A Feasibility Study Evaluating Flexitouch® Plus With a Therapy Cycle Software Modification in Patients With Unilateral Breast Cancer-Related Lymphedema (BCRL)
Phase: NA
Conditions: Breast Cancer Related Lymphedema
Sponsor: Tactile Medical

 
 
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A Feasibility Study Evaluating Flexitouch® Plus with Novel 
Simultaneous Therapy Cycle Software in Patients with 
Unilateral Breast Cancer-Related Lymphedema (BCRL) 
 
 
 
 
Protocol Number: 4070 
NCT04073823 
 
 
May 15, 2019 
Protocol Version 2.0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Investigator Signature 
 
 
 
Protocol Title: A Feasibility Study Evaluating Flexitouch Plus with Novel Simultaneous Therapy 
Cycle Software in Patients with Unilateral Breast Cancer-Related Lymphedema (BCRL) 
 
 
Protocol Number: 4070 
 
 
I confirm that I have read this protocol.  I will comply with the protocol and the principles of 
Good Clinical Practices (GCP), institutional research policies and procedures, and other 
appropriate regulatory requirements. 
 
 
 
_______________________________ 
Site Principal Investigator Name (Print) 
 
 
_______________________________ 
 
 __________________ 
Site Principal Investigator Signature   
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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SYNOPSIS 
 
Study Title 
A Feasibility Study Evaluating Flexitouch Plus with Novel Simultaneous 
Therapy Cycle Software in Patients with Unilateral Breast Cancer-Related 
Lymphedema (BCRL) 
Protocol Date 
15 May 2019 
Protocol Version 
2.0 
Protocol Number 
4070 
Name of Sponsor 
Tactile Medical 
Investigational Product 
Flexitouch Plus (FT) with Novel Simultaneous Therapy Cycle Software 
(FT-SW) 
Study Objective 
To demonstrate the treatment equivalency of the Flexitouch Plus with novel 
simultaneous therapy cycle software and the standard Flexitouch Plus in 
patients with unilateral BCRL. 
Endpoints 
To compare the effects of the Flexitouch Plus (FT) to Flexitouch Plus with 
novel simultaneous therapy cycle software (FT-SW) in unilateral BCRL 
patients after one treatment by evaluating: 
• 
Flow of lymph in the affected and contralateral limb using near 
infrared-fluorescence (NIRF) imaging 
• 
Swelling in the affected and contralateral limb as assessed by: 
o Perometry (LymphaTech 3D Scanner) 
o Local tissue water (MoistureMeterD) 
• 
Skin changes 
o Skin thickness (Ultrasound) 
• 
Safety 
Study Design 
This is a prospective, randomized, two-arm feasibility study.  
Treatments 
Eligible patients will be randomized to receive one of the following 
treatments:   
• 
Flexitouch Plus (FT) 
• 
Flexitouch Plus with Novel Simultaneous Therapy Cycle 
Software (FT-SW) 
The compression treatment will be conducted on the affected limb. 
Inclusion/Exclusion 
 
Inclusion Criteria: 
1. Female 18 years of age or older 
2. Diagnosis of unilateral breast cancer-related lymphedema  
3. Stage I or early Stage II lymphedema without severe fibrosis at the 
time of enrollment 
4. ≥ 5% volume difference between affected and unaffected arm as 
verified via perometry (LymphaTech 3D scanner) 
5. Willing and able to give informed consent 
6. Willing and able to comply with the study protocol requirements 
and all study-related visit requirements 
Exclusion Criteria: 
1. In-home use of pneumatic compression device (PCD) within 
previous 3 months 

 
 
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2. Therapist or self-administered manual lymph drainage (MLD) 
within previous 1 week 
3. Mastectomy or lymph node removal on side without lymphedema 
4. Bilateral lymphedema 
5. Heart failure (acute pulmonary edema, decompensated acute heart 
failure) 
6. Acute venous disease (acute thrombophlebitis, acute deep venous 
thrombosis, acute pulmonary embolism)  
7. Active skin or limb infection/inflammatory disease (acute cellulitis, 
other uncontrolled skin or untreated inflammatory skin disease) on 
the arms or trunk 
8. Active cancer (cancer that is currently under treatment, but not yet 
in remission) 
9. Poorly controlled kidney disease (glomerular filtration rate < 30 mls 
per minute), hypoproteinemia, pulmonary hypertension, 
hypothyroidism, cyclic edema, or Munchausen Syndrome 
10. Body Mass Index (BMI) >50 
11. Any circumstance where increased lymphatic or venous return is 
undesirable 
12. Currently pregnant or trying to become pregnant 
13. Allergy to iodine 
Treatment Duration 
A single treatment lasting: 
• 
FT-SW: Approximately 40 minutes OR 
• 
FT: Approximately 60 minutes  
Number Planned 
20 subjects randomized (minimum of 10 in each arm) with replacement of 
up to 5 early withdrawals. 
 
 
 
 
 
 
 
 
 

 
 
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TABLE OF CONTENTS 
1.0 
Contact Information ............................................................................................................. 7 
 
Sponsor Contact Information........................................................................................ 7 
 
Principal Investigator Information ................................................................................ 7 
 
Clinical Investigator Information ................................................................................. 7 
2.0 
Abbreviations ....................................................................................................................... 8 
3.0 
Introduction ........................................................................................................................ 10 
 
Background and Rationale .......................................................................................... 10 
 
Device Description ..................................................................................................... 10 
4.0 
Study Objective .................................................................................................................. 13 
5.0 
Study Design ...................................................................................................................... 13 
 
Endpoints .................................................................................................................... 13 
 
Subject Selection ........................................................................................................ 14 
 
Point of Enrollment and Randomization .................................................................... 15 
 
Treatment Assignment and Duration .......................................................................... 15 
 
Study Timeline ........................................................................................................... 15 
6.0 
Study Assessments ............................................................................................................. 15 
 
Screening/Baseline ..................................................................................................... 16 
 
Randomization ............................................................................................................ 16 
 
Treatment .................................................................................................................... 17 
 
Post-Treatment Testing............................................................................................... 17 
 
24-Hour Follow-up ..................................................................................................... 17 
7.0 
Study Schedule of Activities .............................................................................................. 17 
8.0 
Study Procedures ............................................................................................................... 18 
 
Informed Consent ....................................................................................................... 18 
 
Demographics & Medical History .............................................................................. 18 
 
Pregnancy Test ........................................................................................................... 18 
 
Vital Signs .................................................................................................................. 18 
 
Subject Surveys .......................................................................................................... 18 
 
Lymphedema Evaluation ............................................................................................ 19 
 
Perometry.................................................................................................................... 19 
 
Marking Anatomical Sites .......................................................................................... 19 
 
ICG Injections............................................................................................................. 20 
 
MoistureMeterD Measurements ................................................................................. 21 
 
Ultrasound .................................................................................................................. 21 

 
 
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NIRF Imaging ............................................................................................................. 22 
 
Randomization ............................................................................................................ 22 
 
Treatment .................................................................................................................... 23 
 
