Phase 2, Randomized Study of the Tolerability and Safety of the OsciPulse Device for the Prevention of VTE
Phase: NA
Conditions: Venous Thromboembolism, Deep Vein Thrombosis, Pulmonary Thromboembolisms
Sponsor: University of Pennsylvania



 
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Table of Contents 
List of Abbreviations .........................................................................................................5 
PRINCIPAL INVESTIGATOR SIGNATURE ..............................................................6 
1 
Study Summary ..........................................................................................................7 
1.1 
Key Roles and Study Governance ......................................................................10 
1.2 
Schema ..................................................................................................................10 
Figure 1. Study Schema 
10 
2 
Background and Study Rationale ...........................................................................10 
2.1 
Study Rationale ....................................................................................................11 
2.2 
Background and Relevant Literature ................................................................11 
2.3 
Name and Description of the Investigational Product......................................12 
2.3.1 
Clinical Data to Date ......................................................................................13 
2.4 
Known Potential Risks ........................................................................................13 
2.5 
Risk Benefit Assessment ......................................................................................14 
3 
Study Objectives .......................................................................................................14 
3.1 
Primary Objective ................................................................................................14 
3.2 
Secondary Objectives...........................................................................................14 
4 
Study Plan..................................................................................................................14 
4.1 
Study Design .........................................................................................................14 
4.2 
Justification for treatment regimen ...................................................................14 
4.2.1 
Screening and Enrollment Phase ..................................................................15 
4.2.2 
Study Intervention Phase ..............................................................................15 
4.3 
End of Study Definition .......................................................................................15 
4.4 
Allocation to Interventional Group ....................................................................16 
4.5 
Protocol-defined Enrollment Hold .....................................................................16 
4.6 
Study Endpoints ...................................................................................................16 
4.6.1 
Primary Study Endpoints..............................................................................16 
4.6.2 
Secondary Study Endpoints ..........................................................................16 
5 
Study Population and Duration of Participation ...................................................17 
5.1 
Inclusion Criteria .................................................................................................17 
5.2 
Exclusion Criteria ................................................................................................17 
5.3 
Subject Recruitment ............................................................................................18 
5.4 
Duration of Study Participation .........................................................................18 
5.5 
Total Number of Subjects and Sites ...................................................................18 
5.6 
Vulnerable Populations .......................................................................................18 
6 
Study Intervention; OsciPulse Device .....................................................................18 
6.1 
OsciPulse Description ..........................................................................................18 
Figure 2 OsciPulse Device 
19 
6.2 
Intervention Regimen ..........................................................................................19 
6.3 
Receipt ...................................................................................................................19 
6.4 
Storage ..................................................................................................................20 
6.5 
Preparation and Packaging .................................................................................20 
6.6 
Blinding .................................................................................................................20 
6.7 
Administration and Accountability ....................................................................20 
6.8 
Product Problems and Complaints ....................................................................21 

 
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6.9 
Return or Destruction of Investigational Product ............................................21 
7 
Study Procedures ......................................................................................................21 
Figure 3 Schedule of Study Procedures .........................................................................21 
7.1 
Pre-screening ........................................................................................................22 
7.2 
Screening and enrollment....................................................................................22 
7.3 
Study Intervention Phase ....................................................................................23 
7.3.1 
Part 1 Hour 0-3...............................................................................................23 
7.3.2 
Part 2 Hour 1-3...............................................................................................23 
7.3.3 
Part 2 Hour 3(+/-1)-6 .....................................................................................23 
7.4 
Subject Withdrawal .............................................................................................23 
7.4.1 
Data Collection and Follow-up for Withdrawn Subjects ...........................23 
7.5 
Early Termination Visits .....................................................................................23 
8 
Study Evaluations and Measurements....................................................................24 
8.1 
Demographics .......................................................................................................24 
8.2 
Medical Record Review (Part 2 only) ................................................................24 
8.3 
Laboratory Tests (Part 2 only) ...........................................................................24 
8.4 
Vital Signs (Part 2 only) ......................................................................................24 
8.5 
Hemodynamic ultrasonography .........................................................................25 
8.6 
Questionnaires ......................................................................................................25 
8.7 
Safety Evaluations ................................................................................................25 
9 
Statistical Plan ...........................................................................................................25 
9.1 
Part 1 .....................................................................................................................25 
9.2 
Part 2 .....................................................................................................................26 
9.2.1 
Primary Endpoint ..........................................................................................26 
9.2.2 
Secondary Endpoints .....................................................................................26 
9.2.3 
Sample Size and Power Determination ........................................................26 
9.2.4 
Statistical Methods .........................................................................................26 
9.2.5 
Baseline Data ..................................................................................................27 
9.2.6 
Efficacy Analysis ............................................................................................27 
9.2.7 
Safety Analysis ...............................................................................................27 
9.3 
Subject Population(s) for Analysis .....................................................................27 
10 Safety and Adverse Events .......................................................................................27 
10.1 
Definitions .............................................................................................................27 
10.1.1 
Adverse Event/Adverse Device Effect (AE/ADE) .......................................27 
10.1.2 
Unanticipated Adverse Device Effect (UADE) ............................................28 
10.1.3 
Serious Adverse Event (SAE) .......................................................................28 
10.1.4 
Adverse Events of Special Interest (AESI) ..................................................28 
10.2 
Recording and Classification of Adverse Events ..............................................28 
10.2.1 
Severity of Event ............................................................................................29 
10.2.2 
Relationship of AE to Study ..........................................................................29 
10.3 
Reporting of Adverse Events, Adverse Device Effects and Unanticipated 
Problems ...............................................................................................................30 
10.3.1 
Follow-up report ............................................................................................30 
10.3.2 
Investigator Reporting: Local Reporting Requirements ...........................31 
10.4 
Investigator Reporting: Notifying the study Sponsor.......................................31 
10.4.1 
SAE and UADE ..............................................................................................31 

