Assessment of Quality of Life Changes on Lower Extremity Lymphedema Patients Using an Advanced Pneumatic Compression Device at Home
Conditions: Lymphedema
Sponsor: Tactile Medical

Form – 038-07; REV C 12/2013 
Tactile Medical 
 
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Assessment of Quality of Life Changes on Lower Extremity 
Lymphedema Patients using an Advanced Pneumatic 
Compression Device at Home.   
 
 
Protocol# 5010 
 
 
03 July 2019 
Protocol Version 3.1 
 
 
 
 
 

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Tactile Medical 
 
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Investigator Signature 
 
 
Protocol Title: Assessment of Quality of Life Changes on Lower Extremity Lymphedema 
Patients using a Pneumatic Compression Device at Home.   
 
 
 
 
Protocol Number: 5010 
Date:  03 July 2019, Version 3.1 
 
 
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 
 
Title of Study 
Assessment of Quality of Life Changes on Lower Extremity Lymphedema Patients 
using an Advanced Pneumatic Compression Device at Home.   
Protocol Date 
3 July 2019 
Protocol Version 
3.1 
Name of Sponsor 
Tactile Medical™ 
Device 
Flexitouch® system or Flexitouch® Plus 
Primary Endpoint 
Quality of life (QoL), lymphedema symptoms, lymphedema and venous related 
complication rate, lymphedema and venous related unscheduled visits 
Secondary Endpoint 
Limb circumference changes, Flexitouch compliance, skin changes, QoL 
METHODOLOGY 
Study Design 
Multi-center, single arm, observational clinical trial  
Treatments 
Subjects will be instructed to use the Flexitouch system or Flexitouch Plus as 
prescribed and will be followed for 52 weeks.  The subjects will be seen in clinic 4, 
8, 12, 24 and 52 weeks after completion of device training.  The subject will also 
have phone call follow-ups at 1, 18, 32 and 40 weeks after device training.  
Treatment Duration 
As prescribed 
SUBJECT POPULATION 
Number Planned  
300 
Inclusion Criteria  
1) Age 18 or older  
2) Diagnosis of primary or secondary, unilateral or bilateral, LE lymphedema  
3) Ability and willingness to participate in all aspects of the study including 
following prescribed care 
4) Ability to provide informed consent 
5) Must have a prescription for the Flexitouch (Flexitouch system or Flexitouch 
Plus) 
Exclusion Criteria 
1) Diagnosis of active or recurrent cancer, or less than 3 months at the time of 
initial evaluation from the completion of chemotherapy, radiation therapy or 
primary surgery for the treatment of cancer. 
2) Active skin or limb infection/inflammatory disease (acute cellulitis, or other 
uncontrolled skin or untreated inflammatory skin disease) 
3) Acute thrombophlebitis (in last 2 months) 
4) Pulmonary embolism within the previous 6 months 
5) Deep Vein Thrombosis (DVT) within the previous 3 months 
6) Severe peripheral artery disease (critical limb ischemia including ischemic rest 
pain, arterial wounds, or gangrene) 
7) Pulmonary edema  
8) Heart failure (acute pulmonary edema, decompensated acute heart failure) 
9) Patients with poorly controlled asthma  
10) Previous use of the study pneumatic compression device (PCD) 
11) Currently using multi-layer bandaging (MLB) unless bandages can be removed 
for limb circumference measurements 
12) Pregnant women or women of childbearing potential not on contraception  
13) Any condition where increased venous and lymphatic return is undesirable 
14) Currently participating in another medical device or drug clinical trial 
15) Signs of noncompliance at the week 4 visit, including: using the device less 
than 3 times per week and/or not attending the scheduled visit 
 