Adverse Event Assessment ......................................................................................... 23 
9.0 
Subject Discontinuation or Withdrawal ............................................................................. 24 
10.0 Accountability .................................................................................................................... 25 
11.0 Risk Analysis and Adverse Events .................................................................................... 25 
 
Risk Analysis .............................................................................................................. 25 
12.0 Provisions to Protect the Privacy of Study Participants/Information Security Plan .......... 26 
13.0 Deviation from Study Plan................................................................................................. 27 
14.0 Quality Assurance Procedures ........................................................................................... 27 
 
Site Qualification ........................................................................................................ 27 
 
Site Initiation .............................................................................................................. 27 
 
Onsite Monitoring....................................................................................................... 27 
 
Data Safety Monitoring .............................................................................................. 28 
 
Reports and Records ................................................................................................... 28 
15.0 Change to Investigational Plan .......................................................................................... 30 
16.0 Statistical Methods ............................................................................................................. 30 
17.0 Publication Plan ................................................................................................................. 30 
18.0 References .......................................................................................................................... 30 
 
 
 

 
 
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1.0 
Contact Information 
 
Sponsor Contact Information 
Tactile Medical™ 
Suzanne Hansel, Clinical Trial Manager 
1331 Tyler Street NE, Suite 200 
Minneapolis, MN 55413 
612-540-5325 
shansel@tactilemedical.com 
 
Principal Investigator Information 
John C. Rasmussen, PhD 
Assistant Professor of Molecular Imaging 
Center for Molecular Imaging (CMI) 
The Brown Foundation Institute of Molecular Medicine (IMM) 
McGovern Medical School 
University of Texas Health Science Center at Houston (UTHealth) 
1825 Pressler Street, SRB 330D 
Houston, TX 77030 
713-500-3393 
John.Rasmussen@uth.tmc.edu 
 
Clinical Investigator Information 
The sponsor will maintain a document with contact information for all investigators 
participating in the study. The information maintained will include full name, 
addresses, telephone, and, if available, email addresses and mobile phone numbers 
for the site principal investigators and Institutional Review Board (IRB) 
chairperson.  
 
 
 

 
 
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2.0 
Abbreviations 
Abbreviation Term 
AE 
Adverse Event 
BCRL 
Breast Cancer-Related Lymphedema 
BMI 
Body Mass Index 
CFR  
Code of Federal Regulations 
CMI 
Center for Molecular Imaging  
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CTA 
Clinical Trial Agreement 
DCF 
Data Clarification Form 
ESAS-R 
Edmonton Symptom Assessment System  
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
FT 
Flexitouch Plus 
FT-SW 
Flexitouch Plus with Novel Simultaneous Therapy Cycle Software 
GCP 
Good Clinical Practice 
ICG 
Indocyanine Green  
IMM 
The Brown Foundation Institute of Molecular Medicine  
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
LTW 
Local Tissue Water 
PCD 
Pneumatic Compression Device 
mg/kg 
milligram/kilogram 
MLD 
Manual Lymphatic Drainage  
mm 
millimeter  
MMD 
MoistureMeterD™  
NIRF 
Near Infrared-Fluorescence 
NSR 
Nonsignificant Risk 
PI 
Principal Investigator 
SAE 
Serious Adverse Events  
SAP 
Statistical Analysis Plan 

 
 
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Abbreviation Term 
TDC 
Tissue Dielectric Constant  
US 
Ultrasound 
USA 
United States of America 
HCPCS 
Healthcare Common Procedure Coding System  
UADE 
Unanticipated Adverse Device Effect 
μg 
microgram  
μg/ml  
micrograms/millimeter 
UTHealth 
University of Texas Health Science Center at Houston 
 
 

 
 
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3.0 
Introduction 
 
Background and Rationale  
Lymphedema is a chronic debilitating disease marked by accumulation of protein 
rich fluid in the interstitium of the skin (1). This insufficiency in the lymphatic 
system leads to limb edema in early stages and progresses to thickened skin or 
fibrosis over time. As a result, persons afflicted with lymphedema are prone to 
develop impaired extremity function, recurrent episodes of soft tissue inflammation 
and infection, lymphorrhea, unsatisfactory cosmesis, and a variety of psychological 
and social issues (2).  
Lymphedema may be inherited (primary) or caused by injury to the lymphatic 
vessels (secondary). While the exact cause of primary lymphedema is unknown, it 
generally occurs due to congenital malformations with the onset of symptoms 
presenting at birth, during puberty, or well into adulthood. Secondary lymphedema 
typically results from trauma to the lymphatic system, surgery, radiation therapy, 
obesity, and chronic venous insufficiency (3-4). Breast Cancer-Related 
Lymphedema (BCRL) is a common complication from breast cancer treatment, 
with reported frequencies ranging from 6% to 65% (5).  
There is currently no cure for lymphedema, thus treatment focuses on symptom 
management and improved patient-reported outcomes. Using a multimodal 
approach, accepted interventions include: limb elevation, manual lymphatic 
drainage, compression therapy, skin hygiene, and in very severe cases, lymphatic 
exchange (6). Pneumatic Compression Devices (PCDs) are a fairly recent addition 
to the armamentarium clinicians offer patients in the treatment of lymphedema. 
Studies have demonstrated continual use of PCDs is associated with a significant 
patient-reported improvement in overall symptoms, decreased limb-girth, decreased 
limb volume, increased elasticity of tissues, and fewer episodes of infection (7-10).  
The efficacy of PCD therapy depends on the applied force (pressure) mobilizing 
stagnant edema fluid, time of compression to move fluid to the root of the limb, and 
elasticity of skin and subcutaneous tissue. Thus, adherence to prescribed, at-home 
self-care is a critical factor in the treatment of lymphedema (11-12). One of the 
most robust findings in adherence literature concerns aspects of the therapy itself – 
the more complex and complicated a therapeutic regimen is (e.g., treatment 
duration), the less likely patients are to adhere to all aspects of prescribed care (12).   
To address non-adherence, the FT was updated with the novel simultaneous therapy 
software to shorten treatment time. Currently, the FT takes approximately 1 hour of 
treatment to provide clearing of the trunk, chest, and arm. With the novel 
simultaneous therapy cycle software engaged, the device will run two simultaneous 
therapy cycles. Thus, the simultaneous therapy cycle program will provide the same 
number therapy cycles as a traditional FT while reducing treatment time.  
The purpose of this study is to demonstrate equivalency in treatment effect between 
the novel simultaneous therapy cycle software and the standard FT. 
 
