The Effect of Inelastic Compression System on Quality of Life in People With Chronic Venous Insufficiency
Phase: NA
Conditions: Chronic Venous Insufficiency
Sponsor: University of Miami

PI:  Dr. Lev-Tov
Date:  07Sep2022     Version: 2.0
Page 1 of 12
Revised: June 17, 2020
The Effect of Inelastic Compression System on Quality of Life in People with 
Chronic Venous Insufficiency
IRB Number (eProst ID): 20210807
Protocol Version Number: 2.0
Protocol Version Date: 9/7/2022
PI Name: Hadar Lev-Tov, MD, MAS
NCT Number:  NCT05051540
-       Study #: 20210807        Effective Date: 9/12/2022

PI:  Dr. Lev-Tov
Date:  07Sep2022     Version: 2.0
Page 2 of 12
Revised: June 17, 2020
1)
Protocol Title
The Effect of Inelastic Compression System on Quality of Life in People with 
Chronic Venous Insufficiency 
2)
Objectives
The purpose of this protocol is to measure the effect of the use of an inelastic 
compression system (ICS) on quality of life (QOL) in patients with chronic venous 
insufficiency (CVI) who have demonstrated limited or no compliance with 
prescribed compression stockings or bandage wraps. The primary outcome of 
interest is the change in QOL of people who have CVI and use ICS over 6 weeks. 
3)
Background 
Chronic venous insufficiency (CVI) is a common condition that affects about one 
third of adults in the US1. The social and economic burden on both patients and society is 
significant; for instance, venous leg ulcers, a severe manifestation of CVI, costs the US 
healthcare system billions in dollars and the UK an amount of similar magnitude2,3.                    
Notably, CVI negatively impacts patients’ quality of life (QOL), particularly in 
those at advanced stages of disease4. This has been reported throughout various domains 
of well-being, including pain, physical functioning and mobility, and social isolation5.  
While generic scales like the 36-Item Short Form Survey (SF-36) are helpful to discern 
QOL measures across different disease groups, tools with specificity towards chronic 
venous diseases have been established6,7. For instance, the Chronic Venous Insufficiency 
Questionnaire (CIVIQ-20) has been demonstrated to appropriately assess QOL in patients 
with CVI8 These tools may be used to guide clinical research practices in efforts to 
improve the well-being of these patients. 
Several decades ago, the Clinical, Etiology, Anatomic, Pathophysiology (CEAP) 
classification was created to standardize the diverse manifestations of chronic venous 
insufficiency to allow for easier classification and communication of disease severity9. 
Specifically, within the Clinical portion of the CEAP system, the subcomponents C3-C5 
refer to edema (C3), changes in skin and subcutaneous tissue (C4 -pigmentation, 
dermatitis, lipodermatosclerosis or atrophie blanche), and a healed ulcer (C5); these 
subcomponents increase numerically in proportion to the severity of the patient’s 
condition10.
 Currently, compression therapy is the first line treatment for all the manifestations 
of CVI 11. However, existing compression hosiery are met with resistance by some 
patients. This results in a gap in compliance as for example up to 80% of patients who are 
prescribed compression stockings or bandaging wraps do not wear them as prescribed12. 
This practice gap may contribute to the overall burden of CVI and solutions that address 
the need of patients who cannot wear compression stockings are needed. Inelastic 
compression wraps may help to solve this practice gap by offering easier application 
without compromising outcomes. One example of such a system is the Compreflex 
Compression Wrap system (Sigvaris Inc. Peachtree City, GA). This proposal is focused 
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PI:  Dr. Lev-Tov
Date:  07Sep2022     Version: 2.0
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Revised: June 17, 2020
on determining if the usage of this specific inelastic compression wrap system in patients 
with CVI stages C3, C4, and C5 improves their quality of life. 
4)
Inclusion and Exclusion Criteria
Inclusion Criteria

Subject is age 18 or older, able and willing to provide consent and agrees to comply 
with the study procedures

Subject must have chronic venous insufficiency of stages C3, C4, or C5 according 
to the CEAP classification system   

Not compliant with their currently prescribed compression system
Exclusion Criteria

