Clinical trial NCT02603835: Evaluation of Intracoronary Hyperoxemic Oxygen Therapy in Anterior Acute Myocardial Infarction Patients (IC-HOT)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Anterior Wall Acute Myocardial Infarction
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
Lead sponsor: TherOx
Sponsor class: INDUSTRY
First posted: 2015-11-13
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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 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.

Primary outcomes:
measure: Rate of Net Adverse Clinical Events (NACE)
timeFrame: 30-Day
Secondary outcomes:
measure: Rate of Target Lesion Failure
timeFrame: 30 days
measure: Rate of Net Adverse Clinical Events (NACE)
timeFrame: 1 year
measure: Target Lesion Failure
timeFrame: 1 year
measure: Median Infarct Size by Cardiac MRI
timeFrame: 30 days
measure: Microvascular Obstruction by Cardiac MRI
timeFrame: 4 days post-procedure
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Heart Center, Inc.
state: Alabama
city: La Jolla
country: United States
facility: Scripps Hospital
state: California
city: Danbury
country: United States
facility: Danbury Hospital
state: Connecticut
city: Elk Grove Village
country: United States
facility: Alexian Brothers Heart & Vascular Institute
state: Illinois
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Medical Center
state: Michigan
city: Detroit
country: United States
facility: St. John Hospital & Medical Center
state: Michigan
city: Royal Oak
country: United States
facility: Beaumont Hospital
state: Michigan
city: Southfield
country: United States
facility: Providence-Providence Park Hospital
state: Michigan
city: Raleigh
country: United States
facility: WakeMed Heart Center
state: North Carolina
city: Allentown
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: Camp Hill
country: United States
facility: Holy Spirit Cardiology
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hospital/Rhode Island Hospital
state: Rhode Island
city: Kingsport
country: United States
facility: Wellmont CVA Heart Institute
state: Tennessee
Study officials:
affiliation: Columbia University
name: Gregg W. Stone, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen S, David SW, Khan ZA, Metzger DC, Wasserman HS, Lotfi AS, Hanson ID, Dixon SR, LaLonde TA, Genereux P, Ozan MO, Maehara A, Stone GW. One-year outcomes of supersaturated oxygen therapy in acute anterior myocardial infarction: The IC-HOT study. Catheter Cardiovasc Interv. 2021 May 1;97(6):1120-1126. doi: 10.1002/ccd.29090. Epub 2020 Jul 10.