Wave Crossover ECP Study for Simplified Therapy
Phase: NA
Conditions: Chronic Stable Angina, Refractory Angina
Sponsor: Pression

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WaveCRESST 
Wave Crossover ECP Study for Simplified Therapy 
 
Unique Protocol Identification 
Number: 
RA-C01 
National Clinical Trial (NCT) Identified 
Number: 
NCT06571370 
Sponsor: 
Pression, LLC 
190 W. Lincoln Hwy 
Coatesville, PA 19320 
Funded By: 
Sponsor 
Version Number: 
2.0 
Version Date: 
22-Nov-2024 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confidentiality Statement 
This document is the sole property of Pression, LLC. This document and all information 
contained herein must be considered and treated as strictly CONFIDENTIAL. This document 
shall be used only for the purpose of the disclosure herein provided. No disclosure or 
publication shall be made without the prior written consent of Pression, LLC. 
 
 

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Table of Contents 
Sponsor Approval Page ............................................................................................................................................. 4 
Investigator Statment of Compliance ....................................................................................................................... 5 
1 Protocol Summary ................................................................................................................................................... 6 
1.1 Synopsis (Brief) ................................................................................................................................................ 6 
1.2 Schedule of Activities (SoA) ......................................................................................................................... 11 
2 Introduction ............................................................................................................................................................. 12 
2.1 Study Rationale .............................................................................................................................................. 12 
2.2 Background ..................................................................................................................................................... 12 
2.3 Risk/Benefit Assessment .............................................................................................................................. 13 
2.3.1 Known Potential Risks ............................................................................................................................ 13 
2.3.2 Known Potential Benefits ....................................................................................................................... 14 
2.3.3 Assessment of Potential Risks and Benefits....................................................................................... 14 
3 Objectives and Endpoints ..................................................................................................................................... 17 
4 Study Design .......................................................................................................................................................... 19 
4.1 Overall Design ................................................................................................................................................ 19 
4.2 Justification of Study Design......................................................................................................................... 22 
4.3 End of Study Definition .................................................................................................................................. 23 
5 Study Population .................................................................................................................................................... 24 
5.1 Inclusion Criteria ............................................................................................................................................. 24 
5.2 Exclusion Criteria............................................................................................................................................ 24 
5.3 Recruitment Strategies and Considerations ............................................................................................... 25 
5.4 Screen Failures ............................................................................................................................................... 26 
6 Study Description................................................................................................................................................... 27 
6.1 STUDY ECP DEVICE Administration – Wave PRO System ................................................................... 27 
6.1.1 WAVE PRO ECP DEVICE Description ................................................................................................ 27 
6.1.2 Wave PRO Device Test Session .......................................................................................................... 27 
6.2 Predicate ECP DEVICE Administration – Applied Cardiac systems (ACS) NCP-2 External Counter-
pulsation (ECP) system........................................................................................................................................ 29 
6.2.1 ACS ncp-2 ECP Device Description .................................................................................................... 29 
6.2.2 ACS NCP-2 (Predicate) Device Test Session .................................................................................... 29 
6.3 DATA ACQUISITION Wave PRO ................................................................................................................ 31 
6.3.1 BIOPAC MP35 Data Acquisition system description ......................................................................... 31 
6.3.2 Preparation and utilization ..................................................................................................................... 31 
6.3.3 SIGNAL PROCESSING ......................................................................................................................... 32 
6.4 DATA ACQUISITION acs NCP-2 ................................................................................................................. 32 
6.4.1 ACS Data Acquisition system description ........................................................................................... 32 
6.4.2 Preparation and utilization ..................................................................................................................... 33 
6.4.3 Signal Processing ................................................................................................................................... 33 
6.5 Preparation/Handling/Storage/Accountability ............................................................................................ 34 
6.5.1 Acquisition and accountability ............................................................................................................... 34 
6.5.2 Appearance, Packaging, and Labeling ................................................................................................ 34 
6.5.3 Product Storage ...................................................................................................................................... 35 
6.6 Measures to Minimize Bias: Randomization and Blinding ....................................................................... 35 

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6.7 Study Intervention Compliance .................................................................................................................... 36 
6.8 Concomitant Therapy .................................................................................................................................... 36 
7 Study Procedure Discontinuation and Participant Discontinuation/Withdrawal ........................................... 37 
7.1 Discontinuation of Study Procedures and/or Assessments ..................................................................... 37 
7.2 Participant Discontinuation/Withdrawal from the Study ............................................................................ 37 
7.3 Lost to Follow-Up............................................................................................................................................ 37 
8 Study Assessments and Procedures .................................................................................................................. 38 
8.1 General and Administrative Procedures ..................................................................................................... 38 
8.2 Effectiveness Assessments .......................................................................................................................... 38 
8.3 Safety and Other Assessments .................................................................................................................... 38 
8.4 Adverse Events and Serious Adverse Events ........................................................................................... 38 
8.4.1 Definition of Adverse Event (AE) .......................................................................................................... 38 
8.4.2 Definition of Serious Adverse Event (SAE) ......................................................................................... 39 
8.4.3 Classification of an Adverse Event ....................................................................................................... 39 
8.4.4 Adverse Event Reporting ....................................................................................................................... 41 
8.4.5 Serious Adverse Event Reporting ........................................................................................................ 41 
9 Statistical Methods ................................................................................................................................................ 42 
9.1 General considerations .................................................................................................................................. 42 
9.2 Populations for Analysis ................................................................................................................................ 42 
9.3 endpoints and Statistical Analyses .............................................................................................................. 42 
9.3.1 Primary Effectiveness endpoint ............................................................................................................ 42 
9.3.2 safety endpoints ...................................................................................................................................... 44 
9.3.3 secondary EFFECTIVENESS endpoints ............................................................................................. 45 
9.3.4 poolability ................................................................................................................................................. 46 
9.3.5 Sub-Group Analyses .............................................................................................................................. 46 
9.3.6 Exploratory Analyses .............................................................................................................................. 47 
10 Supporting Documentation and Operational Considerations ........................................................................ 48 
10.1 Regulatory, Ethical, and Study Oversight Considerations ..................................................................... 48 
10.1.1 Informed Consent Process .................................................................................................................. 48 
10.1.2 Study Discontinuation and Closure .................................................................................................... 49 
10.1.3 Confidentiality and Privacy .................................................................................................................. 49 
10.1.4 Safety Oversight.................................................................................................................................... 50 
10.1.5 Clinical Monitoring ................................................................................................................................ 50 
10.1.6 Quality Assurance and Quality Control .............................................................................................. 51 
10.1.7 Data Handling and Record Keeping .................................................................................................. 51 
10.1.8 Protocol Deviations ............................................................................................................................... 53 
10.1.9 Publication and Data Sharing Policy .................................................................................................. 53 
10.1.10 Conflict of Interest Policy ................................................................................................................... 54 
10.2 NON-SIGNIFICANT RISK (NSR) STUDY ................................................................................................ 54 
10.3 Abbreviations ................................................................................................................................................ 55 
10.4 Protocol Amendment History ...................................................................................................................... 56 
11 References ........................................................................................................................................................... 57 
 

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SPONSOR APPROVAL PAGE 
 
Version 
Summary of Revision Change and Rationale 
Sponsor Authorized Signature 
 1 
N/A – Initial Version 
  
 
 
 
[Signature on File] 
 
Adam Salamon, CEO 
2 
Inclusion and Exclusion Criteria: 
• 
Subjects that are unable to lie on their backs 
for long periods of time may experience 
discomfort. (Inclusion added) 
• 
The goal of this study is to enroll subjects 
with mild to moderate disease; therefore the 
age minimum has been reduced to 35, as 
long as they do meet all other eligibility 
requirements. (Inclusion expanded) 
• 
In Version 1, many subjects on anticoagulant 
use were excluded. Newer novel oral 
anticoagulants target different proteins as 
opposed to warfarin, and act for a shorter 
period of time reducing the risk of bleeds. 
Therefore, the exclusion was clarified to only 
exclude those on warfarin, or those with a 
PT-INR >2.5 or those who have and need 
routine INR or PTT testing. (Exclusion 
clarification) 
Analysis Methods: 
• 
The analysis methods for the predicate and 
investigational devices have been adjusted 
to employ the same steps to process and 
analyze the respective collected PPG data 
• 
In Version 1, human-in-the-loop analysis 
was employed for the predicate device which 
required subjective placement of points. 
Incorporation of the same analysis steps as 
the investigational device removes any 
potential human bias in the analysis and 
instead employs a consistent, fixed 
algorithmic analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adam Salamon, CEO 

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INVESTIGATOR STATMENT OF COMPLIANCE 
The trial will be carried out in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH E6(R2)), United States (US) Code of Federal Regulations (CFR) 
applicable to medical device clinical studies (21 CFR Part 50, 21 CFR Part 56, the abbreviated 
IDE requirements of 21 CFR Part 812), and ISO 14155:2020, Clinical investigation of medical 
devices for human subjects – Good clinical practice. 
I agree, as an Investigator conducting this study, to the following: 
• 
The protocol, informed consent form(s), recruitment materials, and all participant 
materials will be submitted to the Institutional Review Board (IRB) for review and 
approval.  Approval of both the protocol and the consent form must be obtained before 
any participant is enrolled.  Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study.  In addition, all 
changes to the consent form will be IRB-approved; a determination will be made 
regarding whether a new consent needs to be obtained from participants who provided 
consent, using a previously approved consent form. 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
Not to implement any deviations from or changes to this protocol without agreement 
from the Sponsor, except where necessary to eliminate an immediate hazard to the 
participants or for administrative aspects of the study (where permitted by all applicable 
regulatory requirements). 
• 
That I am aware of, and will comply with, Good Clinical Practice and all applicable 
regulatory requirements. 
• 
To ensure that all persons assisting me with the study are adequately informed about 
the investigational device and that they are qualified to perform their study-related duties 
and functions, as described in this protocol. 
• 
That I have been informed that certain regulatory authorities require the Sponsor to 
obtain and supply details about the Qualified Investigator’s ownership interest in the 
Sponsor or the study device and more generally about his/her financial ties with the 
Sponsor. The Sponsor will obtain and disclose any relevant information in this regard 
solely for the purpose of complying with regulatory requirements. Hence,  
o 
I Agree to supply the Sponsor with all information regarding ownership interest 
and financial ties with the Sponsor (including those of my spouse and dependent 
children); 
o 
Agree to promptly update this information if any relevant changes occur during 
the study and for 1 year following completion of the study; and 
o 
Agree that the Sponsor may disclose this information about such ownership 
interests and financial ties to regulatory authorities. 
Printed Name of Investigator: 
 
Site Name/Number: 
 
Site Address: 
 
 
Signature: 
 

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1 PROTOCOL SUMMARY 
1.1 SYNOPSIS (BRIEF) 
Title: 
Wave Crossover ECP Study for Simplified Therapy  
Short Title: 
WaveCRESST  
Sponsor: 
Pression, LLC 
Investigational Device 
Type: 
External Counter-Pulsation (ECP) 
Investigational Device 
Name: 
Pression Wave PRO External Counter-pulsation System 
Control Predicate Device: Applied Cardiac Systems (ACS) NCP-2 External Counter-Pulsation 
System 
 
Intended Use/Indication(s) 
for Use: 
The Pression Wave PRO External Counter-Pulsation System is indicated 
for the treatment of chronic stable angina (CSA) that is refractory to 
optimal anti-anginal medical therapy and without options for 
revascularization. In addition, it is intended for use in healthy patients to 
provide improvement in vasodilation, increased VO2, and increased blood 
flow.  
 
It is intended for use under the oversight of a healthcare professional.  
Device Description 
(Brief): 
The Pression Wave PRO External Counter-Pulsation System applies 
compression to the calves, timed to ventricular diastole, with the aim of 
increasing blood flow towards the coronary arteries when the heart is 
relaxed, thereby increasing cardiac perfusion.  
Clinical Background 
(Brief): 
• 
Ten human volunteer studies were conducted with the predecessor 
technology to the Wave PRO System that support the safety and 
effectiveness of the Wave device. A combined total of 150 healthy 
volunteers ranging from 18-85 years of age were studied. In all 
previous studies, the primary effectiveness endpoints were related to 
increasing athletic performance.   
• 
There were no reported adverse events in any of the studies.  
• 
Furthermore, the studies identified that patients found the 
pressure applied to the calves of up to 100 mmHg comfortable. 
Recent research on the Wave PRO System found that individuals 
easily tolerated pressure up to 300 mmHg. 
 