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Table of Contents 
Investigator Signature ................................................................................................................................... 2 
SYNOPSIS ....................................................................................................................................................... 3 
1.0 
Contact Information .......................................................................................................................... 7 
1.1 
Sponsor Contact Information ........................................................................................................ 7 
1.2 
Study Principal Investigator Information ...................................................................................... 7 
2.0 
Abbreviations .................................................................................................................................... 7 
3.0 
Introduction ...................................................................................................................................... 7 
3.1 
Background and Rationale ............................................................................................................ 7 
3.2 
Device Description ........................................................................................................................ 8 
4.0 
Study Objectives ............................................................................................................................... 8 
5.0 
Study Design...................................................................................................................................... 8 
5.1 
Study Endpoints ............................................................................................................................ 9 
5.1.1 
Primary Endpoints ................................................................................................................. 9 
5.1.2 
Secondary Endpoints ............................................................................................................ 9 
5.2 
Subject Selection ......................................................................................................................... 10 
5.2.1 
Inclusion Criteria ................................................................................................................. 10 
5.2.2 
Exclusion Criteria ................................................................................................................. 10 
5.2.3 
Subject Withdrawal or Early Termination ........................................................................... 11 
5.3 
Dosage and Rationale ................................................................................................................. 11 
5.4 
Study Timetable .......................................................................................................................... 11 
6.0 
Study Visit Summaries .................................................................................................................... 11 
6.1 
Screening/Baseline Visit .............................................................................................................. 11 
6.2 
Week 0/Training .......................................................................................................................... 12 
6.3 
Weeks 1 (+7 days), 18, 32, & 40 (± 14 days) Follow-up Phone Calls ........................................... 12 
6.4 
Weeks 4, 8, 12 (± 7 days), 24, and 52 (± 14 days) In-Clinic Follow-Up Visit(s) ............................ 12 
7.0 
Study Procedures ............................................................................................................................ 12 
7.1 
Informed Consent ....................................................................................................................... 12 
7.2 
Demographics & Medical History ............................................................................................... 13 
7.3 
Vital Signs .................................................................................................................................... 13 
7.4 
Skin Assessment .......................................................................................................................... 13 

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7.4.1 
Fibrosis Grading .................................................................................................................. 13 
7.4.2 
Assessment of Skin Changes ............................................................................................... 13 
7.4.3 
Lymphedema Staging .......................................................................................................... 14 
7.5 
Limb Circumference Measurements ........................................................................................... 14 
7.5.1 
Mark Anatomical Sites ........................................................................................................ 14 
7.5.2 
Circumference Measurements ........................................................................................... 15 
7.6 
Photograph (Legs) ....................................................................................................................... 15 
7.7 
Prescribed Care & Treatment Protocol ....................................................................................... 16 
7.8 
Medication Review ..................................................................................................................... 16 
7.9 
QoL Questionnaires..................................................................................................................... 16 
7.10 
Flexitouch Compliance Assessment & Subject Diary .................................................................. 17 
7.11 
Lymphedema and Venous Related HCU, Device-Related Adverse Events, & Device 
Observations ........................................................................................................................................... 17 
7.11.1 
Lymphedema and Venous Related HCU ............................................................................. 17 
7.11.2 
Device-Related Adverse Events .......................................................................................... 18 
7.11.3 
Device Observations ........................................................................................................... 18 
7.12 
Flexitouch Administration & Training ......................................................................................... 18 
7.13 
Study Schedule of Activities ........................................................................................................ 19 
8.0 
Study Device Accountability............................................................................................................ 20 
9.0 
Risk Analysis and Adverse Events ................................................................................................... 20 
9.1 
Risk Analysis ................................................................................................................................ 20 
9.2 
Adverse Events ............................................................................................................................ 20 
10.0 
Deviation from Study Plan .............................................................................................................. 20 
11.0 
Quality Assurance Procedures ........................................................................................................ 20 
11.1 
Site Qualification ......................................................................................................................... 21 
11.2 
Data Collection Procedures ......................................................................................................... 21 
11.3 
Clinical Site Monitoring ............................................................................................................... 21 
11.4 
Data Safety Monitoring ............................................................................................................... 21 
12.0 
Change to Investigational Plan........................................................................................................ 23 
13.0 
Statistical Methods and Determination of Sample Size .................................................................. 23 
13.1 
Statistical Analysis Plan ............................................................................................................... 23 
13.2 
Determination of Sample Size..................................................................................................... 23 
14.0 
Compensation ................................................................................................................................. 23 

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15.0 
Publication Plan .............................................................................................................................. 23 
16.0 
References ...................................................................................................................................... 23 
17.0 
Appendices ...................................................................................................................................... 24 
Appendix A: Lymphedema Quality of Life Tool (LYMQOL) ......................................................................... 25 
Appendix B: SF-36 Health Survey v.2 (SF-36) .............................................................................................. 28 
Appendix C: Subject Diary ........................................................................................................................... 35 
 
 
 
 

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1.0 
Contact Information 
1.1 
Sponsor Contact Information 
Tactile Medical™ 
Jill Christensen, Clinical Research Manager 
1331 Tyler Street NE, Suite 200 
Minneapolis, MN 55413 
612-355-5123 
jchristensen@tactilemedical.com 
1.2 
Study Principal Investigator Information 
Thomas Maldonado, MD 
New York Vascular Surgery Associates 
530 First Avenue Suite F 
New York City, NY 10016 
212.263.7311 
Thomas.maldonado@nyumc.org 
2.0 
Abbreviations 
CFR 
Code of Federal Regulations 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
DVT 
Deep Vein Thrombosis 
ER 
Emergency Room 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HCU 
Health Care Utilization 
IC 
Informed Consent 
IRB 
Institutional Review Board 
LE 
Lower Extremity 
MLB 
Multi-Layer Bandaging 
PCD 
Pneumatic Compression Device 
QoL 
Quality of Life 
SAE 
Serious Adverse Event 
SF-36 
Short Form-36 
 