 
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10.4.2 
Failure to Obtain Informed Consent and Withdrawal of IRB Approval .31 
10.4.3 
Product Complaints .......................................................................................31 
10.4.4 
Protocol Deviations ........................................................................................31 
10.5 
Stopping Rules ......................................................................................................31 
10.6 
Data and Safety Monitoring ................................................................................32 
10.7 
Data Safety Monitoring Board (DSMB) ............................................................32 
11 Study Administration, Data Handling and Record Keeping ................................32 
11.1 
Data Collection and Management Responsibilities ..........................................32 
11.2 
Records Retention ................................................................................................32 
11.3 
Protocol Deviations ..............................................................................................33 
11.4 
Regulatory, Ethical, and Study Oversight Considerations ..............................33 
11.4.1 
Informed Consent Process / HIPAA Authorization ...................................33 
11.4.2 
Study Discontinuation and Closure ..............................................................34 
11.4.3 
Confidentiality and Privacy ..........................................................................34 
11.4.4 
Quality Assurance and Quality Control ......................................................35 
11.4.5 
Funding Source ..............................................................................................35 
11.4.6 
Conflict of Interest Policy ..............................................................................35 
11.4.7 
Subject Stipends or Payments ......................................................................36 
11.4.8 
Part 1 ...............................................................................................................36 
11.4.9 
Part 2 ...............................................................................................................36 
11.5 
Publication and Data Sharing Policy .................................................................36 
11.6 
Protocol Amendment History .............................................................................36 
12 References ..................................................................................................................38 
 
 
Table of Figures 
Figure 1. Study Schema ...................................................................................................10 
Figure 2 OsciPulse Device ...............................................................................................19 
Figure 3 Schedule of Study Procedures .........................................................................21 
 
 

 
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PRINCIPAL INVESTIGATOR SIGNATURE 
 
STUDY 
SPONSOR: 
University of Pennsylvania 
STUDY TITLE: 
Phase 2, Randomized Study of the Tolerability and Safety of the OsciPulse 
Device for the Prevention of VTE 
STUDY ID 
PROTOCOL 
VERSION 
IRB # 844294; NCT04625673 
Version 6.0, 01 Jun 2022 
I have read the referenced protocol. I agree to conduct the study in accordance to this protocol, in 
compliance with the Declaration of Helsinki, Good Clinical Practices (GCP), and all applicable 
regulatory requirements and guidelines. 
Principal 
Investigator Name  
Adam Cuker, MD 
 
Signature 
 
Affiliation: 
University of Pennsylvania 
 
Date 
 
 
 
 
 
 
 
 

 
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1 STUDY SUMMARY 
Title 
A phase 2, randomized study of the tolerability and safety of the 
OsciPulse device for the prevention of VTE 
Short Title 
OsciPulse tolerability trial 
Phase 
Phase 2 
Methodology 
Randomized, crossover study 
Study Duration 
4 months  
Study Center(s) 
Penn Presbyterian Medical Center 
Objectives 
Part 1:  
Primary  
• To determine the tolerability of the OsciPulse device on healthy 
individuals. 
Secondary: 
• To determine the hemodynamic impact of the OsciPulse device 
on venous blood flow. 
 
Part 2: 
Primary: 
● To determine the tolerability and safety of the OsciPulse device   
● To evaluate device design with respect to initial clinical safety 
and device functionality. 
Secondary: 
• To assess the compliance of the OsciPulse device compared to a 
standard intermittent pneumatic compression device. 
• To evaluate the ultrasonographic hemodynamic parameters of 
the OsciPulse device compared to a standard intermittent 
pneumatic compression device. 

 
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Part 2: Adverse events will be collected.  Expected AEs in this 
population include VTE, skin ulceration, peripheral nerve palsy, limb 
ischemia, and falls.  
Data and Safety 
Monitoring Plan  
The Sponsor is responsible for monitoring the data quality and the 
ongoing safety of subjects.  
 
 
 

 
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all applicable Federal and state laws and regulations including Good Clinical Practice standards. 
All episodes of noncompliance will be documented. 
2.1 
Study Rationale 
Venous thromboembolism (VTE) is a major complication occurring in hospitalized subjects. 
Although anticoagulants and mechanical prophylaxis are commonly used to prevent VTE it 
remains a leading cause of complications and death in the hospital population. Anticoagulation 
has been demonstrated to reduce the rates of hospital acquired VTE, but also has increased rates 
of bleeding complications. Mechanical prophylaxis is typically used together with 
anticoagulation and has no bleeding risk. However, existing methods of mechanical 
thromboprophylaxis have some limitations including equivocal efficacy and subject discomfort, 
which may undermine adherence.  The new OsciPulse device was designed based on recent 
advancements in our understanding of the molecular basis of deep vein thrombosis (DVT) 
formation to improve the efficacy of mechanical devices in preventing DVT/VTE. The objective 
of this study is to evaluate device design with respect to initial clinical safety and device 
functionality.  
2.2 
Background and Relevant Literature 
Venous thromboembolism (VTE), which includes deep-vein thrombosis (DVT) and pulmonary 
embolism (PE), is the third most common cardiovascular disease with over 1 million new cases 
per year in the United States1. VTE is associated with significant morbidity and mortality. The 
mortality rates after first VTE events are 6% at 30 days and 21% at 1 year2. Long term 
complications include recurrent VTE, post-thrombotic syndrome, and chronic thromboembolic 
pulmonary hypertension. Approximately 50% of VTE cases are attributable to current or 
preceding hospitalization, while 12% and 7% are associated with trauma and neurological 
disease with extremity paresis, respectively3. Immobilization and lower-limb paralysis are 
independent risk factors for VTE in hospitalized subjects4. These well-recognized risks establish 
the need for effective VTE prevention in high-risk populations. If administered appropriately, a 
significant number of VTE cases will be preventable by thromboprophylaxis.   
Thromboprophylaxis strategies can be categorized into pharmacological (with anticoagulants) 
and mechanical (with gradual compression stockings [GCS] or intermittent pneumatic 
compression [IPC] devices). Current clinical practice guidelines suggest using pharmacological 
thromboprophylaxis over mechanical thromboprophylaxis, and they are often used in 
conjunction with each other 5,6. However, many subjects are not suitable candidates for 
anticoagulants because of contraindications such as bleeding or thrombocytopenia. In such cases, 
mechanical thromboprophylaxis provides the only prophylactic option. In suitable acutely ill 
medical subjects who do not receive pharmacological thromboprophylaxis, the American Society 
of Hematology VTE guideline suggests mechanical prophylaxis over no prophylaxis. One of the 
advantages of mechanical prophylaxis is its favorable safety profile. Although possible, the risk 
of serious harmful effects associated with the currently available options for mechanical 
thromboprophylaxis, such as limb ischemia or skin ulceration, are exceedingly rare. 
The benefit of mechanical prophylaxis, however, remains controversial. In a systematic review 
of randomized controlled trials (RCT) of stroke subjects7, mechanical prophylaxis (GCS and 
IPC) did not show a significant reduction in VTE or death. In another large RCT in stroke 