Active malignancy other than non-melanoma skin cancer

Study ulcer suspicious for cancer

Unable to provide consent

Subjects who are pregnant and/or breastfeeding

In the opinion of the PI the subject cannot comply with study procedures
5)
Study Design
a) Primary Purpose: Treatment
b) Interventional Study Model: Single Group
c) Allocation: N/A
d) Enrollment: 40
This is a single center, single intervention, unblinded, prospective cohort study. 
6)
7)
Procedures Involved
This is a single center prospective cohort study that will last up to six 6 
weeks per subject. A total of 30 patients will be enrolled, through the 
University of Miami Hospital and Clinics. The study is comprised of 3 
visits per subject (see table 1) two in person and one over the phone. V0 
will occur on the first day of the study. V1 will occur during the second 
week (between days 714) and the final visit, V2 on day 42 of the study. 
At the enrollment visit (V0), subjects will undergo baseline assessments to 
determine eligibility for the study (inclusion and exclusion criteria, 
demographics, medical history, medication history, focused physical 
exam). Medical records will be reviewed for the subject’s basic 
demographics, medical and surgical history, and current treatments.  
Once eligibility is confirmed, the patient will be assessed for 
measurements of disease severity (presence of varicose veins, atrophe 
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PI:  Dr. Lev-Tov
Date:  07Sep2022     Version: 2.0
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blanche, lipodermatosclerosis, hyperpigmentation, the Venous Clinical 
Severity Score VCSS (See Appendix A), itch severity using itch 
Numerical Rating Scale NRS (See Appendix B), pain using the Visual 
Analogue Scale VAS (See Appendix C), and limb circumference in mm.) 
Upon proper consent, photographs of the extremity will be captured and 
quality of life assessments will be completed. The two quality of life 
assessments used will be the Chronic Venous Disease Quality of Life 
Questionnaire (CIVIQ – 20) (See Appendix D), and the Short Form 
Healthy Survey (SF-36) (See Appendix E). The initial visit will conclude 
with proper product application training and time to address any questions. 
Subjects will report for 2 successive follow-up visits. The first follow-up 
visit will be completed at least one week but no later than 14 days after the 
initial visit and be completed via phone (V1). During this visit, study staff 
will document concomitant medications, itch severity, pain, and assess 
patient adherence to usage of the inelastic compression system. If in the 
opinion of the study staff the subject is not able to apply the ICS 
effectively, they may convert the visit to video conferencing or even in 
person visit.
The third and final visit (V2) will be completed in person at the University 
of Miami Hospital Dermatology Clinical Trials Unit 6 weeks after the 
initial in person visit. During this visit, similar to the initial visit, study 
staff will document concomitant medications, perform a focused exam, 
measure disease severity and itch severity, and assess pain. Additionally, 
limb circumference measurements will be obtained and photographs of the 
extremity will be captured again. The visit will conclude with the same 
two quality of life assessments and assessment of adherence. 
All subjects will continue to follow their care for all medical conditions as 
prescribed by their physician.  
Visit
V0 
V1 (phone) 
V2 
Day
0
7-14
42 (+/- 3)
Informed consent 
X 
 
 
Eligibility 
X 
 
 
Medical history 
X 
 
 
Concomitant medications  
X 
x 
X 
Focused exam 
X 
 
X 
Disease severity assessments  
X 
 
X 
Itch severity 
X 
X 
X 
Pain assessment 
X 
X 
X 
Limb circumference  
X 
 
X 
Photography 
X 
 
X 
QOL assessment (CIVIQ-20, SF 36) 
X 
 
X 
Product application training 
X 
 
 
Adherence assessment  
 
X 
X 
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Date:  07Sep2022     Version: 2.0
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8)
Study Endpoint
a) Primary Outcome Measure
i)
Title: Change in the Quality of Life
ii) Description: As measured by the Chronic Venous Disease Quality of Life 
Questionnaire (CIVIQ-20) which is a questionnaire made up of 20 multiple 
choice  questions subdivided into four categories: psychology , pain, physical 
repercussion and social repercussions. The questions are equally weighted and 
the value indicates the degree of deterioration of quality of life; 0 being the 
highest quality of life and 100 being the lowest. It has been tested to be a 
reliable measurement tool in evaluating the quality of life in those with CVI.
iii) Timeframe: Baseline to 6 weeks
9)
Data Banking
Physical study records will be in a locked cabinet in the Dermatology 
Clinical Trials Unit at University of Miami (University of Miami Hospital 
West Building, 1321 NW 14th St, Suites 504-507, 33136). Technological 
study records will be located on a spreadsheet within a project file located 
within a password protected server on Microsoft Teams. 
10) Data Management
The collected, deidentified data will be arrayed in a spreadsheet within a project file 
located within a password protected server on Microsoft Teams. Only the PI and 
approved study staff will have access to this file. Subject identities as participants in 
this study will be kept confidential for the remainder of the study and in any 
publication, and no identifiable patient information will be attributed to the dataset, 
thereby keeping them anonymous.
11) Risks to Subjects
The risks to the patient proposed by this trial are minimal as they do not pose greater 
potential for harm than routine clinical care. The potential risks are discussed below:
Potential Risks of the Inelastic Compression System 

