A Feasibility Study Evaluating the Impact Flexitouch Plus With Connectivity Has on Compliance in Patients With Breast Cancer-Related Lymphedema (BCRL)
Phase: NA
Conditions: Breast Cancer Lymphedema
Sponsor: Tactile Medical

 
 
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A Feasibility Study Evaluating the Impact Flexitouch® Plus with 
Connectivity has on Compliance in Patients with Breast Cancer-
Related Lymphedema (BCRL)  
 
 
 
Protocol Number: 4090 
 
 
February 11, 2021 
Protocol Version 4.0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Principal Investigator Signature Page 
 
 
 
A Feasibility Study Evaluating the Impact Flexitouch Plus with Connectivity has on Compliance 
in Patients with Breast Cancer-Related Lymphedema (BCRL) 
 
Protocol Number: 4090 
 
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 the Impact Flexitouch Plus with 
Connectivity has on Compliance in Patients with Breast Cancer-
Related Lymphedema (BCRL) 
Protocol Date 
February 11, 2021 
Protocol Version 
4.0 
Protocol Number 
4090 
Name of Sponsor 
Tactile Medical™ 
Device 
Investigational Flexitouch Plus with Cellular Connectivity (FT-CC) 
Study Objective 
To demonstrate the feasibility of using the FT-CC to actively monitor device 
use data to: 
• 
Determine if patient reminders impact the rate of compliance, 
• 
Identify the impact device compliance has on arm girth, quality of 
life, and symptoms. 
Primary Endpoint 
• 
Compare the rate of compliance in patients treated with PASSIVE FT-
CC and ACTIVE FT-CC  
Exploratory Endpoints 
• 
Assess the impact device compliance has on arm girth 
• 
Determine the impact device compliance has on measures of quality of 
life (QOL) and symptom assessment: 
o Lymphedema Quality of Life Tool (LYMQOL ARM) 
o Short Form-36 (SF-36) 
o Lymphedema Symptom Intensity and Distress Survey-Arm 
(LSIDS-A)  
Study Design 
This is a multi-center, on label, prospective, randomized, two-arm feasibility 
study.  
Treatment(s) 
Eligible patients will be randomized to one of the following groups for 60 
days:   
• 
ACTIVE FT-CC – Text message reminders will be sent if 
subject does not use the device for 2 consecutive days 
• 
PASSIVE FT-CC – Text message reminders will not be sent to 
subjects 
Eligibility 
 
Inclusion Criteria: 
1. Female 18 years of age or older 
2. Diagnosis of unilateral breast cancer-related lymphedema 
3. Willing and able to give informed consent (remotely or in-person) 
4. Willing and able to comply with the study protocol requirements 
and all study-related visit requirements, including the ability to 
participate remotely 
5. Willing and able to receive text messages from sponsor  
Exclusion Criteria: 
1. In-home use of pneumatic compression device (PCD) within 
previous 3 months 

 
 
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2. Phase-one complete decongestive therapy (CDT) within previous 1 
month or planned phase-one CDT during study participation  
Phase-one CDT defined as professionally administered manual 
lymphatic drainage (MLD) and/or multi-layer short stretch 
compressive bandaging. 
3. Inability to be fit for PCD garments 
4. Heart failure (acute pulmonary edema, decompensated acute heart 
failure) 
5. Acute venous disease (acute thrombophlebitis, acute deep venous 
thrombosis, acute pulmonary embolism)  
6. Active skin or limb infection/inflammatory disease (acute cellulitis, 
other uncontrolled skin or untreated inflammatory skin disease) on 
the arms or trunk 
7. Currently receiving treatment for cancer with curative intent. 
8. Any circumstance where increased lymphatic or venous return is 
undesirable 
9. Currently pregnant or trying to become pregnant 
10. Known inability to receive cell phone connection where FT-CC 
therapy will be administered 
Treatment Duration 
60 days 
Number Planned 
30 Randomized Subjects 

 
 
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TABLE OF CONTENTS 
 
Contact Information ............................................................................................................. 7 
 
Sponsor Contact Information........................................................................................ 7 
 
Site Principal Investigator Information ........................................................................ 7 
 
Abbreviations ....................................................................................................................... 7 
 
Introduction .......................................................................................................................... 7 
 
Background and Rationale ............................................................................................ 7 
 
Device Description ....................................................................................................... 8 
 
Study Objective .................................................................................................................... 9 
 
Study Design ........................................................................................................................ 9 
 
Endpoints ...................................................................................................................... 9 
 
Subject Selection ........................................................................................................ 10 
 
Point of Enrollment and Randomization .................................................................... 11 
 
Subject Discontinuation or Withdrawal ..................................................................... 11 
 
Randomization Assignment and Treatment Duration ................................................ 12 
 
Study Timeline ........................................................................................................... 12 
 
Study Assessments ............................................................................................................. 12 
 
Screening/Baseline Visit............................................................................................. 13 
 
Day 0 – Training ......................................................................................................... 13 
 
Day 30 (±7 days) Follow-Up Visit ............................................................................. 13 
 
Day 60 (±7 days) Follow-Up Visit ............................................................................. 13 
 
Study Schedule of Activities ...................................................................................... 14 
 
Study Procedures ............................................................................................................... 15 
 
Informed Consent ....................................................................................................... 15 
 
Demographics & Medical History .............................................................................. 15 
 
Pregnancy Test ........................................................................................................... 15 
 
Height and Weight ...................................................................................................... 15 
 