 
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2.5 
Risk Benefit Assessment 
The risks of participating in the study are outweighed by the potential benefits of participating in 
the study. Study procedures, including, the hemodynamic ultrasonography are not known to pose 
any additional health risk. If during the hemodynamic ultrasonography a DVT is incidentally 
identified, the findings will be reported to the subject’s treating clinical team. The subject will be 
removed from the study and further testing or treatment will be at the discretion of the clinical 
team.  
Direct benefits to the participating subjects include the potential benefit of VTE prevention by 
mechanical thromboprophylaxis. Indirect benefits include collecting more clinical data in terms 
of safety and tolerability to assist the development of better devices for VTE prevention in the 
future. 
3 STUDY OBJECTIVES 
3.1 
Primary Objective 
Part 1: To determine the tolerability of the OsciPulse device on healthy individuals. 
Part 2: To assess the safety and tolerability of the OsciPulse device compared to a standard 
intermittent pneumatic compression device. 
3.2 
Secondary Objectives  
Part 1: To determine the hemodynamic impact of the OsciPulse device on venous blood flow. 
Part 2: To assess the compliance of the OsciPulse device compared to a standard intermittent 
pneumatic compression device. 
To evaluate the ultrasonographic hemodynamic parameters of the OsciPulse device compared to 
a standard intermittent pneumatic compression device. 
4 STUDY PLAN  
4.1 
Study Design 
This is a single site, two-part study.  Part 1 is in healthy subjects testing the tolerability of the 
device. Part 2 is a Phase 2, randomized crossover study in subjects with the potential to develop 
VTE evaluating the OsciPulse device compared to a standard intermittent pneumatic 
compression device. Our hypothesis is that the safety and tolerability of the OsciPulse device is 
equivalent to the standard compression device. 
4.2 
Justification for treatment regimen 
Three hours of use for each device to allow for sufficient time for subjects to become familiar 
with the functional differences in each device to provide meaningful feedback on their 
experiences. 

 
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4.2.1 
Screening and Enrollment Phase 
Part 1: Subjects who are recruited from the general population will be screened for eligibility by 
answering questions about their general health and foot or ankle injuries. Subject demographics 
will be collected; however no medical record review will be conducted. Written informed 
consent will be obtained from eligible subjects. 
Part 2: Subjects who are admitted for inpatient care following admission to Penn Presbyterian 
Medical Center will be identified and screened for eligibility. Written informed consent will be 
obtained from eligible subjects by Pennsylvania licensed medical professional. Video consent 
may be used. 
4.2.2 
Study Intervention Phase  
Part 1: Enrolled healthy subjects will have the OsciPulse device applied by study or medical 
personnel according to the OsciPulse Instructions for Use. The subject will wear the device for a 
maximum of 3 hours while laying down. At the end of the study period the subject will receive 
an ultrasound scan of the deep venous system of the thigh/groin region to measure 
hemodynamics at a venous valve during immobility and during use of the OsciPulse device. 
Finally, the subject will participate in a questionnaire evaluation of their comfort and experience 
with the OsciPulse device. Participants will be compensated at $50/ hour for their participation. 
Part 2: After informed consent is obtained, baseline demographic and clinical data will be 
collected. The subjects will be randomized with equal allocation to either of the two treatment 
sequence groups:  
• Group A (OsciPulse device then standard IPC device)  
• Group B (standard IPC device then OsciPulse device)  
For group A, the OsciPulse device will be applied  to the subject on both legs in the first 3 hours. 
The subject will wear the device for the maximum number of hours as possible up to 3 hours. 
The 
research team inquire with the subject if the device was removed during the testing 
period.. During the 3-hour period the study team will monitor for adverse events and a 
hemodynamic ultrasonography may be performed (when feasible) following the Ultrasound 
SOP. After 3 hours, the subject will complete the questionnaire evaluating the tolerability and 
safety of the device. In the following 3 hours, the standard IPC will be applied. Subjects will 
undergo the same procedure for compliance monitoring, adverse event monitoring, 
hemodynamic ultrasonography (when feasible), and questionnaire evaluation.  
For group B, the same procedure will be performed but with the standard IPC in the first 3 hours 
and the OsciPulse device in the next 3 hours.  
Participants will be compensated $100 for their participation. 
4.3 
End of Study Definition 
A participant is considered to have completed the study if he or she has completed the 
intervention phase of the study.  

 
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4.4 
Allocation to Interventional Group  
All enrolled subjects will be assigned to both interventions. 
 will allocate the treatment 
sequence groups (group A: OsciPulse then IPC and group B: IPC then OsciPulse) in a 1:1 ratio 
by using block randomization. Prior to the study launch, 
 will create 4 envelopes.  Each 
envelope will contain a GreenPhire card that will contain subject compensation, and a 
randomization form for either group A or for group B. This group of 4 envelopes will maintain 
the 1:1 ratio of randomization to group A or group B. Once all 4 envelopes have been sealed, 
they will be shuffled so that none of the research team knows which envelope contains each 
randomization form. Once the envelopes have been shuffled, the 
study team member will 
place them in a random order and write subject study ID number on the outside of the envelope, 
indicating which subject they will be used for. For the first group, this will generate 
randomization for subjects one through four. When a subject is enrolled, the subject will be 
assigned a study identification number and the CRC will select the envelope with corresponding 
study-ID number—this will serve as the patient randomization. This process will be repeated 4 
additional times in order to provide randomization for subjects 5 – 20. Once the envelope has 
been selected, the study team member will open the envelope, deliver the GreenPhire card to the 
subject and record the subject’s intervention group onto a spreadsheet.  The randomization 
sequence spreadsheet, randomization assignment sheet, and envelope will be kept and 
maintained a
, which will be secure and accessible only by 
 staff and the nursing 
staff.  
4.5 
Protocol-defined Enrollment Hold 
Part 2: In the event a disproportionate number of subjects are enrolled with a singular diagnosis, 
the Investigator in consultation with the Sponsor may pause the study to enrollment to reevaluate 
or revise, or both, the enrollment strategy, the intended subject population, the statistical 
analysis, or several of these activities. 
4.6 
Study Endpoints  
4.6.1 
Primary Study Endpoints 
The primary endpoint will be subject safety and tolerability. Safety will be evaluated by the 
presence of adverse events (See section 10) during the intervention. Tolerability will be 
evaluated by a subject reported questionnaire. Tolerability will be measured by the 100-mm 
visual analog scale (VAS) and through open ended question answers. The average distance on 
the VAS in each domain of the questionnaire will be compared between the OsciPulse device 
and standard IPC. 
4.6.2 
Secondary Study Endpoints 
• Percentage of time wearing the OsciPulse and standard IPC devices  
• Ultrasonographic hemodynamic parameters (Change in venous centerline velocity in the 
femoral vein and volume of venous valve sinus reversing flow at the sapheno-femoral 
junction or other valve site imaged) 