Minor severity:
o
Skin Irritation or Discomfort
o
Pain

Major severity
o
Soft tissue injury
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PI:  Dr. Lev-Tov
Date:  07Sep2022     Version: 2.0
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o
Nerve Injury
These potential risks are unlikely. The risks listed under major severity have 
a lower likelihood of occurrence compared to the risks located under the 
minor severity category. Proper application of the inelastic compression 
system minimizes the probability of experiencing these potential risks.
12)
Adverse Events and Serious Adverse Events
DEFINITION OF ADVERSE EVENTS (AE) 
Adverse event means any untoward medical occurrence associated with the use of an 
intervention in humans, whether or not considered intervention-related (21 CFR 312.32 
(a)). In the context of our study, an intervention refers to a study research procedure. 
DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) 
A Serious Adverse Event (SAE) is any serious unfavorable and unintended sign, 
symptom, or disease temporally associated with this study protocol, whether or not 
considered related, including those that: 
o
Results in death 
o
Is life-threatening 
o
Requires inpatient hospitalization or causes prolongation of existing 
hospitalization 
o
Results in persistent or significant disability/incapacity 
o
Is a congenital anomaly/birth defect 
o
Requires intervention to prevent permanent impairment or damage 
Medical and scientific judgment should be exercised in determining whether an event is 
an important medical event. An important medical event may not be immediately life-
threatening and/or result in death or hospitalization. However, the important medical 
event should be reported as serious, if it is determined that the event may jeopardize the 
Participant and/or may require intervention to prevent one of the other adverse event 
outcomes. 
CLASSIFICATION OF AN ADVERSE EVENT 
 SEVERITY OF EVENT 
The Investigator will provide an assessment of the severity of each adverse reaction by 
recording a severity rating on the appropriate SAE reporting page of the Participant’s 
file. Severity, which is a description of the intensity of manifestation of the SAE, is 
distinct from seriousness, which implies a patient outcome or SAE-required treatment 
measure associated with a threat to life or functionality. Severity will be assessed 
according to the following scale. If required on the adverse event case report forms, the 
investigator will use the adjectives MILD, MODERATE, or SEVERE to describe the 
maximum intensity of the adverse event. For purposes of consistency, these intensity 
grades are defined as follows: 
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MILD 
Does not interfere with Participant's usual 
function. 
MODERATE 
Interferes to some extent with Participant's 
usual function. 
SEVERE 
Interferes significantly with Participant's 
usual function. 
RELATIONSHIP TO STUDY INTERVENTION 
For all collected AEs, the clinician who examines and evaluates the participant will 
determine the AE’s causality based on temporal relationship and his/her clinical 
judgment. A binary assessment (related/not related) will be made and take into 
consideration the natural history of the underlying disease, concurrent illness, 
concomitant therapy, study-related procedures, accidents, and other external factors. 
While the relationship to the study tissue biopsy procedure (study research intervention) 
(related/not related) is part of the documentation process, it is not a factor in determining 
what is or is not reported in the study. All AEs are recorded regardless of relatedness. 
Related:  The AE is known to occur with the study research procedure, there is a 
reasonable possibility that the study research procedure caused the AE, or there is a 
temporal relationship between the study agent and event. Reasonable possibility means 
that there is evidence to suggest a causal relationship between the study research 
procedure and the AE. An AE can be deemed related even if other factors may have 
contributed to the event.
Not Related: There is not a reasonable possibility that the study research procedure 
caused the event, there is no temporal relationship between the study research procedure 
