Anterior Wall Acute Myocardial Infarction
Conditions
Keywords
SSO2 Therapy, Acute myocardial infarction, Anterior myocardial infarction, SuperSaturated oxygen delivery, Left main coronary artery, Myocardial infarction, Heart attack, Percutaneous coronary intervention, Cardiac catheterization laboratory, PCI, Stent, Stenting, Stents, Angioplasty, LMCA, Delivery of supersaturated oxygen (SSO2) therapy for the treatment of anterior acute myocardial infarction
Brief summary
The primary objective of the study is to collect confirmatory data supporting the safety and effectiveness of SSO2 Therapy in treatment of anterior acute myocardial infarction (AMI) patients who have undergone successful percutaneous coronary intervention (PCI) with stenting within six hours of experiencing AMI symptoms.
Detailed description
A Multi-Center, Consecutively Enrolled Single-Arm Study to confirm the safety and effectiveness of the delivery of supersaturated oxygen (SSO2) Therapy for 60 minutes selectively into the left main coronary artery (LMCA) with a commercially available qualified SSO2 delivery catheter used with the TherOx® DownStream® System and Cartridge in the treatment of qualified patients presenting with anterior acute myocardial infarction in whom reperfusion with PCI is successful within six hours after symptom onset.
Interventions
DEVICESSO2 Therapy
Delivery of SSO2 Therapy for 60 minutes selectively into the left main coronary artery (LMCA) using the TherOx DownStream System along with a single use disposable device called the TherOx DownStream Cartridge and a commercially available, qualified SSO2 delivery catheter
Sponsors
TherOx
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
GENERAL INCLUSION CRITERIA: Candidates for this study must meet ALL of the following criteria: Pre-PCI: 1. The subject must be ≥18 and ≤80 years of age. 2. AMI must be anterior (ST-segment elevation \>1 mm in two or more contiguous leads between V1 and V4 or new left bundle branch block). 3. Subject is experiencing clinical symptoms consistent with anterior AMI of ≤6 hour duration from time of symptom onset until admission to the emergency room. 4. The subject or legally authorized representative has been informed of the nature of the study, agrees to its provisions and has been provided and signed written informed consent, approved by the appropriate Institutional Review Board (IRB). 5. Subject and his/her physician agree to all required follow-up procedures and visits. ANGIOGRAPHIC INCLUSION CRITERIA: These are evaluated after the subject has provided signed informed consent but prior to enrollment: 6. Based on coronary anatomy, PCI is indicated for revascularization of the culprit lesion(s) with use of a commercially available coronary stent (bare metal or drug-eluting, at operator discretion) in the LAD. 7. The primary stented infarct-related lesion(s) must be in the proximal and/or mid-LAD coronary artery (other lesions in the LAD target vessel, including diagonal branches, may be treated if clinically indicated). 8. Baseline (pre-PCI) TIMI flow grade 0, 1, 2, or 3 flow in the LAD. 9. Successful angioplasty as documented by \<50% diameter residual angiographic stenosis within all treated culprit lesions with TIMI 2 or 3 flow and no major complications such as perforation or shock. 10. Expected ability to place the SSO2 delivery catheter in the coronary ostium of the left main coronary system to deliver SSO2 Therapy with stable, coaxial alignment. GENERAL
Exclusion criteria
Pre-PCI: 1. Prior CABG surgery. 2. Prior myocardial infarction, or known prior systolic dysfunction (known ejection fraction \<40% by any prior measure or regional wall motion abnormalities; this criterion does not include left ventricular dysfunction induced by the acute MI). 3. Thrombolytic therapy administered for this STEMI. 4. An elective surgical procedure is planned that would necessitate interruption of anti-platelet agents during the first 30 days post-enrollment. 5. Subjects who previously underwent coronary stent implantation and in whom coronary angiography demonstrates stent thrombosis to be the cause of the anterior AMI. 6. Subjects who have previously undergone an angioplasty or stenting procedure in the left anterior descending coronary artery. 7. Subjects with ventricular pseudoaneurysm, VSD, or severe mitral valve regurgitation (with or without papillary muscle rupture). 8. Any contraindication to MRI imaging. This will include any of the following exclusions: * Cardiac pacemaker or implantable defibrillator; * Non-MRI compatible aneurysm clip; * Neural Stimulator (i.e., TENS unit); * Any implanted or magnetically activated device (insulin pump); * Any type of non-MRI compatible ear implant; * Metal shavings in the orbits; * Any metallic foreign body, shrapnel, or bullet in a location which the physician feels would present a risk to the subject; * Any history indicating contraindication to MRI, including claustrophobia or allergy to gadolinium; * Inability to follow breath hold instructions or to maintain a breath hold for \>15 seconds; and * Known hypersensitivity or contraindication to gadolinium contrast. 9. Known impaired renal function (creatinine clearance \<30 ml/min/1.73 m2 10. Known platelet count \<100,000 cells/mm by the MDRD formula) or on dialysis. 