 
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5 STUDY POPULATION AND DURATION OF PARTICIPATION  
5.1 
Inclusion Criteria 
Part 1: 
1. Adult age ≥40 years old 
2. Generally healthy without a current foot or ankle injury 
3. No history of diagnosed vascular disease including: DVT, PE, VTE, peripheral vascular 
disease, post-phlebitic syndrome, or chronic venous insufficiency. 
4. Mentally alert and understand English proficiently. 
5. Able to give informed consent. 
Part 2: 
1. Adult age ≥18 years old 
2. Admitted to Penn Presbyterian Medical Center. 
3. Anticipated decreased level of mobility for at least 6 hours as determined by the clinical 
team in collaboration with 
. 
4. Mentally alert and understand English proficiently. 
5. Able to give informed consent. 
5.2 
Exclusion Criteria 
Part 1: 
1. Injury to the lower limbs 
2. Skin breaks, abrasion, or irritation in the area of the limb in contact with the OsciPulse 
device 
Part 2: 
1. Inability or contraindication to applying IPC to both legs  
o Evidence of bone fracture in lower extremities  
o Burns in the lower extremities, lacerations, ulcers, active skin infection or 
dermatitis, & ischemic limb in the legs at the site of IPC placement  
o Acute ischemia in the lower extremities  
o Severe peripheral vascular disease  
o Amputated foot or leg on one or two sides 
o Compartment syndrome  
o Severe lower extremity edema 
2. Subjects anticipated to require surgical intervention within six (6) hours of admission 
3. Subjects with history of VTE (DVT or PE)  

 
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• Adverse Events 
Part 2: 
● Informed consent  
● Review inclusion/exclusion criteria 
● Medical record review & Demographics 
● Vital signs 
● Randomization of treatment sequence  
● Adverse Events 
7.3 
Study Intervention Phase 
7.3.1 
Part 1 Hour 0-3 
• Application of the OsciPulse device 
• Adverse Event monitoring 
• Hemodynamic ultrasonography 
• Tolerability Questionnaire 
7.3.2 
 Part 2 Hour 1-3 
● Application of OsciPulse device (Group A) or IPC device (Group B) 
●  
● Hemodynamic ultrasonography (when feasible) 
● Questionnaire assessment at the end of 3 hours  
● Adverse Events 
● Laboratory Results 
7.3.3 
 Part 2 Hour 3(+/-1)-6 
● Application of IPC device (Group A) or OsciPulse device (Group B) 
● Hemodynamic ultrasonography (when feasible) 
● Questionnaire assessment at the end of 6 hours  
● Adverse Events 
7.4 
Subject Withdrawal 
Subjects may withdraw from the study at any time without impact to their care. 
7.4.1 
Data Collection and Follow-up for Withdrawn Subjects 
There will be no attempts to collect data from participants who have withdrawn consent.  
However, the Sponsor will retain all data collected for each subject prior to withdrawal.  
7.5 
Early Termination Visits 
Subjects who terminate their participation early will receive no further follow up. 

 
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8 
STUDY EVALUATIONS AND MEASUREMENTS 
8.1 
Demographics 
The following demographic information will be obtained 
• Date of birth 
● Gender 
● Race 
8.2 
Medical Record Review (Part 2 only) 
The Medical Record review will be conducted to provide a description of the enrolled patients to 
aid in the interpretation of the reported outcomes of the study. 
● Height 
● Weight 
● Admitting diagnosis and co-morbidities related to DVT/VTE risk, including: 
Heart Failure; diabetes; known thrombophilic states (protein C, protein S, or antithrombin 
deficiency; thrombotic thrombocytopenic purpura; hemolytic-uremic syndrome; activated 
protein C resistance; factor V Leiden thrombophilia, prothrombin gene mutation; 
antiphospholipid antibody; hyperhomocysteinemia); post-partum status (within 6 
months); estrogen therapy (oral contraceptive or hormone replacement); active 
malignancy (treatment within the past 6 months or palliation); history of malignancy 
(within the past 5 years, other than non-melanoma skin cancer); paralysis or 
immobilization of a lower or upper extremity related to stroke or injury before this 
hospital admission; hospitalization in the past 3 months for any reason (excluding this 
hospital admission); trauma (including acute spinal cord injury, hip fracture, pelvic 
fracture, femoral fracture and tibial, fibular, knee or other fractures below knee); recent 
surgery (in the last 48 h); acute stroke (in this index hospital admission); prior DVT or 
VTE; tumor or malignancy; hospitalization in previous 3 months 
● Length of stay 
● Use of pharmacological thromboprophylaxis and types of agents if used 
● Use of pharmacological anticoagulant/antiplatelet therapy, type, dose 
● Injury Severity Score (ISS) 
8.3 
Laboratory Tests (Part 2 only) 
Of the initial labs drawn by the clinical team upon patient admission to the hospital, results from 
the complete blood count (hemoglobin, platelets) and coagulation panel (PT, PTT, INR) will be 
recorded on the case report form. 
8.4 
Vital Signs (Part 2 only) 
Body temperature, heart rate, respiratory rate, and blood pressure will be measured by standard 
procedure at the time of subject enrollment.  

