiac Events (MACE) in Randomized Subjects | Cardiac Death | 0 Participants |
Primary
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.
Time frame: 4-6 Days
Population: Per-protocol population with available infarct size. 19 Test Arm subjects were excluded from the analysis due to not meeting eligibility criteria, having a repeat MI before 4-6 day cMRI, unavailable cMRI, or did not follow cooling per protocol.~9 Control Arm subjects were excluded from the analysis population due to not meeting eligibility criteria, having a repeat MI before 4-6 day cMRI, or unavailable cMRI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cooling + PCI | 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). | 21.6 LV% | Standard Deviation 11.5 |
| PCI Only | 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). | 20.9 LV% | Standard Deviation 12.6 |