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
Phase: NA
Conditions: Anterior Wall Acute Myocardial Infarction
Sponsor: TherOx

TherOx SSO2 Therapy 
IC-HOT Clinical Trial 
IC-HOT Investigational Plan 
Revision: November 3, 2015 
 
Confidential and Proprietary 
Do not distribute or reproduce without prior written permission of TherOx, Inc. 
 
 
 
 
 
 
 
SSO2
 
 THERAPY: IC-HOT STUDY 
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 
 
Principal Investigator  
 
 
Gregg W. Stone, M.D. 
 
 
 
 
 
 
Professor of Medicine 
Columbia University 
New York, NY 
 
Sponsor 
 
 
 
 
TherOx, Inc. 
 
 
 
 
 
 
17500 Cartwright Road, Suite 100 
 
 
 
 
 
 
Irvine, CA 92614  USA 
 
 
 
 
 
 
TEL: (949) 757-1999 
 
 
 
 
 
 
FAX: (949) 757-1989 
 
 
Contract Research Organization 
 
Experien Group, LLC 
Clinical Monitoring  
 
 
755 N. Mathilda Avenue, Suite 100 
Data Management  
 
 
 
Sunnyvale, CA 94085 
Clinical Events Committee 
 
 
TEL:  (408) 400-0856 
 
 
 
 
 
 
FAX: (408) 400-0865 
 
Core Laboratories 
 
 
 
Cardiovascular Research Foundation 
Data Analysis 
111 East 59th Street 
Data and Safety Monitoring 
New York, NY 10022-1202 
TEL: (646) 434-4500 
 

TherOx SSO2 Therapy 
IC-HOT Clinical Trial 
IC-HOT Investigational Plan 
Revision: November 3, 2015 
 
TABLE OF CONTENTS 
 
PROTOCOL SIGNATURE PAGE
 
 ...................................................................................... v
IC-HOT PROTOCOL SUMMARY ..................................................................................... 1 
DATA COLLECTION PROCEDURES AND TIMEFRAMES
 
 ....................................... 9
1 
INTRODUCTION
 
........................................................................................................ 10
2 
BACKROUND INFORMATION
 
............................................................................... 10
2.1 
Description of Device
 
 ......................................................................................... 15
2.1.1 
DownStream System
 
 ............................................................................. 15
2.1.2 
DownStream Cartridge
 
 .......................................................................... 19
2.1.3 
SSO2 
 
Delivery Catheter ......................................................................... 22
2.1.4 
Patient Connections
 
 ............................................................................... 22
3 
STUDY OBJECTIVE
 
 .................................................................................................. 24
4 
STUDY DESIGN
 
 .......................................................................................................... 24
4.1 
Patient Enrollment
 
 .............................................................................................. 24
4.2 
Patient Follow-Up
 
 ............................................................................................... 24
4.3 
Cardiac Magnetic Resonance Imaging (MRI)
 
 .................................................... 24
4.4 
Early Study Termination
 
 ..................................................................................... 25
4.5 
Measures Taken To Avoid / Minimize Bias
 
 ....................................................... 25
5 
SSO2
 
 THERAPY PROCEDURAL AND SAFETY DATA ...................................... 25
5.1 
SSO2
 
 Therapy Procedural Data .......................................................................... 25
5.2 
Safety Data
 
 .......................................................................................................... 26
5.3 
Number of Sites
 
 .................................................................................................. 26
5.4 
Sample Size
 
 ......................................................................................................... 26
6 
PATIENT SELECTION AND WITHDRAWAL
 
 ..................................................... 26
6.1 
Patient Population
 
 ............................................................................................... 26
6.2 
Patient Screening
 
 ................................................................................................ 26
6.3 
Informed Consent
 
 ................................................................................................ 27
6.4 
Eligibility Criteria
 
 ............................................................................................... 27
6.4.1 
Inclusion Criteria
 
 ................................................................................... 27
6.4.2 
Exclusion Criteria
 
 .................................................................................. 28

TherOx SSO2 Therapy 
IC-HOT Clinical Trial 
IC-HOT Investigational Plan 
Revision: November 3, 2015 
6.5 
Patient Discontinuation
 
 ....................................................................................... 31
6.5.1 
Lost To Follow-Up
 
 ................................................................................ 31
7 
STUDY PROCEDURES
 
 ............................................................................................. 32
7.1 
Patient Evaluation Procedures
 
 ............................................................................ 32
7.2 
Procedure Medications
 
 ........................................................................................ 32
7.3 
Cardiac Catheterization Laboratory (CCL) Procedure
 
 ....................................... 34
7.3.1 
Patient Anticoagulation
 
 ......................................................................... 34
7.3.2 
Coronary Angiography
 
 .......................................................................... 35
7.3.3 
PCI / Stenting Procedure
 
 ....................................................................... 35
7.4 
SSO2
 
 Therapy ..................................................................................................... 36
7.4.1 
Arterial Sheath Selection
 
 ....................................................................... 36
7.4.2 
SSO2
 
 Therapy Infusion ......................................................................... 36
7.5 
Other Procedural Considerations
 
 ........................................................................ 38
7.6 
Post Cardiac Catheterization Laboratory (CCL)
 
 ................................................. 39
7.6.1 
In-Hospital Procedures
 
 .......................................................................... 39
7.6.2 
Post-procedure ECG
 
 .............................................................................. 39
7.6.3 
Cardiac Enzymes, Clinical Chemistry, and Hematology
 
 ...................... 39
7.6.4 
Medications
 
 ........................................................................................... 39
7.6.5 
Cardiac MRI Scan
 
 ................................................................................. 39
7.6.6 
Arterial Sheath Removal and Ambulation
 
 ............................................ 39
7.7 
Hospital Discharge
 
 .............................................................................................. 39
7.7.1 
Post Discharge Medications
 
 .................................................................. 40
7.8 
30-Day Clinical Visit Follow-up
 
 ........................................................................ 40
7.9 
6-Month and 12-Month Telephone Follow-up
 
 ................................................... 40
8 
RISKS AND ADVERSE EVENTS
 
 ............................................................................. 41
8.1 
Risk Analysis
 
 ...................................................................................................... 41
8.2 
Clinical Assessments
 
 .......................................................................................... 44
8.2.1 
Clinical Follow-Up
 
 ................................................................................ 44
8.2.2 
Additional Event Driven Visits
 
 ............................................................. 45
8.3 
Adverse Events
 
 ................................................................................................... 45
8.4 
Unanticipated Adverse Events
 
 ............................................................................ 46
8.5 
Serious Adverse Events (SAEs)
 
 .......................................................................... 46
8.6 
Clinical Events Committee (CEC)
 
 ...................................................................... 47
8.7 
Data Safety Monitoring Board (DSMB)
 
 ............................................................. 49
9 
REPORTING OF TRIAL DATA
 
 ............................................................................... 49
 
9.1       Overview ............................................................................................................ 48 

TherOx SSO2 Therapy 
IC-HOT Clinical Trial 
IC-HOT Investigational Plan 
Revision: November 3, 2015 
 
9.2      Endpoints and Statistical Analysis Plan .............................................................. 49 
10 STUDY ADMINISTRATION
 
 .................................................................................... 54
10.1 Roles of Sponsor and CRO
 
 ................................................................................. 54
10.2 Investigator Responsibilities
 
 ............................................................................... 54
10.3 Direct Access to Source Data / Documents
 
 ........................................................ 55
10.4 Institutional Review Board (IRB)
 
 ....................................................................... 55
10.5 Consent Material
 
 ................................................................................................. 56
10.6 Sponsor Responsibilities
 
 ..................................................................................... 56
10.6.1 Study Specific Duties
 
 ............................................................................ 56
10.7 Regulatory Responsibilities
 
 ................................................................................ 58
10.7.1 Maintaining Records
 
 ............................................................................. 58
10.7.2 Submitting Reports
 
 ................................................................................ 58
10.7.3 Device Accountability
 
 ........................................................................... 58
10.7.4 Site Initiation
 
 ......................................................................................... 58
10.8 Monitor Responsibilities
 
 ..................................................................................... 59
10.8.1 Obligations / Qualifications of Study Monitors
 
 .................................... 59
10.8.2 Periodic Monitoring Visit Activities
 
 ..................................................... 59
10.8.3 Study Close-Out Activities
 
 .................................................................... 59
10.8.4 Documentation of Monitoring Visits and Communications
 
 ................. 60
10.9 Contract Research Organization Responsibilities
 
 ............................................... 60
10.10 Records and Reports
 
 ........................................................................................... 60
10.10.1 Required Data
 
 ........................................................................................ 60
10.10.2 Data Submission
 
 .................................................................................... 61
10.10.3 Investigator Reports
 
 ............................................................................... 61
10.11 Investigational Site Termination
 
 ......................................................................... 62
10.12 Study Committees
 
 ............................................................................................... 63
10.12.1 Executive Committee
 
 ............................................................................ 63
APPENDIX A:  CASE REPORT FORMS (CRFs) 
APPENDIX B:  INFORMED CONSENT 
APPENDIX C:  DOWNSTREAM SYSTEM OPERATORS MANUAL 
APPENDIX D:  INSTRUCTIONS FOR USE 
APPENDIX E:   CORE LABORATORY INFORMATION (ANGIOGRAPHIC AND 
CARDIAC MRI) 
APPENDIX F:   CLINICAL EVENTS COMMITTEE CHARTER 
APPENDIX G:  DATA SAFETY MONITORING BOARD CHARTER 
APPENDIX H:   STATISTICAL ANALYSIS PLAN 
 
 

TherOx SSO2 Therapy 
IC-HOT Clinical Trial 
IC-HOT Investigational Plan 
Revision: November 3, 2015 
PROTOCOL SIGNATURE PAGE 
 
IC-HOT CLINICAL STUDY 
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 
 
I have read this protocol and agree to adhere to the requirements.  I will provide copies 
of this protocol and all pertinent information to the study personnel under my 
supervision.  I will discuss this material with them and ensure they are fully informed 
regarding the investigational devices and conduct of the study according to 21 CFR 
parts 50, 54, 56 and 812, to GCP as described in ICH guideline E6 and to hospital 
IRB/ethics committee requirements. 
 
 
Clinical Site   
 
 
 
 
 
 
 
 
 
 
Investigator Signature  
 
 
 
 
 
 
 
 
 
Date   
 
 
 
 
 
 
 
 
 
 
 
Investigator (PRINT)  
 
 
 
 
 
 
________ 
 
 
 
 
 
 
 

TherOx SSO2 Therapy 
IC-HOT Clinical Trial 
 
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IC-HOT Investigational Plan 
 
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IC-HOT PROTOCOL SUMMARY 
Study 
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. 
Investigational 
Product 
The TherOx IC-HOT Clinical Study incorporates the use of three 
primary components.  These include a hardware device called the 
TherOx DownStream System (“system”), a single-use disposable 
device called the TherOx DownStream Cartridge (“cartridge”) and a 
commercially available, qualified SSO2 delivery catheter (“delivery 
catheter”).  The cartridge is loaded into and operated by the 
DownStream System; the cartridge has a tubing set that connects to an 
arterial sheath on the patient blood draw side and the SSO2 delivery 
catheter on the supersaturated infusate patient return side. SSO2 
Therapy is delivered selectively into the LMCA via the SSO2 delivery 
catheter, which is positioned at the ostium of the left coronary arterial 
tree proximal to the bifurcation. 
Indications for 
Use 
The TherOx DownStream System, DownStream Cartridge, and SSO2 
delivery catheter are indicated for: the preparation and delivery of 
SuperSaturated Oxygen Therapy (SSO2 Therapy) to targeted ischemic 
regions of the patient’s coronary vasculature immediately following 
revascularization by means of percutaneous coronary intervention 
(PCI) with stenting that has been completed within 6 hours after the 
onset of anterior acute myocardial infarction (AMI) symptoms. 
Objective 
To collect confirmatory data supporting the safety and effectiveness of 
SSO2 Therapy in the 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. 
Study Design 
This is a non-randomized, single-arm study.  Subjects who present 
with anterior STEMI requiring stent placement in the proximal and/or 
mid LAD who meet all inclusion and exclusion criteria and provide 
informed consent will be treated with primary PCI with stenting, and 
if successful and uncomplicated then immediately with post-procedure 

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IC-HOT Clinical Trial 
 
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IC-HOT Investigational Plan 
 
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delivery of SSO2 Therapy for a duration of 60 minutes. 
Patient  
Enrollment 
One hundred (100) patients enrolled and treated with SSO2 Therapy at 
up to fifteen (15) centers in the US. 
Patient 
Population 
Qualifying anterior STEMI patients (1 mm or greater of ST-segment 
elevation in 2 or more contiguous leads in V1-V4) successfully treated 
with PCI and stenting within 6 hours from time of symptom onset. 
Study Blinding This study is not blinded. 
Inclusion 
Criteria 
Patients must meet ALL of the following 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 
acute MI 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 

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IC-HOT Clinical Trial 
 
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IC-HOT Investigational Plan 
 
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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 is completed <6 hrs from symptom 
onset, 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. 
Exclusion 
Criteria 
Patients will be excluded if ANY of the following conditions apply:  
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:   
a. Cardiac pacemaker or implantable defibrillator; 

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IC-HOT Clinical Trial 
 
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IC-HOT Investigational Plan 
 
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b. Non-MRI compatible aneurysm clip; 
c. Neural Stimulator (i.e., TENS unit); 
d. Any implanted or magnetically activated device (insulin 
pump); 
e. Any type of non-MRI compatible ear implant; 
f. Metal shavings in the orbits; 
g. Any metallic foreign body, shrapnel, or bullet in a location 
which the physician feels would present a risk to the 
subject; 
h. Any history indicating contraindication to MRI, including 
claustrophobia or allergy to gadolinium; 
i. Inability to follow breath hold instructions or to maintain  a 
breath hold for >15 seconds; and 
j. 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, eptifibatide, 

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IC-HOT Clinical Trial 
 
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tirofiban 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. 
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
25. Treatment during the index procedure of any lesion in either 
the left main, LCX (including the ramus), and/or RCA. 
 delivery catheter. 
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%. 