 
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paired t-test. We will evaluate the primary endpoint of tolerability through quantification of the 
difference between the visual analog scale markings on the patient questionnaire for each device. 
We will also use a paired t-test to evaluate the changes in venous flow that occur in each patient 
during use of both devices. 
9.2.5 
Baseline Data 
Baseline and demographic characteristics will be summarized by standard descriptive statistics 
(including mean and standard deviation for continuous variables such as age and standard 
percentages for categorical variables such as gender). 
9.2.6 
Efficacy Analysis  
Efficacy will be scored by the ultrasound measurements of venous blood flow during the use of 
the OsciPulse device and reference therapy device. Ultrasound measurements during device 
action will provide quantification of centerline venous flow velocity, the amount of flow within 
the sinus of the valve at the sapheno-femoral junction, and the amount of reversing flow in the 
sinus of the sapheno-femoral junction valve. Measurements may be taken at other vascular sites 
if the visualization window is not of sufficient quality for data collection at the sapheno-femoral 
junction. These measurements will be compared for each device and difference for each 
individual patient will be quantified and a paired t-test will be used to evaluate the overall 
efficacy. 
9.2.7 
Safety Analysis  
All subjects entered into the study and randomized at the baseline visit will have detailed 
information collected on adverse events for the overall study safety analysis 
9.3 
Subject Population(s) for Analysis 
We will analyze the Protocol-compliant population defined as any subject who was randomized 
and received the protocol required investigational product exposure, the reference therapy 
product exposure, and completed the required questionnaires and ultrasound examinations. 
Subjects who are enrolled but do not complete the protocol requirements will not be analyzed. 
10 SAFETY AND ADVERSE EVENTS 
10.1 Definitions 
10.1.1 
Adverse Event/Adverse Device Effect (AE/ADE) 
An adverse event (AE) is any untoward medical occurrence that develops or worsens in severity 
during the course of the study. Intercurrent illnesses or injuries should be regarded as adverse 
events.  A pre-existing condition should be recorded as an adverse event if the frequency, 
intensity or the character of the condition changes. A clinical laboratory abnormality should be 
documented as an adverse event if any of the following conditions is met: 
● Is not otherwise refuted by a repeat test to confirm the abnormality  
● Suggests a disease and/or organ toxicity 
● Is of a degree that requires active management  

 
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10.1.2 
Unanticipated Adverse Device Effect (UADE) 
Unanticipated adverse device effect is any serious adverse effect on health or safety, 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 application, 
or any other unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of subjects. 
10.1.3 
Serious Adverse Event (SAE) 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that, 
in the view of either the investigator or the sponsor, is:  
● fatal 
● life-threatening 
● requires or prolongs hospital stay 
● results in persistent or significant disability or incapacity 
● a congenital anomaly or birth defect 
● an important medical event  
● require intervention to prevent permanent impairment or damage 
Important medical events are those that may not be immediately life threatening but are clearly 
of major clinical significance. They may jeopardize the subject and may require intervention to 
prevent one of the other serious outcomes noted above. For example, drug overdose or abuse, a 
seizure that did not result in in-patient hospitalization, or intensive treatment of bronchospasm in 
an emergency department would typically be considered serious. 
10.1.4 
Adverse Events of Special Interest (AESI) 
Newly developed DVT, pulmonary embolism, peripheral nerve palsy, skin ulceration NPUAP 
category III and IV, limb ischemia due to OsciPulse or IPC device are adverse events of special 
interest.  These events may be related to use of the OsciPulse device and any incidence of these 
events should be reported to the sponsor.  
10.2 Recording and Classification of Adverse Events 
While admitted to the hospital and enrolled in the study, the electronic medical record will be 
screened upon completion of the subject’s participation in the study for the presence of adverse 
events by the 
 research team. The subject will be questioned about adverse events during 
the 6-hour Interventional Phase of the study.. Information on all adverse events will be recorded 
in a timely manner in the appropriate adverse event module of the case report form (CRF) in 
PennCTMS.   
While in-hospital, the 
 team will assess for the development of adverse events by talking 
to the clinical team and reviewing the electronic medical record. The development of adverse 
events will be reported to the principal investigator daily. After discussions with the clinical team 
it will classify these events as definitely related, probably related, possibly related, unlikely or 
unrelated to the OsciPulse device or study procedures.  Serious adverse events (SAE), will be 
reported to the principal investigator (PI) by telephone within 12 hours of the event. The 
SAE CRF will be completed within 24 hours and the PI and Medical Director will be notified.  

 
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All adverse events occurring during the study period will be recorded. The clinical course of 
each adverse event will be followed until resolution, stabilization, or until it has been determined 
that the study intervention or participation is not the cause.  Serious adverse events that are still 
ongoing at the end of the study period will be followed up to determine the final outcome.  Any 
serious adverse event that occurs after the study period and is considered to be possibly related to 
the study intervention or study participation will be recorded and reported immediately. 
10.2.1 
Severity of Event 
The following guidelines will be used to describe severity. 
• Grade 1 (Mild): Awareness of symptoms that are easily tolerated, causing minimal 
discomfort and not interfering with everyday activities.  
• Grade 2 (Moderate): Sufficient discomfort is present to cause interference with normal 
activity.  
• Grade 3 (Severe): Extreme distress, causing significant impairment of functioning or 
incapacitation. Prevents normal everyday activities.  
• Grade 4: Life threatening or disabling adverse event.  
• Grade 5: Death related to the adverse event.  
10.2.2 
Relationship of AE to Study  
All adverse events (AEs) must have their relationship to the study intervention assessed by the 
clinician who examines and evaluates the participant based on temporal relationship and his/her 
clinical judgment. The degree of certainty about causality will be graded using the categories 
below. In a clinical trial, the study product must always be considered. 
• Definitely Related – There is clear evidence to suggest a causal relationship, and other 
possible contributing factors can be ruled out. The clinical event, including an abnormal 
laboratory test result, occurs in a plausible time relationship to study intervention 
administration and cannot be explained by concurrent disease or other drugs or 
chemicals. The response to withdrawal of the study intervention (de-challenge) should be 
clinically plausible. The event must be pharmacologically or phenomenologically 
definitive, with use of a satisfactory re-challenge procedure if necessary. 
• Probably Related – There is evidence to suggest a causal relationship, and the influence 
of other factors is unlikely. The clinical event, including an abnormal laboratory test 
result, occurs within a reasonable time after administration of the study intervention, is 
unlikely to be attributed to concurrent disease or other drugs or chemicals, and follows a 
clinically reasonable response on withdrawal (de-challenge). Re-challenge information is 
not required to fulfill this definition. 
• Possibly Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the trial medical device). 
However, other factors may have contributed to the event (e.g., the participant’s clinical 
condition, other concomitant events). Although an AE may rate only as “possibly related” 