• 
The most recent volunteer pilot study for the Wave PRO System itself 
involved seven age-appropriate participants in a head-to-head 
comparison with the ACS NCP-2 (predicate ECP device). The Wave 
PRO device produced the intended hemodynamic effects with no 
adverse events. 
Purpose of Study: 
The purpose of this study is to demonstrate substantial equivalence 
between Pression’s Wave PRO System and a commercially available 
predicate ECP device to support a U.S. 510(k) Premarket Notification for 
the Wave PRO System.  

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Study Objectives: 
The study objective is to demonstrate substantial equivalence (non-
inferiority) of the hemodynamic effect between the Wave PRO System and 
the predicate ECP device (ACS NCP-2) as measured by the diastolic 
augmentation (DA) ratio and systolic unloading. 
Study Design: 
Participants will receive compressions from both ECP systems, one 
system at a time, in random order. Diastolic augmentation ratio will be 
evaluated for each participant on each test ECP system. 
 
Participants will be aged 35+, with a history of mild to moderate coronary 
artery disease, serve as their own control, and meet the Inclusion Criteria 
and none of the Exclusion Criteria. 
 
Total participant time is approximately 2.5 – 3 hours. 
 
Data to be collected includes pulse photoplethysmography (PPG) and vital 
sign information. Demographic data and a device-related questionnaire will 
be collected. 
 
Data Analysis will include calculating the average DA ratio for each ECP 
system from the pulse waveforms collected, for each participant. Systolic 
unloading level will be recorded for Wave PRO.  
Number of Participants: 
The required sample size is 44 participants with paired DA ratio data. 
Allowing up to 12% attrition, approximately 50 participants will be 
randomized to the ECP device order. 
Number and Location of 
Investigational Sites: 
One study site in the United States. 
Expected Study Duration: Recruitment: 6 Weeks 
Participant Follow-up: Phone call 1 day after the ECP session 
Total Study Duration: 10 Weeks 
Randomization: 
The order in which the participant will receive the two ECP sessions will be 
randomized. 
Safety Endpoint 1: 
Occurrence of device-related Serious Adverse Events (SAEs). 
Safety Endpoint 2: 
Rate of device-related Adverse Events (AEs). 
Follow up questionnaire to address bruising, abrasion, soreness. 
Primary Performance 
and/or Effectiveness 
Endpoint: 
The average DA ratio for each ECP session, calculated from the eighth 
minute of compressions for each participant.   
Secondary Performance 
and/or Effectiveness 
Endpoint(s): 
• 
The level of systolic unloading for the Wave PRO based on the systolic 
peaks during compressions compared to baseline of the PPG data, 
captured using the independent data acquisition system.  
• 
Number of participants that complete 10 mins of each of the ECP 
devices (Wave PRO and predicate ECP device) 
• 
Participant comfort level with the Wave PRO and predicate ECP 
device, assessed at the conclusion of each ECP session 

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• 
Time to set up a participant (i.e., sleeved up and sensors attached) 
and ready to start treatment 
• 
Participant preference for one of the two ECP systems (assuming 35 
hours for a full course of ECP) 
Key Inclusion Criteria: 
o 
Age 35 years or greater 
o 
History of mild to moderate coronary artery disease (CAD) 
o 
Able to ambulate without assistance 
o 
Able to lay down (approximately 5 degree angle) for the duration of the 
protocol required procedures 
o 
Able and willing to give informed consent 
o 
Able and willing to participate in the clinical study and complete all 
questionnaires provided 
Key Exclusion Criteria: 
o 
Unstable angina within prior 3 months 
o 
Canadian Cardiovascular Society (CCS) Class III or IV Angina 
o 
Moderate to severe peripheral arterial disease (PAD) 
o 
Myocardial infarction in the past 3 months 
o 
Coronary artery bypass grafting (CABG) in the past 3 months 
o 
Any major surgery within the past 3 months 
o 
Decompensated heart failure  
o 
Cardiac catheterization or arterial femoral puncture in the past 2 weeks 
o 
Presence of mechanical circulatory support (MCS) device 
o 
Pacemaker or other implantable pulse generating device 
o 
Valve disease, including aortic insufficiency 
o 
Abdominal or thoracic aortic dissection or aortic/cerebral aneurysms 
requiring clinical intervention 
o 
Severe pulmonary disease 
o 
Bleeding diathesis 
o 
Patients undergoing warfarin anti-coagulation therapy, or with PT-INR > 2.5, or 
who have routine INR or prothrombin time tests 
o 
Active thrombophlebitis 
o 
Uncontrolled hypertension (greater than 180/110 mmHg) 
o 
Baseline heart rate >120 BPM or <40 BPM 
o 
Arrhythmia and/or abnormal heart rhythm 
o 
Major hand injuries or amputation that would interfere with finger PPG 
o 
Unhealed wounds/fractures below the waist or lower limb amputation, 
major lower body musculoskeletal injuries 
o 
Lower body vascular stents (arterial/venous)  
o 
Currently undergoing ECP treatment 
o 
Pregnancy 
o 
Currently participating in any other clinical study of an investigational 
device or drug where treatment has not yet been completed 
o 
Any medical condition that, in the opinion of the principal investigator 
(PI), would present undue risk to the participant 

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Key Data to be Collected: Baseline Data: 
• 
Demographics: age, sex, race, ethnicity 
• 
Relevant medical history and vital statistics 
Hemodynamic Measurements During ECP: 
• 
PPG: Flow and heart rate 
• 
EKG (aka. ECG): Heart rhythm  
Follow-up and Safety: 
• 
Participant Survey 
• 
Safety/AE Assessment 
Statistical Analysis: 
Assuming a true difference in DA Ratio of 0 with standard deviation of 0.30 
for Wave PRO – predicate ECP, a sample size of 44 participants is 
adequately powered with at least 90% power with a 1-sided alpha of 0.025 
to test non-inferiority of Wave PRO vs predicate with a margin of –0.15. 
Factoring in 12% attrition, approximately 50 participants will be 
randomized. 
 
Primary effectiveness: An analysis of variance (ANOVA) model for 
crossover design will be performed and the pairwise difference between 
two treatments DA ratios (Wave PRO – predicate ECP) in the treatment 
least square mean and its 95% CI will be constructed.  If the lower bound 
of this 95% confidence interval is greater than -0.15, then the null 
hypothesis will be rejected, concluding that Wave PRO is not inferior to the 
predicate ECP. A p-value will be constructed using the LS means 
parameter estimates and standard error to test the hypothesis. 
 
Descriptive statistics will be used to summarize all other secondary 
endpoints. 
 
 
 

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1.2 SCHEDULE OF ACTIVITIES (SOA) 
Study Assessment/Procedure 
Time Frame, Days (Window) 
Pre-Screen 
(-14 to 0) 
Baseline 
Procedure 
(0) 
Follow-Up 
(+1 to +3) 
Phone Screen/Eligibility Determination1 
X 
X 
 
Participant Orientation Material 
X 
X 
 
Informed Consent 
 
X 
 
Eligibility Review 
 
X 
 
Data Collection (Medical History, Medications, 
Etc.) 
X 
X 
 
Presenting Vitals and Limited Physical Exam 
 
X 
 
Pression Wave PRO Procedure2 and associated 
Data Collection 
 
X 
 
ACS NCP-2 Procedure2 and associated Data 
Collection 
 
X 
 
Participant Questionnaire 
 
X 
X 
Safety Assessment 
 
X 
X 
Phone Call 
 
 
X 
Study Exit 
 
 
X 
1 Phone screen to assess potential eligibility may be performed with IRB approved phone script; Eligibility 
to be confirmed at the time of Baseline Procedure Visit. 
2 To be performed in random order. 
 
 
 

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2 INTRODUCTION 
2.1 STUDY RATIONALE 
The purpose of this study is to demonstrate substantial equivalence between Pression’s Wave 
PRO External Counter-pulsation (ECP) System and a commercially available predicate ECP 
device to support a U.S. 510(k) Premarket Notification for the Wave PRO System.  
 
Existing ECP systems are based on technology originating from the 1980s. As a result, current 
ECP systems are large, heavy, loud, and require constant input from a dedicated clinical 
operator. Pression’s Wave PRO system is significantly lighter, easily moved and incorporates 
automation features that support accurate treatment delivery in terms of pneumatic inflation and 
deflation, without the need for a dedicated operator. 
 
In accordance with prior FDA feedback, the study objective is to demonstrate substantial 
equivalence (non-inferiority) of the hemodynamic effect between the Wave PRO System and 
the predicate ECP device as measured by the diastolic augmentation (DA) ratio and secondary 
endpoints, including levels of systolic unloading. 
2.2 BACKGROUND 
External counter-pulsation (ECP) is a non-invasive circulatory enhancement treatment currently 
cleared for Chronic Stable Angina (CSA). Per FDA’s 2013 re-classification of ECP devices, ECP 
is classified as “Class II (special controls) when the device is intended for the treatment of 
chronic stable angina that is refractory to optimal antianginal medical therapy and without 
options for revascularization.” ECP enhances circulation by applying compressions to the lower 
limbs timed to the cardiac cycle.  
 
Current ECP systems are large, loud, expensive, are only accessible in clinics, and must be 
operated by dedicated staff. Compressions in commercially available ECP systems are applied 
to the entire leg and buttocks and are timed to the patient’s EKG. Treatment effectiveness is 
measured using a pulse photoplethysmography (PPG) finger sensor. A typical treatment course 
is a 1-hour session in a dedicated clinical facility five times per week for seven weeks (35 total 
sessions). 
 
The Wave PRO ECP system consists of calf-worn sleeves which contain five pneumatically-
inflated bladders that peristaltically compress the calf muscles distally to proximally towards the 
heart. This compression generates retrograde arterial flow back to the heart, thus augmenting 
coronary flow during ventricular diastole. Unlike existing systems, Pression’s technology uses 
PPG for both detection and to measure treatment effectiveness, enabling direct hemodynamic 
feedback of the treatment.  
 
Prior in-house testing data collected using the Wave PRO system demonstrated that Pression's 
underlying compression technology and algorithm worked in synchrony with the cardiac cycle to 

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enhance early-diastolic velocities, measured by ultrasonography at the abdominal aorta. This 
translates to improved perfusion of the coronary arteries during ventricular diastole. Prior 
studies related to athletic performance and recovery (combined total of 150 healthy participants) 
using the predecessor technology to the Wave PRO demonstrated that compressions increased 
retrograde arterial flow, mean arterial pressure and cardiac output, arterial blood flow to the 
heart and brain, and vascular conductance with no reported adverse events in any of the 
studies.  
 
In accordance with ECP literature and available instructions for use, this study will measure the 
Diastolic Augmentation (DA) ratio, also referred to as Diastolic/Systolic (D/S) ratio and 
Effectiveness Ratio (ER), which noninvasively characterizes the hemodynamic effect and thus 
the clinical effectiveness of ECP treatment. DA ratio is a unitless measure which is “calculated 
as the ratio of the peak diastolic amplitude divided by the peak systolic amplitude” 1. In a typical, 
non-augmented, cardiac cycle, the diastolic peak is seen as a small increase in the arterial 
waveform just after the aortic valve closes (dicrotic notch). With augmentation, the peak 
diastolic amplitude is distinctly elevated and may reach a significant proportion of the peak 
systolic amplitude or in some cases exceed it. “In general, [ECP] therapists attempt to obtain the 
maximum DA [ratio] obtainable by finger [PPG]” 2. 
2.3 RISK/BENEFIT ASSESSMENT 
2.3.1 KNOWN POTENTIAL RISKS 
Pression completed a hazard analysis/risk assessment through design failure modes and 
effects analysis (DFMEA), classifying risk based on severity of harm and anticipated occurrence 
with the Wave PRO ECP system, in accordance with ISO 14971. As Pression has mitigated 
almost all risks of the Wave PRO device, only the residual clinical risks are discussed here. 
 
The risk analysis identifies that the participant may experience minor abrasions, bruising and/or 
calf muscle soreness/tenderness from the pressure application during compression. Both 
abrasions and bruising can be minimized by using an interfacing layer, such as a tight-fitting 
knee-high sock or sleeve, between the participant’s skin and the compression sleeve of the 
Wave PRO. Calf muscle soreness/tenderness as a result of normal compressions during 
system operation is expected to resolve without medical intervention. 
 
Known side effects for existing ECP systems on the market, including the predicate ACS NCP-2 
device, include skin abrasion, bruising, muscle ache, blistering, and paresthesia (prickling 
sensation), all of which are also potential side effects of the Wave PRO ECP system. Side 
effects of ECP treatment are generally well tolerated and can be minimized with additional 
padding at the interface of the compression cuffs and the participant. Other side effects can be 
resolved with the application of topical creams. 
 
Rare side effects of ECP may include skin breakdown and increase in adverse cardiac events. 

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Any discomfort during an ECP session will be recorded for each participant, along with any 
adverse events during testing. 
 