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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. 
Treatment 
Strategy 
Study clinical investigators and research staff will be trained according 
to the clinical protocol, device Instructions for Use, and study 
regulatory and reporting requirements.  The procedural strategy is as 
follows: 
• Subjects presenting with anterior STEMI with symptom to 
presentation time of less than or equal to 6 hours will be 
screened for clinical eligibility. 
• If all clinical eligibility criteria are met, the subject or legal 
representative must sign an IRB-approved Subject Informed 
Consent Form. 
• After Informed Consent is signed, if not already administered, 
subject will receive a loading dose of aspirin 324 mg chewed 
or 250-500 mg IV, and at least one ADP antagonist, either 
clopidogrel 600 mg p.o. or prasugrel 60 mg p.o. or ticagrelor 
180 mg p.o. per investigator discretion. These loading doses 
must be given even if the patient is on home dual anti-platelet 
therapy. 
• Subject will undergo coronary arteriography and left 
ventriculography (required before enrollment). 
• Subject is screened for angiographic eligibility criteria. 
Patients who are being considered as potential subjects for 
enrollment into study may be treated with standard 
anticoagulation prior to and during the procedure. Procedural 
anticoagulation must consist of either bivalirudin with or 
without the addition of cangrelor (in which case GP IIb/IIIa 
inhibition is not recommended unless required for refractory 
procedural thrombotic complications) or heparin with either 
cangrelor or a GP IIb/IIIa inhibitor.  If bivalirudin is used, an 
infusion of 1.75 mg/kg/hr should be continued during the SSO2 
infusion and for 3-4 hours post procedure. Note: if a GP 

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IC-HOT Clinical Trial 
 
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IC-HOT Investigational Plan 
 
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IIb/IIIa inhibitor is used, it should be continued during the 
SSO2
• The 
patient 
must 
receive 
a 
commercially 
available 
intracoronary stent with post-index procedure angiographic 
TIMI flow grade 2 or 3. 
 infusion and for a total of at least 12 hours post 
procedure, as per local standard of care. The dose of the GP 
IIb/IIIa inhibitor and bivalirudin infusions should be down-
adjusted for renal insufficiency as per FDA labeled 
instructions. Intravenous cangrelor may also be used according 
to label per investigator discretion, administered as a bolus plus 
infusion, with the infusion continued for 2-4 hours post-PCI. 
• Post index procedure, if all clinical and angiographic entry 
criteria are met, the patient is formally enrolled into the study 
and may receive SSO2 Therapy.  The introduction of the 
infusion catheter is the point of intent-to-treat enrollment, 
whether SSO2
• The patient will remain in the cardiac catheterization 
laboratory for the entire SSO
 Therapy is successfully administered or not. 
2 Therapy procedure. Cine 
angiography w/o contrast will be performed at the beginning of 
and 30 minutes into the SSO2 infusion procedure 
• Post SSO
to document 
stable position of the delivery catheter. 
2 Therapy control angiography will be obtained in 
each enrolled patient to document position of the delivery 
catheter, TIMI flow, and to assess for intravascular 
complications. 
Patient 
Follow-Up  
Baseline, procedural, post-procedure, in-hospital, and clinical follow-
up at 30 days.  Cardiac MRI will be performed at 4 days (acceptable 
range 3-5 days) and at 30 days (±7 days; range 23-37 days) to evaluate 
device effectiveness.  Primary data collection including adverse event 
reporting is through 30 days; patient safety will be tracked and 
reported through one year.  
Safety 
Endpoint 
 
The primary endpoint of the study is the rate of Net Adverse Clinical 
Events (NACE), comprised of the composite incidence of death, 
reinfarction, clinically-driven target vessel revascularization, stent 
thrombosis (ARC definite or probable), new onset heart failure or 
readmission for heart failure, and TIMI major or minor bleeding.  

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Additional 
Study 
Endpoints 
 
Effectiveness is a secondary endpoint for this study. Effectiveness data 
from dual time point cardiac MRI scans at day 4 and day 30 will be 
collected and reported, using 30-day median infarct size (% left 
ventricle (LV) necrosis) as the primary effectiveness outcome 
measure. Infarct size data in this study will be compared to a matched 
control population from the INFUSE-AMI clinical trial, and to the 
AMIHOT II study.  In addition, myocardial structural and functional 
data, including microvascular obstruction at 4 days, and global and 
regional LV volumes and function at both time periods will be 
evaluated. Data will only be analyzed in subjects completing the 
cardiac MRI study in which the imaging data is received and 
analyzable by the core laboratory.   
Additional 
Safety Data 
In addition to 30-day NACE, the following information will be 
reported and summarized: 
• Additional bleeding events through 30 days, categorized by the 
BARC criteria  
• All other 30-day adverse events  
• Individual NACE component event rates through 1 year  
Event 
Assessment 
An independent Clinical Events Committee (CEC) will review and 
adjudicate all significant study adverse events, including any potential 
NACE events or cardiac-related events.  Adjudication will be 
performed in accordance with a prospective CEC Charter including 
clinical event definitions. 
Safety 
Oversight 
An independent Data Safety Monitoring Board (DSMB) will review 
and assess overall study safety both during and at the conclusion of the 
study. 
Economic 
Data 
In addition to safety and effectiveness data, hospital charge data as 
reported on the UB -04 claim form will be collected. The economic 
data will be used to support applications to the Center for Medicare 
and Medicaid Services and other health plans for additional 
reimbursement for procedures using the TherOx DownStream System. 
Study Sponsor 
TherOx, Inc. 
17500 Cartwright Road, Suite 100  
Irvine, CA 92614 USA 
TEL: (949) 757-1999 
FAX: (949) 757-1989 
 
 

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DATA COLLECTION PROCEDURES AND TIMEFRAMES 
Table 1.  Data Collection Procedures 
PROCEDURE / TEST 
Pre-PCI - Stent 
PCI / 
Stent Procedure 
Post- PCI / Stent 
Baseline SSO2  
30 min SSO2 
60 min SSO2  
60 (±30) min 
post-SSO2 
12 (±2) hrs 
24 (±2) hrs 
Cardiac MRI  
(4 ± 1 days) 
30 (±7) days 
6 and 12 mos     
(±30 days) 
Subject Medical / Clinical History / 
Physical Exam 
√ 
 
 
 
 
 
 
 
 
 
 
 
Subject Informed Consent  
√ 
 
 
 
 
 
 
 
 
 
 
 
General Inclusion / Exclusion Criteria 
√ 
 
 
 
 
 
 
 
 
 
 
 
Angiographic Inclusion / Exclusion 
Criteria 
 
 
√ 
 
 
 
 
 
 
 
 
 
Cardiac Enzymes: CK, CK-MB, and 
Troponin  
√ 
 
 
 
 
 
 
√ 
√ 
√
 
1 
 
Arterial blood gas 
 
 
 
√ 
 
 
 
 
 
 
 
 
WBC, hemoglobin, creatinine, platelet 
count 
√
 
8 
 
 
 
 
 
 
√
 
2 
 
 
Cardiac MRI 
 
 
 
 
 
 
 
 
 
√
√
3 
 
4 
HR, BP 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
 
 
 
 
ECG  
√ 
 
 
 
 
 
√
 
5 
 
√ 
√ 
 
Anticoagulation (per protocol) 
√ 
 
 
 
 
 
 
 
 
 
 
 
Antiplatelet loading dose  
√ 
 
 
 
 
 
 
 
 
 
 
 
Cardiac cath lab procedures and 
information 
 
√ 
 
 
 
 
 
 
 
 
 
 
Cine angiogram w/o contrast of 
angiographic delivery catheter 
 
 
 
√ 
√ 
√ 
 
 
 
 
 
 
Coronary angiogram with TIMI flow 
grade assessment 
√ 
√
√ 
6 
 
 
√ 
 
 
 
 
 
 
ACT ( per protocol) 
 
√ 
 
√ 
√
√ 
9 
 
 
 
 
 
 
SSO2
 
 Therapy Procedure 
 
√ 
√ 
√ 
√ 
 
 
 
 
 
 
Per Protocol Medications 
√ 
√ 
√ 
√ 
√ 
√ 
 
√ 
 
 
√ 
√ 
Dual Antiplatelet Medication  
√ 
√ 
√ 
 
 
 
 
√
 
7 
 
√
√ 
7 
Concomitant Cardiac Medications 
√ 
√ 
√ 
√ 
√ 
√ 
 
√ 
 
 
√ 
√ 
Adverse Events 
 
 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
1Required only if cardiac events. 
2 Measured the day after the index procedure and then daily until the nadir value for Hgb, Hct, platelet count and the peak value for serum 
creatinine is reached or the patient is discharged.  Baseline and nadir information will be collected. 
3All subjects to have in hospital cardiac MRI. 
4A protocol deviation will be recorded if the MRI is performed between 38 and 90 days but those images will be evaluated by the core 
laboratory and the results will be analyzed. 
5 ECG to be performed 60±30 minutes after the last angiogram after the SSO2 procedure. 
6 Left ventriculography required prior to enrollment. 
7 Post procedure DAPT is according to current recommended standards as published by the AHA/ACC/ESC, which recommends a 
minimum of twelve (12) months DAPT for subjects receiving a stent. 
8 Must have screening HCT, HGB, platelet count and creatinine measurement per inclusion/exclusion criteria; however, lab results do not 
need to be available prior to enrollment. 
9
 
 
 The mid-procedure 30-min ACT sample is required if patients receive heparin for procedural anticoagulation. 

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1 
INTRODUCTION  
The IC-HOT clinical study presented in this Investigational Plan is designed as a 
confirmatory study enrolling 100 patients with qualifying anterior acute myocardial 
infarction (AMI) treated with successful percutaneous coronary intervention (PCI) with 
stenting within 6 hours of symptom onset.  This study population is similar to a previously 
examined IDE study population enrolled as a sub-group of the AMIHOT I clinical trial, and 
the entire AMIHOT II and Optimized SSO2 pilot study populations1
2 
BACKROUND INFORMATION 
.  A brief synopsis of 
the previous IDE study experiences is provided below. 
TherOx has conducted four FDA-approved IDE clinical studies for treatment of AMI 
patients.  The first study was a pilot effort conducted on twenty-nine patients; study results 
included promising trend data towards improved left ventricular ejection fraction and wall 
motion score in SSO2 Therapy treated subjects2, and served as a foundation for the 
AMIHOT I multi-center randomized trial.  No safety concerns were noted during this early 
pilot study.  The AMIHOT I study3 was a randomized trial that examined outcomes in AMI 
subjects treated with SSO2
During the AMIHOT I study, two hundred eighty-nine (289) patients were enrolled and 
followed from January 16, 2002 through April 3, 2004, including 20 run-in subjects and 269 
randomized patients.  Three independent biomarkers (infarct size reduction, regional wall 
motion score improvement at three months, and reduction in ST segment elevation) were 
designated as co-primary endpoints to evaluate the effectiveness of SSO
 Therapy following PCI with stenting as compared to a Control 
group receiving PCI with stenting alone for patients experiencing inferior or anterior AMI 
treated within 24 hours.  Study results showed improvement in infarct size reduction, 
reduced ischemic burden, and left ventricular contractility for a subgroup of patients with 
anterior wall infarctions treated within six hours of symptom onset.  This promising 
AMIHOT I patient cohort was the target population for the pivotal AMIHOT II study. 
2 Therapy.  The 
study was designed to demonstrate superiority of the SSO2 Therapy group as compared to 
Controls for each of these endpoints, and to demonstrate non-inferiority of the SSO2
                                                 
1 An I/E change was made prior to the Optimized SSO2 pilot study to include pre-PCI TIMI flow 3 patients, who were excluded by 
protocol in AMIHOT II but were still found to comprise 7.4% of SSO2 Therapy subjects (core lab measurement). 
 
2 Dixon SR, Bartorelli AL, Marcovitz PA, et al.  Initial Experience with Hyperoxemic Reperfusion after Primary Angioplasty for Acute 
Myocardial Infarction.  J Am Coll Cardiol 2002:39(3);387-92. 
3 O’Neill WW, Martin JL, Dixon SR, et al.  Acute Myocardial Infarction with Hyperoxemic Therapy (AMIHOT).  J Am Coll Cardiol 
2007:50(5);397-405. 

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Therapy group as compared to Control with respect to 30-day MACE.  The study population 
was comprised of qualifying AMI patients treated with either PCI alone or with SSO2
Results for the SSO
 
Therapy as an adjunct to successful PCI within 24 hours of symptom onset.  
2 Therapy group compared to the Control group for the three co-primary 
effectiveness endpoints demonstrated a nominal improvement in the test group; this nominal 
improvement did not achieve clinical and statistical significance in the entire population.  
However, an analysis of SSO2
Infarct size results were expressed as a percentage of the left ventricle.  This endpoint was 
established on the basis of numerous peer-reviewed publications of this biomarker that 
demonstrate a 5% median infarct size reduction is clinically meaningful.  The all-patient 
< 24-hour group showed a 2% absolute reduction in median infarct size, from 13% in 
Control subjects to 11% in the SSO
 Therapy patients who were revascularized within 6 hours of 
AMI symptom onset and who had anterior wall infarction showed a marked improvement in 
all three co-primary endpoints as compared to Controls.   
2 Therapy group (Wilcoxon rank-sum test; one-sided p-
value = 0.3).  The infarct size reduction for anterior STEMI subjects treated within 6 hours 
of symptom onset showed that SSO2 Therapy subjects exhibited a 14% absolute reduction in 
median infarct size from 23% in the Control group to 9% in the SSO2
Effectiveness results for the other two co-primary endpoints (regional wall motion score 
index improvement, ST area reduction) in the AMIHOT I trial were consistent with the 
infarct size data.  The results for regional wall motion score index improvement (decrease) 
at 3 months (90 days), as compared to baseline, demonstrated a nominal improvement in all 
patients in the SSO
 Therapy group 
(Wilcoxon rank-sum test; one-sided p-value = 0.04).   
2 group as compared to Controls (-0.62 vs. –0.57, respectively, 
ANCOVA one-sided p-value = 0.24); the results were statistically significant when only the 
anterior <6 hr population was examined (-0.75 vs. –0.54 for SSO2 and Controls, ANCOVA 
one-sided p-value =0.03).  As seen in the infarct size measurements, the observed 
improvement in SSO2
ST-segment area reduction was believed to represent the continuing ischemic burden on the 
heart in the post-acute phase for AMI patients.  Results for this biomarker obtained at 3 
hours post-PCI were consistent with both infarct size and wall motion data; results were 
comparable for all patients studied (median ST area = 0 µV-min for both groups, Wilcoxon 
rank-sum test one-sided p-value = 0.5) and significantly better in the anterior <6 hr patient 
 Therapy subjects versus Controls was greatest in the <6 hr anterior 
patient population. 

