Evaluation of Intracoronary Hyperoxemic Oxygen Therapy in Anterior Acute Myocardial Infarction Patients (IC-HOT)

A Multi-Center Evaluation of the Delivery of Intracoronary Hyperoxemic Supersaturated Oxygen Therapy for 60 Minutes in Anterior Acute Myocardial Infarction Patients With Successful Reperfusion (Via PCI) ≤ Six Hours After Symptom Onset

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.

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.

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 EXCLUSION CRITERIA: These are evaluated after the subject has provided signed Informed Consent but prior to enrollment:

24. Anticipated inability to achieve a stable coaxial position in the left main coronary artery with the SSO2 delivery catheter.

25. Treatment during the index procedure of any lesion in either the left main, LCX (including the ramus), and/or RCA.

26. Post-index procedure planned intervention within 30 days (i.e., PCI of non-target lesions in any vessel, or CABG). Note: Planned revascularization (PCI or bypass) of a non-target lesion >30 days following the index procedure is allowed.

27. Anterior MI is due to thrombosis within or adjacent to a previously implanted stent.

28. Left ventriculography demonstrates severe mitral regurgitation, a ventricular septal defect, or a pseudoaneurysm.

29. Any left main coronary artery stenosis >20%.

30. Any untreated LAD or diagonal branch lesion is present with diameter stenosis > 50% in a vessel with reference vessel diameter > 2.0 mm (visually estimated), or for which PCI will be required before the MRI study.

31. Presence of a non-stented coronary dissection with NHLBI grade >B upon completion of the PCI procedure.