Device Description  
3.2.1 Flexitouch Plus (FT) 

 
 
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The FT (Tactile Medical™, Minneapolis, MN, USA) is a segmental, 
programmable, gradient advanced pneumatic compression device cleared 
for market in the USA (K170216, HCPCS code E0652). The device 
stimulates the lymphatic system by directing and moving excess fluid 
from an impaired lymphatic region to healthy regions where fluid can be 
absorbed and processed naturally by the body.  
The FT consists of two primary components: a controller unit and 
garments. The controller unit has connector outlets for garment hoses to 
plug into such that air can pass through the hoses and deliver treatment 
through sequential inflation and deflation of air chambers within the 
garments. The garments are constructed of nylon and have 27-32 
chambers, depending upon garment size. The pressure setting is variable 
between “decreased,” “normal,” and “increased.”  
The device is intended to provide Manual Lymphatic Drainage (MLD) 
therapy for approximately 1 hour treatment duration. Indications for use 
include lymphedema, primary lymphedema, post-mastectomy edema, 
edema following trauma and sports injuries, post immobilization edema, 
venous insufficiency, reducing wound healing time, and treatment and 
assistance in healing stasis dermatitis, venous stasis ulcers, or arterial and 
diabetic leg ulcers.  
3.2.2 Flexitouch Plus with Novel Simultaneous Therapy Cycle Software (FT-
SW) 
The investigational device utilized in this study is the FT-SW. The 
software was developed for use with the current-generation FT and allows 
the device to run two simultaneous waves of therapy. As shown in Figure 
1, the novel software provides the same number of therapy cycles as a 
traditional FT, however 2 simultaneous waves are applied instead of one. 
Application of these simultaneous waves results in a reduction in 
treatment time.  The intended use, indications, and garments for the FT-
SW are identical to the FDA cleared FT system.  
 
The FT-SW will be labeled, “CAUTION – Investigational Device, 
Limited by Federal Law to Investigational Use” and will have the unique 
10 character serial number.  

 
 
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Figure 1. FT and FT-SW 
 
3.2.3 NIRF Imaging 
The investigational imaging techniques of near-infrared fluorescence 
(NIRF) are focused on addressing unmet clinical diagnostic needs in 
lymphatic imaging through point of care, non-radioactive, clinical imaging 
diagnostic platform based on image intensifier technology.  NIRF imaging 
has been used under the investigational new drug (IND) experience by the 
FT: 1 wave = 1 cycle 
FT-SW:  2 simultaneous waves = 1 cycle 

 
 
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Principal Investigator (PI) to map lymphatic structure and visualize 
lymphatic function in hundreds of patients without adverse effects. This 
method of imaging has shown efficacy in detecting impaired lymphatic 
function with dermal backflow, defined as abnormal fluorescent signal 
observed in networks of lymphatic capillaries and/or in the extravascular 
space, presenting as one of the earliest signs of lymphedema onset (13-15).  
NIRF lymphatic imaging provides real-time imaging of the lymphatic 
anatomy and its function.  Following intradermal injections of 25 
micrograms of indocyanine green (ICG) in 0.1 cc sterile saline, a dim laser 
diode light of 785 nm is illuminated on the tissue surface.  The light 
penetrates the tissues and excites the ICG and the resultant fluorescence 
emanates from tissues and is collected using an intensified camera system.   
4.0 
Study Objective 
The objective of the study is to demonstrate equivalency in treatment effect, as determined 
by objective measurements, between the novel simultaneous therapy cycle software and 
the FDA-cleared FT. 
5.0 
Study Design 
This is an acute, prospective, randomized, two-arm, feasibility study (Figure 2) comparing 
the FT-SW to FT.  
 
   
 Figure 2. Study Design 
 
Endpoints  
To compare the effects of FT to FT-SW in BCRL patients after one treatment based 
upon:  
• Lymphatic activation in the affected and contralateral limb using the 
investigational technique of near infrared-fluorescent (NIRF) imaging 
• Swelling in the affected and contralateral limb as assessed using: 
o Perometry (LymphaTech 3D Scanner) 
o Local tissue water content (MoistureMeterD) 
• Skin changes on the affected and contralateral limb as assessed by: 
o Skin thickness (Ultrasound) 
• Safety 
 
 
 
Baseline 
(N=20)
FT-SW 
(N=10)
FT (N=10)

 
 
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    Table 1. Outcome Measures 
Endpoint 
Outcome Measure 
Lymphatic activation 
• Proportion of subjects who show an increase in the number of 
functional vessels and/or area of dermal backflow per NIRF 
imaging of the affected and contralateral arm when comparing 
post-treatment values to pre-treatment values 
• Proportion of subjects who show an increase of lymphatic 
propulsion events immediately after treatment 
Changes in Swelling 
• Proportion of subjects who show a decrease in arm perometry 
(limb volume) when comparing post-treatment values to pre-
treatment values for the affected and contralateral arm 
• Proportion of subjects who show a decrease in local tissue 
water at target sites when comparing post-treatment values to 
pre-treatment values for the affected side 
• Mean change in perometry and local tissue water post-
treatment will be compared for all sites 
Skin Changes 
• Proportion of subjects who show a decrease in skin thickness at 
target site when comparing post-treatment values to pre-
treatment values for the affected side 
• Mean change in skin thickness post-treatment will be compared 
for all sites 
Safety 
• Adverse events will be presented in data listings 
 
Subject Selection 
The target population includes patients who have received breast cancer therapy 
and developed unilateral lymphedema secondary to their cancer treatment. Patients 
will be recruited from the clinical investigator’s patient population.  
5.2.1 Inclusion Criteria: 
1. Female 18 years of age or older 
2. Diagnosis of unilateral breast cancer-related lymphedema  
3. Stage I or early stage II lymphedema without severe fibrosis at the 
time of enrollment 
4.  ≥ 5% volume difference between affected and unaffected arm as 
verified via perometry (LymphaTech 3D scanner) 
5. Willing and able to give informed consent 
6. Willing and able to comply with the study protocol requirements 
and all study-related visit requirements 
5.2.2 Exclusion Criteria: 
1. In-home use of PCD within previous 3 months 
2. Therapist or self-administered manual lymph drainage (MLD) 
within previous 1 week 
3. Mastectomy or lymph node removal on side without lymphedema 
4. Bilateral lymphedema 
5. Heart failure (acute pulmonary edema, decompensated acute heart 
failure) 

 
 
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6. Acute venous disease (acute thrombophlebitis, acute deep venous 
thrombosis, acute pulmonary embolism) 
7. Active skin or limb infection/inflammatory disease (acute 
cellulitis, other uncontrolled skin or untreated inflammatory skin 
disease) on the arms or trunk 
8. Active cancer (cancer that is currently under treatment, but not yet 
in remission) 
9. Poorly controlled kidney disease (glomerular filtration rate < 30 
mls per minute), hypoproteinemia, pulmonary hypertension, 
hypothyroidism, cyclic edema, or Munchausen Syndrome 
10. BMI >50 
11. Any circumstance where increased lymphatic or venous return is 
undesirable 
12. Currently pregnant or trying to become pregnant 
13. Allergy to iodine 
 
Point of Enrollment and Randomization 
Subjects will be considered enrolled in the study once the Informed Consent Form 
is signed and all inclusion/exclusion criteria are met. The investigator will keep a 
record, the subject screening log, of subjects who enter screening. Any subjects 
who do not meet inclusion/exclusion criteria will be considered screen failures. 
Randomization codes will be generated by a Statistician in a permuted block 
design. The block size will be balanced within each block and will maintain a 1:1 
ratio between the treatment groups. The randomization assignment will be obtained 
from the database and assigned sequentially as soon as an eligible subject 
completes the pre-treatment measurements.  
If a subject does not meet all the eligibility criteria or meets any of the exclusion 
criteria but is randomized in error, or incorrectly started on treatment, the 
Investigator should inform Tactile Medical immediately. 
Up to 5 enrolled subjects may be replaced if the subject is withdrawn prior to 
completion of the study. If a subject withdraws from participation in the study, his 
or her randomization code cannot be reused. 
 