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group (median areas = 0 vs. 311 µV-min for SSO2
Key safety data revealed no statistically significant differences in the composite primary 
endpoint of one-month (30 days) Major Adverse Cardiac Event (MACE) rates between the 
SSO
 and Controls, Wilcoxon rank-sum test 
one-sided p-value = 0.01).   
2 Therapy and Control groups.  MACE includes the combined incidence of death, 
reinfarction, target vessel revascularization, and stroke.  In total, 9/134 (6.7%) subjects in 
the SSO2
Following the experience of the AMIHOT I study, which suggested that anterior AMI 
patients treated with PCI and stenting within 6 hours could benefit from SSO
 Therapy group and 7/135 (5.2%) subjects in the Control group experienced 30-day 
MACE (p=ns).   
2 Therapy, the 
AMIHOT II study4 was designed as a prospective randomized evaluation of this focused 
study population.  The AMIHOT II study objective was to determine whether intracoronary 
perfusion of hyperoxemic blood in the SSO2
A total of 317 patients were enrolled in the AMIHOT II trial, including 13 run-in (training) 
patients and 301 randomized patients (222 SSO
 Therapy group immediately after successful 
PCI/stenting within 6 hours of symptom onset for the treatment of anterior acute myocardial 
infarction reduces the area of infarction (% left ventricle) as measured by Tc-99m Sestamibi 
SPECT imaging at 14 days post-PCI, with no worse than a 6% (absolute) increase in the 
incidence of Major Adverse Cardiac Events (MACE), comprising the combined incidence of 
death, re-infarction, target vessel revascularization, and stroke at the latter of either 30 days 
post-PCI or hospital discharge, when compared to a Control group receiving PCI/stenting 
alone. 
2
The AMIHOT II study results demonstrated effectiveness of SSO
, 79 Control).  The study enrollment was 
conducted from September 13, 2005, the date of the first patient enrollment, to June 28, 
2007, the date of completion for the last 30-day patient follow up. 
2 Therapy in reducing 
median infarct size from 26.5% of the left ventricle in the Control group to 20.0% in the 
SSO2
                                                 
4 Stone GW, Martin JL, de Boer MJ, et al.  Effect of Supersaturated Oxygen Delivery on Infarct Size after Percutaneous Coronary 
Intervention in Acute Myocardial Infarction.  Circ Cardiovasc Intervent 2009:2;366-75. 
 Therapy group in the AMIHOT II study, an absolute median reduction of 6.5%.  This 
infarct size reduction was evaluated using a pre-specified formal Bayesian hierarchical 
model that considered AMIHOT I data as well.  The Bayesian posterior probability of 
superiority was 96.9% using the pre-specified model, achieving the study endpoint. 

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The primary safety endpoint for the AMIHOT II trial required a determination of non-
inferiority in the 30-day MACE rate, comparing the SSO2 Therapy group with the Control 
group, using a one-sided safety delta of 6.0%.  Endpoint evaluation was performed using a 
Bayesian hierarchical model that factored in the 30-day MACE data from both the AMIHOT 
I and II studies.  Study results demonstrated that the primary safety endpoint was achieved 
successfully, with observed 30-day MACE rates of 3.8% in the Control group and 5.4% in 
the SSO2 group in the AMIHOT II trial.  The posterior probability of an increase of less 
than 6% in 30-day MACE rate was 99.5%, successfully achieving the study endpoint.  The 
30-day rates of mortality were 0% in the Control arm vs. 1.8% in the SSO2 arm (P=0.58). 
Stent thrombosis occurred in 2.5% of patients in the Control arm vs. in 4.1% of patients 
treated with SSO2
In summary, the AMIHOT II study demonstrated that SSO
 (P=0.73).  
2 Therapy administered 
adjunctively following PCI with stenting significantly reduces infarct size with no 
statistically significant difference in 30-day Major Adverse Cardiac Events (MACE).  
Following the results of an FDA Advisory Committee hearing regarding SSO2 Therapy on 
March 18, 2009, FDA requested additional safety data regarding SSO2 Therapy in the target 
patient population.  TherOx management made the decision to refocus its clinical study 
plans on Optimized SSO2 Therapy.  Specifically, the previous studies were conducted by 
administering SSO2 Therapy through an infusion catheter placed within the infarct-related 
artery and adjacent to the recently implanted stent site for 90 minutes. The AMIHOT 
Executive Committee and TherOx management team decided that the risk of procedural 
complications would be minimized if SSO2
The key advantage with Optimized SSO
 delivery could be achieved without the 
requirement for the in-dwelling infusion catheter. 
2 Therapy administration is the delivery point 
change for the infusion, from the sub-selective coronary artery to a proximal position in the 
left main coronary artery (LMCA).  Figure 1 shows a side-by-side schematic comparison of 
the two approaches. 

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Figure 1.  Comparison of SSO2
 
 Therapeutic Delivery Approaches 
The Optimized SSO2 Therapy approach offers advantages in both real and perceived safety 
and effectiveness, as well as operator preference.  By moving the infusion point proximally, 
patient safety is improved due to elimination of mechanical manipulation near the PCI injury 
zone.  The infusion may be performed through a qualified SSO2 delivery catheter (i.e., a 5F 
angiographic catheter qualified through testing for this procedure) in the LMCA, eliminating 
the need for the extra infusion catheter.  The use of a guidewire through the target vessel and 
placement of the infusion catheter near the freshly placed stent is therefore unnecessary 
using this approach.  In addition, the infusion is performed in a higher flow main artery, 
reducing concerns about restricting flow in part of the sub-selective target vessel.   
Advantages in effectiveness may be observed because flow of superoxygenated blood will 
be directed to the entire left coronary system (including collateral vessels) instead of just the 
target vessel.  Infarct data from the AMIHOT studies show that anterior AMI patients may 
benefit from the collateral supply of SSO2
TherOx conducted an IDE pilot study in 20 patients enrolled at 3 US sites to confirm the 
viability of the modified infusion.  The target population was the same as previous IDE 
studies – qualifying anterior AMI patients treated with PCI within six hours of symptom 
onset.  Primary data collection was performed through 30 days, including adverse event 
 to treat the entire ischemic zone and thus further 
reduce the extent of infarction. 
Guide catheter
Infusion
catheter
SSO2 delivery
catheter
Traditional SSO2 Therapy 
Optimized SSO2 Therapy 

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reporting and cardiac MRI (cMRI) imaging.  Results showed a low complication rate – one 
patient (5%; 1/20) experienced a 30-day MACE event (stent thrombosis and reinfarction).  
This event was attributed to an underdeployed stent placement during the index PCI 
procedure and non-use of aspirin.  Post SSO2
2.1 
Description of Device 
 infusion angiography showed no thrombus in 
this patient. No patient deaths were observed and all patients were followed through 30 
days.  MRI results were obtained in 90% (18/20) of patients had at 30 days (2 were not 
obtainable due to patient claustrophobia).  The median [interquartile range] infarct size at 30 
days was 9.6% [2.1%, 14.5%], representing a potential reduction as compared to infarct size 
measured in AMIHOT II at 14 days (20% [6%, 37%]). The IC-HOT clinical trial is designed 
to confirm these safety and efficacy results in a larger 100-patient IDE study in the target 
patient population. 
SuperSaturated Oxygen Therapy (“SSO2 Therapy”) is an adjunctive cardiac catheterization 
laboratory initiated procedure with superoxygenated blood delivered via a qualified delivery 
catheter to the left main coronary artery (LMCA) in a patient with acute myocardial 
infarction (AMI) after successful percutaneous intervention (PCI) with stenting has been 
performed.  The equipment necessary for SSO2 Therapy is comprised of three components: 
the DownStream® System (“system”), the DownStream® Cartridge (“cartridge”), and the 
SSO2 delivery catheter (“delivery catheter”).  The system and cartridge function together to 
create a highly oxygen-enriched saline solution called SuperSaturated Oxygen solution 
(“SSO2 solution”).  A small amount of autologous blood is mixed with the SSO2 solution 
producing oxygen-enriched hyperoxemic blood which is then delivered to the LMCA via the 
SSO2 delivery catheter at a flow rate of 100 ml/min.  The duration of SSO2
2.1.1 
DownStream System 
 Therapy is 60 
minutes as detailed in this protocol. 
The system is the electromechanical device (console) that controls the cartridge and 
monitors performance and safety during administration of SSO2 Therapy.  The system has 
safety features that continuously monitor system parameters such as the blood flow rate and 
pressure, and detect potentially unsafe conditions such as the presence of air-in-line.  A 
display screen guides the health care professional through setup and clinical operation.  The 
system is non-sterile and has no direct contact with the patient or the blood flow path.  The 
system is intended to be mains-operated (AC-powered) and stationary during use but is 
equipped with battery backup power.  The system is designed for operation in a cardiac 

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catheterization laboratory and must be operated and monitored by trained personnel when 
providing SSO2
 
 Therapy.  The DownStream System is shown in Figure 1a and Figure 1b 
(closeup).  
 
Figure 1a. TherOx®  DownStream® System 

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Figure 1b.  Close-up of DownStream®
 
 System Components 
 
Flow Probe
Transducer Port
Power Lever in 
ON position
Blood Pump
IV Pole with IV bag
Cartridge Housing 
with cartridge loaded
Return Clamp

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The major subsystems of the DownStream System are the Cartridge Control Subsystem 
(“CCS”), Display Subsystem (“Display”), Power Supply Subsystem (“Power Supply”), and 
Oxygen Supply Subsystem (“Oxygen Supply”). 
 
The CCS monitors and controls the operation of the cartridge during operation.  The CCS 
has a cartridge housing that contains the cartridge.  An oxygen valve controls the flow of 
oxygen to the cartridge from the E-bottle source that is securely mounted onto the system.  
A piston actuator operates the piston (syringe) inside the cartridge to withdraw saline from 
the IV bag and pump it into the cartridge to make superoxygenated saline.  A peristaltic 
blood pump operates on the cartridge draw tubing to withdraw arterial blood from the 
patient and pump it through the cartridge, returning hyperoxemic blood back to the patient.  
A modular jack on the front panel of the CCS connects to the cartridge transducer assembly.  
The transducer communicates with the system and is written to after use to prevent re-use.  
An ultrasonic probe (for bubble/air in line detection and flow monitoring) and return clamp 
on the front panel of the CCS operate on the Cartridge Return tubing.  A Prime switch and 
Emergency Stop switch located on the Display are also part of the CCS.  
The Display Subsystem located at the top of the system is the user interface.  A keypad 
provides user control of system operation.  An LCD display provides visual feedback, and a 
speaker provides audible feedback for the user.  Users are cardiologists and nurses 
administering the treatment in the cardiac catheterization laboratory (CCL).  The user has 
seven keys (buttons) on the Display Subsystem that control system operation.  An LCD 
display provides visual feedback, and a speaker provides audible feedback for the user. 
The Power Supply Subsystem is an electronic assembly that provides DC power to the CCS 
and Display Subsystems.  The Power Supply receives power from the AC Mains or an 
internal battery.  Component features of the Power Supply include:  appliance inlet 
receptacle with fuses, medical grade 15 VDC power supply, battery charger, DC-to-DC 
power supplies, and a battery.  The battery provides at least one half hour of system 
operation when fully charged.  When connected to AC Mains, the system automatically 
charges the battery. 
The Oxygen Supply Subsystem is a mechanical assembly that provides regulated oxygen to 
the CCS.  The Oxygen Supply uses pressurized oxygen from a medical grade E-bottle, 
which it regulates to 750 ± 50 psig.  Component features of the Oxygen Supply include:  E-
bottle (yoke-type) connection, oxygen regulator with 900 psi relief valve, bottle pressure 

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gauge, and oxygen filter.  The Oxygen Supply can support over 50 treatments on one E-
bottle. 
2.1.2 
DownStream Cartridge 
The cartridge is a single-use disposable device that is loaded into the system by a trained 
healthcare professional.  The cartridge has a three-chambered body that creates SSO2 
solution from inputs of hospital-supplied oxygen and physiologic saline and mixes the SSO2 
solution with arterial blood within the cartridge blood path.  The cartridge has a tube set that 
draws the patient’s arterial blood through the draw line, and returns oxygen-enriched 
hyperoxemic blood through the return line to the SSO2 delivery catheter.  The cartridge 
draw line connects to the sidearm of an arterial sheath.  Sheath placement may be coaxial 
(single arterial access site) or contralateral (two arterial access sites) at the physician’s 
discretion.  A physician makes two line connections during the initiation of SSO2 Therapy: 
the cartridge draw line is attached to the arterial sheath before priming the blood flow path, 
and the return line is attached to the SSO2 delivery catheter after the blood flow path is 
successfully primed.  The priming volume of the cartridge is approximately 60 ml.  The 
cartridge is shown in Figure 2. 