2.3.2 KNOWN POTENTIAL BENEFITS 
  
Predicate ECP devices are indicated for the treatment of chronic stable angina (CSA) by 
creating diastolic augmentation during cardiac diastole. As noted in the literature, ECP 
treatment “create[s] a pressure wave that significantly increases peak diastolic pressure, 
benefiting circulation to the heart muscle and other organs, while also reducing systolic pressure 
and systemic vascular resistance to the general benefit of the vascular system” 3. “[ECP] has 
marked effects on the magnitude of diastolic retrograde and systolic antegrade blood flow in the 
descending aorta” 1. “[ECP] unequivocally and dramatically increases directly measured 
coronary flow velocity and pressure. This noninvasive counter pulsation technique generates a 
significant increase in diastolic pressure measured in the central aorta and the mid to distal 
coronary artery, representing diastolic augmentation” 4. “Coronary blood flow velocity measured 
by both angiographic and intracoronary Doppler techniques is significantly increased during 
[ECP], whereas left ventricular afterload is reduced because of systolic unloading, thereby 
lowering left ventricular work” 4,5. ECP treatments have been shown to reduce angina class by 
at least one Canadian Cardiovascular Society (CCS) score in 86% of patients, decrease 
nitroglycerin usage by over 80%, and increase exercise tolerance by 25% in patients with 
refractory angina, with benefits sustained for up to five years 6–8. 
 
With compression of the calf muscles timed to the cardiac cycle, the Wave PRO ECP device 
imparts similar physiological and therapeutic benefits compared to commercially available ECP 
systems with anticipated greater patient comfort. Additional benefits include an ergonomically 
improved and lighter form factor and automation features controlling inflation and deflation 
timing, obviating the need for a dedicated technician to operate the system for all 35 treatment 
hours. 
 
For the purposes of this study, participants are not expected to benefit from the two 10-min ECP 
sessions. However, data and knowledge acquired from this study are expected to positively 
impact future patients requiring ECP for anginal symptom relief. 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS 
 
The anticipated risks of the Wave PRO ECP system and this study protocol are minor and 
unlikely to cause serious harm to study participants. While study participants are not expected 
to gain any immediate health benefits, existing and future patients with CSA are expected to 
benefit from an ECP device that is more readily available and comfortable. 
 
The Wave PRO ECP system does not meet any of the criteria defined by the FDA for a 
Significant Risk device, therefore the Sponsor considers this study to be Non-Significant Risk. 

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The Investigational Device Exemption (IDE) regulation (21 CFR 812) describes three types of 
device studies: significant risk (SR), nonsignificant risk (NSR), and exempt studies.  An 
investigational device is considered NSR if it does not meet the definition for an SR device.   
 
21 CFR 812.3(m) defines a Significant Risk device as an investigational device that:  
1. Is intended as an implant and presents a potential for serious risk to the health, safety, 
or welfare of a subject; 
2. Is purported or represented to be for use supporting or sustaining human life and 
presents a potential for serious risk to the health, safety, or welfare of a subject; 
3. Is for a use of substantial importance in diagnosing, curing, mitigating, or treating 
disease, or otherwise preventing impairment of human health and presents a potential 
for serious risk to the health, safety, or welfare of a subject; or 
4. Otherwise presents a potential for serious risk to the health, safety, or welfare of a 
subject.  
 
Since the Wave PRO system does not meet any of the criteria defined by the FDA for an SR 
device, the Sponsors consider this study to be NSR. 
 
Risk controls have been implemented to minimize harm to the user and the recipient of the ECP 
treatment. Per Pression’s DFMEA and resulting Risk Management Report, residual risks 
associated with the Wave PRO and the controls implemented to reduce those risks are 
presented in the Risk Benefit Analysis below:  
 
Risk 
What are the Medical 
Benefits? 
Risk-Benefit Analysis 
(Why do the medical 
benefits outweigh the 
residual risk?) 
Is the Risk-
Benefit 
Analysis 
Acceptable? 
DFMEA 2.10.011 – 
2.10.015  
Electrical shock from 
the Control Unit 
resulting in death due 
to water intrusion, line 
cord abrasion or 
damage, poor dielectric 
protections, leakage 
current, and poor 
ground continuity 
The benefits of the Control Unit 
are that it powers the device 
and provides timed air pressure 
pulses to the sleeves to provide 
ECP therapy. Without the 
Control Unit, the sleeves and 
connecting tubing would not 
provide the air needed for 
efficient ECP therapy for the 
patient.  
Product safety testing 
was conducted to reduce 
electrical shock risks as 
far as possible, thereby 
reducing the rate of 
occurrence of these risks 
as far as possible. The 
expected clinical benefits 
outweigh the residual risk 
of electrical shock. 
 
 
Yes 
DFMEA 2.10.021 
The Control Unit emits 
electromagnetic 
interference (EMI) that 
causes other nearby 
devices from operating 
properly, resulting in 
death 
The benefits of the Control Unit 
are that it powers the device 
and provides timed air pressure 
pulses to the sleeves to provide 
ECP therapy. Without the 
Control Unit, the sleeves and 
connecting tubing would not 
provide the air needed for 
efficient ECP therapy for the 
Product safety testing 
was conducted to reduce 
EMI risks as far as 
possible, thereby 
reducing the rate of 
occurrence of these risks 
as far as possible. The 
expected clinical benefits 
outweigh the residual risk 
Yes 

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Risk 
What are the Medical 
Benefits? 
Risk-Benefit Analysis 
(Why do the medical 
benefits outweigh the 
residual risk?) 
Is the Risk-
Benefit 
Analysis 
Acceptable? 
patient.  
of EMI. 
 
Per Pression’s DFMEA and resulting Risk Management Report, the Benefit Risk Analysis is as 
follows: 
 
What are the Overall Medical 
Benefits? 
Risk-Benefit Analysis (Why do the overall 
medical benefits outweigh all risks?) 
Is the Overall 
Risk-Benefit 
Analysis 
Acceptable? 
The overall medical benefit of the 
Wave PRO device is to provide 
External Counter-Pulsation 
treatment to reduce angina 
symptoms in patients with chronic 
stable angina that is refractory to 
optimal anti-anginal medical 
therapy and without options for 
revascularization. 
Use of the Wave PRO ECP device carries risk 
from procedural error, inherent use hazards, and 
device failure. Pression LLC has taken measures 
to ensure the device is designed, manufactured, 
and tested appropriately to mitigate and control 
these risks through systematic risk analysis, in-
process controls and final inspection, labeling, 
instructions for use, and usability testing.  As a 
result, the residual risk is reduced as far as 
possible. 
 
In conclusion, the benefits outweigh the risks in 
the use of the Wave PRO device. 
 
Yes 
 

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3 OBJECTIVES AND ENDPOINTS 
OBJECTIVES ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
Primary  
 Performance/Effectiveness: DA Ratio 
of the Wave PRO system as 
compared to the predicate ECP 
device at the eighth minute of ECP 
compressions (out of 10 total 
compression minutes) 
DA ratio was chosen as the primary endpoint of 
this study because it is a direct and objective 
measure of the hemodynamic effect of ECP. DA 
ratio is a unitless measure which is “calculated 
as the ratio of the peak diastolic amplitude 
divided by the peak systolic amplitude” 1. ECP 
causes diastolic amplitude to increase relative to 
systolic amplitude. DA ratio noninvasively 
characterizes the hemodynamic effect of ECP 
and is correlated to clinical effectiveness of the 
treatment, as described in the literature cited in 
this protocol. DA ratio can be measured by use 
of a second independent PPG sensor for the 
Wave PRO and by the onboard PPG sensor on 
the predicate ECP device. Due to these 
characteristics, DA ratio is an appropriate 
endpoint for assessing substantial equivalence 
of Wave to the predicate device. 
Secondary 
 
Safety:  
o Occurrence of device-related 
Serious Adverse Events 
o Device-related Adverse Event 
rate 
Occurrence of device-related SAEs and AEs are 
appropriate endpoints for evaluation of safety 
because they are direct measures of the effect of 
the Wave PRO device on study participants. It is 
reasonable to consider only device-related 
AEs/SAEs and not all AEs/SAEs when evaluating 
the investigational device, as non-device-related 
AEs/SAEs will be irrelevant. 

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OBJECTIVES ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
Performance/Effectiveness:  
o 
The level of systolic unloading for 
the Wave PRO based on the 
systolic peaks during 
compressions compared to 
baseline of the PPG data, 
captured using the independent 
data acquisition system.  
 
o 
Number of participants that 
complete 10 mins of each of the 
ECP devices (Wave PRO and 
predicate ECP device) 
 
 
 
o 
Participant comfort level with the 
Wave PRO and predicate ECP 
device, assessed at the 
conclusion of each ECP session 
 
o 
Time to set up a participant (i.e., 
sleeved up and sensors attached) 
and ready to start treatment 
 
 
 
 
 
o 
Participant preference for one of 
the two ECP systems (assuming 
35 hours for a full course of ECP) 
 
 
o 
Systolic unloading is a corollary to DA ratio 
discussed above and is a suitable secondary 
endpoint for the same reasons – it is a direct 
and objective measure of the hemodynamic 
effect of ECP. 
 
 
 
o 
Proportion of participants that completed the 
10-minute treatment sessions is an 
appropriate endpoint because it is a 
surrogate measure of the tolerability of the 
Wave PRO device compared to the predicate 
ECP device. 
 
o 
Participant comfort levels is an appropriate 
endpoint because it is measured on a 
standard scale and reflects direct patient 
response to the two devices. 
 
o 
Tracking participant setup time enables 
Pression to quantify ease of use compared to 
the predicate ECP technology. It is 
appropriate as it quantifies the amount of 
time that can be reduced from patient visits 
and can help maximize treatments that 
clinical entities can provide in a day. 
 
o 
Participant preference for either one of the 
ECP systems helps validate the Wave PRO 
as a viable product with the potential of being 
more accessible for a population that may 
have limited mobility due to chest pain. 

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4 STUDY DESIGN 
4.1 OVERALL DESIGN 
Potential study participants will be recruited per standard practices of the clinical research 
facility (may include advertising/publicity). Participants will be consented prior to any study 
related assessments/procedures. Only eligible participants that meet the required criteria 
(inclusion/exclusion) will be enrolled in the study and subsequently randomized to the ECP 
devices. Overall study design is shown in Figure 1. For the Wave PRO, PPG waveforms will be 
collected with an independent data acquisition system, BIOPAC (Goleta, CA). The predicate 
device has onboard data capture and analysis functionalities. 
 
Steps for the Clinical Site for each randomized participant (see Section 6): 
o For the Wave PRO: setup (recorded time), rest period (supine, recorded blood pressure and 
heart rate), pre-compression baseline PPG (recorded on BIOPAC), compression period 
(automated inflation/deflation tuning, PPG recorded on BIOPAC), post-compression PPG 
(recorded on BIOPAC), and end of session procedures (recorded blood pressure and heart 
rate, Wave PRO questionnaire administered).  
o For the predicate ACS NCP-2: setup (recorded time, participant profile created), rest period 
(supine, recorded blood pressure and heart rate), compression period (manual 
inflation/deflation tuning required, PPG recorded on predicate device), and end of session 
procedures (recorded blood pressure and heart rate, predicate questionnaire administered). 
 
There will be a 20-minute washout period between the two ECP device sessions, requiring the 
participant to walk around (no strenuous or high-intensity activities). An observation period will 
be required after the last test session. A final questionnaire will be conducted during the follow-
up call the next day. 
 
Signal Processing steps include (see Section 6): 
o For the Wave PRO: average DA ratio will be measured using an R script that processes the 
BIOPAC waveform data at the 8th minute of compression (i.e., minute 7 to minute 8 of 
compressions). Average systolic amplitude of the last 10 waveforms of baseline before 
compressions and the average amplitude of the systolic amplitude of the first 10 waveforms 
during compressions will be recorded for systolic unloading calculations. 
o For the predicate ACS NCP-2 device: average DA ratio in the 8th minute of compressions 
will be calculated using an R script that processes the waveforms collected by the ACS 
software. The predicate device only allows for analysis of 8-second time strips at a time. No 
systolic unloading calculation for the predicate device. 
 
During Signal Processing, the evaluator will be blinded to the paired participant testing (i.e., 
blinded to the participant ID). The blinded evaluator will not be able to match a participant’s test 
on the Wave PRO with that of the predicate device. However, given the nature of the data 
collected, the evaluator will not be blinded to which ECP device the data pertains to. The 

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blinded evaluator will record the DA ratio in the CRF for each tested ECP device. For the Wave 
PRO, the blinded evaluator will also record the average systolic amplitudes. 
 