Treatment Assignment and Duration 
Patients with unilateral BCRL will be randomized (1:1) to receive one of the 
following treatments in the affected limb:   
• Approximately 60 minutes of treatment with Flexitouch Plus (FT); or  
• Approximately 40 minutes of treatment with Flexitouch Plus with Novel 
Simultaneous Therapy Cycle Software (FT-SW)  
 
Study Timeline  
The expected study duration is approximately 8 months with 2-3 months spent on 
activation, 3 months enrolling subjects, and 2 months completing the data analysis.  
6.0 
Study Assessments 

 
 
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Case Report Forms (CRFs) and Data Clarification Forms (DCFs) will be used for data 
collection and query handling. The Investigator will ensure the accuracy, completeness, 
and timeliness of the data recorded and responses to data queries according to the Clinical 
Trial Agreement (CTA). NIRF data collected and recorded by the Investigator, and 
perometry data collected and recorded by LymphaTech, will be obtained and reconciled 
against study data.   
All data entry, storage, transmission, and management will be conducted using iMedNet, a 
21 CFR Part 11 compliant electronic data capture (EDC) system. When all data have been 
validated, signed, and locked, the database will be locked and available for analysis. 
All devices and testing procedures outlined are standard of care or approved/cleared for use 
by the FDA with the exception of FT-SW and NIRF imaging (which is approved by the 
FDA for investigational use in humans under an existing IND #102,765). Prior to taking 
endpoint measurements, delegated personnel will receive training and will demonstrate 
proficiency. 
 
Screening/Baseline  
If a patient appears eligible to participate based on medical history, he or she will 
be approached to participate in the study and consented if interested in 
participating. All consented subjects will undergo the following procedures: 
• Obtain medical history 
• Administer a serum or urine pregnancy test for all female subjects of child-bearing 
potential (for imaging purposes, the pregnancy test should be done ≤ 36 hours 
prior to NIRF imaging)  
• Vital signs – historic values within past 7 days may be used 
• Subject survey – Edmonton Symptom Assessment System (ESAS-R) 
• Lymphedema evaluation 
• Perometry via LymphaTech 3D scanner to determine volume of affected and 
unaffected arm 
o If the subject’s volume difference is <5% between affected and unaffected 
arm, they will be considered a screen failure and will not continue in the 
study 
• Mark Anatomical Sites 
• ICG Injections 
• The following assessments will be performed on the affected and unaffected arm 
in the order listed 
o MoistureMeterD (MMD) to assess local tissue water (LTW) content 
o Ultrasound to assess skin thickness  
o NIRF imaging to assess lymphatic activation 
• Randomization  
 
Randomization 
Randomization will occur after all of the screening/baseline assessments are 
complete. The study personnel performing study assessments will remain blinded 
to the treatment assignment. 

 
 
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Treatment 
The randomized treatment assignment will be administered to the affected limb. 
The personnel administering the treatment will not perform any study assessments 
as they will be unblinded to the treatment. 
 
Post-Treatment Testing 
After the subject has completed treatment, the Flexitouch garments will be 
removed. The following assessments will be performed on affected and unaffected 
arm in the order listed and should begin within approximately 15 minutes of the 
completion of treatment: 
• Perometry via Lymphatech 3D Scanner to determine volume 
• MoistureMeterD (MMD) to assess local tissue water (LTW) content 
• Ultrasound to assess skin thickness  
• NIRF imaging to assess lymphatic activation  
• Subject surveys 
o ESAS-R  
o Treatment Perception Survey 
• Adverse Event Assessment 
 
24-Hour Follow-up 
Subjects will return to the clinic or be contacted via telephone 18-28 hours after 
ICG injection for assessment of adverse events. 
7.0 
Study Schedule of Activities  
The study schedule of activities is shown below (Table 2).  
 
 

 
 
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Table 2. Schedule of Activities 
Procedures 
Day 0 (Acute Study) 
24 hour 
follow-up 
Screening  
Treatment 
Post-
Treatment 
Informed Consent 
X 
 
 
 
Demographics & Medical History 
X 
 
 
 
Inclusion/Exclusion Assessment 
X 
 
 
 
Pregnancy Test (if applicable) 
X 
 
 
 
Vital Signs 
X 
 
 
 
Subject Surveys 
X 
 
X 
 
Lymphedema Evaluation 
X 
 
 
 
Perometry (LymphaTech 3D Scanner) 
X 
 
X 
 
Mark Anatomical Sites 
X 
 
 
 
ICG Injection 
X 
 
 
 
LTW (MoistureMeterD) 
X 
 
X 
 
Ultrasound  
X 
 
X 
 
NIRF Imaging  
X 
 
X 
 
Randomization 
X 
 
 
 
FT or FT-SW Treatment 
 
X 
 
 
Adverse Event Assessment 
X 
X 
X 
X 
8.0 
Study Procedures 
 
Informed Consent  
Subjects will need to sign an informed consent form that has been approved by 
both the Sponsor and reviewing IRB to be considered for participation in this study. 
Subjects must meet all of the inclusion and none of the exclusion criteria.   
Each subject (or a legally authorized representative) must give written consent, in 
accordance with local requirements, after the nature of the study has been fully 
explained and questions answered. The consent form must be signed prior to any 
study-related procedures, and the process of informed consent must be documented 
in the subject’s record.  
 
Demographics & Medical History 
Demographics will be collected including the age at time of participation, ethnicity, 
race, and sex.  
Significant medical history, including lymphedema history, will be collected.  
 
Pregnancy Test  
Women of childbearing potential will be tested for pregnancy according to the site 
specific procedures at the Screening/Baseline visit. If the pregnancy test is positive, 
the subject will not be enrolled in the study. 
 
Vital Signs 
Height and weight will be collected to confirm subject’s BMI is <50. 
 
Subject Surveys 

 
 
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Prior to treatment the subject will complete the ESAS-R. After treatment and 
assessments are completed, the subject will complete the ESAS-R and a Treatment 
Perception survey. 
 
Lymphedema Evaluation 
Research personnel will confirm the presence of Stage I or early Stage II 
lymphedema and severity of fibrosis at Screening/Baseline. The clinical stage of 
lymphedema will be evaluated by a clinician using the following definitions: 
• Stage 0: Latent – No clinical signs (no evident swelling) 
• Stage 1: Soft swelling (pitting) that resolves with elevation 
• Stage 2: Spongy swelling (pitting and non-pitting) that does not resolve with 
elevation; fibrosis may or may not be present 
• Stage 3: Symptoms of lymphostatic elephantiasis where pitting is absent and 
trophic skin changes develop; extensive fibrotic swelling, blistering, 
ulceration, lymphorrea, papilloma, and/or recurrent infections may be 
present 
Severity of fibrosis, to distinguish between early and late Stage II lymphedema, 
will be based on the definitions below: 
Table 3. Fibrosis Assessment 
None 
No fibrotic tissue 
Minimal 
Able to move skin parallel to plane (sliding) and 
perpendicular to skin (pinching up), <20% of affected 
limb noted to have fibrotic tissue 
Moderate 
Able to slide skin, unable to pinch skin, 20-40% of 
affected limb noted to have fibrotic tissue 
Severe 
Unable to slide or pinch skin, >40% of affected limb 
noted to have fibrotic tissue 
 
Perometry 
Perometry will be performed on both limbs before and after treatment. The 
LymphaTech 3D Scanner will be utilized by appropriately trained research 
personnel in accordance with the instructions for use provided by LymphaTech. 
 