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Figure 2.  TherOx® DownStream®
 
 Cartridge 
A fluid manifold in the Oxygen Chamber provides the fluid path between the three 
chambers.  The IV tubing set connects the Piston Chamber to a 1-liter bag of sterile saline 
provided by the hospital.  The draw tubing set connects the blood mixing chamber to an 
arterial draw sheath (blood from the patient), and the return tubing set connects the blood 
mixing chamber to the delivery catheter (hyperoxemic blood to the patient).  Figure 3 
depicts the fluid flow paths through the cartridge and the fluid flow control features. 
 
IV Tubing
Oxygen 
Chamber
Blood Mixing 
Chamber
Pressure Transducer
Draw Tubing
Piston Chamber
Fluid Manifold
IV Tubing
Piston 
Chamber
Oxygen 
Chamber
Blood 
Mixing 
Chamber
Fluid 
Manifold
Pressure 
Transducer
Draw Tubing
Return Tubing

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Figure 3.  DownStream®
 
 Cartridge Fluid Flow Path 
 
The DownStream Cartridge utilizes medical grade polyvinyl chloride (“PVC”) tubing for 
blood withdrawal and return to the patient.  The cartridge housing is constructed primarily of 
injection-molded medical grade polycarbonate, a common plastic material used in medical 
devices.  The tubing and Blood Mixing Chamber (“BMC”) comprise the blood-wetted fluid 
path of the cartridge. 
The production and flow of SSO2 solution are continuous within the DownStream 
Cartridge; control of these processes is maintained through the use of the Fluid Manifold 
shown in Figure 3.  The Fluid Manifold connects and controls the flow of saline and SSO2 
solution between the three chambers of the cartridge with three needle valves and one check 
valve.  The Piston Chamber delivers saline to the Fluid Manifold through a small tube.  The 

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saline can be delivered to the Oxygen Chamber through the atomizer to create SSO2 
solution, through a dilution port to adjust concentration, or directly to the BMC to flush the 
capillary tube.  The SSO2
The DownStream Cartridge is equipped with a pressure transducer that monitors the blood 
mixing chamber pressure in the device during operation; the transducer connects to the 
DownStream System.  An IV spike and flexible tube are attached to the Piston Chamber, 
enabling easy connection to an IV bag during the procedure.  The draw and return tubing are 
equipped with luer connections.  The DownStream Cartridge is a single-use Ethylene Oxide 
(“EO”)-sterilized device. 
 solution’s dissolved oxygen concentration is controlled by the 
DownStream System.   
The draw tubing is connected to the patient with a luer fitting that is attached to the femoral 
access sheath.  The return tube is attached to the SSO2
2.1.3 
SSO2 Delivery Catheter 
 delivery catheter that has been placed 
in the ostium of the left main coronary artery.   
The SSO2 delivery catheter is a 5F (O.D.) over-the-wire catheter that is equipped with a 
standard luer fitting at the proximal end for attachment to the return line of the cartridge.  
The SSO2 delivery catheter has a total length of 100 cm and is placed over a guidewire to 
reach the coronary vasculature.  During administration of SSO2 Therapy, the SSO2 delivery 
catheter is placed in the ostium of the LMCA and connected to the cartridge by the trained 
physician. 
 
Only a catheter that is qualified by TherOx may be used as the SSO2 delivery catheter.  The 
qualified SSO2 delivery catheter is the 5F Boston Scientific Impulse® angiographic catheter.  
Superoxygenated blood may not be infused with a non-qualified catheter because of the risk of 
bubble nucleation and the introduction of air emboli to the patient, therefore the use of a non-
qualified delivery catheter is contraindicated.  TherOx has qualified the 5F Boston Scientific 
Impulse® 
2.1.4 
Patient Connections 
for compatibility with superoxygenated blood and this catheter must be used in this 
study. 
The DownStream Cartridge draw tubing connects to a femoral arterial sheath that may be 
used for angioplasty and stenting procedures.  Sheath placement may be coaxial (using one 
femoral arterial access site) or contralateral (using both the right and left femoral arteries for 

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access sites), at the physician’s discretion.  A single sheath is recommended as prior studies 
have shown that single femoral artery access, even with a larger sheath, results in less 
bleeding and fewer vascular complications that bilateral femoral access.  In the preferred 
coaxial configuration, a single introducer sheath can be used.  The DownStream Cartridge 
draw tubing luer fitting connects to the sheath sidearm.  The SSO2 delivery catheter (the 5F 
Boston Scientific Impulse®
Figure 4 provides a schematic of the patient connections during SSO2 Therapy 
administration. 
 angiographic catheter) is placed to the ostium of the left main 
coronary artery using standard cath lab techniques.  When extracorporeal blood flow is 
initiated, the delivery catheter and DownStream Cartridge return tubing are wet-connected 
to ensure that no gaseous emboli are introduced to the patient during priming.  The cartridge 
return tubing luer fitting connects to the luer hub of the delivery catheter.  For the 
contralateral approach, a 5F introducer sheath is used in a second femoral access site for 
blood withdrawal.  This alternative approach may be used by physicians who prefer to use 
two smaller sheaths for arterial access instead of a single sheath. 
 
Figure 4.  Patient Connections  
 
SHEATH 
SSO2 DELIVERY CATHETER
HYPERBARIC PO2
ARTERIAL 
BLOOD

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3 
STUDY OBJECTIVE 
To collect confirmatory data supporting the safety and effectiveness of SSO2 Therapy in the 
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. 
 
4 
STUDY DESIGN 
This is a non-randomized, single-arm study.  Subjects who present with anterior STEMI 
requiring stent placement in the proximal and/or mid LAD who meet all inclusion and 
exclusion criteria and provide informed consent will be treated with primary PCI with 
stenting, and if successful and uncomplicated then immediately with post-procedure delivery 
of SSO2 Therapy for a duration of 60 minutes. 
4.1 
Patient Enrollment 
100 qualifying patients with anterior acute myocardial infarction will be enrolled into this 
study and treated with SSO2 Therapy only after successful and uncomplicated 
revascularization of the LAD infarct artery. 
4.2 
Patient Follow-Up 
Subjects will be followed clinically at baseline, procedural, in hospital, at 30-days (±7 days; 
i.e., between 23 and 37 days), at 6-months (±30 days) and at 12-months (±30 days) 
following the index procedure.  The clinical investigator or designee will conduct the 30-day 
follow-up assessment as an office visit, and the 6-month and 12-month follow-up 
assessments via telephone call.  Patient adverse events will be tracked, monitored, and 
adjudicated through 12 months post-procedure.  For the purpose of reporting study results, a 
clinical summary report will be issued after 30-day data are finalized and a supplementary 
report will be issued upon completion of 12-month assessments. 
4.3 
Cardiac Magnetic Resonance Imaging (MRI) 
Patients will be evaluated with two cardiac MRI scans.  The first scan will be conducted 
between day 3 and day 5 post-procedure (day 4 ± 1).  The second scan will be conducted in 
conjunction with the mandatory 30-day clinical follow-up visit, on day 30 (±7) post-
procedure (between days 23-37).  Every effort will be made to obtain the required MRI 

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scans, and scans obtained outside the protocol window will be reported.  The necessary 
procedural details for conducting the cardiac MRI scans are provided in Appendix E. 
Cardiac MRI images will be evaluated by the MRI Core Laboratory and the following 
information will be reported: microvascular obstruction (MVO) at day 3-5, infarct size at 
both imaging time points, and left ventricular volume at both imaging time points.  Other 
standard MRI measures will also be reported at each time point. 
4.4 
Early Study Termination 
No statistical rule for early termination is defined.  However, TherOx, Inc. may discontinue 
the study at any stage with written notice to the investigators.  Possible reasons for early 
termination may include identification of safety risks that pose an unreasonable risk to the 
patient.  The independent Data Safety Monitoring Board will have responsibility for study 
oversight, including the timely review of critical safety events, and may make 
recommendations for study modification, suspension, or termination. 
The study Executive Committee makes a final decision for early study termination.  If the 
trial is terminated early, TherOx will provide a written statement describing why premature 
termination will occur, and notify the participating clinical investigators, investigational site 
IRBs, and FDA.  All applicable clinical study documents will be subject to the same 
retention policy as detailed in Section 10.10.1 Required Data. 
4.5 
Measures Taken To Avoid / Minimize Bias 
In order to minimize bias in assessing both effectiveness and safety data, the independent 
cardiac MRI Core Laboratory will evaluate patient scans independent of clinical outcome 
data, and an independent Clinical Events Committee (CEC) will be utilized for adverse 
event coding and relationships after review of original source documentation, blinded to the 
MRI results.  An independent Data and Safety Monitoring Board (DSMB) will conduct 
reviews of overall study conduct and safety both during the enrollment period and at the 
conclusion of the study. 
5 
SSO2 THERAPY PROCEDURAL AND SAFETY DATA 
5.1 
SSO2 Therapy Procedural Data 
Procedural information will be collected and reported for every patient treated with SSO2 
Therapy in this trial.  The data collected and reported will include: 

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• SSO2 Therapy device and infusion specifics   
• Confirmation of stable delivery catheter position 
• Intra-procedural hemodynamics   
• Procedural complications, therapy interruptions or device shutdowns 
5.2 
Safety Data 
All major adverse events will be evaluated and reviewed by an independent Clinical Events 
Committee (“CEC”).  The following safety and procedural information will be reported and 
summarized: 
• AEs and SAEs  
• Adverse event relationships 
• Intraprocedural complications 
• Clinical, technical and procedural success 
 
5.3 
Number of Sites 
Up to fifteen (15) centers located in the U.S. 
5.4 
Sample Size 
One hundred (100) patients, non-randomized.  All patients will receive a 60-minute SSO2 
Therapy infusion. 
6 
PATIENT SELECTION AND WITHDRAWAL 
6.1 
Patient Population 
Patients must meet all of the study criteria outlined below in Section 6.4.1 and 6.4.2 
(reference Inclusion/Exclusion Criteria Case Report Form (CRF), Appendix A).  No 
exclusion criteria outlined in Section 6.4.2 may apply in order to be enrolled. 
6.2 
Patient Screening 
All patients admitted to the emergency room or cardiac catheterization laboratory with 
symptoms <6 hours after symptom onset and ECG findings suggestive of acute anterior 
AMI (ST-segment elevation  of ≥1 mm in 2 or more contiguous leads in V1-V4, or new left 
bundle-branch block), and who are considered potential candidates for percutaneous 

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revascularization with stenting, are potentially eligible for this protocol.  All patients who 
meet clinical inclusion criteria should be documented (entered) on the site’s study screening 
log.  Thus, patients without ST-segment elevation and those with non-anterior MI or new 
left bundle branch block do not need to be recorded in the screening log.  Reasons for 
screening failure will be noted in the final study report. If the potential study candidate has 
one or more clinical exclusion criteria present, or subsequently fails to meet angiographic 
selection criteria, the reason for screening failure must be entered on the screening log.  A 
member of the research team should screen all eligible patients to determine eligibility and 
document any applicable reasons for non-enrollment on the screening log.     
A signed Informed Consent must be obtained before cardiac catheterization begins, and 
before any study-related tests or procedures are undertaken. 
6.3 
Informed Consent 
A member of the research team will approach the patient (or legal representative) to obtain 
written Informed Consent.  The Informed Consent will be carefully explained to the patient.  
The patient (or legal representative) must sign the consent form approved by the Sponsor, 
FDA, and the study site’s Institutional Review Board (“IRB”).  The sample Informed 
Consent Form is attached as Appendix B.  Signed Informed Consent Forms will be 
maintained at each investigational site. 
6.4 
Eligibility Criteria 
6.4.1 
Inclusion Criteria 
Candidates for this study must meet ALL of the following criteria: 
General Inclusion 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 acute MI of <6 hour 
duration from time of symptom onset until admission to the emergency room. 

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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 is completed <6 hrs from system onset, 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. 
 
6.4.2 
Exclusion Criteria 
Subjects will be excluded if ANY of the following conditions apply:  
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. 

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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:   
a. Cardiac pacemaker or implantable defibrillator; 
b. Non-MRI compatible aneurysm clip; 
c. Neural Stimulator (i.e., TENS unit); 
d. Any implanted or magnetically activated device (insulin pump); 
e. Any type of non-MRI compatible ear implant; 
f. Metal shavings in the orbits; 
g. Any metallic foreign body, shrapnel, or bullet in a location which the physician 
feels would present a risk to the subject; 
h. Any history indicating contraindication to MRI, including claustrophobia or 
allergy to gadolinium; 
i. Inability to follow breath hold instructions or to maintain  a breath hold for >15 
seconds; and 
j. 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. 

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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, 
eptifibatide, tirofiban 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. 
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. 

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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.  
Subjects who meet the selection criteria will be enrolled into this multi-center clinical trial 
after successful screening and providing Informed Consent.  
Please note: An Enrollment Notification Form should be completed and sent via facsimile to 
the study CRO after the procedure has been completed.  
 
6.5 
Patient Discontinuation 
 
Once enrolled, each patient should remain in the study until the required follow-up period is 
complete.  However, the patient has the right to withdraw from the study at any time.  The 
following events will result in terminating the patient’s follow-up: 
- 
Patient death 
- 
Patient voluntary withdrawal 
- 
Patient withdrawn by investigator as clinically indicated  
- 
Patient lost to follow-up (unofficial withdrawal) 
- 
Study is terminated according to Section 4.4 Early Study Termination 
 
Appropriate case report forms must be completed for both study-terminated patients and 
patients who complete the entire follow-up.  TherOx, Inc. must be notified of the reason of 
patient discontinuation.  The site will provide this information on the appropriate case report 
form.  Investigators must also report this information to their IRBs as defined by their 
institutions’ procedures. 
 