3.0 
Introduction 
3.1 
Background and Rationale 
The purpose of this study is to evaluate the effect of an advanced pneumatic 
compression device in improving symptoms and quality of life in patients with 
lower extremity lymphedema.  
Lymphedema is a chronic and disfiguring disease usually secondary to excessive 
fluid and protein accumulation in the interstitium as result of lymphatic system 
obstruction.1  It can occur either primarily (as a result of congenital malformations) 

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or secondarily (as a result of trauma to the lymphatic system, surgery, radiation 
therapy, obesity and chronic venous insufficiency).2,3 This leads to limb swelling in 
early stages with progression to thickening skin and fibrosis leaving the affected 
extremity susceptible to skin breakdown and repeated infections. There is no cure 
for lymphedema, and the available treatment modalities consist of manual 
lymphatic drainage, compression therapy, and in very severe cases lymphatic 
exchange, a costly and invasive procedure.4 
Pneumatic Compression Devices (PCDs) offer a novel modality for treatment of 
lymphatic obstruction. The Flexitouch®System and Flexitouch® Plus are PCDs that 
target all major lymphatic beds and release pressure in a systematic manner, 
mimicking a functional drainage system.5 Prior studies demonstrated improvement 
in control of edema and ease of use; however improvement in quality of life (QoL) 
and decrease in symptoms has not been thoroughly evaluated.6,7,8 Therefore we 
propose to demonstrate improved QoL and symptoms in patients with lower 
extremity (LE) lymphedema.   
3.2 
Device Description  
The Flexitouch system and Flexitouch Plus (Tactile Medical™, Minneapolis, MN, 
USA) are segmental, programmable, gradient PCDs which have been cleared by 
the Food and Drug Administration (FDA) for market in the US (K013061), (US 
HCPCS code E0652).  The devices consist of a controller and garment set.  The 
garments are constructed of nylon and have 27-32 chambers, depending upon 
garment size.  The pressure setting is variable between “normal” and “increased.”  
The Flexitouch system and Flexitouch Plus are intended for the treatment of 
lymphedema, primary lymphedema, post mastectomy edema, edema following 
trauma and sports injuries, post immobilization edema, venous insufficiencies, 
reducing wound healing time and assistance in healing stasis dermatitis, venous 
stasis ulcers, or arterial and diabetic leg ulcers.  
The Flexitouch Plus is functionally equivalent to the Flexitouch system, however it 
permits bilateral treatment of the lower extremities, incorporates a color display 
with larger buttons on the controller, and provides more comfortable garments that 
are easier to put on and take off.   
4.0 
Study Objectives 
The study will assess QoL, lymphedema symptoms, lymphedema and venous related 
complication rate, lymphedema and venous related unscheduled visits, Flexitouch 
compliance, and skin and limb circumference changes in primary or secondary, unilateral 
or bilateral, lower extremity lymphedema patients using the Flexitouch system or 
Flexitouch Plus during the 52 week study period.     
5.0 
Study Design 
This investigation is a post-market, on label, multi-center, single arm, observational 
clinical trial of a prospective cohort of 300 subjects with primary or secondary, unilateral 
or bilateral, lower extremity lymphedema in the United States. All subjects will receive 
PCD treatment for 52 weeks (Figure 1).  

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Figure 1. Study Design 
 
5.1 
Study Endpoints  
5.1.1 Primary Endpoints 
The following primary endpoints for this study will compare changes after 
12 weeks of treatment to baseline for the following parameters:  
 QoL  
 Lymphedema symptoms  
In addition, the number of occurrences after 52 weeks of treatment will be 
compared to the number of occurrences in the year preceding treatment for 
the following variable:  
 Lymphedema and venous related health care utilization  
5.1.2 Secondary Endpoints  
Yes 
No 
Screening – Assess for 
Eligibility 
Not Eligible - 
Exclude 
Eligible  
Obtain IC 
Baseline 
Follow Up 
Visits 
Exit 
Screen Fail 
 Week 4 
Follow-up 
Is Subject 
Compliant? 
Screen Fail 