Statistical analysis steps include (see Section 9) 
o An ANOVA model for crossover design will be performed and the pairwise difference 
between two treatments DA ratios (Wave PRO – predicate ECP) in the treatment least 
square mean and its 95% CI will be constructed.  Non-inferiority margin will be set at -0.15. 
o Descriptive analysis will be conducted for all secondary endpoints. 
 
During Statistical analysis, the statistician will be provided the DA ratio values (per ECP device) 
matched to each participant ID. 
 

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Figure 1: Study design schematic, including steps at the Clinical Site, Signal Processing, and Statistics. 1Washout 
period between the ECP devices for each randomized participant will include walking around, 2Duration of setup will 
be recorded, 3Average DA ratio in the 8th minute of compressions (BIOPAC data, R script analysis), 4Average DA 
ratio in the 8th minute of compressions (ACS NCP-2 data, R script analysis), 5Average systolic amplitude of the last 
10 waveforms of baseline and the systolic amplitude of the first 10 waveforms during compressions, 6Compared to 
non-inferiority margin (see stats description). 

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4.2 JUSTIFICATION OF STUDY DESIGN  
As the purpose of the study is to demonstrate substantial equivalence of hemodynamic effect of 
the Wave PRO ECP system to a predicate ECP device, the study is intended to test the two 
devices in head-to-head fashion.  
 
This study is a randomized crossover study enrolling up to 50 participants in order to have 44 
completing participants. Each participant will receive ECP compressions from the Wave PRO 
device and from the predicate (ACS NCP-2) ECP device, one at a time, and with the sequence 
of device use randomized to control bias. Pression has utilized accepted biostatistical study 
design principles to calculate the sample size of the clinical study to reach adequate power to 
prove substantial equivalence (non-inferiority) of the DA ratio achieved by the Wave PRO 
compared to the predicate ECP device.  
 
The Diastolic Augmentation (DA) ratio, also referred to as Diastolic/Systolic (D/S) ratio and 
Effectiveness Ratio (ER), noninvasively characterizes the hemodynamic effect, and thus the 
clinical effectiveness, of ECP treatment. Predicate device Instructions for Use (IFU) and ECP 
literature direct medical professionals to utilize this metric to optimize the treatment: “The 
treatment aims to create an enhanced [DA ratio] during cardiac diastole” and “[DA] ratio [is] 
monitored using standard finger photoplethysmography [PPG]” 9. Medical professionals 
delivering ECP treatment are further trained to recognize permutations of the PPG waveform 
that indicate whether a treatment is being effectively delivered or whether the treatment 
parameters require adjustment. The hemodynamic impact of these adjustments is measured 
solely by way of the PPG waveform.  
 
While the predicate device has built-in functionality to capture PPG waveforms, the Wave PRO 
has no onboard PPG waveform capturing capability. Therefore, for the purposes of this study, a 
dedicated and independent data acquisition system, BIOPAC, will be used.  
 
DA ratio will be calculated by a qualified blinded evaluator (blinded to participant ID and ECP 
session pairing). A computer containing the ACS software (provided by Pression) will be used to 
review the ACS NCP-2 data and capture screenshots of the data, enabling the R script 
(provided by Pression) to process the data and calculate DA ratio, in accordance with the IFU. 
For the Wave PRO, raw data obtained from the dedicated BIOPAC data acquisition system will 
be evaluated using a seperate custom R-script code (which Pression will provide). In effect, the 
same DA ratio calculation of the eighth minute of compressions for both systems will be 
conducted. 
 
Internal testing has demonstrated that diastolic augmentation can be observed almost 
immediately at the start of an ECP session. The initial response of the participant to the ECP 
device can be assessed after the first 5 minutes of compression, so the 10 minute compression 
time is appropriate. 
 

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Per the ACS NCP-2 IFU regarding compression pressures on the first day (to be set by the 
operator at the clinical site), pressures will be set to 3PSI, from a maximum of 6PSI. Pressures 
are typically set to however much patients are able to tolerate, and more pressure does not 
always equate to higher augmentation in the predicate ECP device. 
 
4.3 END OF STUDY DEFINITION 
There will be approximately 10 minute observational period at the conclusion of the second ECP 
device session. The participant will be provided a post-session questionnaire regarding their 
ECP experience after each ECP device test. Once the participant has received their +1-day 
follow-up phone call and questionnaire, they will be considered exited from the study. 

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5 STUDY POPULATION 
5.1 INCLUSION CRITERIA 
Each participant must meet all of the following Inclusion Criteria to be considered eligible for the 
study. 
o 
Age 35 years or greater 
o 
History of mild to moderate coronary artery disease (CAD), as evidenced by one or more of the 
following: 
o 
Angina pectoris 
 
Canadian Cardiovascular Society (CCS) Angina classes I or II 
o 
Prior confirmation of CAD from invasive or noninvasive studies 
o 
Prior myocardial infarction (MI) 
o 
Prior coronary artery bypass graft (CABG) surgery 
o 
Prior cardiac stents 
o 
Able to ambulate without assistance (no cane or walker) 
o 
Able to lay down (approximately 5 degree angle) for the duration of the protocol required procedures 
o 
Able and willing to give informed consent 
o 
Able and willing to participate in the clinical study and complete all questionnaires provided 
 
5.2 EXCLUSION CRITERIA 
Participants must not meet any of the following Exclusion Criteria to be considered eligible for 
the study. 
o 
Unstable angina within prior 3 months 
o 
Canadian Cardiovascular Society (CCS) Class III or IV Angina 
o 
Moderate to severe peripheral arterial disease (PAD) 
o 
ABI < 0.8 
o 
Myocardial infarction in the past 3 months 
o 
Coronary artery bypass grafting (CABG) in the past 3 months 
o 
Any major surgery within the past 3 months 
o 
Decompensated heart failure  
o 
Cardiac catheterization or arterial femoral puncture in the past 2 weeks 
o 
Presence of mechanical circulatory support (MCS) device 
o 
Pacemaker or other implantable pulse generating device 
o 
Valve disease, including aortic insufficiency 
o 
Abdominal or thoracic aortic dissection or aortic/cerebral aneurysms requiring clinical intervention 
o 
Severe pulmonary disease 
o 
Bleeding diathesis 
o 
Patients undergoing warfarin anti-coagulation therapy, or with PT-INR > 2.5, or who have routine INR or prothrombin 
time tests Active thrombophlebitis 
o 
Uncontrolled hypertension (greater than 180/110 mmHg) 
o 
Baseline heart rate > 120 beats per minute or < 40 beats per minute 
o 
Arrhythmia and/or abnormal heart rhythm 

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o 
Major hand injuries or amputation that would interfere with finger PPG 
o 
Unhealed wounds/fractures below the waist or lower limb amputation, major lower body 
musculoskeletal injuries 
o 
Lower body vascular stents (arterial/venous)  
o 
Currently undergoing ECP treatment 
o 
Pregnancy 
o 
Currently participating in any other clinical study of an investigational device or drug where treatment 
has not yet been completed 
o 
Any medical condition that, in the opinion of the principal investigator (PI), would present undue risk 
to the participant 
5.3 RECRUITMENT STRATEGIES AND CONSIDERATIONS 
The recruitment efforts by the clinical study site will aim for a representative population with the 
following enrollment targets: 
o Randomize no more than 60% of one sex   
o Randomize no more than 50% White participants 
Additional considerations for the day of the Study Visit: 
o Participants must remove all nail polish or artificial nails on their hands to ensure that the 
PPG sensor can accurately detect the participant’s pulse and blood volume changes.  
o Participants must not eat on the test day prior to their visit.  
*Extended fasting may be required if a later test time is scheduled.  
o Participants must abstain from alcohol and caffeine by 8PM the night before their scheduled 
test day.  
o Water is permitted. 
*Compressions may induce the urge to urinate; regulated water consumption is 
recommended. 
o Participants must not take diuretics the morning of the visit if it is scheduled in the morning. 
If it is scheduled in the afternoon, the diuretics can be taken as usual in the morning. Any 
other changes or modifications to any dosing schedules should be at the direction of the 
participant’s physician.  
o Participants should wear or bring loose-fitting clothing to be worn during the visit  
 
For clothing tops, loose shirt or blouse is required to enable placement of EKG leads to 
enable the operation of the ACS NCP-2 predicate ECP device. 
 
For clothing bottoms: shorts are required to allow better interfacing with the inflation 
cuffs/sleeves. 
• 
Ensure that clothing bottoms do not have non-removable buckles or metal/hard 
plastic accessories. 
 
Cotton stockinettes will be made available to cover exposed skin on the legs. 
o Participants should bring a written list of all current medications; dosage information 
included. 

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5.4 SCREEN FAILURES 
In order for an individual to participate in the study, the participant must meet all Inclusion 
Criteria and none of the Exclusion Criteria. The participant must also be able to comply with the 
additional considerations listed in Section 5.3. Failure to meet eligibility will result in the 
individual being a Screen Failure. The reason for Screen Failure will be documented for each 
prospective participant.  

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6 STUDY DESCRIPTION 
6.1 STUDY ECP DEVICE ADMINISTRATION – WAVE PRO SYSTEM 
6.1.1 WAVE PRO ECP DEVICE DESCRIPTION 
 
The Pression Wave PRO External Counter-Pulsation System applies compression to the 
calves, timed to peripheral diastole, to positively affect the patient’s blood flow. It utilizes a pair 
of calf sleeves worn by the patient that are attached by tubing to a mobile compression control 
system, which houses the pneumatic, mechanical, electrical components, and an easy-to-use 
touch screen control interface. The patient’s cardiac cycle is monitored by a pulse 
photoplethysmography (PPG) sensor worn and secured on the patient’s finger by a clip and 
connected to the compression control system.  
 
The calf sleeves inflate and deflate in synchrony with the phases of the patient’s cardiac cycle, 
which is detected by the finger PPG sensor. These calf sleeves have a series of five inflatable 
bladders that are inflated sequentially, distally to proximally, towards the heart in the timeframe 
between heart beats. This compression generates retrograde arterial flow back to the heart, 
thus augmenting coronary flow during ventricular diastole.  
6.1.2 WAVE PRO DEVICE TEST SESSION 
This section pertains to the test session using the Wave PRO device with a participant that has 
been randomized. 
• 
Setup (approx. 10mins): Time needed to get the participant ready for compressions will 
be recorded 
o Participant will be lying on the clinical bed with their back propped head-up at 
approximately 5° angle 
o Cotton stockinettes will be placed around the participant’s legs between the knees 
and the ankles (if not already) 
o The clinical operator/technician will ensure that the Wave PRO is connected to an air 
supply source in the session room. 
 
Clean air rated at 55 ± 1PSI. 
o Timer to record setup time will be started 
o The compression sleeves (with tubing attached) will be fitted around the participant’s 
calves by a clinical operator/technician 
 
The sleeves are differentiated by a left and a right sleeve 
 
There are three different sleeve sizes (small, medium, large)  
 
The sleeves are placed between the participant’s ankles and knees 
• 
with the compression bands wrapped around the calf muscle  
• 
with the tubing ports on the medial side of the legs, pointing towards the feet 
o The compression sleeves should be snug against the participant’s legs (tight but 
comfortable) 

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 
The clinical operator should not be able to fit an index finger between the 
Compression Sleeve and the legs, but should not be so tight that the participant 
can feel their pulse through their leg 
• 
Rest (supine), blood pressure and heart rate (approx. 5 mins): Participant should be 
completely set up and then asked to lie back and relax 
o Amount of time it took to set up will be recorded 
o The participant’s systolic/diastolic pressures and heart rate will be recorded 
• 
Baseline PPG (2 mins): With the Wave PRO system powered ON and on standby (not 
compressing), recording will be conducted to capture baseline PPG waveforms using the 
dedicated BIOPAC data acquisition system 
o Two PPG sensors will be placed on the participant’s hand: 
 
One for the Wave PRO 
 
One for the dedicated Data Acquisition System 
 
The sensors should be placed on the index (Wave PRO) and middle fingers 
(BIOPAC) on the right hand (if the Data Acquisition System signal is noisy, the 
sensor can be switched to another finger on the same hand) 
o The User Pause Button will be given to the participant to hold in the left hand  
 
The User Pause Button allows the participant to temporarily stop the 
compressions at any time. 
• 
Compression (10 mins): Participants will be asked to relax and minimize all movement 
and the operator will begin compressions 
o To be able to start compressions, the clinical operator should make sure of the 
following: 
 
The E-Stop on the front panel is disengaged 
 
System Check checklist items on the screen all have blue checkmarks 
 
“Next” button has been pressed. 
 
60 minutes Treatment Time has been selected 
 
“Start Treatment” button has been selected 
o PPG waveform data will be recorded on the BIOPAC data acquisition system. 
 