6.5.1 
Lost To Follow-Up 

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Patients who do not complete the scheduled 30-day follow-up clinical visit or who cannot be 
contacted for their 6 and 12-month telephone surveys and have not officially withdrawn 
from the study are considered lost to follow-up; this term does not apply to missed visits. 
Site personnel should make considerable effort to locate and communicate with the patient 
using all available methods (e.g., telephone, email and postcards).  The following contact 
procedure is recommended at the 30-day follow-up time point: 
 
- 
A minimum of 2 telephone calls on different days after discharge and over the 
30-day follow-up window.  This should be recorded including date, time, and site 
personnel initials for staff attempting to contact the patient.   
- 
If these attempts are unsuccessful, a certified letter should be sent to the patient. 
- 
If the patient misses two (2) consecutive scheduled contact time points and the 
above mentioned attempts at communicating with the patient are unsuccessful, 
the patient will be considered lost to follow-up. 
 
7 
STUDY PROCEDURES 
7.1 
Patient Evaluation Procedures 
For those patients who agree to participate in the study by signing the approved Informed 
Consent, the following baseline examinations and tests will be performed: 
•  Medical History and physical examination  
•  12 Lead ECG  
•  Administration of protocol required procedure medications  
•  Cardiac Biomarkers (CK, CKMB and troponin) 
•  Clinical Chemistry and Hematology  
• Coronary Angiography 
 
7.2 
Procedure Medications 
All enrolled patients receive the following protocol required medications: 
Patients must receive one of the following oral ADP antagonist regimens: 
• Clopidogrel 600 mg in the ER, followed by 75 mg to 150 mg per day.  
• Prasugrel 60 mg in the ER followed by 5 mg to 10 mg per day. 

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• Ticagrelor 180 mg in the ER followed by 90 mg b.i.d.   
• Ticagrelor or prasugrel is preferred to clopidogrel in patients without bleeding 
contraindications, according to FDA labeled instructions for use.  Prasugrel (but not 
ticagrelor) is contraindicated in patients with prior stroke or TIA.  Ticagrelor is 
recommended rather than prasugrel in patients <60 kg or >75 years of age. 
• These loading doses must be given even if the patient is on home dual anti-platelet 
therapy. 
 
Patients must also receive: 
• 
Aspirin – 324 mg chewable aspirin given in ER prior to catheterization (regardless 
of earlier administration of aspirin).  Alternatively, 250-500 mg IV may be 
administered5
• 
Intravenous bivalirudin or unfractionated heparin (as in Section 7.3.1 below), 
initiated either before or in the catheterization laboratory, but in all cases before the 
first balloon inflation.  At operator discretion, the patient may have received 
unfractionated heparin prior to cardiac catheterization, and then be switched to 
bivalirudin in the cath lab prior to PCI as described in Section 7.3.1 below. 
.  Thereafter, 81 mg of oral aspirin per day is administered. 
• 
Low-flow nasal oxygen (3-5 l/min) or oxygen mask (5-10 l/min) to maintain 
systemic arterial pO2 > 80 mmHg.   
 
Use of cangrelor or glycoprotein IIb/IIIa receptor inhibitors is required prior to PCI in 
patients treated with only unfractionated heparin.  For patients receiving bivalirudin as their 
procedural anticoagulant, routine use of cangrelor is allowed but use of glycoprotein IIb/IIIa 
receptor inhibitors is not recommended, but may be administered during the procedure if 
refractory thrombotic complications occur.  If a GP IIb/IIIa inhibitor is used, abciximab 
(bolus + a 12 hour infusion) is recommended, although eptifibatide (double bolus + a 12-18 
hour infusion) or tirofiban according to label is an acceptable alternative.  Dosing of either 
should be performed per the package insert, adjusted for renal insufficiency.  The IIb/IIIa 
inhibitor may be initiated prior to catheterization (e.g., in the emergency room), or in the 
cardiac catheterization laboratory prior to first balloon inflation. 
 
The use of procedure medications will be documented on the appropriate Case Report 
Forms. 
                                                 
5 IV aspirin is applicable to EU sites only. 

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7.3 
Cardiac Catheterization Laboratory (CCL) Procedure 
7.3.1 
Patient Anticoagulation 
Patient anticoagulation throughout the SSO2 Therapy procedure is aligned with current 
practice in STEMI patients treated with primary PCI as outlined below.  Bivalirudin is 
recommended for this study, but patient anticoagulation must consist of one of the following 
regimens: 
 
1) Bivalirudin and cangrelor, with provisional (bail-out) use of GP IIb/IIIa 
inhibitors allowed 
2) Bivalirudin, with provisional (bail-out) use of GP IIb/IIIa inhibitors allowed 
3) Heparin and cangrelor, with provisional (bail-out) use of GP IIb/IIIa inhibitors 
allowed 
4) Heparin and routine use of GP IIb/IIIa inhibitors 
 
If bivalirudin is selected as the procedural anticoagulant, it should be administered as a bolus 
of 0.75 mg/kg IV prior to PCI, followed by an infusion of 1.75 mg/kg/h initiated as soon as 
possible.  The infusion is continued at this rate through the end of SSO2 Therapy 
administration and for 3-4 hours post-procedure.  The infusion dose should be adjusted for 
renal insufficiency as per the FDA labeled Instructions for Use. 
Exception: If the patient received intravenous heparin prior to cardiac catheterization (bolus 
or infusion), the heparin should be discontinued, and the bivalirudin should be started 30 
minutes after the last dose of heparin or prior to PCI whichever occurs first.  An ACT or 
aPTT does not need to be checked before starting the bivalirudin.  In all cases the bivalirudin 
should be initiated before the first PCI balloon inflation or aspiration. 
The use of bivalirudin is preferred but unfractionated heparin along with the routine pre-PCI 
use of a GP IIb/IIIa inhibitor or bivalirudin with the provisional (bailout) post-PCI use of a 
GP IIb/IIIa inhibitor may be used as the procedural anticoagulant in the IC-HOT clinical 
study.  
If unfractionated heparin is selected, local dosing regimens may be used, although it is 
recommended that an initial bolus of 60 IU/kg is administered, followed by titration to the 
ACT of 200-250 seconds.  Heparinized patients must also receive a GP IIb/IIIa inhibitor or 
cangrelor.   

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For all subjects, ACT is measured as a baseline reading prior to starting SSO2 Therapy and 
after the 60-min infusion is completed.  For patients receiving heparin, a 30-min ACT is also 
required and bolus administration of heparin to maintain ACT levels may be necessary. 
Intravenous cangrelor may also be used according to label per investigator discretion, 
administered as a bolus plus infusion, with the infusion continued for 2-4 hours post-PCI.  
For patients receiving bivalirudin, cangrelor may be administered in the same IV. 
 
7.3.2 
Coronary Angiography 
It is recommended that the prospective patient be transferred to the catheterization 
laboratory as quickly as possible.  Once in the catheterization laboratory, the patient should 
be prepared for the interventional procedure according to standard hospital procedures.  Left 
ventriculography is required and must be obtained prior to study enrollment. 
When performing coronary angiography, all of the distal target vessel with capillary and 
collateral flow should be filmed to allow for assessment of pre-procedure and post-
procedure TIMI flow and blush score.  Left ventriculography should be performed in the 
right anterior oblique view (pre- or post-PCI, but before study enrollment) with at least two 
consecutive sinus beats available for analysis.  Pre- and post-PCI angiographic data will be 
sent to the Angiographic Core Laboratory for analysis as per the instructions provided in 
Appendix E.  Study investigators should follow procedural guidelines for angiographic 
imaging provided in Appendix E. 
Patients must be excluded if an additional staged procedure is planned within 30 days. 
7.3.3 
PCI / Stenting Procedure 
Following a successful diagnostic catheterization and identification of the target lesion(s) in 
the proximal and/or mid LAD as suitable for PCI with stenting, if heparin plus a GP IIb/IIIa 
inhibitor was used as the procedural anticoagulant, additional heparin boluses may need to 
be administered to maintain the ACT between 200 and 250 seconds.  If bivalirudin alone 
was used as the procedural anticoagulant, the ACT should be verified to be >250 seconds. 
Only commercially available bare metal or metallic drug-eluting stents are to be used in this 
study.  Bioresorbable vascular scaffolds, if available during the enrollment period, are not 
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eligibility criteria are met and none of the baseline laboratory or angiographic exclusion 
criteria apply, the patient may be enrolled.  
7.4 
SSO2 Therapy 
7.4.1 
Arterial Sheath Selection 
The coaxial (single arterial stick) approach is strongly recommended for SSO2 Therapy as 
prior studies have shown that single femoral artery access, even with a larger sheath, results 
in less bleeding and fewer vascular complications than bilateral femoral access.  When only 
one arterial site (coaxial access) is used with the DownStream System, an 8F sheath may be 
used, or a qualified 7F sheath6
The TherOx SSO2 delivery catheter requires a qualified 7F or 8F arterial sheath for coaxial 
setup because of the need for an adequate blood flow path for blood withdrawal between the 
catheter and sheath.  If contralateral access is preferred, a minimum 5F sheath is required to 
withdraw blood from the second arterial access site. 
.  Contralateral access with a second sheath may be used as an 
alternative if desired, in which case a smaller 5F introducer sheath in the contralateral 
femoral artery may be used.  Ipsilateral insertion of a second sheath into the same femoral 
artery is strictly prohibited.  
If a 5-6F radial sheath was used for PCI, a second 5F sheath should be placed in a femoral 
artery for blood withdrawal.  
7.4.2 
SSO2 Therapy Infusion 
Note:  Refer to the DownStream System Operators Manual (Appendix C) for proper setup 
and operation of the DownStream System. 
1. For coaxial (one arterial access site) setup with the SSO2 delivery catheter:  
introducer sheath with sidearm must be in place.   
2. For dual access site setup, the investigator has the option of inserting a smaller 
sheath (minimum 5F) in a femoral artery for blood withdrawal (note: ipsilateral dual 
sheath insertion into the same femoral artery is prohibited). 
3. The SSO2 delivery catheter (i.e., 5F Boston Scientific Impulse®
                                                 
6 The Merit Medical 7F Short Sheath Introducer supports blood withdrawal for SSO2 Therapy. 
 angiographic 
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appropriate curve shape of the catheter so it seats in the left main as securely and 
coaxially as possible.  After placement, inspect the SSO2 delivery catheter under 
fluoroscopic visualization and with a small injection of contrast to ensure that it is 
seated correctly in the LMCA, and does not restrict blood flow (contrast “blowback” 
is present, and no pressure damping is seen).  Record this injection on 
cineangiographic film for review in the core laboratory. 
4. Ensure that fluoroscopic contrast and infusate agents delivered through the SSO2 
delivery catheter have been flushed with saline prior to priming circuit; these viscous 
solutions may result in a flow stoppage after connection to the cartridge return line is 
made. 
5. SSO2 Therapy must be performed in the cardiac catheterization laboratory for the 
duration of the infusion.   
6. The DownStream System and DownStream Cartridge are set up per the Instructions 
For Use (Appendix D).  The draw tubing of the DownStream Cartridge is connected 
to the sidearm of the draw sheath prior to circuit priming. 
7. To prime the circuit, the system operator must depress and hold the PRIME button 
on the DownStream System display keypad.  Blood flow is initiated and when the 
cartridge is fully primed (blood flow is present from the return line), the return 
tubing of the cartridge is connected to the proximal end of the SSO2 delivery 
catheter. 
8. The target blood flow rate of the DownStream Cartridge is 100 ml/min and is 
controlled by the DownStream System.  
9. Prior to initiation of SSO2 Therapy, baseline systemic arterial pO2 and blood pressure 
are recorded (reference SSO2 Therapy Procedure CRF, Appendix A).  The patient’s 
systemic arterial pO2 must be greater than or equal to 80 mmHg to proceed with 
SSO2 Therapy.     
10. When the DownStream System indicates readiness, infusion of SSO2 solution may 
now be initiated.  The time of initiation of SSO2 infusion must be noted on the SSO2 
Therapy Procedure CRF. 
11. SSO2 Therapy infusion runs for 60 minutes for each enrolled patient.  During this 
time the patient parameters such as blood pressure and heart rate/rhythm will be 
obtained at 15-minute intervals and recorded on the SSO2 Therapy Procedure CRF.   

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12. At 30 minutes after the infusion has been initiated, the cath lab operator must 
confirm the position of the SSO2 delivery catheter with a fluoroscopic (no contrast 
required) image.  Record this position on a brief cineangiographic run for review in 
the angiographic core laboratory.  If the delivery catheter has moved from its initial 
infusion position or is not moving in concert with the cardiac silhouette with each 
heartbeat, SSO2 Therapy must be stopped in order to re-seat the delivery catheter and 
finish the infusion with a new cartridge. 
13. After patients complete the 60-minute SSO2 Therapy infusion, the user must press 
“End Procedure”.  The time of cessation of SSO2 infusion must be noted on the SSO2 
Therapy Procedure CRF. 
14. The delivery catheter is withdrawn from the patient per standard practice.  The 
DownStream Cartridge tubing is disconnected from the sidearm of the arterial sheath 
and the delivery catheter.  The cartridge and the blood contained therein should be 
discarded per hospital practice (do not return this blood to the patient).  The cartridge 
transducer is retained for shipment to the sponsor. 
15. After the SSO2 Therapy procedure is complete and all components removed the cath 
lab operator must take a final angiogram according to the procedural guidelines for 
angiographic imaging provided in Appendix E. 
7.4.2.1 
Device Performance 
DownStream System and DownStream Cartridge device usage information, including date 
and time of SSO2 Therapy infusion, the number of DownStream Cartridges used, 
DownStream Cartridge tracking information, and total SSO2 Therapy infusion time, is 
recorded on the SSO2 Therapy Procedure CRF.  System and cartridge usage information is 
also retained in electronic files stored on the DownStream System and will be retrieved by 
the Sponsor or their authorized representative. 
Concerns related to device performance should be reported immediately to the TherOx, Inc. 
Technical Support function at 1-888-2-THEROX or 1-949-757-1999.  This service is 
available 24-hours a day, 7-days a week. 
7.5 
Other Procedural Considerations 

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If an IABP, Impella, or other hemodynamic support device is indicated at any point after 
initiation of SSO2 Therapy, prior to the completion of the 60-minute SSO2 infusion, the 
SSO2 procedure must be discontinued.  These devices may not be operated simultaneously 
in this protocol. 
7.6 
Post Cardiac Catheterization Laboratory (CCL) 
7.6.1 
In-Hospital Procedures 
Following treatment, patients will be sent to the CCU, Step-Down Unit, or Coronary Care 
Floor at the discretion of the Investigator. 
7.6.2 
Post-procedure ECG 
A 12-lead post-procedure ECG must be obtained at 60 minutes (±30 minutes) after the last 
angiogram, which is taken after the final SSO2 discontinuation. 
7.6.3 
Cardiac Enzymes, Clinical Chemistry, and Hematology 
Cardiac enzymes (CK, CK-MB, and Troponin) are drawn at baseline, and at 12 and 24 hours 
(±2 hours) post-PCI.  Clinical chemistry and hematology are obtained at baseline and at 24 
hours (±2 hours) post-PCI. 
 