Marking Anatomical Sites 
Have the subject pull-up/remove clothing if covering arms. Using a pen or marker, 
with the subject in a seated or standing position with arms completely relaxed at 
sides, mark the skin at the locations outlined in Figures 3-5 on affected and 
unaffected sides. 
If a subject experiences pain at a targeted measurement site, an alternate location 
may be measured, recorded, and used for the duration of the study. 
 

 
 
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Figure 3.  Site A is on the anterior 
forearm 6 cm below (distal to) the 
midline of the antecubital fossa. 
Figure 4.  Site B is 6 cm above 
(proximal to) the dorsal aspect of the 
wrist (midline).  
 
 
 
Figure 5. Site C is 3 cm distal to the 
midline dorsal aspect of the wrist. 
 
 
ICG Injections 
ICG (25 mg vial) will be reconstituted with 10 ml sterile water provided by the 
manufacturer; further dilutions will be made in saline to achieve the final 
concentration of 0.32 ml, or 250 μg/ml ICG. Up to 16 intradermal injections, each 
consisting of 0.1 mL or less, using conventional 30 or 31-gauge needles may be 
administered by a clinician. However, typically each subject will only receive 8 
intradermal injections in the arms and the additional 8 injections may be 
administered if the clinician identifies areas of lymphatic drainage that may not be 
covered by the typical injections. Subjects will typically receive 2 injections in the 

 
 
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dorsum of each hand and 2 in each medial wrist. Subjects will not receive more 
than 400 μg of ICG.  
Vital signs (blood pressure, heart rate, temperature) and redness or inflammation at 
the injection sites will be monitored and recorded at baseline (pre-injection of ICG) 
and at 15 and 30 minutes after the initial injection. Study subjects will be contacted 
between 18 and 28 hours after ICG administration to ensure no adverse events have 
occurred 
 MoistureMeterD Measurements 
Local tissue water (LTW) measures will be obtained using the FDA-cleared 
MoistureMeterD™ (MMD) with the M25 (2.5 mm) and L50 (5.0 mm) probes 
(Delfin Technologies, Finland). This non-invasive, rechargeable, battery-operated 
device and technology has been demonstrated to provide a measure of LTW and its 
change based on measurements of the skin’s tissue dielectric constant at a 
frequency of 300 MHz. The method has been widely used in clinical studies as a 
highly sensitive measurement of water content and edema in the skin and subcutis 
(16-19). There are no risks associated with the use of this data collection device. In 
addition, data collected from this device will not be used in the diagnosis or 
treatment of lymphedema. 
The MMD measurements will be performed on the affected and unaffected side 
before and after treatment. Measurements may only be conducted by research 
personnel with documented training showing the individual was able to 
independently and accurately conduct the measurements. 
The following measurement procedures will be followed to assess the upper 
extremity tissue dielectric constant (TDC) values as indices of skin/tissue water:  
• Ensure the subject remains in a seated position with the arms relaxed 
• Turn on the MoistureMeter D unit, select the correct probe size on the 
display, and wait for the word “wait” to disappear from the display before 
taking any measurements.   
• Measure and record the TDC values at sites A, B, and C (See Figures 3-5) 
by firmly placing the probe on the marked site such that the entire probe 
depresses the skin and leaves a slight indentation. 
• All measurements will be made in duplicate using the L50 (5 mm) probe 
alternating in a consistent fashion (A, B, C, A, B, C) to ensure tissue water 
is not displaced at the time the second measurement is taken.  
• Clean the L50 probe with an antiseptic cleansing towel or ethanol and 
return to the storage case.  
• Repeat steps 1 through 5 (in duplicate) using the M25 (2.5 mm) probe.  
• Turn off the MoistureMeterD unit, clean the M25 probe with an antiseptic 
cleansing towel or ethanol, and return both the probe and MoistureMeterD 
unit to the storage case.  
 Ultrasound 
Tissue ultrasound measurements will be collected from the affected and unaffected 
arms using a 4-13 MHz linear transducer with the probe placed longitudinally on 

 
 
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the tissue. Measurements may only be conducted by a study team member with 
documented training. Field size and gain may be adjusted as necessary to optimize 
image quality and boundary definition. 
Ultrasound measurements will be taken to assess the thickness of the epidermis 
(skin) and the thickness of the subcutaneous layer from the epidermis (skin) to the 
muscular fascia. When the dermo-hypodermal junction is clearly identified, the full 
skin thickness (epidermis and dermis) from the anterior echogenic border of the 
epidermis to the posterior echogenic border of the dermis may be measured in B-
mode. Subcutaneous tissue thickness is measured as the distance between the 
posterior echogenic border of the dermis and the anterior echogenic border of the 
muscular fascia. When the dermo-hypodermal junction or the muscular fascia is not 
clearly identified, measurements will not be performed, and the reported result will 
be classified as a “blurred border.” 
The following measurement procedures will be followed to assess skin thickness: 
• Ensure the subject remains in a seated position with the arms relaxed   
• Measure and record skin and subcutaneous thickness measurements at sites A, 
B, and C (See Figures 3-5) 
Additional guidance on ultrasound measurements and analysis will be provided in 
an ultrasound user guide. 
 NIRF Imaging 
After all injections are made and the water content and skin thickness 
measurements are made, NIRF imaging will commence. From the images of each 
region, the lymphatic activation (anatomy and propulsion) will be quantified as 
follows: 
• Intact, fluorescent lymphatic vessels observed before and after the treatment 
will be recorded as an increase in vessels, decrease in vessels, or no change. 
The two-dimensional, projected area or extent of dermal backflow, before 
and after treatment, will be quantified using ImageJ (NIH, Bethesda, MD) 
by adjusting the brightness of the images to 20% of the maximum pixel 
value and measuring the area of regions of interest drawn around 
fluorescent areas not associated with intact and well-defined (i.e., “normal”) 
lymphatic vessels. 
• The rate of lymphatic propulsion events observed immediately before and 
after treatment will be quantified by counting the total number of propulsion 
events observed and dividing by the total observation time at each region of 
interest. 
Prior to injection and after NIRF imaging is complete, digital photographs of the 
arms will be acquired.  Images of the front and back of the arms will be acquired 
with the subject standing up and the arms held out away from the sides. 
 Randomization 
If the subject meets all of the inclusion criteria and none of the exclusion criteria, 
they will be randomly assigned to FT or FT-SW. The appropriate unblinded staff 

 
 