Mark pre-compression baseline PPG start and end using the study laptop 
 
Mark compression start and end using the study laptop 
 
Mark post-compression PPG start and end using the study laptop 
• 
Stop compressions: The clinical operator/technician will stop the delivery of 
compressions after 10mins has elapsed by pressing the “Cancel Treatment” button. 
• 
Post-Compression PPG (2 mins): At the conclusion of the 10 minute ECP session, a 
post-compression PPG signal will be recorded 
o Participant will be asked to relax and minimize all movement. 
• 
End-of-Session procedure, blood pressure and heart rate, device-related 
questionnaire: The clinical operator/technician will perform the following: 
o The participant’s systolic/diastolic pressures and heart rate will be recorded 
o Participant questionnaire related to the ECP device will be conducted 
o Wave PRO system will be turned off (if applicable) 

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o Air supply line to the Wave PRO system will be disconnected (if applicable) 
o Sensors will be removed from the participant’s fingers 
o Compression sleeves will be removed from the participant’s calves 
o If this is the second test session, an observation period of approx. 10 minutes should 
be made available for each participant 
 
6.2 PREDICATE ECP DEVICE ADMINISTRATION – APPLIED CARDIAC SYSTEMS 
(ACS) NCP-2 EXTERNAL COUNTER-PULSATION (ECP) SYSTEM 
6.2.1 ACS NCP-2 ECP DEVICE DESCRIPTION 
  
The Applied Cardiac Systems (ACS) NCP-2 is an FDA cleared ECP system (K042413) 
indicated for the treatment of chronic stable angina. The ACS system is similar to other 
commercially available ECP devices on the market. It utilizes three inflation cuff sets (calf, thigh, 
buttocks) to deliver sequential compressions timed to the cardiac cycle. Compressions are 
timed to the patient’s EKG and treatment efficacy is measured using a PPG sensor. 
The user interface of the ACS NCP-2 device requires the clinical operator/technician to input 
inflation and deflation timing of the cuffs and must input pressure settings manually. As a result, 
the clinical operator/technician must have an understanding of EKG and PPG waveform shapes 
to ensure the input parameters are appropriately set. 
6.2.2 ACS NCP-2 (PREDICATE) DEVICE TEST SESSION 
This section pertains to the test session with the predicate ACS NCP-2 device with a participant 
that has been randomized. 
• 
Setup (approx. 10 mins): Time needed to get the participant ready for compressions will 
be recorded 
o Participant will be lying on the ACS NCP-2 bed with their back propped head-up at 5° 
angle 
o Cotton stockinettes will be placed around the participant’s legs between the knees 
and the ankles (if not already) 
o The ACS NCP-2 system will be powered on (if not already) along with the connected 
computer and monitor 
o The ACS NCP-2 software must be loaded once the boot-up sequence is complete 
o Participant profile must be created before starting new treatment session 
 
Profile must not contain identifying information 
• 
Treatment ID (see Treatment_ID_LookupSheet) will be used for both name 
and participant ID on the ACS software query 
• 
For the birthday query, use 01/01/19XX, where XX is the participant’s actual 
birth year  
o Treatment session screen should be opened 
o Timer to record setup time will be started 

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o The clinical operator/technician will attach three EKG electrode pads on the 
participant 
 
Refer to the ACS NCP-2 training packet for electrode placement 
o With the participant lying down, the compression cuffs (with tubing attached) will be 
fitted around the participant’s calves, thighs, and hips by a clinical operator/technician 
 
The compression cuffs are differentiated by left and right. 
 
The compression cuffs are positioned such that the tubing ports are on the medial 
side of the legs, and the ports are pointing towards the bed. 
 
There are two different sizes of cuffs (small, large) 
 
All compression cuffs should be snug around the participant’s legs and hips (snug 
but comfortable) 
• 
Operator should not be able to fit two fingers inside the cuffs at the top edge 
(thigh and calf) 
 
The clinical operator/technician will connect the EKG leads to the electrode pads 
based on the lead labeling. 
 
The clinical operator/technician may need to loosen the cuff around the hips to 
place one of the EKG leads on the participant’s left lower rib. 
• 
Rest, blood pressure and heart rate (approx. 5 mins): Participant should be 
completely set up and then asked to lie back and relax 
o Amount of time it took to set up will be recorded 
o The participant’s systolic/diastolic pressures and heart rate will be recorded 
• 
Compressions (10mins): The clinical operator/technician will begin compressions.  
o The ACS NCP-2 PPG sensor will be placed on the participant’s right pointer finger 
o The clinical operator/technician will adjust the device pressure and the inflation and 
deflation timing based on the red and blue colored marker bars, respectively, on the 
monitor 
 
The timing (red and blue colored marker bars) needs to be adjusted to generate a 
PPG waveform that has the appropriate shape (refer to IFU for inflation and 
deflation timing and resulting PPG waveform shapes) 
 
As a starting point, the red colored region should start at the peak of T-wave 
(inflation) and the blue colored region should terminate just prior to the 
subsequent P-wave (deflation) 
 
The 10 minutes of compressions start once the “Start Pump” button has been 
clicked (i.e., includes timing search) 
o PPG waveform data will be recorded on the ACS NCP-2 software (waveforms are 
only recorded when the pump is running) 
o Compression pressure will be increased in small increments until a maximum of 3 PSI 
is reached, per the ACS software readout 
 
In accordance with pressure settings for the first day of ECP treatment per the 
predicate device IFU 
 
3 PSI will be reached as fast as possible along with the correct inflation/deflation 
timing 

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• 
Stop compressions: Compressions will be concluded by pressing the “Pump Start” 
button again after 10 mins have elapsed 
o Proper steps to exit out of the treatment screen will be followed to prevent loss of data 
o The participant’s profile will be revisited immediately to ensure that the test data was 
saved (Full Disclosure screen) 
• 
End-of-Session procedure: The clinical operator/technician will perform the following: 
o The participant’s systolic/diastolic pressures and heart rate will be recorded 
o Participant questionnaire related to the ECP device will be conducted 
o ACS NCP-2 will be turned off (if applicable) 
o EKG leads and electrodes will be removed from the participant 
o Sensors will be removed from the participant’s finger 
o The three compression cuff sets will be removed from the participant 
o If this is the second test session, an observation period of approx. 10 minutes should 
be made available for each participant 
 
6.3 DATA ACQUISITION WAVE PRO 
 
6.3.1 BIOPAC MP35 DATA ACQUISITION SYSTEM DESCRIPTION 
The BIOPAC MP35 Data Acquisition system paired with the BSL 4.1 software will serve as the 
dedicated PPG waveform and data extraction system to acquire waveforms that will 
subsequently be used to calculate DA ratio and select secondary endpoints as a result of Wave 
PRO compressions. The MP35 is a four channel system with a 24-bit A/D sampling resolution. 
The MP35 is capable of recording 100,000 samples per second. 
 
The BIOPAC SS4LA PPG Transducer, which connects to the 9-pin female DSUB connector on 
the MP35, will be attached to the participant’s finger using the built-in hook-and-loop strap to 
capture PPG signals. The SS4LA is a reflectance type PPG sensor that utilizes a matched 
infrared emitter and photo diode to detect changes in blood density due to blood pressure 
fluctuations. The emitter/detector wavelength is 860nm ± 60nm, with a built-in low pass filter 
cutoff wavelength of 800nm. 
 
6.3.2 PREPARATION AND UTILIZATION 
Baseline data as well as compression session data will be captured using the dedicated 
BIOPAC data acquisition system. A laptop running Windows OS will be provided containing the 
BSL 4.1 software bundle. To launch the software, double click on the BSL 4.1 (BIOPAC) 
software icon on the desktop. 
• 
The operator will load a pre-set template located on the study laptop 
• 
During data capture, the clinical operator/technician can use specific function keys to tag 
events during the ECP session, including: 
o F1 key to tag Start Baseline,  

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o F2 key to tag End Baseline,  
o F3 key to tag Start of Wave PRO compressions, 
o F4 key to tag End of Wave PRO compressions 
o ESC key to tag any other miscellaneous notes deemed necessary such as 
irregular PPG waveform due to participant movement  
o NOTE: All keys are labeled with their function on the keyboard itself 
• 
The clinical operator/technician will save the entire session with the following naming 
convention: 
o RA-C01_TreatmentID 
 
(see Treatment_ID_LookupSheet) 
A dedicated directory on the desktop will be used to save the Wave PRO data for each  
participant 
• 
Data will be backed up on to a dedicated secure data storage for the study 
 
6.3.3 SIGNAL PROCESSING 
Signal processing will be conducted by a blinded evaluator working under the requirements of 
an Analysis Charter. The laptop provided for the data acquisition and processing will be 
equipped with RStudio integrated development environment software as well as the R script 
used to extract DA ratio and systolic amplitude values.   
• 
The evaluator will load the data from the secure data storage 
• 
The evaluator will extract waveforms using the BSL 4.1 software and process the 
waveforms using a custom R script  
• 
The evaluator must run the script and answer the prompts in the Console tab to have the 
script calculate the DA ratio 
o This script analyzes PPG data from .csv files, prompts the user for key waveform 
features, and outputs DA ratio values and systolic amplitude, as well as the PPG 
waveform graphs  
 
An Analysis Charter will be used to guide the evaluator through the process of extracting the DA 
ratio and systolic amplitude values. The DA ratio and systolic amplitude values will be uploaded 
via CRF to the EDC. 
6.4 DATA ACQUISITION ACS NCP-2 
 
6.4.1 ACS DATA ACQUISITION SYSTEM DESCRIPTION 
The ACS NCP-2 software (NCPPLUS) records participant PPG and EKG waveforms throughout 
the duration of compressions. The ACS software will serve as the dedicated PPG waveform and 
data extraction system to acquire waveforms that will be used to calculate DA ratio as a result of 
ECP compressions on the ACS NCP-2. 
 
The ACS PPG sensor is a transmission type PPG sensor that utilizes an infrared emitter and 
photo diode to detect changes in blood density due to blood pressure fluctuations. 

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6.4.2 PREPARATION AND UTILIZATION 
A computer running Windows OS will be provided to the clinical research site containing ACS 
software. To launch the software, double click on the NCPPLUS program icon on the desktop. 
• 
Before data capture, the clinical operator/technician must create a patient profile 
o No participant identifying information will be logged on the software 
 
For patient I.D. use the treatment ID (see Treatment_ID_LookupSheet) 
 
For patient name use treatment ID (see Treatment_ID_LookupSheet) 
 
For patient’s sex use participant’s sex 
 
For patient’s birth date, use 01/01/19XX, where XX is the participant’s 
actual birth year. 
• 
Data capture begins when the operator/technician starts the pump on the control 
console and the software starts recording 
• 
The entire session will automatically save with the following naming convention: 
o NCP_T_ParticipantID 
 
In this instance, ParticipantID is TreatmentID (see 
Treatment_ID_LookupSheet) 
• 
A dedicated directory on the trial site desktop will contain ACS data for each participant, 
categorized by the Participant ID (which is treatment ID, in this instance) 
• 
The operator/technician must copy this directory in its entirety to the provided USB drive 
o Data should be backed up after every participant 
• 
Data will be backed up to a dedicated secure data storage for the study 
 
6.4.3 SIGNAL PROCESSING 
After the ACS NCP-2 sessions are complete, data extraction will be conducted by the 
Statistician and data processing will be conducted by a blinded evaluator. Both the Statistician 
and blinded evaluator will be working under the requirements of an Analysis Charter. 
• 
The Statistician will load the data from the secure data storage 
• 
The Statistician will open each participant’s ACS data file in the ACS NCP-2 Software 
(NCPPLUS) 
• 
The Statistician will load the Full Disclosure page to access the test data 
• 
The Statistician will use built-in Augmentation Cursor Screen capture all the waveforms 
within the 8th minute (i.e., minute 7 to minute 8) via screenshots 
o The onboard analysis tool uses 8-second strips. Each of these strips will need to 
be captured within the 8th minute 
• 
The Statistician will upload the captured data to the secure data storage 
• 
The evaluator will load the captured data from the secure data storage 
• 
The evaluator must run the script and answer the prompts in the Console tab to have the 
script calculate the DA ratio 
o This script isolates PPG data from the screenshot files, analyzes the PPG data, 
prompts the user for key waveform features, and outputs DA ratio values, as well 
as the PPG waveform graphs  
An Analysis Charter will be used to guide the evaluator through the process of extracting the DA 
ratio. The DA ratio values will be uploaded via CRF to the EDC. 

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6.5 PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
6.5.1 ACQUISITION AND ACCOUNTABILITY 
  
The study site will receive both ECP devices, the Wave PRO and the ACS NCP-2, from the 
Sponsor.  
 