7.6.4 
Medications 
 
All medications administered to study subjects must be recorded. 
 
7.6.5 
Cardiac MRI Scan 
 
A Cardiac Magnetic Resonance Imaging scan must be performed on day 4 (±1) post-
procedure (see Appendix E for detailed instructions).  If the patient is unable to undergo 
cardiac MRI during this time window for any reason, a protocol deviation must be noted 
along with the reason for the inability to perform the scan. 
 
7.6.6 
Arterial Sheath Removal and Ambulation 
 
Arterial sheath removal and ambulation are to be conducted per standard hospital care. 
 
7.7 
Hospital Discharge 

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Timing of hospital discharge is at the discretion of the investigator for each individual 
patient.  An appointment for the 30-day follow-up visit should be made for a time agreeable 
to the patient prior to discharge.  This evaluation must be performed at 30 (±7; range 23-37 
days) days after index PCI and include the follow-up cardiac MRI scan (see Appendix E). 
7.7.1 
Post Discharge Medications 
Post discharge medications must be recorded on the Medications CRF. 
7.8 
30-Day Clinical Visit Follow-up 
A clinical follow-up visit is required at 30 days (±7 days; range 23-37 days) post-procedure 
and must be completed no later than day 37 post-procedure.  If the patient is hospitalized 
longer than 37 days the follow-up should be completed at discharge.  Refer to Table 1 for 
details on the assessments to be performed and the information to be collected. 
7.9 
6-Month and 12-Month Telephone Follow-up 
A telephone follow-up call is required at 6 months (±30 days) and 12 months (±30 days) 
post-procedure.  Refer to Table 1 for details on the assessments to be performed and the 
information to be collected. 
7.10 
Medical Economics Data Collection 
In conjunction with this clinical trial, an economic study of hospital charges for all patients 
enrolled in the study will be conducted. The economic study is based on the information 
contained in UB-04 claim forms that are generated by the hospital billing department after 
patient discharge to request reimbursement from health insurance plans. The Informed 
Consent form authorizes us to obtain a copy of this claims information.  At the study’s 
conclusion, UB-04 data will be reported in the aggregate form; that is, no individual 
patient’s results will be disclosed when reporting the economic study findings.   
The goal of the economic study is to allow the study sponsor, TherOx, to apply to the Center 
for Medicare and Medicaid Services (CMS) for additional reimbursement for this 
technology so that once approved by the FDA, there will be adequate payment for this 
technology. 

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8 
RISKS AND ADVERSE EVENTS  
8.1 
Risk Analysis 
The risk management approach used by TherOx is based upon ISO 14971.  The risk analysis 
for SSO2 Therapy was developed by a multidisciplinary team within TherOx to assess the 
potential hazards and causes of hazards that need to be considered in product design, testing, 
training, and labeling.  The risk analysis applies to the design and use of the DownStream 
System, DownStream Cartridge, and SSO2 delivery catheter. 
The risk analysis focuses on the incremental risk associated with SSO2 Therapy, as 
compared to performing PCI alone for acute myocardial infarction (“AMI”) patients.  SSO2 
Therapy is initiated in the cardiac catheterization laboratory (“CCL”) with the AMI patient 
following revascularization.  One healthcare professional (operator) installs the 
DownStream Cartridge and operates the DownStream System during treatment.  A second 
health care professional (physician) places the delivery catheter and is present when 
treatment is set-up and initiated.  The users are trained to perform a sequence of steps, which 
are defined in the DownStream System Operators Manual (Appendix C).  Hazards are 
identified and evaluated based upon these conditions of use and foreseeable misuse in this 
setting. 
Risk Mitigation 
 
Safety measures have been implemented to mitigate the risk of potential hazards.  These 
safety measures include methods to detect unsafe conditions and a DownStream System 
Safety Response to isolate the patient from the extracorporeal circuit.  When an unsafe 
condition is detected, the patient is isolated from the DownStream System and the treatment 
is stopped. 
Safety Response 
If the DownStream System detects an unsafe condition, the Safety Response isolates the 
patient from the system and stops treatment.  The SSO2 flow stops, the blood pump stops, 
and the draw and return tubes are clamped, and the oxygen pressure is vented.  The system 
provides visual and audible notification.  After a Safety Response, the cartridge must be 
replaced to continue treatment.  System valves are designed for fail-safe conditions, so the 
patient is isolated in the event of a power loss. 

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In order to mitigate the occurrence of Safety Responses during treatment, the system 
performs tests (software checks) when certain processes are initiated.  When the system 
preps (saline primes) the cartridge, several checks verify functions of the SSO2 solution 
production and delivery process.  During blood priming of the EC circuit, several checks 
verify functions of the Safety Response are ready.  The system also provides the ability to 
recover from momentary restrictions in the tube set that would otherwise cause a shutdown.  
In addition, the Operators Manual (see Appendix C) and Instructions for Use (see 
Appendix D) clearly states that this procedure shall be supervised during therapy, allowing 
timely recovery from detected occlusions.  The system in transportable and has battery back-
up, but is intended to deliver SSO2 Therapy when stationary and connected to AC Mains.     
The specific mitigations for two important hazards, air emboli and blood loss/hemorrhage, 
are described below. 
Mitigation of Air Emboli 
After the blood path is primed, an ultrasonic bubble detector continuously monitors the 
return side of the blood path for gas emboli.  The bubble detector also monitors signal 
strength, ensuring the return tube is properly loaded in the bubble detector probe.  If the 
cumulative bubble volume reaches 10-microliters during the 60-minute treatment, or the 
signal strength is out of range, the bubble detector triggers the Safety Response. 
Several other design features mitigate the possibility of gas in the blood path.  The 
DownStream Cartridge blood mixing chamber is designed to be a gas trap for bubbles 
introduced in the draw tubing.  Also, the DownStream System has a low-level sensor that 
verifies safe blood level in the blood mixing chamber.  The BMC low-level sensor can 
trigger the Safety Response. 
Mitigation of Blood Loss/Hemorrhage 
The blood priming volume of the extracorporeal circuit is approximately 60 ml.  A cause of 
the potential hazard of blood loss is leakage from the extracorporeal circuit.  A pressure 
transducer monitors for either insufficient or excessive pressure that could potentially result 
in a leak.  In addition, a blood mixing chamber high-level sensor will detect if the blood 
level is too high, which could indicate a blood leak at that location.  Either the BMC high 
level sensor or return pressure transducer can trigger the Safety Response, mitigating the 
risk of blood loss.  In addition, the IFU clearly states that this procedure shall be supervised. 

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The risk of hemorrhage is present in most interventional procedures, considering that these 
patients are given anticoagulants.  The risk may be slightly greater for SSO2 Therapy due to 
the increased time of catheterization and anticoagulation.  The IFU identifies potential 
adverse events, including hemorrhage. 
Risk Analysis Summary 
The DownStream System Instructions for Use identifies potential adverse events, which 
include hazards identified by risk analysis and the inherent condition of the patient 
population post-AMI.  These adverse events are listed below in order of severity: 
• Death 
• Myocardial Rupture 
• Acute Myocardial Infarction (AMI) 
• Cardiogenic Shock 
• Stroke/TIA 
• Coronary Artery Occlusion 
• Revascularization (CABG or PCI) 
• Thrombosis 
• Congestive Heart Failure 
• Restenosis 
• Tamponade 
• Abrupt Vessel Closure/Spasm 
• Hemorrhage 
• Embolism (including air emboli and thromboemboli) 
• Aneurysm 
• Arteriovenous Fistula/Pseudoaneurysm 
• Arrhythmias 
• Vascular Damage (dissection, perforation, rupture, or other mechanical injury) 
• Blood Loss/Damage 
• Pericardial Effusion 
• Renal Complications 
• Pulmonary Edema 
• Respiratory Complications 
• Hematoma 

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• Hemolysis 
• Infection 
• Allergic Reactions 
• Chest Pain/Angina 
• Hypertension/Hypotension 
• Neck/Back/Groin Pain 
• Nausea/Vomiting 
• Anxiety/Dizziness 
 
These adverse events are associated with interventional cardiology procedures.  SSO2 
Therapy introduces no new or incremental adverse events other than those known to exist 
within the standard of care (PCI with stenting).   
Based upon the extended time of cath lab intervention required for SSO2 Therapy, the 
accompanying requirement for anticoagulation throughout the procedure, and the 
extracorporeal circuit, SSO2 Therapy may increase the following specific risks:  
• Air emboli 
• Vascular damage from the placement of an infusion catheter 
• Bleeding requiring treatment, particularly at the catheterization site 
8.2 
Clinical Assessments 
8.2.1 
Clinical Follow-Up 
Clinical follow-up with a cardiac MRI scan and an office visit will occur at 30 days (±7  
days; range 23-37 days) or date of discharge, whichever is later. Additional telephone 
follow-up will occur at 6 months (±30 days) and 12 months (±30 days).  
If available, the following data should be collected at the specified time points: 
- 
Clinical events including event description, symptom onset, medical intervention, 
and resolution. 
- 
AE related data including laboratory test results, ECG, and subsequent repeat 
coronary angiography results, at the time of the event. 
- 
Patient compliance and therapy interruptions with adjunctive antiplatelet therapy 
and SAE bleeding. 

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- 
Chronic concomitant medications (selected cardiac list). 
 
8.2.2 
Additional Event Driven Visits 
Additional event driven visits may occur clinically as warranted.  If available, the following 
data should be collected at these visits: 
- 
Clinical event descriptions.  Also, AE related data including laboratory test 
results, ECG, details and subsequent coronary angiography results. 
- 
 Patient compliance and therapy interruptions with adjunctive antiplatelet therapy 
and major bleeding complications. 
- 
Chronic concomitant medications (selected cardiac list). 
 
If a patient completes a clinic visit independent of this protocol and outside of the protocol 
required follow-up time point, this information should be obtained from the patient’s source 
documents.  All efforts must be made to obtain follow-up information on study patients that 
have been treated for adverse events (AEs) in a non-study related health care facility. 
 
8.3 
Adverse Events 
An adverse event is defined as follows for this study: 
Adverse Event:  Any undesirable clinical occurrence in a study patient, whether or not it is 
related to the investigational intervention, is considered an adverse event.  Any condition 
that was recorded as pre-existing is not an AE unless there is a change in the nature, severity 
or degree of the condition. 
During clinical follow-up, the investigator will determine adverse event (AE) occurrences.   
Collection of adverse events begins after informed consent has been provided and the SSO2 
Therapy procedure begins (defined as SSO2 delivery catheter insertion into the patient).  
Adverse events will be reported for all subjects through 12 months post-procedure.  The 
Adverse Event CRF is to be completed for each adverse event experienced by an individual 
subject.  Serious adverse events are also reported on the Serious or Device Related Adverse 
Event CRF.  Selected serious adverse events are further detailed on individual CRFs for 
greater specificity. 

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8.4 
Unanticipated Adverse Events  
All unanticipated adverse events MUST be reported to the study Contract Research 
Organization (CRO) within 24 hours of knowledge of the event.  If an observed adverse 
event is not associated with any of the categories on the list found in Section 8.1 Risk 
Analysis Summary, the event may be unanticipated and must be reported within 24 hours. 
An Unanticipated Adverse Device Effect (UADE) is defined as follows for this study: 
Unanticipated Adverse Device Effect: Any serious adverse effect on health or safety or 
any life-threatening problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of incidence in 
the protocol, investigator’s brochure, labeling, or published literature, or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or 
welfare of subjects. 
8.5 
Serious Adverse Events (SAEs) 
Serious Adverse Events must be reported to the CRO within 24 hours of occurrence of the 
event.  A serious adverse event is defined as follows for this study: 
Serious Adverse Event: An event that is fatal or leads to a serious deterioration in health 
that:  
1. Results in death 
2. Is life threatening   
3. Requires inpatient hospitalization or prolongation of existing hospitalization  
4. Results in a persistent or significant disability/incapacity 
5. Results in a congenital anomaly/birth defect 
6. Results in medical or surgical intervention to prevent permanent impairment to body 
structure or a body function 
7. Is an important medical event that may not result in death, be life-threatening, or 
require hospitalization but may be considered serious when, based upon appropriate 
medical judgment may jeopardize the subject and/or may require intervention to 
prevent one of the outcomes listed in this definition.  Examples of such medical 
events include allergic bronchospasm requiring intensive treatment in an emergency 
room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse. 
 

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8.6 
Clinical Events Committee (CEC) 
During the course of the study, an independent Clinical Events Committee (CEC) will be 
responsible for the adjudication of clinical events. 
 
The CEC shall consist of three members with the appropriate medical background in 
cardiology, including at least one interventional cardiologist, and will be appointed by the 
Sponsor.  The CEC must consist of individuals who are impartial, independent of the 
investigator(s) and who have no financial, scientific, or other conflict of interest with the 
study.  Written documentation attesting to absence of conflict of interest will be required. 
 
Should a CEC member not be able to fulfill their commitment to the committee and the 
study for any reason, another member will be appointed to replace them according to the 
qualifications noted above. 
 