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The secondary endpoints for this study will compare changes after 12 and 
52 weeks of treatment to baseline for the following:  
 Limb circumference  
 Skin evaluation  
In addition, changes after 24 and 52 weeks of treatment to baseline for the 
following parameter: 
 QoL  
To assess Flexitouch compliance, subjects will be categorized as 
noncompliant, partially compliant, or compliant (Table 1). Primary and 
secondary outcomes will then be compared across the defined compliance 
categories. 
Table 1. Compliance Category Definitions 
Compliance Category 
Definition 
Noncompliant 
Prescribed care followed an average of 0-2 days per week.   
Partially Compliance 
Prescribed care followed an average of 3-4 days per week.   
Compliant 
Prescribed care followed an average of 5-7 days per week.   
5.2 
Subject Selection 
5.2.1 Inclusion Criteria  
1. Age 18 or older  
2. Diagnosis of primary or secondary, unilateral or bilateral, LE lymphedema  
3. Ability and willingness to participate in all aspects of the study including 
following prescribed care 
4. Ability to provide informed consent 
5. Must have a prescription for the Flexitouch (Flexitouch system or 
Flexitouch Plus) 
5.2.2 Exclusion Criteria 
1. Diagnosis of active or recurrent cancer, or less than 3 months at the time of 
initial evaluation from the completion of chemotherapy, radiation therapy 
or primary surgery for the treatment of cancer. 
2. Active skin or limb infection/inflammatory disease (acute cellulitis, or 
other uncontrolled skin or untreated inflammatory skin disease) 
3. Acute thrombophlebitis (in last 2 months) 
4. Pulmonary embolism within the previous 6 months 
5. Deep Vein Thrombosis (DVT) within the previous 3 months 
6. Severe peripheral artery disease (critical limb ischemia including ischemic 
rest pain, arterial wounds, or gangrene) 
7. Pulmonary edema  
8. Heart failure (acute pulmonary edema, decompensated acute heart failure) 
9. Patients with poorly controlled asthma  
10. Previous use of the study PCD 

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11. Currently using multi-layer bandaging (MLB) unless bandages can be 
removed for limb circumference measurements 
12. Pregnant women or women of childbearing potential not on contraception  
13. Any condition where increased venous and lymphatic return is undesirable 
14. Currently participating in another medical device or drug clinical trial 
15. Signs of noncompliance at the week 4 visit, including: using the device less 
than 3 times per week and/or not attending the scheduled visit 
5.2.3 Subject Withdrawal or Early Termination 
Subjects will exit the study if they meet any of the following criteria: 
 Subject death 
 Subject voluntarily withdraws 
 Subject acquires one or more of the exclusion criteria whereby the 
investigator deems study discontinuation a necessity 
o If subject acquires an infection, they may be treated for the 
infection and continue in the trial at the investigator’s discretion. 
Detailed information regarding the infection, nature, treatment, and 
duration will be recorded. 
 Subject diary shows an unwillingness to remain partially compliant or 
compliant with prescribed care (subject will be considered a screen 
failure if he or she uses the device <3 times per week on average at the 
Week 4 visit). 
5.3 
Dosage and Rationale 
Study subjects will be instructed to conduct LE treatment as prescribed by their 
physician. They will also be instructed to wear clinically appropriate compression 
garments and participate in proper skin care as part of their routine care.  
5.4 
Study Timetable 
Table 2. Study Timetable 
 
1-6 months 
7-12 months 
12-24 months 
24-36 months 
IRB Review 
X 
 
 
 
Enrollment 
X 
X 
X 
X 
Treatment 
X 
X 
X 
X 
Data Entry 
X 
X 
X 
X 
Data Analysis 
 
 
 
X 
Manuscript Draft 
 
 
 
X 
Publication 
 
 
 
2021 
6.0 
Study Visit Summaries  
The sections below provide a summary of procedures at each study visit. For further detail 
for each procedure, please refer to section 7 (Study Procedures) of the protocol.  
In the event a patient is unwilling or unable to attend a scheduled Follow-Up Visit, the site 
will have the discretion to offer a home visit to the patient. 
6.1 
Screening/Baseline Visit 
 Informed Consent Discussion 