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member will obtain the randomization assignment by entering the appropriate 
randomization CRF in the EDC system.  
The randomization assignment cannot be changed or chosen by the subject or the 
investigator.  
 Treatment 
After all pre-treatment assessments have been performed, the subject will undergo 
the treatment that they have been randomized to. The personnel administering the 
treatment will not perform any study assessments as they will be unblinded to the 
treatment. If the subject has been randomized to the FT-SW, treatment will begin 
approximately 20 minutes after they enter the room where treatment is being 
performed to ensure the blinded study staff remain unaware of the treatment 
allocation. 
 Adverse Event Assessment 
Adverse event assessment will occur during the acute study period and ~24 hours 
after the acute study. 
Reportable events, as defined below, will be recorded on the subject’s case report 
forms (CRFs).  
8.15.1 Adverse Event (AE) 
An adverse event is any untoward medical occurrence in a clinical research 
study subject which may or may not be related to use of the medical device 
under investigation.   
Adverse events will be reported to the IRB in accordance with IRB policy. 
8.15.2 Serious Adverse Event (SAE) 
A serious adverse event is an untoward medical occurrence where the 
outcome is:  
• Death; 
• Life-threatening event (places the subject at immediate risk of death 
from the experience as it occurred);  
• Hospitalization (initial or prolonged) if admission to hospital was 
warranted as a result of an adverse event; 
• Disability or permanent damage (substantial disruption of one’s 
ability to carry out normal life functions);  
• Congenital anomaly or birth defect; 
• Required intervention to prevent permanent impairment or damage; 
or 
• Important medical event that required medical or interventional 
treatment to prevent one of the previous outcomes. 
Investigators must report all Serious Adverse Events (SAEs) to Tactile 
Medical within 10 work days of becoming aware of the event. SAEs will 

 
 
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be summarized is writing and reported to the IRB in accordance with IRB 
policy. 
8.15.3 Unanticipated Adverse Device Effect (UADE) 
A serious adverse effect on the 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 product labeling, published literature, or 
Investigational Plan, or any other unanticipated serious problem associated 
with a device that relates to the rights, safety, or welfare of subjects. 
Investigators must report all Unanticipated Adverse Device Effects 
(UADEs) to Tactile Medical within 10 work days of becoming aware of the 
event. UADEs will be summarized in writing and reported to the IRB in 
accordance with IRB policy. 
8.15.4 Device Observations 
Device observations will be recorded and reported to Tactile Medical. 
Device observations include device failures, device malfunctions, use 
errors, device issues, and user preferences, as defined below:  
• Device Failure: A device failure has occurred when the device is 
used in accordance with the IFU, but does not perform as described 
in the IFU and also negatively impacts treatment of the study 
subject. 
• Device Malfunction: A device malfunction occurs when an 
unexpected change to the device that is contradictory to the IFU is 
observed, which may or may not affect device performance.  
• Use Error: A device use error is an act or omission of an act that 
results in a different medical device response than intended by the 
manufacturer or expected by the user. Use error includes slips, 
lapses, and mistakes. An unexpected physiological response of the 
subject does not itself constitute a use error. 
• Device Issue: Any other issue with the device that does not fall into 
one of the above categories.  
• User Preference: Information on user expectations, likes, dislikes, 
motivations, and inclinations that drive subject satisfaction with the 
device.  
9.0 
Subject Discontinuation or Withdrawal  
Subject participation may be discontinued prior to study completion for any of the 
following reasons: 
• Withdrawal of Consent   
Subjects may withdraw their consent to participate at any time. If a subject withdraws 
consent, previous information that has already been obtained will be available for 
analysis. 
• Adverse Event  

 
 
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Subject experiences an adverse event that in the investigator’s clinical judgement 
necessitates discontinuation of their participation in this study.  
• Discretion of the Principal Investigator 
Subjects may be withdrawn at the investigator’s discretion in the event of subject 
noncompliance, changes in the subject’s health, or other reasons based on the 
investigator’s clinical judgment. 
When a subject withdraws prior to completing the study, the reason for withdrawal will be 
documented in the subject’s record, and up to five replacement subjects may be enrolled to 
complete the cohort.  
10.0 Accountability  
The FT, FT-SW, garments, MMD, and LymphaTech 3D Scanner (with iPad) will be 
provided at no cost to the site and applied/utilized with the assistance of study personnel. 
The site will maintain a record of device accountability to ensure all study devices are 
properly tracked and accounted for throughout the study. The record will include the 
receipt, location, use, disinfection, and final disposition of all controllers and garments. 
Study devices will be stored in a secure area with restricted access. At the conclusion of the 
study, the FT, FT-SW Controllers, MMD, and LymphaTech 3D Scanner (with iPad) will be 
returned to Tactile Medical.  
A record of lot number and expiration date will be maintained for all ICG used during the 
study to complete the investigational NIRF imaging. Information related to the NIRF 
system used for the imaging session, including the name(s) of the system operator(s) and 
performance verification, will also be documented. 
11.0 Risk Analysis and Adverse Events   
Study subjects will be informed of any significant new findings that develop during the 
course of this study that may affect their willingness to continue participation. The 
principal investigator will oversee all safety aspects of the study, report all adverse events 
to the IRB, and ensure each subject is treated identically. Should a subject choose to 
terminate his or her participation in the study, he or she will be treated according to the 
standard of care that applies at the point of withdrawal. 
 Risk Analysis  
11.1.1 Pneumatic Compression  
Pneumatic compression is a minimal risk therapy with minimal known 
complications or adverse events. However, as with any treatment, there is 
the possibility of undesirable events such as a local skin reaction to the 
device materials. The subject will be made aware of known complications 
and adverse events at time of consent and monitored closely throughout 
the study.  
In addition, since the FT-SW simulates manual lymphatic drainage, the 
lymphangions in the existing lymphatics will be stimulated to contract 
more frequently and the interstitial fluid may be propelled up the limb in a 
more rapid manner with the FT system. To minimize any risk associated 

 
 
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with the moderate increase in fluid reduction, patients with heart failure 
are excluded from the study.  
There are nominal possible adverse effects associated with the therapy. 
The expected adverse effects that are experienced by patients using this 
device are often due to the natural history of the primary disease, or a 
failure to achieve an adequate response to the compressive therapeutic 
intervention, and are thus not related to the therapy itself.  In some cases, 
lymphedema adverse events can be serious, long lasting, or may be 
permanent.  The risks listed below are symptoms or signs of lymphedema 
and may be experienced by all subjects with lymphedema: 
Likely: 
• Pain or discomfort 
• Increased swelling 
Less Likely: 
• Cellulitis – Infection of the skin which may include swelling, 
redness, and tenderness of the infected tissue 
• New or increased edema in the trunk and/or genital region 
11.1.2 NIRF Imaging 
Participants may have an allergic reaction to ICG that can include 
itchiness and/or swelling; there is a rare possibility of a severe reaction, 
including death. Two anaphylactic deaths have resulted from IV injection 
of ICG at the maximal approved dose (2 mg/kg). Because we will inject a 
maximum dose of 400 µg of ICG, the risk of severe adverse event is 
extremely low. Members of the research team will be present during the 
entire imaging procedure and physicians will be nearby to provide 
antihistamines or other interventions if needed. To minimize discomfort 
from intradermal injections, subjects may have a topical anesthetic agent 
(ethyl chloride spray) applied to the injection sites prior to administering 
ICG. 
To generate the fluorescent signal for NIRF imaging, the subject’s arms 
and sides will be illuminated with the diffused output of a 785 nm laser 
diode.  Risks associated with Class IIIB/IV lasers are not applicable for 
this study, since the fluence rate at which the laser diode is operated (≤ 1.9 
mW/cm2) constitutes no skin hazard.  However, participants will be 
instructed in general laser safety precautions as applicable to their 
participation and will be required to wear laser safety goggles during 
NIRF imaging.  Additional laser safety goggles will be available for other 
individuals in the room if they wish to wear them. 
12.0 Provisions to Protect the Privacy of Study Participants/Information Security Plan 
The most likely risk posed to participants would be a breach of confidentiality if someone 
other than the research team obtained access to the data.  