 
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soon after discovery, it can be flagged as requiring more information and later be 
upgraded to “probably related” or “definitely related”, as appropriate. 
• Unlikely to be related – A clinical event, including an abnormal laboratory test result, 
whose temporal relationship to study intervention administration makes a causal 
relationship improbable (e.g., the event did not occur within a reasonable time after 
administration of the OsciPulse device) and in which other drugs or chemicals or 
underlying disease provides plausible explanations (e.g., the participant’s clinical 
condition, other concomitant treatments). 
• Unrelated – The AE is completely independent of study intervention administration, 
and/or evidence exists that the event is definitely related to another etiology. There must 
be an alternative, definitive etiology documented by the clinician. 
10.3 Reporting of Adverse Events, Adverse Device Effects and Unanticipated 
Problems 
The PI must conform to the adverse event reporting timelines, formats and requirements of the 
various entities to which they are responsible.  
If the report is supplied as a narrative, the minimum necessary information to be provided at the 
time of the initial report includes: 
● Study identifier 
● Subject number 
● A description of the event 
● Duration (start and end 
dates) 
● Expectedness 
● Action taken 
● Severity Grade 
● Relationship to study treatment or process 
● Current status 
● Whether study intervention was discontinued 
● Whether the event is serious and the reason 
why the event is classified as serious 
● Investigator assessment of the association 
between the event and study intervention 
Additionally, all other events (unanticipated problems, adverse reactions, unanticipated adverse 
device effects and subject complaints) will be recorded and reported with respect to institutional 
and federal policies.  
Reporting Period: Adverse events will be reported from the time of informed consent until study 
completion at 3 hours for Part 1 and 6 hours for Part 2. 
The study investigator shall complete an SAE Form and submit to the study sponsor and to the 
reviewing Institutional Review Board (IRB). The study sponsor is responsible for conducting an 
evaluation of the event and shall report the results of such evaluation to the FDA Center for 
Device and Radiologic Health (CDRH) and to all reviewing IRBs and participating investigators 
per the applicable regulation. 
10.3.1 
Follow-up report 
If an SAE/UADE has not resolved at the time of the initial report and new information arises that 
changes the investigator’s assessment of the event, a follow-up report including all relevant new 
or reassessed information (e.g., concomitant medication, medical history) should be submitted. 

 
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The investigator is responsible for ensuring that all SAEs are followed until either resolved or 
stable.  
10.3.2 
Investigator Reporting: Local Reporting Requirements  
The investigator will adhere to local regulatory reporting requirements including the IRB/EC of 
record reporting requirements as well as IRB reporting requirements per 21 CFR 812.  These 
additional reporting requirements include: failure to obtain informed consent, UADEs, device 
recall/repair/disposal, change in risk determination, or FDA or IRB withdrawal of the study. 
10.4 Investigator Reporting: Notifying the study Sponsor 
The following shall be reported to the Sponsor and Medical Director within 24 hours.   
10.4.1 
SAE and UADE 
Every SAE and UADE regardless of suspected causality (e.g., relationship to study product(s) or 
study procedure(s) or disease progression) must be reported to the sponsor within 24 hours of 
learning of its occurrence. 
Recurrent episodes, complications, or progression of the initial SAE must be reported to the 
Sponsor as a follow-up to the original episode within 24 hours of the investigator receiving the 
follow-up information. A SAE considered completely unrelated to a previously reported one 
should be reported separately as a new event. 
New information regarding the SAE will be reported as it becomes available and in the same 
manner that the initial SAE (i.e. SAE form). The investigator must follow the event to resolution 
or until the event is deemed and documented irreversible, whichever is longer. 
10.4.2 
Failure to Obtain Informed Consent and Withdrawal of IRB Approval 
The PI must report to the Sponsor within 24 hours if informed consent is not obtained for any 
subjects enrolled on the trial or if the IRB withdrawals approval of the study. 
10.4.3 
Product Complaints  
OsciPulse device imperfections, malfunctions, or service required shall be reported to 
 
 and the Sponsor on the IP Quality Complaint Form.  
 will arrange for service 
or replacement of products for trial use.  
10.4.4 
Protocol Deviations 
Protocol deviations of significant impact (see section 11.3) must be reported to the Study sponsor 
within 3 business days of learning of the deviation.  Reporting shall be done using the Sponsor 
Exception & Deviation Form. 
10.5 Stopping Rules  
There are no specific stopping rules for the study.  

 
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10.6 Data and Safety Monitoring  
Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants 
are protected, that the reported trial data are accurate, complete, and verifiable, and that the 
conduct of the trial is in compliance with the currently approved protocol/amendment(s), with 
International Council for Harmonisation Good Clinical Practice (ICH GCP), and with applicable 
regulatory requirement(s). Monitoring will be conducted by the University of Pennsylvania 
assigned monitor according to the Sponsor Data & Safety Monitoring Plan (DSMP). 
Independent audits or compliance reviews may be conducted to ensure monitoring practices are 
performed consistently across all participating sites and that monitors are following the DSMP. 
10.7 Data Safety Monitoring Board (DSMB) 
The Sponsor has assessed that a DSMB is not needed for this trial. 
11 STUDY ADMINISTRATION, DATA HANDLING AND RECORD 
KEEPING 
11.1 Data Collection and Management Responsibilities 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the site investigator. The investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data. 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets 
for recording data for each participant enrolled in the study. Data recorded in the electronic case 
report form (eCRF) derived from source documents should be consistent with the data recorded 
on the source documents. 
Clinical data and clinical laboratory data will be entered into the University of Pennsylvania’s 
clinical trial management system (CTMS), a 21 CFR Part 11-compliant data capture system 
provided by the Sponsor. The data system includes password protection and internal quality 
checks, such as automatic range checks, to identify data that appear inconsistent, incomplete, or 
inaccurate. Clinical data will be entered directly from the source documents. 
Clinical and laboratory data will be entered into a 21 CFR Part 11-compliant electronic data 
capture system (EDC) that includes individual user account level password protection. This EDC 
supports programmable data entry validation rules and edit checks to identify data entry errors. 
11.2 Records Retention  
Study documents should be retained for a minimum of 2 years after the approval of a marketing 
application in an International Council for Harmonization (ICH) region and until there are no 
pending or contemplated marketing applications in an ICH region or until at least 2 years have 
elapsed since the formal discontinuation of clinical development of the OsciPulse device. These 
documents should be retained for a longer period, however, if required by local regulations. No 
records will be destroyed without the written consent of the sponsor, if applicable. It is the 