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 Inclusion/Exclusion criteria assessment 
 Collection of demographics, significant medical history, and lymphedema 
history 
 Urine pregnancy test (as applicable) 
 Weight (kg) and height (cm) 
 Skin assessment 
 Limb circumference  
 Photographs (Leg) 
 Prescribed care and treatment protocol 
 Medication review 
 Qol Questionnaires 
o SF-36 
o LYMQOL 
 Subject Diary (dispense) 
6.2 
Week 0/Training 
 The subject will receive the Flexitouch system or Flexitouch Plus and be 
instructed on use from a Tactile Medical trainer. Device treatment will 
commence following the visit from the trainer. 
6.3 
Weeks 1 (+7 days), 18, 32, & 40 (± 14 days) Follow-up Phone Calls 
 Prescribed care and treatment protocol 
 Medication review 
 Flexitouch compliance assessment 
 Complication, adverse event, and device observation assessment  
6.4 
Weeks 4, 8, 12 (± 7 days), 24, and 52 (± 14 days) In-Clinic Follow-Up Visit(s) 
 Weight (kg) 
 Skin assessment 
 Limb circumference  
 Photographs (Leg) 
 Prescribed care and treatment protocol  
 Medication review 
 QoL Questionnaires (Weeks 12, 24, and 52 only) 
o LYMQOL 
o SF-36 
 Subject diary collection 
 Flexitouch compliance assessment  
 Complication, adverse event, and device observation assessment  
7.0 
Study Procedures 
7.1 Informed Consent  
Signed consent for participation in this study will be obtained prior to any research 
procedures. All study participants are required to sign an Intuitional Review Board 

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(IRB) approved informed consent document that outlines the purpose of the study, 
requirements for participation, risks and benefits to participation, and subject’s 
rights. Adequate time will be given for patients to read the consent form, to confirm 
their comprehension, and to decide on consent. Comprehension and capacity for 
consent will be assessed by the research staff.  
The study staff will ensure that a valid consent is documented and placed in the 
patient’s medical chart. A signed copy will be given to the subject/authorized 
representative and a copy will be maintained in the study file.  
7.2 
Demographics & Medical History 
Demographics will be collected at baseline including the date of birth, ethnicity, 
race, gender, and employment status.  
If the subject is female and of childbearing potential, a urine pregnancy test will be 
performed to ensure the subject is not pregnant. Per exclusion criterion 11, if a 
subject is pregnant or a women of childbearing potential not on contraception, they 
will be excluded from the study. 
Significant medical history and lymphedema history will be collected at baseline 
including number of lymphedema and venous related visits that required health 
care utilization (HCU) (includes clinic visits, hospitalization, walk-in clinic/urgent 
care, and ER visits).  
7.3 
Vital Signs 
At the screening/baseline visit, height (cm) and weight (kg) will be collected. 
Weight will be collected at all other clinic visit follow-ups. 
7.4 
Skin Assessment 
Skin will be assessed at each clinic visit by fibrosis grading, assessment of skin 
changes, and staging of lymphedema using ISL guidelines.  
7.4.1 Fibrosis Grading 
Fibrosis grading will use the following guidelines: 
 Grade 0: Latent with no evident fibrosis  
 Grade 1: Soft tissues responds only minimally or moderately to 
elevation (raising the limb) or compression; texture is moderately 
firm or spongy 
 Grade 2: Marked increase in density and firmness; “tethering” of 
skin (changes in texture that makes skin look as it is being pulled 
from within) 
 Grade 3: Very marked density and firmness with evident tethering 
7.4.2 Assessment of Skin Changes 
The assessment of skin changes will be done by recording the presence or 
absence of: 
 Hyperpigmentation, Discoloration 
 Hyperkeratosis 

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 Dermatitis, Eczema 
 Ulceration, Blisters 
 Positive Stemmer Sign 
 Squaring of Toes 
 Deep Creasing at Flexion Points 
 Papillomas 
 Puffy Forefoot/Swelling on Dorsum 
 Increase of Fat or Muscle Bulk 
 Lymphorrhea, Weeping Edema 
7.4.3 Lymphedema Staging 
The staging of lymphedema will follow ISL guidelines as shown in Table 
3. 
Table 3. ISL Staging Guidelines 
Stage 
Description 
Stage 0  
Latent with 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 elephantitis where pitting is absent and tropic 
skin changes develop; extensive fibrotic swelling, blistering, ulceration, 
lymphorrea, papilloma, and/or recurrent infections may be present. 
7.5 
Limb Circumference Measurements 
Limb circumference measures will be taken at each in-clinic visit for both legs. The 
circumference measurements will be completed by research personnel with 
documented training showing the individual was able to independently and 
accurately conduct the measurements. Measurements will be collected using a 
Gulick II tape measure provided by Tactile Medical. In addition, if possible, the 
same clinician will be asked to take the measurements for each subject serially.  
Standard limb measurement will involve taking two circumference measurements 
at 18 cm from the floor and 10 cm above the popliteal. 
7.5.1 Mark Anatomical Sites 
Using a pen or skin marker, with the subject standing upright and bearing 
weight on the limb being measured, mark the subject at the lateral aspect 
of the leg 18 cm from the floor (see Figure 2), at the popliteal, and 10 cm  
from the popliteal (Figure 3). 

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Figure 2. Site A is 18 cm from the floor 
on lateral aspect of the leg. 
 