The study site will also be provided the BIOPAC MP35 data acquisition system, paired with a 
BIOPAC SS4LA PPG finger transducer, for capturing PPG data.  
 
A laptop (Windows OS) will be provided and will include the BIOPAC BSL 4.1 software bundle 
to interface with the BIOPAC hardware. Dedicated digital storage directories will be created to 
save the data files. 
 
A flash drive storage device will be provided to back up raw data on the laptop on a daily basis. 
 
Data will also be uploaded to a dedicated secure data storage for the study. 
 
Consumables include EKG electrodes, stockinette material (for interfacing the compression 
sleeves/cuffs to the participants legs), surgical tape, and ultrasound gel (to help interface noisy 
EKG electrodes) will be provided by the Sponsor. 
 
The Sponsor will also provide an air compressor that the Wave PRO will connect to, to receive 
compressed air.  
 
All devices and ancillary supplies will be logged on device accountability form(s).  
6.5.2 APPEARANCE, PACKAGING, AND LABELING 
Shipping: Both the Wave PRO and the ACS NCP-2 will be shipped to the study site via courier. 
Pression will custom package all devices and supplies for safe transport. Neither of the ECP 
systems requires calibration prior to powering up. Installation validation (Pression protocols) will 
be conducted for both systems prior to participant enrollment. 
 
Labeling for Wave PRO: 
CAUTION: Investigational Device – Limited by Federal (or United States) Law to Investigational 
Use. 
This device is manufactured and assembled by Pression LLC, Coatesville, PA 19320. 
 
Labeling for ACS NCP-2: 
Per 510(k) Number K042413: ACS Model NCP-2 External Counter-pulsation Device is a 
noninvasive external Counter-pulsation device intended for the use in the treatment of patients 

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with stable or unstable angina pectoris, acute myocardial infarction, cardiogenic shock or 
congestive heart failure*. 
*Original indications. FDA reclassified the uses of ECP devices in December 2013: Class II 
(special controls) when the device is indicated for the treatment of chronic stable angina that is 
refractory to optimal antianginal medical therapy and without options for revascularization. 
 
Labeling for BIOPAC MP35 Data Acquisition System: 
Per BIOPAC Product Sheet: 
Safety: 
The MP35 satisfies the Medical Safety Test Standards affiliated with IEC 60601-1. The MP35 is 
designated as Class I Type BF medical equipment 
  
EMC: 
The MP35 satisfies the Medical Electromagnetic Compatibility (EMC) Test Standards affiliated 
with IEC 60601-1-2. 
 
Ancillary supplies: 
Laptop: Windows operating system containing BIOPAC BSL 4.1 software bundle for data 
acquisition and R Studio for data analysis and quantification. This laptop is intended for 
research use, specifically for the acquisition and quantification of PPG waveforms recorded from 
the Pression sponsored clinical trial. Only personnel explicitly authorized by Pression LLC will 
be allowed to access this laptop. 
EKG electrode pads: single use, commercially available for EKG leads 
Stockinette: cotton interfacing layer that is commercially available to minimize abrasions  
Ultrasound gel: to be used in the event of very noisy EKG signal 
Surgical tape: to be used in the event of very noisy EKG signal 
Flash drive storage: commercially available USB-A flash drive for backing up raw data from the 
laptop. The flash drive will be used specifically and exclusively for the Pression sponsored 
clinical study. 
6.5.3 PRODUCT STORAGE  
  
All devices and ancillary supplies are to be securely stored at room temperature and only 
accessed by trained and delegated study personnel. While in storage, all devices should be 
unplugged (not powered) and kept away from fluids or flammable sources. All devices and 
ancillary supplies should only be used for the purposes of the Pression sponsored clinical trial. 
Please contact Pression LLC or the CRO (ABio Clinical) in case of damage or misplacement of 
all devices and ancillary supplies. 
6.6 MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
Given the analysis methodologies and the data collection methods, the blinded evaluator who 
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blinded to ECP device, but will be blinded to the participant IDs (only treatment IDs will be 
provided so that the treatments cannot be paired per participant) and to the sequence of ECP 
device used (i.e., Wave PRO used first vs. ACS NCP-2 used first). Due to the nature of the 
devices, participant and operator blinding to the ECP units cannot be performed.  
 
Randomization of ECP device order will be performed within the Electronic Data Capture 
System once eligibility has been determined. The randomization schedule will be generated 
using randomly selected small block sizes to minimize bias for the single site. 
6.7 STUDY INTERVENTION COMPLIANCE 
The Wave PRO System and the ACS NCP-2 ECP device will be operated according to each 
device’s Instructions for Use (IFU), this clinical study protocol, and the training packet (provided 
by Pression).  
 
Any deviations will be documented on a Protocol Device electronic Case Report Form (eCRF).  
6.8 CONCOMITANT THERAPY 
Participants must not be currently undergoing ECP treatment or participating in any other 
clinical study of an investigational device or drug where treatment has not yet been completed. 
 
Participants may need to consult with their primary care physician to discuss their health and 
safety regarding their participation in this clinical trial.  
 
For participants on diuretics, medications may be taken immediately after the session. 
Participants are encouraged to check with their primary care physician regarding any deviations 
in medication scheduling. 

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7 STUDY PROCEDURE DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 DISCONTINUATION OF STUDY PROCEDURES AND/OR ASSESSMENTS 
The site Principal Investigator or study staff may discontinue any of the protocol required study 
assessments or procedures at any time due to participant safety or other concerns. For any 
procedures not completed, the reason for discontinuation will be documented, and Protocol 
Deviation eCRF will be recorded as appropriate.  
7.2 PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants have the right to withdraw their consent to participate at any time during the study. 
In addition, the site Principal Investigator (PI) or study staff may remove participants from the 
study at any time if they feel it is best for the safety and well-being of the participant. Examples 
include: 
o Significant study intervention non-compliance. 
o If any clinical adverse event (AE) or other medical condition or situation occurs such that 
continued participation in the study would not be in the best interest of the participant. 
o If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation. 
The reason for discontinuation/withdrawal will be documented on the Study Exit eCRF. 
7.3 LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if the participant is unable to be contacted by 
the study site for the follow-up phone call. The following actions will be taken if a participant fails 
to return the phone call: 
o 
The site must attempt to contact the participant as soon as possible. 
o 
Before a participant is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the participant (3 telephone calls, and if necessary, a 
certified letter to the participant’s last known mailing address or local equivalent methods 
including email). These contact attempts should be documented in the participant’s 
medical record.  
o 
Should the participant continue to be unreachable, the participant will be considered "lost 
to follow up”. 
 

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8 STUDY ASSESSMENTS AND PROCEDURES 
8.1 GENERAL AND ADMINISTRATIVE PROCEDURES 
The summary of study assessments, procedures and their timing are also provided in Sections 
1.1 and 4.1. Before conducting any non-standard of care assessments or procedures, obtain 
written informed consent. All screening evaluations must be completed and reviewed to confirm 
that potential participants meet all eligibility criteria. The Investigator will maintain a consent log 
to record details of all participants enrolled and to confirm eligibility or record reasons for 
screening failure, as applicable.  
 
Demographic and baseline characteristic data will include sex, age, Fitzpatrick skin type, race, 
and predominant ethnicity. Relevant medical history and current medical conditions and 
medications will be recorded. Where possible, diagnoses but not symptoms will be recorded. 
Body weight will be measured in kilograms (kg) and body height will be measured in centimeters 
(cm).  
8.2 EFFECTIVENESS ASSESSMENTS 
 
Data from the investigational devices will be obtained per Sections 4.1, 6.1, 6.2, 6.3, and 6.4.  
 
As discussed above, analysis of the PPG data will be conducted by a blinded evaluator not 
associated to the study investigators or sponsor and as described in the Analysis Charter. The 
analysis process is briefly described in section 6.3 and 6.4 and is further detailed in a dedicated 
data analysis document (provided by Pression). 
8.3 SAFETY AND OTHER ASSESSMENTS 
Adverse Events/Serious Adverse Events (SAEs) will be recorded on the Adverse Event eCRF 
from the time the participant signs Informed Consent until study exit. The Investigator and any 
qualified designees are responsible for detecting, documenting, and recording events that meet 
the definition of an AE or SAE in the AE eCRF and remain responsible for following up all AEs. 
 
The participant will be asked to complete surveys after each ECP device session and again one 
day after completion of the study procedures. 
8.4 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.4.1 DEFINITION OF ADVERSE EVENT (AE) 
  
An adverse event is any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in participants, users or other 
persons, whether or not related to the investigational medical device and whether anticipated or 

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unanticipated. This definition includes events related to the investigational medical device or the 
predicate, events related to the procedures involved and for users or other persons. 
8.4.2 DEFINITION OF SERIOUS ADVERSE EVENT (SAE) 
  
A serious adverse event is an adverse event that  
a) led to death,  
b) led to serious deterioration in the health of the participant, that resulted in:  
• a life-threatening illness or injury, or  
• a permanent impairment of a body structure or a body function including chronic 
diseases, or  
• in-patient or prolonged hospitalization, or  
• medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function,  
c) led to fetal distress, fetal death or a congenital abnormality or birth defect including 
physical or mental impairment 
 
Planned hospitalization for a pre-existing condition, without serious deterioration in health, is not 
considered a serious adverse event. 
8.4.3 CLASSIFICATION OF AN ADVERSE EVENT 
  
8.4.3.1 SEVERITY OF EVENT 
  
All AEs will be assessed by the Investigator(s). Guidelines for Investigators include the 
following:  
o Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention 
not indicated.  
o Moderate: Minimal, local or noninvasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living (ADL).  
o Severe: Medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care ADL.  
8.4.3.2 RELATIONSHIP TO STUDY INTERVENTION 
  
The Investigator, on the basis of his or her clinical judgment, should determine whether there is 
a reasonable possibility the study device or procedure caused or contributed to the event. 
Guidelines to assess relatedness of an AE are provided below:  

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o Not related: The adverse event is determined to be solely caused by the underlying 
disease, disorder or condition of the participant, or attributable solely to other extraneous 
causes (unrelated to the device, device malfunction, or the procedure).  
o Unlikely related: The adverse event onset does not follow a sequence of time from 
procedure for which the event could be attributed to the administration or procedure, and/or 
can be attributable to the underlying disease, disorder or condition of the participant, or 
attributable to other extraneous causes.  
o Possibly related: The adverse event has onset within a clinically relevant temporal 
relationship to exposure to the device or procedure and is more likely than not to be at least 
partially caused by or aggravated by the use of the device, device malfunction, or the 
procedure. It must also meet both of the following criteria: (1) follows a known or easily 
foreseen pattern of response to device use or procedure; and (2) is not fully attributable to 
the underlying disease, disorder or condition of the participant, or attributable to other 
extraneous causes. In addition, if the adverse effect is reversible upon reoperation or device 
exchange, and such a procedure is done, the effect disappears or lessens in severity within 
the expected time interval.  
o Probable or highly probable related: The adverse event is clearly caused by the use of 
the device, device malfunction, or the procedure. It must meet all the following criteria: (1) 
has a clear temporal relationship between device exposure and onset of the event; (2) 
follows a known pattern of response to device use or procedure; and (3) is not reasonably 
attributable to the underlying disease, disorder or condition of the participant, or attributable 
to other extraneous causes. In addition, if the adverse effect is reversible upon reoperation 
or device exchange, and such a procedure is done, the effect disappears or lessens in 
severity within the expected time interval. 
8.4.3.3 EXPECTEDNESS 
  
Anticipated adverse device effect is an effect which by its nature, incidence, severity or 
outcome has been identified in the risk assessment. 
 
An unanticipated serious adverse device effect (USADE) is a serious adverse device effect 
which by its nature, incidence, severity or outcome has not been identified in the current version 
of the risk assessment.  
 
An unanticipated adverse device effect (UADE) means 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 investigational plan or application (including a supplementary plan or application), or any 
other unanticipated serious problem associated with a device that relates to the rights, safety, or 
welfare of participants. 
 

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8.4.4 ADVERSE EVENT REPORTING 
  
Adverse events will be recorded on the AE eCRF. 
8.4.5 SERIOUS ADVERSE EVENT REPORTING 
  
The reporting requirements are as follows:  
o In the event of a Serious Adverse Event (SAE) Investigators are required to report to 
Sponsor within 24 hours of becoming aware of the SAE.  
o SAE reporting will be performed per the IRB and any local requirements. 
o SAEs will be assessed by the Sponsor to determine if the event is a UADE. Any UADE will 
be reported to the FDA and IRB as soon as possible, but no later than 10 working days 
after the Sponsor first learns of the effect, as required by 21 CFR Part 812. 