3 or \>700,000 cells/mm3 11. Subject has active bleeding or a history of bleeding diathesis or coagulopathy (including heparin induced thrombocytopenia), or refusal to receive blood transfusions if necessary. or a known Hgb \<10 g/dL. 12. History of intracerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke. 13. Stroke or transient ischemic attack within the past six (6) months, or any permanent neurological defect. 14. Gastrointestinal or genitourinary bleeding within the last two (2) months, or any major surgery (including CABG) within six weeks of enrollment. 15. Subject has received any organ transplant or is on a waiting list for any organ transplant. 16. Subject has other medical illness (e.g., cancer, dementia) or known history of substance abuse (alcohol, cocaine, heroin, etc.) that may cause non-compliance with the protocol, confound the data interpretation, or is associated with limited life expectancy of less than one year. 17. Subject has a known hypersensitivity or contraindication to unfractionated heparin, abciximab, aspirin, bivalirudin, cangrelor, clopidogrel, ticlopidine, prasugrel, or ticagrelor that cannot be adequately premeditated. 18. Current use of warfarin, dabigatran, or factor Xa inhibitors, or known intent to administer these agents after the primary PCI. 19. Subjects presenting with or developing in the cath lab prior to completion of the primary PCI procedure any of the following conditions: cardiogenic shock (SBP \<80 mmHg for \>30 minutes), or requiring IV pressors or emergent placement of an intra-aortic balloon pump (IABP), Impella, or other hemodynamic support for hypotension treatment, or cardiopulmonary resuscitation for \>10 minutes, or ventricular fibrillation or tachycardia requiring cardioversion or defibrillation. 20. Severe known cardiac valvular stenosis or insufficiency, pericardial disease, or non-ischemic cardiomyopathy. 21. Any significant medical or social condition which in the investigator's opinion may interfere with the subject's participation in the study or ability to comply with follow-up procedures, including MRI (e.g. alcoholism, dementia, lives far from the research center, etc.). 22. Current participation in other investigational device or drug trials that have not finished the primary endpoint follow-up period. 23. Previous enrollment in this study. ANGIOGRAPHIC
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Net Adverse Clinical Events (NACE) | 30-Day | Composite of death, reinfarction, clinically-driven target vessel revascularization, stent thrombosis (ARC definite or probable), new onset severe heart failure or readmission for heart failure, and TIMI major or minor bleeding. This outcome measure includes a hierarchical sum of the events, meaning if a subject experiences two event types they are only counted once in the overall NACE rate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Target Lesion Failure | 1 year | Composite of cardiac death , target vessel MI, or clinically driven target Lesion revascularization |
| Median Infarct Size by Cardiac MRI | 30 days | Measurement of the % left ventricle (LV) necrosis |
| Rate of Target Lesion Failure | 30 days | Composite of cardiac death , target vessel MI, or clinically driven target Lesion revascularization |
| Rate of Net Adverse Clinical Events (NACE) | 1 year | Composite of death, reinfarction, clinically-driven target vessel revascularization, stent thrombosis (ARC definite or probable), new onset severe heart failure or readmission for heart failure, and TIMI major or minor bleeding. This outcome measure includes a hierarchical sum of the events, meaning if a subject experiences two or more event types they are only counted once in the overall NACE rate. |
| Microvascular Obstruction by Cardiac MRI | 4 days post-procedure | Measurement of the % left ventricle (LV) showing microvascular obstruction |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SSO2 Therapy Delivery of SSO2 Therapy for 60 minutes selectively into the left main coronary artery (LMCA) using the TherOx DownStream System along with a single use disposable device called the TherOx DownStream Cartridge and a commercially available, qualified SSO2 delivery catheter
SSO2 Therapy: Delivery of SSO2 Therapy for 60 minutes selectively into the left main coronary artery (LMCA) using the TherOx DownStream System along with a single use disposable device called the TherOx DownStream Cartridge and a commercially available, qualified SSO2 delivery catheter | 100 |
| Total | 100 |
Baseline characteristics
| Characteristic | SSO2 Therapy |
|---|---|
| Age, Continuous | 59.1 years STANDARD_DEVIATION 10.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 91 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 100 |
| other Total, other adverse events | 68 / 100 |
| serious Total, serious adverse events | 27 / 100 |
Outcome results
Primary
Rate of Net Adverse Clinical Events (NACE)
Composite of death, reinfarction, clinically-driven target vessel revascularization, stent thrombosis (ARC definite or probable), new onset severe heart failure or readmission for heart failure, and TIMI major or minor bleeding. This outcome measure includes a hierarchical sum of the events, meaning if a subject experiences two event types they are only counted once in the overall NACE rate.