Figure 3. Site B is the popliteal and Site 
C is 10 cm above the popliteal. 
7.5.2 Circumference Measurements 
After marking the anatomical sites, measure and record the circumference, 
in cm, at sites A (see Figure 4) and C (see Figure 5). The tape measure 
must be placed precisely over (covering) the skin marking. Adjust the 
tension of the tape measure so that one red ball is visible in the tension 
indicator and record the circumference measurement. 
 
 
Figure 4. Site A circumference 
measurement. 
 
Figure 5. Site C circumference 
measurement. 
7.6 
Photograph (Legs) 
A digital photograph of the subject’s legs will be taken at each study visit. The 
subject’s legs should be exposed, at minimum, from the bottom of the ankle to the 
mid-thigh. Subjects should sit and straighten their legs as much as possible (see 
Figure 6).  
 

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Figure 6. Leg photograph example. 
Additionally, if a subject has areas of hyperpigmentation, ulcers, or excessive 
swelling, a close-up photo of that area should be taken. The image number(s) from 
the digital camera should be recorded on the subject’s source documentation.   
7.7 
Prescribed Care & Treatment Protocol 
At each visit, current lymphedema treatment, including Flexitouch treatment, will 
be reviewed and recorded.  
7.8 
Medication Review 
At each clinic visit, use of the following medications will be documented: 
 Beta blockers 
 Diuretics 
 Oral steroids 
 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) 
7.9 
QoL Questionnaires 
The LYMQOL is an assessment tool designed for measuring QoL in patients with 
lower limb lymphedema.9 It is a 25 item questionnaire which has been designed 
and validated in patients with chronic edema and covers 4 domains: function, 
appearance, symptoms, and mood and in addition has an overall QoL score.  This 
tool has been designed and validated for patients with chronic lymphedema in one 
or both legs to measure QoL. (Appendix A) 
The Short Form-36 (SF-36) is an assessment of functional status and quality of life. 
The SF-36 is a validated QoL tool that has been widely utilized and has been found 
to be appropriate for use in evaluating health related quality of life impacts. The 
SF-36 consists of 36 questions that evaluate eight health concepts including 
physical functioning, role functioning-physical, bodily pain, general health, vitality, 
social functioning, role functioning – emotional, and mental health. (Appendix B) 
 
 

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7.10 Flexitouch Compliance Assessment & Subject Diary 
At each phone call and clinic visit, subject compliance will be assessed by 
collecting the following information: 
 Days Flexitouch used in past week 
 Days compression garments used in past week 
 Difficulty in following treatment 
 Difficulty in putting on Flexitouch garments 
 Difficulty using Flexitouch controller 
 Pain or discomfort experienced when using Flexitouch 
 Position treatment being done in 
If the subject reports difficulty following treatment, putting on the Flexitouch 
garment, difficulty using the Flexitouch controller, or is experiencing pain or 
discomfort when using Flexitouch, the site may refer the subject to Tactile Medical 
clinical services for assistance in addressing the issue(s).  
In addition, the subjects will be provided with a Subject Diary at their 
Screening/Baseline visit and be instructed to begin completing the diary when they 
start using their device after their training visit. The subject will be asked to keep a 
daily record of their use of Flexitouch, Actitouch (if prescribed), and compression 
stockings. (Appendix C) Subjects should bring their diary into each study visit for 
review and collection.  
If the subject is noncompliant or partially compliant in device use, (see Table 1), the site 
should identify barriers to compliance and determine if additional device training by the 
site or Tactile personnel is warranted. If noncompliance continues, the Investigator may 
initiate the subject’s withdrawal from the study. 
At the 4 week in-clinic follow-up visit, if a subject is not using their Flexitouch an 
average of 3 times per week, they will be considered a screen failure.  
If the subject experiences a complication (e.g., active infection, DVT) that requires 
temporary discontinuation of device use and 4 weeks of continuous treatment is not 
possible before the final in-clinic visit takes place, the subject should be withdrawn 
from the study. 
Additionally, a device history log may be downloaded periodically from Flexitouch 
Plus units. 
7.11 Lymphedema and Venous Related HCU, Device-Related Adverse Events, & 
Device Observations 
At each phone call and clinic follow-up visit, assessment of lymphedema and 
venous related HCU, device-related adverse events, and device observations will 
occur and be recorded in Clindex, per the following definitions. 
7.11.1 Lymphedema and Venous Related HCU 
Lymphedema and venous related visits that required HCU (includes clinic 
visits, hospitalization, walk-in clinic/urgent care, and ER visits).  