The CEC is responsible for adjudicating protocol-defined adverse events.  The committee 
determines whether the reported events meet the established definitions for the adverse 
events that will be tracked in this study.  This process includes a thorough review of the 
source documents for the event and an independent adjudication of the event according to 
protocol definitions.   
 
The CEC may or may not agree with conclusions drawn by the investigator from a specific 
investigational site; in this case, the CEC’s conclusion will serve as the final decision for 
submission to regulatory authorities and for reporting and publication.  Furthermore, should 
the committee members become aware of an event through the review of source documents 
from the research subjects, they will be able to adjudicate those events even if the site 
investigator has not reported them. 
 
In the course of reviewing an event, the CEC will determine the following: 
• Agreement or disagreement with event as reported by the study investigator 
• Adverse event classification 
• Relation of adverse event to investigational device 
• Need for additional data 
Events to be adjudicated for this study include: 

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• Disease specific:  
- 
Death (cardiac death, vascular death, non-cardiac death; if the cause of death 
is unknown it will be adjudicated as cardiac death)  
- 
Revascularization (PCI or CABG): clinically driven, non-clinically driven  
- 
Recurrent angina or reinfarction (Q-wave MI, Non-Q-wave MI, target vessel 
related, non-target vessel related)  
- 
Arrhythmias (2nd
- 
Cerebrovascular accident (including stroke and TIA)  
 and third degree heart block, atrial fibrillation, flutter or 
supraventricular tachyarrhythmias, non-sustained or sustained ventricular 
tachycardia or fibrillation) 
- 
Stent thrombosis (ARC definite or probable) 
- 
New onset heart failure  
- 
Hospital readmissions (cardiac heart failure related, cardiac non-heart failure 
related, non-cardiac) 
- 
Embolism (including air emboli and thromboemboli)  
- 
All bleeding (TIMI scale and BARC scale) and blood produce transfusions 
• Procedure related:  
- 
Vascular complications: access site hematoma, pseudoaneurysm, 
arteriovenous fistula peripheral ischemia or nerve injury  
- 
Bleeding complications, including Intracerebral Hemorrhage (ICH), and 
Hemolysis  
- 
Need for surgical intervention at the access site  
- 
Transfusion  
- 
Infection 
• Device specific:  
- 
Dislodgement of the device requiring repositioning  
- 
Dissection of the LMCA or its branches  
- 
Thrombosis (including catheter thrombus)  
- 
Intra-procedural ischemia related to catheter position in LMCA  
- 
Any clinically-driven discontinuation of SSO2 Therapy before 60 minutes 
 
The CEC charter is included in Appendix F of the Investigational Plan. 
 

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8.7 
Data Safety Monitoring Board (DSMB) 
The DSMB is the primary data and safety advisory board for this study.  The DSMB reviews 
study data, monitors for excessive occurrence of adverse events, and makes 
recommendations to the study Sponsor regarding safety issues and risks to research 
participants as well as the continuing validity and scientific merit of the study.  The 
Chairman of the DSMB will notify the Sponsor by way of confidential memo regarding 
modification of the protocol, continuation/discontinuation of enrollment and/or temporary 
suspension of enrollment in the trial.   
 
DSMB Responsibilities 
 
The DSMB is an independent board formed to conduct reviews of safety data in accordance 
with the Protocol or other established procedures.  The DSMB is comprised of three 
interventional cardiologists and one biostatistician.  At periodic intervals during the course 
of the study, the DSMB shall:    
 
• Evaluate all events with regard to interim results of the study for evidence of 
undue risk to research subjects or safety concerns. Establish criteria and assess 
possible early termination of the study because of the ascertainment of study 
objectives, or safety concerns.  
• Evaluate study progress with projections of recruitment and timelines for study 
milestones.  This also includes evaluation of any significant trends of 
performance that may influence the safety or conduct of the study. 
• Advise the sponsor with regard to potential problem areas within the protocol 
regarding procedures, definitions, or endpoints, allowing timely notification of 
the FDA or other regulatory authority for protocol revisions.  
• If applicable and accordance with this charter and the protocol, make 
recommendations regarding adapting the study design. 
 
The IC-HOT DSMB charter is included in Appendix G of this Investigational Plan. 
 
9 
REPORTING OF TRIAL DATA 
9.1 
Overview 
 

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The intent of this study is to collect confirmatory safety and effectiveness data on the 
intracoronary perfusion of hyperoxemic blood into the left main coronary artery in patients 
with anterior acute myocardial infarction with successful PCI/stenting completed within 6 
hours of symptom onset.  100 patients will be enrolled in this trial.  Procedural success, 
cardiac MRI outcome measures, and patient safety outcomes will be analyzed at the 
conclusion of this trial.  Patient data will be reported using categorical presentation and 
descriptive statistics where appropriate, for all treated patients.  Study success will be based 
upon achieving an acceptable observed rate for Major Adverse Cardiac Events as defined in 
the Statistical Analysis Plan (Appendix H). 
A Clinical Summary Report will be prepared at the conclusion of 30-day follow-up 
reporting and data validation activity for all procedural, effectiveness, and safety data.  A 
supplemental report will be prepared after receiving follow-up survey and event data for 
patients 12 months post-procedure. 
All enrolled subjects will be reported on for this study.  All available data, regardless of 
whether data are derived within specified time windows, will be included in the analysis.  
Patients who do not complete the entire course of treatment with SSO2 Therapy will be 
included.   
9.2 
Endpoints and Statistical Analysis Plan 
Criteria for Study Success 
Safety 
The primary endpoint of the IC-HOT trial to achieve study success is the 30-day rate of Net 
Adverse Clinical Events (NACE), compared against an objective performance goal (OPG) 
based from the rate of an appropriate historical control population from the INFUSE-AMI 
trial.  For safety, the composite NACE endpoint includes a hierarchical total of the 
following events: 
• Death (all-cause) 
• Reinfarction 
• Target Vessel Revascularization (clinically driven) 
• TIMI major or minor bleeding 
• New onset severe heart failure or rehospitalization for heart failure 

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• Stent thrombosis (ARC definite or probable) 
This composite endpoint includes safety categories that are of significance in contemporary 
AMI studies and includes the specific risks that were identified as areas of concern by FDA 
with regards to SSO2 Therapy.  It should be noted that an observed event of myocardial 
rupture would be included in the Death category.  The IC-HOT study will use well-
established clinical event definitions for the component NACE event categories as set forth 
in the Statistical Analysis Plan (Appendix H). 
Safety Endpoint: Objective Performance Goal 
As a benchmark with a similar anterior wall AMI population, the INFUSE-AMI study 
yielded a 10.7% 30 day NACE event rate for control subjects receiving no aspiration and no 
intracoronary abciximab (n =112 control subjects data analysis performed for TherOx by the 
INFUSE-AMI Principal Investigator Gregg Stone, MD, and the Biostatistics Department at 
the Cardiovascular Research Foundation).  In INFUSE-AMI all of the components of the 
NACE endpoint were adjudicated using specific definitions, except TIMI bleeding. The 
same definitions will be used for the present study (except that TIMI bleeding will be 
adjudicated). The INFUSE-AMI study reflects current cath lab practice, and therefore the 
use of a composite endpoint benchmark from the control group’s observed event rates is an 
appropriate comparator for the present prospective study. 
The proposed threshold for success of the prospective trial is that the observed 30-day 
NACE rate in the SSO2 group will be no greater than the 30-day MACE rate observed in the 
INFUSE-AMI control group, 10.7%.     
Furthermore, the specific 30-day NACE event categories of death, stent thrombosis, 
myocardial rupture, and SAE bleeding will be examined in terms of individual events.  The 
numbers provided in Table 2 below represent the FDA-recommended 30-day event rate 
guidelines for these individual safety endpoints.  FDA will conduct clinical review of event 
counts, severity, and patient circumstances.  Events will be reviewed and evaluated in the 
context of individual patient circumstances, relationship to the investigational device, and 
overall patient status in an overall determination of device safety.   
Table 2.  FDA Guidelines for Acceptable Adverse Event Rates 

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30-Day MACE Event  
IC-HOT Trial 
FDA Guideline 
Death  
≤3.0%  
Stent Thrombosis (definite)  
≤3.0%  
Myocardial Rupture  
≤1.0%  
TIMI Major and Minor 
Bleeding 
≤3.0%  
 
Weighing the frequency, severity, and causal factors of the observed adverse events in this 
study, the safety profile of SSO2 Therapy will be measured against the observed 
effectiveness results in an overall evaluation of the risk-benefit profile. 
To further evaluate the safety profile of SSO2 Therapy, the treatment cohort will be 
followed throughout the post-approval data collection period (12 months), however the 
primary endpoint will be at 30 days. 
For the purpose of comparing the new, modified NACE endpoint for this confirmatory study 
with previous studies of SSO2 Therapy, the data from the AMIHOT II study were re-
examined using the new, modified NACE endpoint definitions.  In total, 13.1% (29/222) of 
SSO2 patients experienced 30-day NACE.  Therefore, the IC-HOT clinical trial NACE 
endpoint OPG of 10.7% is more conservative than the AMIHOT II results. 
In addition to 30-day NACE, the following data will also be reported and summarized: 
• 
Additional bleeding events through 30 days, categorized by the BARC criteria  
• 
All other 30-day adverse events  
• 
Individual NACE component event rates through 1 year 
 
Additional Study Endpoints 
Effectiveness 
 
Effectiveness is a secondary endpoint for this study.  Effectiveness data from dual time 
point cardiac MRI scans at day 4 and day 30 will be collected and reported, using 30-day 
median infarct size (% left ventricle (LV) necrosis) as the primary effectiveness outcome 

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measure.  30-day cardiac MRI infarct size is often used for final infarct size measurement in 
clinical studies7,8
As an additional effectiveness analysis, the final infarct size at 30 days from the present 
study will be compared to the final infarct size from the SSO2 Therapy group of the 
AMIHOT II study.  The AMIHOT II study utilized 14-day Tc-99m sestamibi SPECT 
imaging for final infarct size measurement, which was the gold standard at that time.  
SPECT has been replaced in favor of cardiac MRI due to several reasons, including the 
greater ease of use and convenient collection of myocardial functional and structural data 
from the scans.  Both techniques measure final infarct size and are validated against 
histological measurements
.  Final infarct size at days 4 and 30 will be analyzed and compared to the a 
matched set of patients from the INFUSE-AMI trial, a study of very similar entry criteria 
(STEMI with proximal or mid LAD treatment) in which infarct size was assessed by cardiac 
MRI at the same core laboratory at the same time frame (both 4 and 30 days).  Matching 
(1:1) will be performed on the following parameters which are known affect infarct size: 
Time from symptom onset to first device; baseline and post PCI TIMI flow (core 
laboratory); proximal vs. only mid LAD treatment; and angiographic collateral flow (if 
possible).  In addition, since intracoronary abciximab was associated with reduced infarct 
size in INFUSE-AMI, these patients will be excluded from the match if possible. Attempts 
will be made to match all 100 SSO2 patients.  However, as the 4-day MRI was pre-specified 
in INFUSE-AMI in only half the patients, this may not be possible for the early time point.  
In this case a 2:1 match will be performed. 
9,10,11
The effectiveness comparisons are not powered, and while statistical comparisons will be 
reported (as described below); they are for descriptive purposes only. 
.   
Study Population for Analysis 
                                                 
7 Stone GW, Maehara A, Witzenbichler B, et al.  Intracoronary abciximab and aspiration thrombectomy in patients with large anterior 
myocardial infarction: the INFUSE-AMI randomized trial.  JAMA 2012 May 2;307(17):1817-26. 
8 Carlsson M, Arheden H, Higgins CB, et al.  Magnetic resoncance imaging as a potential gold standard for infarct quantification.  J 
Electrocardiol 2008;41(6):614-20. 
9 Medrano R, Lowry RW, Young JB, et al.  Assessment of myocardial viability with 99mTc sestamibi in patients undergoing cardiac 
transplantation.  A scintigraphic/pathological study.  Circulation 1996;94:1010-17. 
10 Kristensen J, Mortensen UM, Nielsen SS, et al.  Myocardial perfusion imaging with TC-99m sestamibi early after reperfusion reliably 
reflects infarct size reduction by ischaemic preconditioning in an experimental porcine model.  Nucl Med Com 2004;25:495-500. 
11 Hsu LY, Natanzon A, Kellman P, et al.  Quantitative myocardial infarction on delayed enhancement MRI.  Part I: Animal validation of 
an automated feature analysis and combined thresholding infarct sizing algorithm.  J Magn Reson Imaging 2006;23(3):298-308. 