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9 STATISTICAL METHODS 
9.1 GENERAL CONSIDERATIONS 
 
Data will be summarized using descriptive statistics unless specific hypothesis testing is 
specified. Means, standard deviation, median and range will be summarized for continuous data 
and counts and frequencies for categorical data. Data analyses will be performed using a 
validated statistical software package such as Stata (College Station, TX) or SAS (Cary, NC). 
No imputation for missing data will be performed other than for the sensitivity analysis of the 
primary endpoint. 
9.2 POPULATIONS FOR ANALYSIS 
 
The study has a single test population that will be enrolled according to the inclusion/exclusion 
criteria. 
 
Intent-to-treat (ITT): All participants that are randomized. 
 
Modified intent-to-treat (mITT): All participants that are randomized and receive any ECP 
compressions from either device. Group assignment will be the randomized treatment order 
even if therapy was delivered not according to randomization. 
 
Safety Cohort: Same as the mITT. Only participants that receive any ECP compressions from 
either device will be included. 
 
Per protocol (PP): Participants that are randomized and receive any ECP compressions from 
both devices, are treated as they are randomized, and have no major deviations (i.e., 
inclusion/exclusion criteria, randomization, affect participant safety or validity of primary 
endpoint). 
 
9.3 ENDPOINTS AND STATISTICAL ANALYSES 
9.3.1 PRIMARY EFFECTIVENESS ENDPOINT  
There is a single primary endpoint for this trial for effectiveness. Safety will be summarized 
under secondary endpoints with no hypothesis testing. 
Primary Effectiveness Endpoint:  
The average DA ratio will be calculated by a blinded evaluator for the 8th minute (i.e., between 
minute 7 and minute 8) of treatment with each ECP device tested for each participant via the 
Waveform Analysis Charter. The 8th minute was selected as the pilot data indicated participants 

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moved more in the last minute of therapy and more signal noise was present. Each participant 
will have a single average DA ratio per system (i.e., two values per participant).  
The difference of the average DA ratio attained using the Wave PRO and the predicate device 
will be calculated for all randomized study participants with paired ECP data.  
Hypothesis: 
Null Hypothesis: Wave PRO is inferior to the predicate ECP device 
Ho: µP - µp ≤ - 0.15  
Alternative hypothesis: Wave PRO is not inferior to predicate ECP device 
Ha: µP - µp > - 0.15,  
where µP is the mean diastolic ratio for Wave PRO and µp is the mean diastolic 
ratio for the predicate ECP, and -0.15 is the non-inferiority margin. 
 
Sample size calculation: 
Based on preliminary internal data, the observed mean difference between Wave PRO and the 
predicate ECP was 0.05 ± 0.23, but we will assume a true difference of 0 with a standard 
deviation of 0.30 for sample size calculations. 
 
Table 1: Summaries for the predicate and Pression Wave Pro ECP pilot data. 
 
Predicate  
ACS 
Pression Wave 
Pro ECP 
Difference  
(Wave Pro– ACS) 
Diastolic ratio (N=7) 
0.93± 0.12 
0.98 ± 0.19 
0.05 ± 0.23 
 
Assuming a true difference of 0 with the inflated standard deviation of 0.30, a sample size of 44 
participants is adequate to test the non-inferiority hypothesis with at least 90% power and a 1-
sided alpha of 0.025.  Allowing up to 12% attrition for missing data, approximately 50 
participants may be enrolled and undergo ECP compressions in order to have at least 44 
participants with paired data. 
 
Selection of non-inferiority margin: 
The non-inferiority margin of -0.15 was selected for the difference in diastolic ratio as it seemed 
a reasonable number. DA ratio characterizes the hemodynamic effect of ECP and is predictive 
of CCS angina class improvement. The weighted mean DA ratio calculated using published 
values for predicate ECP devices is 0.79 ± 0.46 (N = 5600). Pression has utilized accepted 
biostatistical study design principles to calculate the sample size of the clinical study to reach 
adequate power to prove substantial equivalence (non-inferiority) of the Wave PRO compared 
to predicate ECP devices using the literature. 
The proposed sample size aligns with the 20-50 number of participants previously suggested by 
FDA at the Pression pre-submission meeting on 8 November 2021.  
 

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Analysis cohort:  
The primary analysis will use the participants in the mITT cohort that have paired data (an 
average DA ratio from each system). The primary analysis will not include any imputation for 
missing data (see missing data section below for planned sensitivity analysis).   
A supplemental analysis of the primary endpoint will be conducted for the participants in the Per 
Protocol cohort with paired data.  
 
Analysis methods: 
Along with descriptive statistics, an analysis of variance (ANOVA) model for crossover design 
will be performed. This ANOVA model includes sequence, participant within sequence, period, 
treatment, and period by treatment interaction factors. The least square (LS) mean of each 
treatment and its 95% confidence interval (CI) will be presented.  A pairwise difference between 
two treatments (Wave PRO – predicate ECP) in the treatment LS mean and its 95% CI will be 
constructed.  If the lower bound of this 95% confidence interval is greater than -0.15, then we 
will reject the null hypothesis and conclude that Wave PRO is not inferior to the predicate ECP. 
A p-value will be constructed using the LS means parameter estimates and standard error to 
test the hypothesis. 
A simple paired Student’s t-test will also be constructed for the difference of Wave PRO – 
predicate ECP to test if greater than -0.15. 
 
Missing Data and Imputations: 
Every effort will be made to obtain required data at each scheduled evaluation from all 
participants who have been randomized. In situations where it is not possible to obtain all data, 
it may be necessary to impute missing data for the primary endpoint. Missing mean diastolic 
ratio for each ECP may need to be imputed and analyzed in a sensitivity analysis. 
 
A sensitivity analysis will be conducted, imputing missing ECP mean DA ratios utilizing a 
Markov Chain Monte Carlo multiple imputation procedure using treatment group as a covariate. 
For this method, 5 imputation datasets will be prepared if more than 10% of data are missing for 
randomized participants. These data will be analyzed by imputations using the same model 
described above and will be combined.  
 
If an mITT participant is missing both ECP mean DA ratios (e.g., unable to tolerate ECP therapy 
of both devices), then the participant will be excluded from all primary endpoint analyses.  Any 
participant unable to tolerate either ECP therapy will be summarized separately. 
 
9.3.2 SAFETY ENDPOINTS  
Safety Endpoint 1: 
Occurrence of device-related Serious Adverse Events (SAEs) as reported on the case report 
forms. 
 
Analysis cohort: Safety cohort. 

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Analysis methods: 
The number of events, number of participants and proportion of participants experiencing any 
device-related SAE will be summarized by treatment arm. There are no hypothesis tests, but 
95% CI for the proportion of participants with an event may be calculated. 
 
Safety Endpoint 2: 
Rate of device-related Adverse Events (AEs) as reported on the case report forms. 
 
Analysis cohort: Safety cohort. 
 
Analysis methods: 
The number of events, number of participants and proportion of participants experiencing any 
device-related AE (including serious) will be summarized by treatment arm. There are no 
hypothesis tests, but 95% CI for the proportion of participants with an event may be calculated. 
 
9.3.3 SECONDARY EFFECTIVENESS ENDPOINTS  
Secondary Effectiveness Endpoint 1: 
The level of systolic unloading will be recorded for the Wave PRO based on the systolic peaks 
during compressions compared to baseline of the PPG data (before compressions and captured 
using the independent data acquisition system). Systolic unloading is the ratio of the systolic 
peak during compressions divided by baseline systolic peak. Previous studies that measured 
systolic pressure using coronary catheterization found that “peak aortic systolic pressure 
decreased 11% during ECP” 4. Based on these findings, systolic unloading is expected to be 
similar when measured via PPG. Systolic unloading will be calculated as the ratio of the 
average systolic amplitude of the last 10 waveforms of baseline PPG before compressions 
divided by the average amplitude of the systolic amplitude of the first 10 waveforms during 
compressions. 
 
Analysis cohort: mITT participants with paired data. 
 
Analysis methods: 
Descriptive statistics will be used to summarize systolic unloading including mean, standard 
deviation, median, and minimum and maximum. Additionally, the count and percentage of 
participants who have systolic unloading values >=11%. 
 
Secondary Effectiveness Endpoint 2: 
Number of participants that complete 10 mins of each of the ECP devices (Wave PRO and 
predicate ECP device). 
 
Analysis cohort: mITT participants with an attempt to receive Wave PRO ECP. 
 
Analysis methods: 

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The count and proportion of participants that successfully completed the planned 10 min of 
Wave PRO ECP and the predicate ECP device will be summarized. 
 
Secondary Effectiveness Endpoint 3: 
Participant comfort level with the Wave PRO and predicate ECP device, assessed at the 
conclusion of each ECP session (i.e., using a Likert scale). 
 
Analysis cohort: mITT participants  
 
Analysis methods: 
Descriptive statistics will be used to summarize the participant’s comfort by ECP device. 
 
Secondary Effectiveness Endpoint 4:  
Time to set up a participant (i.e., sleeved up and sensors attached) and ready to start treatment. 
 
Analysis cohort: mITT participants  
 
Analysis methods: 
Descriptive statistics will be used to summarize the setup time by ECP device. 
 
Secondary Effectiveness Endpoint 5:  
Participant preference for one of the two ECP systems (assuming 35 hours for a full course of 
ECP). 
 
Analysis cohort: mITT participants  
 
Analysis methods: 
The count and proportion of participants that selected their preference as the Wave PRO vs all 
mITT participants. 
 
9.3.4 POOLABILITY 
Since enrollment will occur at only one center due to the challenges of the large size of the 
predicate device, no poolability analysis will be performed.  
9.3.5 SUB-GROUP ANALYSES 
  
Descriptive statistics will be used to summarize primary and secondary effectiveness endpoint 
data by treatment arm and for the difference (Wave PRO – predicate ECP) for the following 
subgroups: 
• 
Gender 
• 
Age groups (above and below median) 

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• 
Race 
• 
Fitzpatrick skin type 
9.3.6 EXPLORATORY ANALYSES 
  
None. 
 

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10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 INFORMED CONSENT PROCESS 
  
Participants may be pre-screened using IRB approved materials prior to informed consent. 
Participants must be fully counseled and informed of their options, risks and benefits, and 
should have every opportunity to ask questions about participation in the clinical investigation. 
This process includes a thorough explanation of the informed consent form that the participant 
will be asked to sign, acknowledging that they understand and desire to participate in the clinical 
investigation.  
 
The Investigator is responsible for assuring that written informed consent is obtained from each 
participant prior to start of study activities. Should the Investigator delegate the responsibility of 
conducting the informed consent process to a designee, the Investigator must ensure and 
document appropriate training of the authorized designee. The Investigator will use an approved 
informed consent form that was prepared in accordance with this protocol, the IRB, and all local 
regulatory requirements.  
 
While an Investigator may discuss availability of the investigation with a prospective participant 
without first obtaining consent, informed consent should always be obtained from a participant 
prior to initiation of any clinical procedures or assessments dictated by the protocol that are 
performed solely for the purpose of determining eligibility to participate in the clinical 
investigation unless the procedures or assessments are conducted as part of the participant’s 
routine care and were obtained before signing the ICF.  
 
If new information regarding the investigational device becomes available and/or the clinical 
investigation plan changes and this information can significantly affect a participant's future 
health and medical care, participants will be informed of the information and may be asked to 
sign a revised informed consent form. The Investigator or the Investigator’s designee will inform 
participants that their medical records will be available for review by the Sponsor or appropriate 
regulatory bodies. The Investigator will explain the conditions of the study, giving the participant 
sufficient time to ask questions and to consider whether or not they want to participate. If the 
participant agrees, they shall be given an approved consent form for signature and date. This 
must be completed by the participant prior to the commencement of study-specific procedures. 
10.1.1.1 CONSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
  
Participant facing materials, including the informed consent, must be approved by the IRB 
before use with participants. 

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10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
  
A statement that written informed consent was obtained before the participant was enrolled in 
the study and the date the written consent was obtained must be entered in the participant’s 
medical record. One signed informed consent copy shall be returned to the Investigator and 
filed in the participant’s case history; the other signed informed consent copy is for the 
participant to keep. 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
  
The Sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study sites will be closed following 
study completion. If the study is prematurely terminated or suspended, the Sponsor shall 
promptly inform the Investigators, the IRB, the regulatory authorities, as applicable, and any 
CRO(s) used in the study of the reason for termination or suspension, as specified by the 
applicable regulatory requirements. The Investigator shall promptly inform the participant and 
should ensure appropriate participant therapy and/or follow-up.  
 