 
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responsibility of the sponsor to inform the investigator when these documents no longer need to 
be retained. 
11.3 Protocol Deviations 
The PI and the study team should document all scenarios where the protocol is not followed and 
provide, in particular: 
• Who deviated from the protocol 
• What was the deviation 
• When did the deviation occur 
• How did the deviation happen 
• What is the impact of the deviation 
• A root cause analysis of why the deviation occurred 
If the assessment results in a determination that any of the following are potentially affected, the 
deviation would be considered of significant impact: 
• having the potential to adversely affect subject safety; OR 
• increases risks to participants; OR 
• adversely affects the integrity of the data; OR 
• violates the rights and welfare of participants, OR 
• affects the subject’s willingness to participate in research.  
• there is a potential for an overall impact on the research that should be shared with the 
IRB for consideration and development of next best steps to address it 
Deviations of significant impact are to be reported to the study sponsor (see section 11.3) and 
according to local reporting requirements.  
11.4 Regulatory, Ethical, and Study Oversight Considerations 
11.4.1 
Informed Consent Process / HIPAA Authorization  
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
the study and continues throughout the individual’s study participation. Video consent may be 
used as well, which will be signed by the subject and a CRC witnessing the consent process, as 
well as the consenting physician at the earliest convenience. Recorded full face images during 
this process will be kept on an encrypted, password protected drive in the 
 offices and will 
only be available to the study team. Consent forms will be Institutional Review Board (IRB)-
approved and the participant will be asked to read and review the document. The investigator 
will explain the research study to the participant and answer any questions that may arise. A 
verbal explanation will be provided in terms suited to the participant’s comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research participants. 
Participants will have the opportunity to carefully review the written consent form and ask 

 
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questions prior to signing. The participants should have the opportunity to discuss the study with 
their family or surrogates or think about it prior to agreeing to participate. The participant will 
sign the informed consent document prior to any procedures being done specifically for the 
study. Participants must be informed that participation is voluntary and that they may withdraw 
from the study at any time, without prejudice. A copy of the informed consent document will be 
given to the participants for their records. The informed consent process will be conducted and 
documented in the source document (including the date), and the form signed, before the 
participant undergoes any study-specific procedures. The rights and welfare of the participants 
will be protected by emphasizing to them that the quality of their medical care will not be 
adversely affected if they decline to participate in this study.  
11.4.2 
Study Discontinuation and Closure 
This study may be temporarily suspended or prematurely terminated by the Sponsor or the PI at 
any site if there is sufficient reasonable cause. Written notification, documenting the reason for 
study suspension or termination, will be provided by the suspending or terminating party. If the 
study is prematurely terminated or suspended, the Principal Investigator (PI) will promptly 
inform study participants, the Institutional Review Board (IRB), and sponsor and will provide 
the reason(s) for the termination or suspension. Study participants will be contacted, as 
applicable, and be informed of changes to study visit schedule. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants 
• Demonstration of efficacy that would warrant stopping 
• Insufficient compliance to protocol requirements 
• Data that are not sufficiently complete and/or evaluable 
• Determination that the primary endpoint has been met 
• Determination of futility 
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the sponsor, IRB and/or Food and Drug Administration (FDA). 
In terminating the study, the Sponsor and the Principal Investigator will assure that adequate 
consideration is given to the protection of the subjects’ interests. 
11.4.3 
Confidentiality and Privacy 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the sponsor(s) and their interventions. This confidentiality is extended to cover 
testing of biological samples and genetic tests in addition to the clinical information relating to 
participants. Therefore, the study protocol, documentation, data, and all other information 
generated will be held in strict confidence. No information concerning the study or the data will 
be released to any unauthorized third party without prior written approval of the sponsor.  
All research activities will be conducted in as private a setting as possible. 

 
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The study monitor, other authorized representatives of the sponsor, representatives of the 
Institutional Review Board (IRB), regulatory agencies or pharmaceutical company supplying 
study product may inspect all documents and records required to be maintained by the 
investigator, including but not limited to, medical records (office, clinic, or hospital) and 
pharmacy records for the participants in this study. The clinical study site will permit access to 
such records. 
The study participant’s contact information will be securely stored at each clinical site for 
internal use during the study. At the end of the study, all records will continue to be kept in a 
secure location for as long a period as dictated by the reviewing IRB, Institutional policies, or 
sponsor requirements. 
11.4.4 
Quality Assurance and Quality Control 
All monitoring and audits are to be performed according to ICH GCP E6 (R2). 
Each clinical site will perform internal quality management of study conduct, data, procedures, 
documentation and completion.  Quality control (QC) procedures will be implemented beginning 
with the data entry system and data QC checks that will be run on the database will be generated. 
Any missing data or data anomalies will be communicated to the site(s) for 
clarification/resolution. 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the 
clinical trial is conducted and data are generated, and procedures are followed, documented 
(recorded), and reported in compliance with the protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), and applicable regulatory requirements (e.g., 
Good Manufacturing Practices (GMP)). 
The investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local 
and regulatory authorities. 
11.4.5 
Funding Source 
This study is financed through a grant from the 
 
. 
11.4.6 
Conflict of Interest Policy 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed 
and managed. Furthermore, persons who have a perceived conflict of interest will be required to 
have such conflicts managed in a way that is appropriate to their participation in the design and 
conduct of this trial.  