 
 
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There are security measures in place to prevent a breach of confidentiality from happening 
including password protected electronic database and the use of subject codes to de-
identify data). 
Precautions will be taken to make sure that only authorized individuals will be accessing 
subject research records.  The collection of sensitive information about subjects is limited 
to the amount necessary to achieve the aims of the research registry, so that no unneeded 
sensitive information is being collected.   
13.0 Deviation from Study Plan  
All deviations will be documented and reported to the IRB as required by IRB policies.   
14.0 Quality Assurance Procedures  
This study will be conducted in accordance with Good Clinical Practice (GCP), Code of 
Federal Regulations (CFR), institutional research policies and procedures, and other 
appropriate regulatory requirements to ensure subject safety and quality of clinical 
procedures related to the conduct of the clinical trial. As required by United States Food 
and Drug Administration (FDA) 21 CFR 56 and the Declaration of Helsinki, the protocol, 
amendments, and Informed Consent form will be reviewed and approved, according to 21 
CFR §50 and §56, by each center’s IRB. This investigational device meets the 
requirements of a nonsignificant risk (NSR) device; therefore, the study will follow the 
abbreviated requirements of 21 CFR 812.2(b). 
 Site Qualification  
Tactile Medical personnel will conduct a Qualification Visit onsite or by telephone 
to verify the resources, staffing, and subject pool are adequate to ensure successful 
enrollment and study completion. 
 Site Initiation  
Tactile Medical personnel will conduct a Site Initiation Visit onsite or by telephone 
to ensure all required regulatory documents are accurate and complete, and site 
personnel has been adequately trained on the protocol. An activation letter will be 
sent to the Principal Investigator once the site is approved to enroll subjects. 
 Onsite Monitoring  
Clinical sites will be monitored for compliance with the clinical protocol, 
investigator agreement, and applicable regulations throughout the study. Prior to 
each visit, the investigator will receive a confirmation letter outlining the scheduled 
dates and activities.  
Regular site contact will be maintained to ensure: 
• Subject safety; 
• Clinical site staff are well informed of regulations and sponsor 
requirements; 
• The clinical protocol is followed; 
• Data is gathered in a complete and timely manner; 
• Problems with data or data collection are addressed appropriately and in a 
timely manner;  

 
 
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• Adverse events are properly reported in a timely manner; and 
• Each onsite visit is recorded on the Site Visit Log. 
After each visit, the investigator will receive a follow-up letter summarizing site 
progress as well as any outstanding items that need to be addressed. 
In addition to site visits, a screening log must be submitted to Tactile Medical as 
requested (by fax or e-mail). This screening log should be reviewed with site staff 
to assess planned versus actual recruitment.   
The Principal Investigator and Institution agree to permit trial related monitoring, 
audits, IRB review, and regulatory inspection(s); providing direct access to source 
data and documents, as appropriate. Monitoring and source verification will be 
performed by a Tactile Medical clinical research associate (CRA) and/or designee. 
Source verification includes reviewing subject source documentation and Case 
Report Forms (CRFs) for accuracy, completeness, and compliance with GCP.  
 Data Safety Monitoring  
The Principal Investigator will be responsible for the monitoring of study data and 
subject safety. Due to the small number of research subjects, the most 
comprehensive and effective method of monitoring will be an individual case 
review by the PI and clinical investigators. As this has always been the policy of 
the PI, the researchers and study team are under specific instructions to make the PI 
aware of all adverse events, expected or unexpected; therefore, the responsibility 
for reporting adverse events is shared with the PI and the research team. 
CRFs containing all monitoring information will be completed by the PI, clinical 
investigator(s), or designee and reviewed by the PI or clinical investigator(s). CRFs 
will be kept in a secure location. 
Additionally, a periodic review may be completed by a designated member of the 
Sponsor’s Scientific Advisory Board. The frequency of the review will be 
determined on a number of parameters including, but not limited to: the rate of 
enrollment, number of AEs and/or SAEs, and number of significant deviations 
from the protocol. At the conclusion of the review, the reviewer may provide 
recommendations pertaining to study continuation, modification, or termination of 
the trial or investigational site.  
 Reports and Records   
Records to be maintained by the investigator in a designated study file include: 
• Investigational plan and all amendments; 
• Signed Investigator Agreement/Research Contract; 
• IRB approval letter, including a copy of the approved consent forms, 
progress reports, and adverse event reports; 
• IRB roster or Assurance number, if applicable; 
• All correspondence relating to the conduct of this study between the site 
and sponsor, IRB, and study monitor; 
• Curriculum Vitae and professional license for all study personnel, if 
applicable; 

 
 
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• Financial Disclosure for all Investigators, if applicable; 
• Site personnel signature and documentation regarding the investigator’s 
delegation of responsibility; 
• Site visit log; 
• Protocol/device related training records for all applicable study personnel; 
• Device accountability log; 
• Device observations; 
• Screening log; and 
• Reports (shown below). 
The Principal Investigator is required to prepare and submit to Tactile Medical, or 
its designees, complete, accurate, and timely reports on this investigation as 
required by regulations (Table 4).  
Table 4. Required Reports 
15.0 
 
Reports 
Submit To 
Timeframe 
SAE or UADE 
Sponsor and 
Reviewing IRB 
Sponsor: Within 10 working 
days of becoming aware of the 
event; 
IRB: In accordance with 
IRB procedure. 
Withdrawal of IRB 
Approval 
Sponsor 
Within 5 working 
days 
IRB determination that 
study is classified as 
Significant Risk (SR) 
Sponsor 
Immediately upon notification 
from the IRB 
Progress 
Sponsor and Reviewing IRB 
Annually, at a 
minimum 
Final 
Sponsor and 
Reviewing IRB 
Within 3 months 
following the completion 
or termination of the 
Investigator’s part 
 
The following records must be maintained for each subject enrolled: 
• Original, signed and dated informed consent form, as well as documentation 
of the process of consent; 
• Completed CRFs, DCFs, and source document worksheets, as applicable; 
and 
• Complete medical records including procedure reports, lab reports, etc., as 
applicable 
Subject study records, correspondence files, all supporting study documentation, 
and reports must remain on file at the site for a minimum of ten years after the 

 
 