and event onset, or an alternate etiology has been established or appears to provide a 
plausible explanation (e.g. the participant’s clinical condition, underlying disease or 
concomitant treatments).
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
At each visit, AEs/SAEs will be evaluated by the Investigator and recorded. All AEs 
must be recorded irrespective of whether they are considered study related. Information 
to be collected includes event description, time of onset, clinician’s assessment of 
severity, relationship to study procedures, and time of resolution/stabilization of the 
event. All AEs occurring while on study must be documented appropriately regardless of 
relationship. 
Any medical condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. 
Changes in the severity of an AE will be documented to allow an assessment of the 
duration of the event at each level of severity to be performed. 
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Date:  07Sep2022     Version: 2.0
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Revised: June 17, 2020
Any AEs/SAEs already documented at a previous assessment and designated as ongoing, 
should be reviewed at subsequent visits as necessary. If these have resolved, this should 
be documented.
ADVERSE EVENT REPORTING 
All adverse events should be tracked from the time the Participant provides informed 
consent, and through the time of discharge from the study. Adverse events (serious and 
non-serious) should be recorded in the CRF for the duration of the reporting period. 
Adverse events reporting, including suspected serious unexpected adverse reactions, will 
be carried out in accordance with applicable local regulations. 
All AEs that occur during the study will be recorded in the case report form and reported 
to IRB. 
SERIOUS ADVERSE EVENT REPORTING 
If a serious adverse event related to the study research procedures occurs, the IRB should 
be notified within 24 hours of awareness of the event by the investigator. In particular, if 
the serious adverse event is fatal or life-threatening, notification to IRB must be made 
immediately, irrespective of the extent of available adverse event information. This 
timeframe also applies to additional new information (follow-up) on previously 
forwarded serious adverse event reports. 
In the rare event that the investigator does not become aware of the occurrence of a 
serious adverse event immediately (e.g., if an outpatient study Participant initially seeks 
treatment elsewhere), the investigator is to report the event within 24 hours after learning 
of it and document the time of his/her first awareness of the adverse event.
13) Potential Benefits to Subjects
A medical benefit cannot be guaranteed by this study. However, since study 
protocols mirror standard of care, subjects can reasonably expect to benefit 
medically (e.g. a decrease in lower extremity swelling or skin discoloration). 
Further, since the participation in the study is conditional of “failing” use of other 
standard care compressions devices, successful use of the ICS as part of this study, 
will be considered an improvement in medical care provided. Since study staff are 
part of the UM Wound Care Team, subjects will be cared for by expert wound care 
clinicians. Subjects’ participation in this protocol will also help future patients with 
chronic venous insufficiency, as future patients may experience a high quality of 
life through usage of inelastic compression systems. Notably, medical care 
including dressings and medical advice are provided at no cost to subjects 
throughout the study period. Finally, as part of the informed consent subjects are 
reminded of alternative therapies that are available. It is our experience that subjects 
are very satisfied with the overall care in the UM clinical trials unit and often return 
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Date:  07Sep2022     Version: 2.0
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for additional trials. Thus they are offered the psychological benefit of knowing that 
the UM clinical trials unit is always an option for them.
14) Setting
Study procedures will take place one of the following locations:

Dr. Philip Frost Department of Dermatology and Cutaneous Surgery 
– Clinical Trials Unit. UMH West Building, Suites 504-508. 1321 
NW 14th street, Miami FL, 33136.

University of Miami Dermatology Outpatient Wound Care Clinic. 
1295 NW 14th St. South building, 1st floor. Miami FL 33136

University of Miami Dermatology Outpatient Clinic. South 
Building, Suites K, L, M. 1295 NW 14th Street, Miami FL, 33136.
15) Resources Available
The University of Miami Wound Center is one of the largest and most advanced 
wound clinics in the United States, and together with its Hyperbaric Oxygen Unit 
attracts a large amount of patients with chronic wounds each week and venous 
disease. The investigators involved in this protocol are experienced clinicians with 
world-renowned expertise in wound healing and venous disease. Their staff consists 
of highly trained doctors, nurses and research fellows with extensive knowledge in 
the diagnosis and management of chronic wounds.
16) Recruitment Methods
Patients with chronic venous insufficiency seen for their routine care at the 
Dermatology or Wound Care outpatient clinics at the University of Miami Hospital 
will be identified for possible study eligibility by any of the dermatologists in our 
practice. If the treating dermatologist is a study team member, the patient will be 
asked if they are interested in being contacted by the study team to learn more about 
a protocol for chronic wounds. If interested, additional information will be provided 
and an informed consent form will be sent to the potential subject before scheduling 
a Screening Visit. A partial HIPAA waiver is needed, so that if the patient gives 
permission to be contacted by a member of the study team they will then be 
approached by a team member in clinic or will be contacted by phone if they consent. 
If the treating dermatologist is not a study team member, they will provide the 
potential subject with the contact information for the study team such that the patient 
can contact the study team for more information. If it is then determined that they are 
interested in participating, they will be scheduled for a visit at our Dermatology 
Clinical Trials Unit where informed consent and all other baseline visit study 
procedures will take place. The risks and benefits of the study will be presented, as 
well as the disclaimer that refusal to participate in the study will in no way, shape or 
form alter the type or quality of their care.
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Will Protected Health Information (PHI) be accessed prior to enrollment/consent? If 
so, please indicate “yes” below to request a Partial Waiver of HIPAA Authorization 
for Recruitment Purposes.
☒Yes 
☐No 
17)
Confidentiality
 PHI will be collected from the EMR or subjects at UHealth.  Data will be 
stored locally:
☒  Other, specify:  PHI will be stored in a binder inside a locked cabinet in 
the UMH Dermatology CTU. All PHI will be stripped of information that 
may be used to identify the subjects.
The research team will maintain the research data in compliance with 
applicable regulatory requirements and University of Miami data retention 
requirements as outlined in the Investigator Manual.
18) Provisions to Protect the Privacy Interests of Subjects
Throughout the duration of the entire study, the privacy interests of participants will 
be maintained by ensuring the presence of members approved to be involved in the 
study and maintaining absence of those who are not. Additionally, phone visits will 
be held in the UMH Dermatology CTU away from the public and personnel from 
other departments of the hospital.
19) Authorization for Use and Disclosure of Protected Health 
Information (HIPAA)
Confirm that you will destroy the Protected Health Information (PHI) you and/or 
your Study Team acquire receive from JHS and/or UHealth at the earliest 
opportunity. 
☒    I confirm 
Confirm that the Protected Health Inform (PHI) you acquire from JHS and/or 
UHealth will not be re-used or disclosed to any other person or entity, except as 
required by law or for authorized oversight of the research study or for other research 
for which the use or disclosure of PHI is permissible.           
☒     I confirm  
Notwithstanding the preceding “I confirm” statements above, I agree that neither I nor 
any member of the study team listed on the IRB submission for this Protocol shall ever 
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Date:  07Sep2022     Version: 2.0
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re-use or re-disclose any of the information acquired from Jackson Health System in any 
format, whether identifiable or de-identified, to any individual or entity without first 
obtaining written permission from Jackson Health System, even if such re-use or re-
disclosure is permissible by law (e.g., HIPAA).
  
 
______________________________________________
PI Signature                                                               Date
20) Consent Process
Once patients are identified and consent to be contacted, they will be approached by 
a member of the study team during their outpatient visit OR will be contacted by a 
member of the study team by phone. Participants will be given ample time to consider 
their agreement.  The study team will be available to answer any question in the 
method the participant prefers to communicate.  No one in a perceived coercive 
position in relation to the participant will engage in the consenting process.  Consent 
will be obtained voluntarily prior to initiating any study procedures. 
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References:
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insufficiency. Angiology. 2001;52:S5–S15.
2. Negus D, Fletcher EW, Cockett FB, Thomas ML.. Compression and band 
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74.  
3. Guest JF, Vowden K, Vowden P. The health economic burden that acute and 
chronic wounds impose on an average clinical commissioning group/health board 
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4. Daciana-Elena Branisteanu, Toni Feodor, Sorin Baila, Iuliana-Alma Mitea, Oana 
Vittos Impact of chronic venous disease on quality of life: Results of vein alarm 
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9. Porter J.M., Moneta G.L. International Consensus Committee on Chronic Venous 
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12. Raju S, Hollis K, Neglen P. Use of compression stockings in chronic venous 
disease: patient compliance and efficacy. Ann Vasc Surg. 2007;21(6):790–5.  
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