Time frame: 30-Day
Population: All treated subjects
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SSO2 Therapy | Rate of Net Adverse Clinical Events (NACE) | Overall NACE | 7 Participants |
| SSO2 Therapy | Rate of Net Adverse Clinical Events (NACE) | Death | 0 Participants |
| SSO2 Therapy | Rate of Net Adverse Clinical Events (NACE) | Reinfarction/Spontaneous MI | 1 Participants |
| SSO2 Therapy | Rate of Net Adverse Clinical Events (NACE) | Clinically Driven Target Vessel Revascularization | 1 Participants |
| SSO2 Therapy | Rate of Net Adverse Clinical Events (NACE) | TIMI Major or Minor Bleeding | 4 Participants |
| SSO2 Therapy | Rate of Net Adverse Clinical Events (NACE) | New Onset Severe Heart Failure | 1 Participants |
| SSO2 Therapy | Rate of Net Adverse Clinical Events (NACE) | ARC Definite/Probable Stent Thrombosis | 1 Participants |
Secondary
Median Infarct Size by Cardiac MRI
Measurement of the % left ventricle (LV) necrosis
Time frame: 30 days
Population: All treated subjects with analyzable cardiac MRI scans
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SSO2 Therapy | Median Infarct Size by Cardiac MRI | 19.4 percentage of myocardial mass |
Secondary
Microvascular Obstruction by Cardiac MRI
Measurement of the % left ventricle (LV) showing microvascular obstruction
Time frame: 4 days post-procedure
Population: All treated subjects with analyzable cardiac MRI scans
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SSO2 Therapy | Microvascular Obstruction by Cardiac MRI | 0.30 percentage of MVO of myocardial mass |
Secondary
Rate of Net Adverse Clinical Events (NACE)
Composite of death, reinfarction, clinically-driven target vessel revascularization, stent thrombosis (ARC definite or probable), new onset severe heart failure or readmission for heart failure, and TIMI major or minor bleeding. This outcome measure includes a hierarchical sum of the events, meaning if a subject experiences two or more event types they are only counted once in the overall NACE rate.
Time frame: 1 year
Population: All treated subjects population (n=100) minus subjects that discontinued the study prior to the 12-month follow-up (n=7).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SSO2 Therapy | Rate of Net Adverse Clinical Events (NACE) | Overall NACE | 10 Participants |
| SSO2 Therapy | Rate of Net Adverse Clinical Events (NACE) | Death | 0 Participants |
| SSO2 Therapy | Rate of Net Adverse Clinical Events (NACE) | Reinfarction/Spontaneous MI | 3 Participants |
| SSO2 Therapy | Rate of Net Adverse Clinical Events (NACE) | Clinically Driven Target Vessel Revascularization | 3 Participants |
| SSO2 Therapy | Rate of Net Adverse Clinical Events (NACE) | TIMI Major or Minor Bleeding | 5 Participants |
| SSO2 Therapy | Rate of Net Adverse Clinical Events (NACE) | New Onset Severe Heart Failure | 1 Participants |
| SSO2 Therapy | Rate of Net Adverse Clinical Events (NACE) | ARC Definite/Probable Stent Thrombosis | 1 Participants |
Secondary
Rate of Target Lesion Failure
Composite of cardiac death , target vessel MI, or clinically driven target Lesion revascularization
Time frame: 30 days
Population: All treated subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SSO2 Therapy | Rate of Target Lesion Failure | 1 Participants |
Secondary
Target Lesion Failure
Composite of cardiac death , target vessel MI, or clinically driven target Lesion revascularization
Time frame: 1 year
Population: All Treated Subjects Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SSO2 Therapy | Target Lesion Failure | 3 Participants |