 
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11.4.7 
Subject Stipends or Payments 
11.4.8 
Part 1 
Subjects enrolled in this study will receive compensation for their time with $150.00 ($50/hour) 
paid through the GreenPhire ClinCard system. 
11.4.9 
Part 2 
Subjects enrolled in this study will receive compensation for their time with $100.00 paid 
through the GreenPhire ClinCard system.  
11.5 Publication and Data Sharing Policy 
Neither the complete nor any part of the results of the study carried out under this protocol, nor 
any of the information provided by the sponsor for the purposes of performing the study, will be 
published or passed on to any third party without the consent of the study sponsor.  Any 
investigator involved with this study is obligated to provide the sponsor with complete test 
results and all data derived from the study.  The Sponsor must approve all sharing of 
information/data prior to its occurrence. 
11.6 Protocol Amendment History 
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by the University of Pennsylvania. A protocol change intended to eliminate an 
apparent immediate hazard to subjects may be implemented immediately, provided the IRB/IEC 
is notified within 5 days. 
Any permanent change to the protocol must be handled as a protocol amendment. The written 
amendment must be submitted to the IRB/IEC and the investigator must await approval before 
implementing the changes.  
If in the judgment of, the sponsor, the IRB/IEC, and/or the investigator, the amendment to the 
protocol substantially changes the study design and/or increases the potential risk to the subject 
and/or has an impact on the subject's involvement as a study participant, the currently approved 
written informed consent form will require similar modification. In such cases, informed consent 
will be renewed for subjects enrolled in the study before continued participation. 
The table below is intended to capture changes of IRB-approved versions of the protocol, 
including a description of the change and rationale.  
 
Version 
Date 
Description of Change  
Brief Rationale 
V1 
2020 
Original Protocol 
 

 
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Version 
Date 
Description of Change  
Brief Rationale 
V2 
02 Feb 2021 
Updated background information, 
clarified randomization procedures, 
updated vulnerable populations section, 
clarified monitoring procedures prior to 
moving to part 2, clarified SAE reporting 
procedures. Other minor and 
administrative changes for clarity and 
completeness.  
To provide most current and 
accurate information.  
V3 
21 Apr 2021 
Updated AE grading criteria to align 
with CTCAE definitions, as planned for 
use.  
To align with CTCAE dictionary 
planned for use.  
V4 
01 Sep 2021 
Updated applicable sections to clarify 
that ultrasound procedures will be 
completed when feasible 
To account for variability in the 
availability of ultrasonographers 
during study procedures.   
V5 
12 Jan 2022; 
addl updates 
17 Feb 2022 
Updated eligibility criteria for Part 2, 
device description. Included description 
of video consenting process. 
To facilitate recruitment and 
provide more current description of 
device. To provide accurate 
description of consenting process. 
V6 
01 Jun 2022 
Updated eligibility criteria for Part 2, 
update study duration for Part 2, 
Removed requirement for physical 
examination, Updated procedure for 
compliance monitoring. 
To facilitate recruitment and 
increase the frequency of subject’s 
completing the study. To update 
study procedures based on the 
reduced study time. 
 
 
 

 
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12 REFERENCES 
1. Benjamin EJ, Muntner P, Alonso A, et al. Heart Disease and Stroke Statistics-2019 
Update: A Report From the American Heart Association. Circulation. 2019;139(10):e56-
e528. 
2. Huang W, Goldberg RJ, Cohen AT, et al. Declining Long-term Risk of Adverse Events 
after First-time Community-presenting Venous Thromboembolism: The Population-
based Worcester VTE Study (1999 to 2009). Thromb Res. 2015;135(6):1100-1106. 
3. Heit JA, O'Fallon WM, Petterson TM, et al. Relative impact of risk factors for deep vein 
thrombosis and pulmonary embolism: a population-based study. Arch Intern Med. 
2002;162(11):1245-1248. 
4. Spyropoulos AC, Anderson FA, Jr., FitzGerald G, et al. Predictive and associative 
models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140(3):706-
714. 
5. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: 
Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of 
Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 
Suppl):e195S-e226S. 
6. Schunemann HJ, Cushman M, Burnett AE, et al. American Society of Hematology 2018 
guidelines for management of venous thromboembolism: prophylaxis for hospitalized 
and nonhospitalized medical patients. Blood Adv. 2018;2(22):3198-3225. 
7. Naccarato M, Chiodo Grandi F, Dennis M, Sandercock PA. Physical methods for 
preventing deep vein thrombosis in stroke. Cochrane Database Syst Rev. 
2010(8):CD001922. 
8. Collaboration CT, Dennis M, Sandercock P, et al. Effectiveness of intermittent pneumatic 
compression in reduction of risk of deep vein thrombosis in patients who have had a 
stroke (CLOTS 3): a multicentre randomised controlled trial. Lancet. 
2013;382(9891):516-524. 
9. Barrera LM, Perel P, Ker K, Cirocchi R, Farinella E, Morales Uribe CH. 
Thromboprophylaxis for trauma patients. Cochrane Database Syst Rev. 
2013(3):CD008303. 
10. Arabi YM, Al-Hameed F, Burns KEA, et al. Adjunctive Intermittent Pneumatic 
Compression for Venous Thromboprophylaxis. New England Journal of Medicine. 
2019;380(14):1305-1315. 
11. Welsh JD, Hoofnagle MH, Bamezai S et. Al.  Hemodynamic regulation of perivalvular 
endothelial gene expression prevents deep venous thrombosis. J Clin Invest. 
2019;129(12):5489–5500. 
12. Welsh, John, PhD, Mechanical Device to Modify Venous Flow, Clinical Study Report of 
an early feasibility study conducted at the University of Pennsylvania to determine the 
tolerability and measure the changes in venous blood flow in subjects using the OsciFlex 
device, 29 January 2020. 
13. Welsh, John, PhD, Mechanical Device to Modify Venous Flow, Clinical Study Report of 
an early feasibility study conducted at the University of Pennsylvania to determine the 
tolerability and measure the changes in venous blood flow in subjects using the Osciflex 
device, Pending.