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conclusion of this study. All investigators must contact Tactile Medical personnel 
prior to destroying or archiving off-site any records and reports pertaining to this 
study to ensure that they no longer need to be retained on-site. Additionally, Tactile 
Medical personnel must be contacted if the investigator plans to leave the 
investigational site to ensure that arrangements for a new investigator or records 
transfer are made prior to the investigator’s departure. 
15.0 Change to Investigational Plan  
Should changes in the study plan or protocol become necessary during the course of the 
clinical research study, proposed changes will be appropriately reviewed and approved by 
Tactile Medical personnel and the investigator, and IRB approval will be obtained before 
any changes are implemented. All changes must be documented.  
16.0 Statistical Methods   
For continuous variables, descriptive statistics will include the number of subjects (n), 
mean, standard deviation, median, inter-quartile range, minimum, and maximum, based 
upon subjects with reported data for the variable being analyzed.  
Frequencies (numerator and denominator), percentages, and 95% confidence intervals will 
be displayed for categorical data. Percentages by categories will be based on the number of 
subjects with no missing (unreported) data for the specific variable being analyzed and the 
count of the patients for each individual level of the categorical variable (the level specific 
numerators). Percentages will add up to 100%, unless otherwise indicated. 
There are no plans to impute missing data and there are no plans to explicitly report 
missing data (counts and/or percentages) in the tables for all variables as part of the 
planned study report content. Variations in the reported sample sizes within and/or between 
relevant tables can be used to ascertain insights into unreported data. In some cases, 
unreported data may be the result of it not being clinically relevant to a particular patient or 
may represent expected data that was not collected. Selected analyses pertaining to 
unreported and/or missing data may be discussed and considered as future findings 
warrant. 
The feasibility nature of the study suggests that the statistical focus will be on estimation 
and hypothesis generation. Thus, formal statistical tests of hypotheses are not planned. 
All data processing, summarization, and analyses will be performed using R Version 3.54.0 
or higher.  
17.0 Publication Plan 
The data collected as part of this research is intended to be used for new product 
development and marketing claims. As the study contains trade secret product 
enhancements, data is intended to be kept “on file” with no plan for publication of the data. 
18.0 References 
1  
Jensen MR, Simonsen L, Karlsmark T, Bulow J. Lymphoedema of the lower 
extremities--background, pathophysiology and diagnostic considerations. Clin 
Physiol Funct Imaging. 2010 Nov;30(6):389-98. 

 
 
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2 
Zaleska M, Olszewski WL, Durlik M. The effectiveness of intermittent pneumatic 
compression in long-term therapy of lymphedema of lower limbs. Lymphat Res 
Biol. 2014 Jun;12(2):103-9. 
3 
Cormier JN, Askew RL, Mungovan KS, Xing Y, Ross MI, Armer JM. 
Lymphedema beyond breast cancer: a systematic review and meta-analysis of 
cancer-related secondary lymphedema. Cancer. 2010 Nov 15;116(22):5138-49. 
4 
Todo Y, Yamamoto R, Minobe S, Suzuki Y, Takeshi U, Nakatani M, et al. Risk 
factors for postoperative lower-extremity lymphedema in endometrial cancer 
survivors who had treatment including lymphadenectomy. Gynecol Oncol. 2010 
Oct;119(1):60-4. 
5 
Perdomo M, Davies C, Levenhagen K, Ryans K. Breast cancer edge task force 
outcomes: Assessment measures of secondary lymphedema in breast cancer 
survivors. Rehabil Oncol 2014; 32:22-35.  
6     Langbecker D, Hayes SC, Newman B, Janda M. Treatment for upper-limb and 
lower-limb lymphedema by professionals specializing in lymphedema care. Eur J 
Cancer Care (Engl). 2008 Nov;17(6):557-64. 
7 
Fife C, Davey S, Maus EA, Guilliod R, Mayorovitz HN. A randomized controlled 
trial comparing two types of pneumatic compression for breast cancer-related 
lymphedema treatment in the home. Support Care Cancer 2012 Dec;20(12):3279-
86.  
8 
Zaleska M, Olszewski WL, Durlik M, Kaczmarek M. A Novel Clinical Test for 
Setting Intermittent Pneumatic Compression Parameters Based on Edema Fluid 
Hydromechanics in the Lymphedematous Calf. Lymphat Res Biol. 2015 
Sep;13(3):208-14.  
9 
Blumberg SN, Berland T, Rockman C, Mussa F, Brooks A, Cayne N, Maldonado 
T. Pneumatic Compression Improves Quality of Life in Patients with Lower-
Extremity Lymphedema. Ann Vasc Surg. 2016 Jan;30:40-4. 
10 Muluk SC, Hirsch AT, Taffe EC. Pneumatic compression device treatment of 
lower extremity lymphedema elicits improved limb volume and patient-reported 
outcomes. Eur J Vasc Endovasc Surg. 2013 Oct;46(4):480-7. 
11 Ridner SH, McMahon E, Dietrich MS, Hoy S. Home-based lymphedema treatment 
in patients with cancer-related lymphedema or noncancer-related lymphedema. 
Oncol Nurs Forum. 2008 Jul;35(4):671-80. 
12 Palmer S. Barriers and Facilitators to Successful Lymphedema Therapy: The Role 
of Adherence. Lymph Link. 2006;18(4):1-5. 
13 Adams K, Rasmussen, J, Darne C, Tan I, Aldrich Melissa, Marshall M, Fife C, 
Maus E, Smith L, Guilliod R, Hoy S, Sevick E. Direct evidence of lymphatic 
function improvement after advanced pneumatic compression device treatment of 
lymphedema. Biomedical optics express. 2010; 1: 114-125.  
14    Rasmussen JC, Aldrich MB, Tan IC, Darne C, Zhu B, O'Donnell TF Jr, Fife CE, 
Sevick-Muraca EM. Lymphatic transport in patients with chronic venous 

 
 
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insufficiency and venous leg ulcers following sequential pneumatic compression. J 
Vasc Surg Venous Lymphat Disord. 2016 Jan;4(1):9-17.  
15 Rasmussen JC, Tan IC, Marshall MV, Fife CE, Sevick-Muraca EM. Lymphatic 
imaging in humans with near-infrared fluorescence. Curr Opin Biotechnol. 2009 
Feb;20(1):74-82.  
16    Nuutinen J, Ikaheimo R, Lahtinen T. Validation of a new dielectric device to assess 
changes on tissue water in skin and subcutaneous fat. Physiol Meas. 2004, 25: 447-
454. 
17    Laaksonen DE, Nuutinen J, Lahtinen T, Rissanen A, Niskanen LK. Changes in 
abdominal subcutaneous fat water content with rapid weight loss and long-term 
weight maintenance in abdominally obese men and women. Int J Obes Relat Metab 
Disord. 2003, 27: 677-683. 
18    Mayrovitz HN. Assessing local tissue edema in postmastectomy lymphoedema. 
Lymphology. 2007. 40:87-94. 
19    Mayrovitz HN, Davey S, Shapiro E. Local tissue water assessed by tissue dielectric 
constant: anatomical site and depth dependence in women prior to breast cancer 
treatment related surgery. Clin Physiol Funct Imaging. 2008. 28: 337-342.