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7.11.2  Device-Related Adverse Events 
Any untoward medical occurrence in a subject that is associated with the 
use of the Flexitouch device. 
7.11.3 Device Observations 
All subject-reported user errors, device failures, malfunctions, or device 
issues. 
7.12 Flexitouch Administration & Training 
After the subject’s screening/baseline visit, Tactile Medical personnel will perform 
in-home device training. The date of device training (Day 0) will be used to 
determine the timing of subsequent follow-up visits.  
 
 
 
 

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7.13 Study Schedule of Activities  
Assessments 
Screening/Baseline 
Training / Day 0 
Week 1 (Phone Call) 
Week 4 
Week 8 
Week 12 
Week 18 (Phone call) 
Week 24 
Week 32 (Phone call) 
Week 40 (Phone call) 
Week 52 
Visit Window 
N/A 
N/A 
+7 Days 
±7 Days 
±7 days 
±7 days 
±14 days 
±14days 
±14 days 
±14 days 
±14 days 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical History/Status 
X1 
 
 
 
 
 
 
 
 
 
 
Vital Signs2 (Height, Weight) 
X 
 
 
X 
X 
X 
 
X 
 
 
X 
Skin Assessment 
X 
 
 
X 
X 
X 
 
X 
 
 
X 
Limb Circumference 
X 
 
 
X 
X 
X 
 
X 
 
 
X 
Photograph (Leg) 
X 
 
 
X 
X 
X 
 
X 
 
 
X 
Prescribed Care & Treatment 
Protocol 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medication Review 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Quality of Life Assessments 
X 
 
 
 
 
X 
 
X 
 
 
X 
Subject Diary 
X3 
 
 
X 
X 
X 
 
X 
 
 
X 
Flexitouch Compliance  
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HCU, Adverse Events, & 
Device Observations  
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Flexitouch Training 
 
X 
 
 
 
 
 
 
 
 
 
1Includes Lymphedema History 
2Height and weight collected at Screening/Baseline, weight collected at all subsequent visits 
3Dispense and train subject on subject diary completion 

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8.0 
Study Device Accountability 
To participate in the study, the Flexitouch must be covered by a payer. The Flexitouch will 
be provided to the subject and tracked according to normal business practices. Subjects’ 
whose payer requires rental of the Flexitouch will be excluded from the study.   
9.0 
Risk Analysis and Adverse Events  
9.1 
Risk Analysis 
This study does not present risks above and beyond those normally associated with 
the use of this market cleared product. 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 at time of consent and monitored closely throughout the study.   
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 and report all 
adverse events to the IRB per the IRB’s reporting requirements. Should a subject 
choose to terminate his or her participation in the study, they will be treated 
according to the standard of care that applies at the point of withdrawal.  
9.2 
Adverse Events  
This study will collect device-related adverse events. A device related adverse 
event is defined as any untoward medical occurrence in a subject that is associated 
with the use of the Flexitouch device. If this device-related event is serious, 
investigators must report the event to Tactile Medical within 72 hours and to their 
IRB per their policy. A serious adverse event is defined as an event that, 1) results 
in death; 2) is life-threatening (places the subject at immediate risk of death from 
the experience as it occurred; 3) results in a persistent or significant 
disability/incapacity (substantial disruption of one’s ability to carry out normal life 
functions); 4) results in medical or surgical intervention; 5) results in or prolongs 
existing hospitalization; 6) is medically unexpected, regardless of severity. 
10.0 Deviation from Study Plan  
All deviations will be documented and reported to the IRB as required by IRB policies. 
11.0 Quality Assurance Procedures  
This study will be conducted in accordance with Good Clinical Practice, 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) CFR (21 CFR 56) and the Declaration of Helsinki, the study 
protocol, amendments, and Informed Consent form will be reviewed and approved, 
according to 21 CFR §50 and §56, by each study center’s IRB. 

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11.1 Site Qualification 
Tactile Medical personnel must conduct on-site Qualification Visits or a telephone 
qualification assessment to verify that there are adequate resources, staffing, and a 
sufficient subject pool to ensure successful enrollment and study completion. 
11.2 Data Collection Procedures 
Raw data will be collected on appropriate source document worksheets, or site-
specific appropriate forms which include but are not limited to, clinic charts and 
site-generated source document worksheets. If the site staff chooses to use site-
specific data collection forms it may be beneficial for these to be reviewed by 
Tactile prior to use. Data collection shall be entered into the validated and secure 
Clindex electronic data capture systems.  
11.3 Clinical Site Monitoring 
Clinical sites will be monitored for compliance with the clinical protocol, 
investigator agreement, and applicable regulations.  Regular contact will be 
maintained to ensure: 
 Subject safety 
 That  clinical  site  staff  is  well  informed  of  regulations  and  sponsor 
requirements 
 That the clinical protocol is followed 
 That data is gathered in an accurate, complete and timely way 
 That problems with data or data collection are addressed appropriately and 
in a timely manner 
 