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Patients who meet the study’s selection criteria and provide informed consent will be 
consecutively enrolled into this multi-center clinical trial.  An all treated subjects population 
will be used as the primary analysis population for safety data.  The all treated subjects 
population is defined as all patients enrolled into the trial.  Study enrollment occurs when 
the study device is introduced into the patient (i.e., the SSO2 delivery catheter).  The all 
treated subjects analyses will include patients who die, are lost to follow up, and patients 
with protocol deviations.  All available data, regardless of whether data are derived within 
specified time windows, will be included in the analysis.  For the all treated subjects 
analysis, patients who do not complete the entire course of treatment with SSO2 Therapy 
will be included. 
9.3 
Medical Economics Data Analysis 
UB-04 claim forms will be requested from the hospital billing department at least 30 days 
after patient discharge.  At the study’s conclusion, UB-04 data will be reported in the 
aggregate form; that is, no individual patient’s results will be disclosed when reporting the 
economic study findings.   
10 
STUDY ADMINISTRATION 
10.1 
Roles of Sponsor and CRO 
As the study sponsor, TherOx, Inc. has the overall responsibility for the conduct of the 
study, including assurance that the study meets the regulatory requirements of the Food and 
Drug Administration, Good Clinical Practice Guidelines, and TherOx standard operating 
procedures.   
In this study, TherOx, Inc. will have certain direct responsibilities and will delegate other 
responsibilities to appropriate consultants and the CRO.  TherOx, Inc., through its CRO and 
the study’s clinical monitors, will adhere to the necessary regulatory requirements for this 
investigational study. 
10.2 
Investigator Responsibilities 
The investigator is responsible for ensuring the clinical study is conducted in accordance 
with the signed Investigator Agreement.  Prior to study initiation, the investigator will 
forward the following essential documentation to TherOx, Inc. or their designee: 

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1. A signed and dated Investigator Agreement and Protocol Signature Page, 
2. A signed and dated Hospital Trial Agreement, 
3. Current medical license and Curriculum Vitae (CV) signed and dated within the 12 
months prior to initiation for each investigator participating in the study, 
4. A completed Financial Disclosure form for each investigator participating in the 
study per the requirements of 21 CFR part 54, 
5. Laboratory certification or proficiency ratings and normal ranges for the 
determinations described by the protocol, 
6. A copy of the laboratory director’s license and CV signed and dated within the last 
12 months prior to study initiation, 
7. A copy of the formal written notification of approval of the protocol and consent 
form, to the investigator from the IRB, 
8. A list of institutional review board/ethics committee members and their respective 
title, occupation, and institutional affiliations, or provide a general assurances 
number for the IRB, 
9. A copy of the IRB approved Informed Consent form, 
10. Disclosure of any potentially conflicting ongoing investigational study the 
investigator may be participating in,  
11. If applicable, an explanation of the circumstances that led to the termination of any 
prior study involvement. 
10.3 
Direct Access to Source Data / Documents 
The investigator, institution or designee will permit direct access to source data/documents 
in order for study-related monitoring, audits, IRB review, and regulatory inspections to be 
performed. 
Consenting patients are agreeing to allow TherOx, Inc. or designee access and copying 
rights to pertinent information in their medical records relevant to study participation.  As 
part of the informed consent, the investigator or designee will obtain permission for 
regulatory authorities to review any records identifying subjects in this study.  TherOx, Inc. 
will not otherwise release any personal information. 
10.4 
Institutional Review Board (IRB)  
The primary investigator at each site must submit the study protocol to the IRB and obtain 
the Committee’s written approval before participating in this study.  The investigator is also 

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responsible for fulfilling any conditions or approval imposed by the IRB, such as regular 
reporting, study timing, etc.  The primary investigator will provide TherOx, Inc. with copies 
of these approvals and reports. 
10.5 
Consent Material 
Part of the IRB approval must include approval of Informed Consent documents specific to 
the study.  The investigator or other qualified personnel must administer this approved 
Informed Consent document to each prospective study patient, and obtain the patients 
signature on the document, prior to enrollment in the study.  The study center, to meet 
specific site requirements, may modify the example Informed Consent; however, the 
Informed Consent must contain all of the elements of Informed Consent as outlined in CFR 
21 Part 50.25.  The primary investigator will provide the sponsor with a copy of the 
approved Informed Consent from his/her site. 
10.6 
Sponsor Responsibilities 
No study site may receive shipment of all of the DownStream System components until 
TherOx or their designee receives the following documents: 
• 
Signed Protocol Acceptance page 
• 
Written IRB approval for conduct of the study 
• 
Signed Investigators Agreement(s) 
• 
Investigators’, Co-Investigators’ and Laboratory Directors current curriculum vitae 
(CV) and current license 
• 
License (if applicable) and CV for study coordinators 
• 
List of IRB members and IRB  contact information 
• 
Copy of all Laboratory Normal Values 
• 
Financial disclosures for all participating physicians 
• 
Confirmation by MRI Core Laboratory of site validation for this measure 
 
10.6.1 
Study Specific Duties 
TherOx is the manufacturer of the DownStream System and the Sponsor of this study.  
TherOx has the overall responsibility for the study and will: 

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• 
Select qualified Principal Investigators, clinical investigators and study sites, as well 
as consultants (e.g., CRO), who will participate in the study. 
• 
Communicate all regulatory standards per federal regulations for clinical study sites, 
core laboratories, and other participants, and perform regular site monitoring to 
assure compliance with them. 
• 
Provide appropriate clinical training to investigators and study staff prior to site 
enrollment, and follow-up training as necessary. 
• 
Ensure proper device usage, uniform data collection and protocol compliance, the 
Sponsor or their designee will present a formal training session to study site 
personnel which will review the instructions for use of the device, the 
Investigational Plan, techniques for identification of eligible patients, instructions 
on in-hospital data collection, methods for soliciting data from alternative sources, 
schedules for follow-up with the study coordinators and regulatory requirements.  
Detailed telephone and/or fax or email feedback regarding completion of forms will 
be provided by the Sponsor or designee, and through regular site monitoring. 
• 
Provide DownStream System and appropriate components to participating study 
sites, in quantities sufficient to support study activities, per agreement executed with 
the study sites. 
• 
Coordinate and host conference calls between the contract research organization 
(“CRO”), the Core Laboratories or any clinical site, as necessary to resolve any 
problems concerning the protocol and/or data collection.  Every effort will be made 
to assure compliance with the protocol. 
• 
Provide financial support to each study site, the CRO, and the Core Laboratories per 
individual contracts. 
• 
Perform or contract for site monitoring of clinical data at clinical study sites, Core 
Laboratories, and the CRO. 
• 
Retain ownership of all clinical data generated in this study.  TherOx will exercise 
no veto over publication of study results in the medical literature, but will retain the 
right to review any such submission, presentation, or publication for confidential 
information. 
 

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10.7 
Regulatory Responsibilities 
10.7.1 
Maintaining Records 
TherOx and/or its designee will maintain correspondence, data, adverse device events, and 
other records related to the clinical trial.  TherOx will maintain records related to the 
shipment of devices and complaints.  TherOx and/or its designee will maintain 
communication/correspondence files for each participating clinical site. 
10.7.2 
Submitting Reports 
TherOx will submit required FDA reports for this investigational study. 
10.7.3 
Device Accountability 
TherOx is responsible for ensuring that the investigational site maintains accurate, up to date 
inventory logs for all study devices supplied by TherOx, Inc.  This includes the following: 
subject number, date study device used, quantity and date received, quantity used, quantity 
returned, and quantity disposed.  All study devices received, used, and returned by the 
investigator will be inventoried and accounted for by TherOx throughout the study.  All 
study devices must be stored in a restricted area with limited access. 
10.7.4 
Site Initiation 
A pre-investigational meeting will be conducted with each potential study site in order to 
orient the prospective investigator and staff to the investigational devices, protocol, 
applicable regulations and requirements, and expectations of the study, including the 
numbers and time frame for patient enrollment, patient selection, Informed Consent, 
required clinical data and record keeping.  The prospective study site will be evaluated to 
ensure that it has an adequate patient population and support staff.  A regulatory binder will 
be left with the site at the completion of site initiation. 
Site initiation monitoring activities will include but not be limited to review of requirements 
for the following: protocol and data forms, ethics committee approvals, obtaining and 
documenting informed consent, device accountability and storage, medical records, adverse 
event reporting procedures, discussion of frequency of monitoring visits, reports and 
document retention and applicable FDA regulations governing investigational studies (21 
CFR Parts 50, 54, 56, 812). 

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10.8 
Monitor Responsibilities 
TherOx personnel or its designees will perform study monitoring.  The monitoring process 
begins with the site initiation activities and continues, in general, until the study close-out 
visit.  While study monitoring normally involves a personal visit to the investigational site, 
some monitoring activities can be carried out by mail, email, or telephone.  Each site will be 
visited regularly to ensure that the study is conducted in full compliance with all applicable 
regulations and study protocol.   
10.8.1 
Obligations / Qualifications of Study Monitors   
Qualified study monitors will oversee the progress of the clinical investigation in 
accordance with 21 CFR Part 52.29.  Monitoring procedures and monitor qualifications (i.e., 
curriculum vitae, training) will be retained by the CRO.  A monitoring log will be 
maintained at each investigational site to document the monitor’s presence and be signed 
and dated by both the monitor as well as a designated investigational site representative. 
10.8.2 
Periodic Monitoring Visit Activities 
TherOx or their designee is responsible for assuring throughout the clinical investigation 
through periodic monitoring visits and personal contact that the investigator’s obligations, as 
set forth in applicable regulations, are being fulfilled and that the facilities used in the 
clinical investigation continue to be acceptable. 
Periodic monitoring visit activities will include but not be limited to the following: patient 
documentation, data form monitoring including comparison and compatibility with 
individual subject records for accuracy and completeness, protocol and informed consent 
compliance and monitoring, investigational device accountability, adverse event reporting 
and documentation, and site file maintenance check. 
10.8.3 
Study Close-Out Activities 
When the study has been completed or terminated, the Monitor should assure that all site 
closeout activities have been addressed.  These activities are documented in more detail in 
the clinical procedure for study close out. 

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10.8.4 
Documentation of Monitoring Visits and Communications 
The monitor will complete a written report for each site visit documenting the visit date, site 
personnel meeting, activities undertaken and a record of the findings, conclusions, and 
actions undertaken or recommended to correct deficiencies.  Accordingly, monitoring 
activities and communications undertaken via email, telephone, electronic mail, and/or 
meetings should be documented in writing as well.  All reports shall be maintained in the 
study files of the sponsor. 
10.9 
Contract Research Organization Responsibilities   
The CRO for the IC-HOT clinical study is the Experien Group.  The CRO will perform the 
below noted activities: 
1. Site Initiation (jointly with TherOx) 
2. Clinical Monitoring 
3. Data base development  
4. Data review 
5. Data query and data clarification resolution 
6. Adverse Event coding  
7. CEC coordination 
8. Database verification and validation 
9. Database back-up, storage and transfer 
10. Data analyses (performed in conjunction with the Cardiovascular Research 
Foundation) 
11. Entry of UB-04 claims data into the database, including verification, validation, 
back-up, storage, and transfer. 
 
10.10 
Records and Reports 
10.10.1 
Required Data 
All required clinical data for this study will be collected on standardized Case Report Forms 
(CRFs).  A set of draft CRFs can be found in Appendix A.  Source and other administrative 
records will be maintained for a minimum of two (2) years after the latter of either the 
completion of the investigational trial or the date the device receives FDA approval for the 
U.S. market release.   

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Investigational site records may not be discarded until the center receives notification by 
TherOx, Inc.  In addition, TherOx, Inc. should be contacted if the investigator plans to leave 
the investigational site so that arrangements can be made for the transfer of records. 
10.10.2 
Data Submission 
All data MUST be sent to the CRO, Experien Group, according to the following schedule: 
Table 3.  Data Submission Schedule 
 
 
 
 
Note: All Serious Adverse Events and Unanticipated Adverse Events must be reported to 
the CRO within 24 hours. 
All clinical sites will be audited periodically by sponsor personnel or a designee for protocol 
adherence, accuracy of CRF completion and compliance to applicable regulations.   
10.10.3 
Investigator Reports  
The investigator for each study center is responsible for the generation of the following 
reports according to the schedule of Table 4. 
Form 
Submission Time 
Notification Form 
Within 24 Hours of Procedure 
Serious Adverse Event or Unanticipated Adverse Event CRFs 
Within 24  Hours of Knowledge 
Repeat Revascularization  or Protocol Deviation CRFs 
Within 14 Days 
All other CRFs  
Within 14 Days 

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Table 4.  Reports Required from Clinical Investigators 
Type of Report 
Prepared by Investigator For: 
Time Constraints of Notification 
Patient death during 
investigation 
TherOx/CRO, IRB 
Verbal within 24-hours followed by written 
report within 48-hours. 
Unanticipated adverse 
event 
TherOx/CRO, IRB 
If serious or life threatening, within 24-hrs by 
facsimile, email or phone, followed by written 
copy and documentation of event within 5 
working days. 
Report of patient 
enrollment 
TherOx/CRO 
ASAP 
Patient withdrawal 
TherOx/CRO 
Facsimile within 5 working days of 
withdrawal   
Withdrawal of IRB 
approval 
TherOx/CRO 
Immediately by telephone followed by a copy 
of the notification within 5 working days. 
Annual progress report 
TherOx 
Submitted annually. 
Investigational Plan 
Deviations 
TherOx/CRO 
Within 5 working days 
Informed Consent not 
obtained 
TherOx/CRO, IRB 
Within 5 working days 
Final summary report 
TherOx/CRO, IRB 
Within 5 working days 
 
10.11 
Investigational Site Termination 
TherOx reserves the right to terminate an Investigational Site for any of the following 
reasons: 
1. Failure to secure Informed Consent from a patient or legal guardian representative 
prior to enrolling the patient into this study. 
2. Repeated protocol violations. 
3. Repeated failure to complete case report forms on a timely basis. 
4. Repeated failure to collect and provide source documentation. 
5. Failure to report adverse events on a timely basis. 
6. Failure to maintain adequate records for product inventory. 
7. Failure to maintain expected enrollment rates over a period of two months. 

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10.12 
Study Committees 
10.12.1 
Executive Committee  
The Executive Committee will review and approve the final trial design and protocol issued 
to the clinical sites.  This committee is responsible for reviewing the final trial results and 
determining the methods of presentation and publication.  The Executive Committee will 
also have discretion for stopping or otherwise modifying the trial based on 
recommendations from the IPA. 
The Executive Committee for the IC-HOT clinical study includes:  
Gregg W. Stone, MD  
Professor of Medicine, Columbia University, Principal 
 
 
 
 
Investigator and Study Chair 
Simon R Dixon, MD 
Chair of Cardiovascular Medicine, Oakland 
University, William Beaumont School of Medicine 
D. Chris Metzger, MD 
Director of Cardiac and Peripheral Labs, Wellmont 
CVA Heart Institute 
Kevin T. Larkin 
 
President and CEO, TherOx, Inc. 
Jeffrey L. Creech, PhD 
Director, Regulatory and Research Programs, TherOx, 
 
 
 
 
Inc.