A study site is considered closed after all participants have exited, data analyses have been 
completed, all required documents and study supplies have been collected, a study-site closure 
visit has been performed and the IRB has been notified. The Investigator may initiate study-site 
closure at any time, provided there is reasonable cause and sufficient notice is given in advance 
of the intended termination. Reasons for the early study closure of a study site by the Sponsor 
may include but are not limited to:  
o Determination of unexpected, significant, or unacceptable risk to participants  
o Demonstration of effectiveness that would warrant stopping  
o Insufficient compliance to protocol requirements  
o Data that are not sufficiently complete and/or evaluable  
o Determination that the primary endpoint has been met  
o Determination of futility  
o Business reasons (e.g., lack of funding) 
For site termination:  
o Failure of the Investigator to comply with the protocol, the requirements of the IRB or 
local health authorities, the Sponsor’s procedures, or GCP guidelines.  
o Inadequate or no recruitment of participants by the Investigator. 
10.1.3 CONFIDENTIALITY AND PRIVACY 
  

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The clinical trial will be conducted in accordance with the relevant local and national 
confidentiality and privacy regulations. Participant confidentiality will be maintained throughout 
the study in a way that assures that data can always be tracked back to the source data. 
Participants will be assigned a unique participant ID and treatment ID that will be utilized for 
data analyses and reporting. Only authorized individuals will have access to identifying 
information and it will require a unique login and password. All data and information collected 
during this study will be considered confidential by the study sponsor. All data used in the 
analyses and summary of this study will be anonymized, and without reference to specific study 
participant names. Access to study participants files will be limited to study sponsor monitors, 
case support and Sponsor designees, the Investigator, and research staff. In the case of an 
audit, authorized regulatory authorities have the right to inspect and copy all records pertinent to 
this study. Any source documents reviewed remotely by the Sponsor or Sponsor designee 
should be redacted of any participant identifying information wherever possible.  
10.1.4 SAFETY OVERSIGHT 
  
A Medical Monitor with licensed medical training will oversee the safety aspects of this study to 
evaluate any AEs and assist in identifying any USADE or UADE.  
  
10.1.5 CLINICAL MONITORING 
  
The Clinical Research Organization (CRO), ABio Clinical Research Partners, LLC, is 
responsible for the monitoring of this study. Clinical Research Associates (CRAs) who are 
employees or contractors of the CRO will monitor each site during the course of the Study. The 
monitor will contact and visit the Investigator regularly and will be allowed, on request, to have 
access to all source documents needed to verify the entries on the CRF and other protocol 
related documents.  It will be the monitor’s responsibility to inspect the CRFs at regular intervals 
throughout the Study, to verify the adherence to the protocol and the completeness, consistency 
and accuracy of the data being entered. ABio’s monitoring standards require full (100%) source 
document verification for the presence of informed consent, adherence to the 
inclusion/exclusion criteria, documentation of AEs and the recording of the main effectiveness 
and safety endpoints. Additional random checks of the consistency of the source data with the 
CRFs may be performed. 
 
The Investigator and Co-investigators agree to cooperate with the monitor(s) to ensure that any 
issue detected in the course of these monitoring visits is resolved.  
 
An onsite initiation visit will be performed before the first participant is enrolled. Monitoring visits 
and contacts will occur at regular intervals thereafter per the study specific Monitoring Plan. A 
close-out visit will be performed after Study closure. 

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10.1.6 QUALITY ASSURANCE AND QUALITY CONTROL 
  
All participant data relating to the study will be recorded on electronic case report forms 
(eCRFs) unless transmitted to the Sponsor or designee electronically (i.e., device data). Access 
to EDC requires a unique login and password and training is required before access is granted. 
If Site, Sponsor or Sponsor designee has trained to the EDC system previously, that training 
document may be used as evidence of training.  
 
The Investigator is responsible for verifying that data entries are accurate and correct by 
electronically signing the eCRFs. Guidance on completion of eCRFs will be provided.  
 
The Investigator must permit study-related monitoring, audits, IRB review, and regulatory 
agency inspections and provide direct access to source documents.  
 
Monitoring details describing strategy, including definition of study critical data items and 
processes, methods, responsibilities, and requirements, including handling of noncompliance 
issues and monitoring techniques, are provided in the monitoring plan.  
 
The CRO or designee is responsible for the data management of this study, including quality 
checking of the data. Details regarding data management will be outlined in a study specific 
data management plan. 
 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for 2 years after study completion or Wave PRO regulatory 
approval, whichever is longer, unless local regulations or institutional policies require a longer 
retention period. No records may be destroyed during the retention period without the written 
approval of the Sponsor. No records may be transferred to another location or party without 
written notification to the Sponsor. 
10.1.7 DATA HANDLING AND RECORD KEEPING 
10.1.7.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES - GENERAL 
  
Data management and quality control will be performed by the CRO.  Data will be entered into 
an EDC system by the clinical sites.  Any data queries will be issued to sites as required for 
resolution and entered into the database. The EDC system is 21 CFR Part 11 compliant.  Only 
Research Coordinators or PIs trained to the use of the EDC will have access for data entry.  
Only trained CRAs and Data Managers from the CRO will have access to the EDC for 
Monitoring and Data Management purposes.   
 
The investigator or his/her delegate will perform primary data collection drawn from original 
documents (printed, optical or electronic document containing source data). All source 
documentation must be available for review by the study monitor during monitor visits. Source 

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data is defined as all information in original records, certified copies of original records of clinical 
findings, observations, or other activities in a clinical investigation, necessary for the 
reconstruction and evaluation of the clinical investigation.  
 
The investigators shall ensure the accuracy, completeness, legibility and timelines of the data 
reported in CRF and in all required documentation. Data reported on the eCRF shall be 
supported by the source documents with any discrepancies being explained. If an item is not 
available or is not applicable, this fact should be indicated; no space is to be left blank. The 
investigator who has signed the study protocol signature page or his/her authorized designee is 
to personally electronically sign the eCRFs to validate that the observations and findings are 
recorded on the eCRFs correctly and completely. The eCRFs are to be completed in a timely 
manner after the participant’s visit.  
10.1.7.2 DATA COLLECTION – SITE DATA 
  
A Participant Screening Log will be maintained, listing all participants screened for this Study.  
For each participant, regardless of procedures or visits completed, CRFs will be completed and 
signed by the Principal Investigator or Co-investigator, as applicable. This includes those 
participants who failed to complete the Study. If a participant withdraws from the Study, the 
reason should be noted on the Exit/Termination CRF. Surveys will be completed by the 
participant and collected and entered by the research staff. 
10.1.7.3 DATA COLLECTION – DEVICE DATA 
In addition to the descriptions in sections 6.3 and 6.4, the following data types are referenced in 
the Analysis Charter. 
Data Collection (during ECP sessions): 
• 
Data collected on the BIOPAC Data Acquisition System is an .acq file type. 
• 
Data collected on the predicate ECP system is an .DAT type 
Data Processing Wave PRO (refer to Analysis Charter): 
• 
The .acq file will then be exported as an .csv file type.  
• 
The .csv file path will be used as input within the RStudio integrated development 
environment. 
• 
Using a custom R script, the .csv file will be used to output graphs of the 8th minute 
which should be saved as a PDF. Additionally, the script will output the average DA 
ratio, both systolic amplitude values, and standard deviation in an Excel spreadsheet. 
Data Processing ACS (refer to Analysis Charter): 
• 
The .DAT file and the .mdb database file will be saved on a USB flash drive. 
• 
Insert the flash drive into a computer with the ACS NCP-2 software (NCPPLUS) 
installed. Transfer the .DAT and .mdb files into a folder called “ncpdata” on the 
computer’s (C:) drive. 
• 
Screenshots of the 8th minute, which should be saved as a PNG, will be uploaded to the 
secure data storage. 

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• 
Signal processing will be performed using the custom R script. As DA ratios are 
gathered, the blinded evaluator will record them via CRF to the EDC. 
 
Raw data will be backed up for each participant on a separate flash drive storage device and 
uploaded to a dedicated secure data storage. 
10.1.7.4 STUDY RECORDS RETENTION 
  
All study records and reports will remain on file at the clinical sites for a minimum of 2 years 
after completion of the Study or regulatory approval of the device, whichever is longer, and will 
further be retained in accordance with local and international guidelines as identified in the 
clinical study agreement.  
10.1.8 PROTOCOL DEVIATIONS 
Investigators may not deviate from this clinical investigation plan without first receiving approval 
in writing from the Sponsor, involved IRB(s), and applicable regulatory authorities, except when 
necessary to eliminate apparent immediate hazards to a participant. All deviations will be 
documented on eCRFs.  
All deviations will be reported to the CRO within 24 hours of the Investigator becoming aware.  
 
With the help of the CRO, the Investigators will also adhere to procedures for reporting 
deviations to the involved IRB(s) in accordance with their specific reporting policies and 
procedures.   
 
Protocol deviations regarding Informed Consent procedures, inclusion/exclusion criteria and 
deviations that affect the primary endpoints are considered major protocol deviations. The 
monitor is responsible for major/minor classification of the deviations.    
10.1.9 PUBLICATION AND DATA SHARING POLICY 
Only the independent data evaluator/analyst and trained study personnel explicitly approved by 
Pression LLC will be allowed to handle the raw and processed data. 
 
During the study, all data will be stored locally on the data acquisition and analysis laptop. Raw 
data will be backed up after each participant on a separate flash drive and uploaded to a 
dedicated secure data storage for the study. 
 
Upon completion of the study, access to clinical trial data will be limited to Pression personnel 
and the clinical study site (for up to 2 years after completion of the Study or regulatory approval 
of the device, whichever is longer, and in accordance with regulatory guidelines). Sharing of 
data to external entities and individuals (outside of Pression and the clinical study) will require 
approval from Pression and a signed non-disclosure agreement (NDA). 
 

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All data pertaining to clinical research conducted or sponsored by Pression is proprietary and 
confidential. Sharing of data from this study requires explicit approval from Pression.  
For intentional dissemination of the clinical research data, as is the case for publications and 
scientific meetings, images, and summaries of collected data can be found in the 
manuscript/presentation itself, having been peer-reviewed and approved for publication. 
Specific requests for metadata, source material, design files, and proprietary code will be 
evaluated internally by Pression. All data and files generated at or for Pression in relation to 
R&D or clinical research of a product is considered proprietary and confidential. Pression 
ultimately reserves the right to admit or revoke data access. Intentional dissemination of clinical 
data collected during research will be anonymized and will not contain personal identifiable 
information. Data and images showcased in the form of publication and or website showcase 
will contain disclaimers dictating their condition for use (unless it is intentionally designated as 
Creative Commons). 
10.1.10 CONFLICT OF INTEREST POLICY 
The clinical study will be managed and monitored by an independent Clinical Research 
Organization (CRO) on behalf of Pression LLC.  
 
Principal Investigators (PI) from the research study centers will not have a financial interest in 
Pression. 
 
A blinded evaluator will be assigned to analyze and score the ECP data recorded during the 
study. The blinded evaluator will not have a financial interest in Pression. 
10.2 NON-SIGNIFICANT RISK (NSR) STUDY 
The Wave PRO System does not meet the below definition of significant risk under 21 CFR 
812.3(m), and therefore this study will be conducted in accordance with the abbreviated IDE 
requirements listed in 21 CFR 812.2(b) for non-significant risk (NSR) devices. As defined in 
812.3(m), a significant risk device means an investigational device that: 
 
• 
Is intended as an implant and presents and potential for serious risk to the health, 
safety, or welfare of a subject; 
• 
Is purported or represented to be for use supporting or sustaining human life and 
presents a potential for serious risk to the health, safety, or welfare of a subject; 
• 
Is for a use of substantial importance in diagnosing, curing, mitigating, or treating 
disease, or otherwise preventing impairment of human health and presents a potential 
for serious risk to the health, safety, or welfare of a subject; or 
• 
Otherwise presents a potential for serious risk to the health, safety, or welfare of a 
subject.  
 

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The Wave PRO System is not an implant, is not purported or represented for use in supporting 
or sustaining human life, and, based on data from prior experience, does not appear to present 
the potential for serious risk to the health, safety or welfare of a participant.   
 
The abbreviated IDE requirements per 21 CFR 812.2(b) apply to this study.  
10.3 ABBREVIATIONS 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and 
Accountability Act 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation 
ICMJE 
International Committee of Medical Journal 
Editors 
IDE 
Investigational Device Exemption 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ISO 
International Organization for 
Standardization 
ITT 
Intention-To-Treat 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
UADE 
Unanticipated Adverse Device Effect 
USADE 
Unanticipated Serious Adverse Device Effect 
US 
United States 

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10.4 PROTOCOL AMENDMENT HISTORY 
Version 
Date 
Description of Change  
Brief Rationale 
 1.0 
TBD 
N/A – Initial Version 
N/A 

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