 That adverse events are properly reported in a timely manner 
Investigator and Institution will 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 Tactile 
Medical Clinical Research Associates (CRAs) and/or designee. Source verification 
includes reviewing subject source documentation and Case Report Forms (CRFs) 
for accuracy, completeness, and compliance with GCP procedures. 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 plan 
vs. actual recruitment. 
11.4 Data Safety Monitoring 
A periodic review may be completed by a designated member of the 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 
complications, and number of significant deviations from the protocol. At the 
conclusion of the review the reviewer may provide recommendations that 
pertaining to study continuation, modification or termination of the trial, or a 
specific investigational site. 
 
 

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11.5 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, Adverse Event Report 
• IRB roster or Assurance number, if applicable 
• All correspondences relating to the conduct of this study between the 
site and sponsor, IRBs, and study monitor 
• Curriculum Vitae and professional license for all study personnel, 
if applicable 
• Site personnel signature and documentation regarding the 
Investigator’s delegation of responsibility 
• Clinical Site Visit log 
• Protocol/device related training records for all applicable study personnel 
• Screening log 
• Reports (Table 4) 
 
The following records must be maintained for each subject enrolled: 
• Signed and dated informed consent forms 
• Completed CRFs, queries, and source document worksheets (if applicable) 
• Complete medical records including procedure reports, lab reports 
(as applicable), etc. 
Investigators are required to prepare and submit to Tactile Medical or its 
designees complete, accurate, and timely reports on this investigation as required 
by regulations. The types of reports to be submitted are summarized in the table 
below. 
Table 4: Investigator Reports 
12.0 
 
Reports 
Submit To 
Timeframe 
Serious Adverse Event 
(SAE) 
Sponsor and Reviewing 
IRB 
Sponsor: 72 hours 
IRB: per their procedure 
Withdrawal of IRB 
Approval 
 
Sponsor 
Within 5 working 
Days 
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 
 

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Subject study records, correspondence files, all supporting study documentation, 
and reports must remain on file at the investigational site for a minimum of ten 
years after the 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. 
12.0 Change to Investigational Plan 
Should changes in the study plan or protocol become necessary in the course of the clinical 
trial, proposed changes will be appropriately reviewed and approved by Tactile Medical 
personnel, Investigator, and appropriate IRB approval obtained before the any changes are 
implemented. All changes must be documented.   
13.0 Statistical Methods and Determination of Sample Size  
13.1 Statistical Analysis Plan 
The analysis will be completed by a qualified statistician or analyst. The Sponsor 
will establish and maintain the trial database.  
13.2 Determination of Sample Size 
The study is planned to have up to 300 subjects enrolled. Each subject will undergo 
treatment as prescribed, using the Flexitouch system or Flexitouch Plus. This 
sample of convenience was selected based on the investigator’s previous pilot study 
and experience with this patient population.  
14.0 Compensation 
Study subjects may be compensated for their time and travel for participating in this study. 
15.0 Publication Plan  
All information obtained during the conduct of the study will be considered to be 
confidential and is the property of Tactile Medical. Written permission from Tactile 
Medical personnel must be obtained before disclosing any information related to this study. 
All publications (e.g. manuscripts, abstracts, and slide presentations) based on this study 
must be submitted to Tactile Medical for review and approval before submission or 
according to the individual site clinical trial agreement. 
16.0 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. 
2. 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. 
3. 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. 

Form – 038-07; REV C 12/2013 
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4. 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. 
5. Mayrovitz HN. Interface pressures produced by two different types of lymphedema therapy devices. Phys 
Ther. 2007 Oct;87(10):1379-88. 
6. 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. 
7. Wilburn O, Wilburn P, Rockson SG. A pilot, prospective evaluation of a novel alternative for maintenance 
therapy of breast cancer-associated lymphedema [ISRCTN76522412]. BMC Cancer. 2006;6:84. 
8. Cannon S. Pneumatic compression devices for in-home management of lymphedema: two case reports. 
Cases J. 2009;2:6625. 
9. Keeley V, Crooks S, Locke J et al. A quality of life measure for limb lymphoedema (LYMQOL), J 
Lymphedema, 2010, 5(1) 
17.0 Appendices 
Appendix A: Lymphedema Quality of Life Tool (LYMQOL) 
Appendix B: SF-36 Health Survey v.2 (SF-36) 
Appendix C: Subject Diary  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix A: Lymphedema Quality of Life Tool (LYMQOL) 
 

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Appendix B: SF-36 Health Survey v.2 (SF-36) 

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Appendix C: Subject Diary