Medication Review ..................................................................................................... 15 
 
Lymphedema Evaluation ............................................................................................ 15 
 
Lymphedema Treatment Review ................................................................................ 15 
 
Arm Girth ................................................................................................................... 15 
 
Randomization ............................................................................................................ 16 
 
Quality of Life Assessments ....................................................................................... 16 
 
Symptom Assessment ................................................................................................. 17 

 
 
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FT-CC Garment Measurements .................................................................................. 17 
 
FT-CC Training .......................................................................................................... 17 
 
AE & Device Observation Assessment ...................................................................... 17 
 
Accountability .................................................................................................................... 18 
 
Risk Analysis ..................................................................................................................... 19 
 Provisions to Protect the Privacy of Study Participants/Information Security Plan .......... 20 
 Deviations from Study Plan ............................................................................................... 20 
 Regulatory Assessment ...................................................................................................... 20 
 Quality Assurance Procedures ........................................................................................... 20 
 
Site Qualification ........................................................................................................ 21 
 
Site Initiation .............................................................................................................. 21 
 
Monitoring .................................................................................................................. 21 
 
Data Safety Monitoring .............................................................................................. 22 
 
Reports and Records ................................................................................................... 22 
 Changes to Investigational Plan ......................................................................................... 23 
 Statistical Methods ............................................................................................................. 23 
 
Sample Size Determination ........................................................................................ 23 
 
Statistical Analysis ..................................................................................................... 24 
 Publication Plan ................................................................................................................. 24 
 References .......................................................................................................................... 24 
 
 
 

 
 
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Contact Information 
 
Sponsor Contact Information 
Tactile Medical™ 
Suzanne Hansel, Clinical Trial Manager 
3701 Wayzata Blvd, Suite 300 
Minneapolis, MN 55416 
612-540-5325 
shansel@tactilemedical.com 
 
Site Principal Investigator Information 
The sponsor will maintain a document with contact information for all investigators 
participating in the study. The information maintained will include full names, 
addresses, telephone numbers, and, if available, email addresses and mobile phone 
numbers for the site principal investigators and Institutional Review Board (IRB) 
chairperson.  
 
Abbreviations 
Abbreviation 
Term 
AE 
Adverse Event 
BCRL 
Breast Cancer-Related Lymphedema 
CDT 
Complete Decongestive Therapy 
CFR  
Code of Federal Regulations 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CTA 
Clinical Trial Agreement 
DCF 
Data Clarification Form 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
FT 
Flexitouch Plus 
FT-CC 
Flexitouch Plus with Cellular Connectivity 
GCP 
Good Clinical Practice 
HCPCS 
Healthcare Common Procedure Coding System  
ICF 
Informed Consent Form 
IRB 
Institutional Review Board 
LSIDS-A 
The Lymphedema Symptom Intensity and Distress Survey-Arm  
LYMQOL ARM 
Lymphedema Quality of Life Tool 
MLD 
Manual Lymphatic Drainage  
NSR 
Nonsignificant Risk 
PCD 
Pneumatic Compression Device 
PHI 
Protected Health Information 
PI 
Principal Investigator 
QoL 
Quality of Life 
SAE 
Serious Adverse Events  
SF-36 
Short Form-36 
UADE 
Unanticipated Adverse Device Effect 
 
Introduction 
 
Background and Rationale  

 
 
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Lymphedema is a chronic debilitating disease marked by accumulation of protein 
rich fluid in the interstitium of the skin. Breast cancer-related lymphedema (BCRL) 
is a common complication from breast cancer treatment, with reported frequencies 
ranging from 6% to 65% (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).  
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, MLD, compression 
therapy, skin hygiene, and in very severe cases, lymphatic exchange (3). 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 (4-7).  
Adherence to prescribed, at-home self-care is a critical factor in the treatment of 
lymphedema (8-9). Research shows PCD compliance diminishes over time (10). 
This study seeks to determine if active monitoring of device use information and 
patient reminders affects compliance. Additionally, there is limited data on how 
various compliance rates impact health outcomes. Therefore, this study also seeks 
to identify the impact compliance rates have on swelling, quality of life, and 
symptoms. 
 
Device Description  
The Flexitouch Plus system (FT) (Tactile Medical™, Minneapolis, MN, USA) is an 
advanced pneumatic compression device clinically proven to stimulate the 
lymphatic system and is cleared for market in the USA (K203178, K170216, 
HCPCS code E0652). The device helps direct and move excess fluid from an 
impaired lymphatic region to healthy regions, where fluid can be absorbed and 
processed naturally by the body. Flexitouch Plus garment chambers inflate 
sequentially with each chamber inflating before the adjacent distal chamber fully 
deflates. This creates a dynamic wave of therapy that directs fluid into the 
lymphatic capillaries while maintaining distal pressure to prevent distal backflow.  
The Flexitouch Plus system consists of two primary components: the controller unit 
and garments.  
The controller unit is a programmable pneumatic compressor with four connector 
outlets. Each connector has eight outflow ports that garment hoses plug into. Air 
passes through the hoses, delivering treatment through the sequential inflation and 
deflation of up to 32 air chambers in the garments. By selecting the appropriate 
treatment program, calibrated gradient pressure is delivered to the chambers and 
assists in moving excess fluid out of the affected limb(s).  

 
 
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The air-chambered garments are made of soft, pliable fabric. They are designed to 
fit the contours of the body by wrapping around the limb(s) and attaching with hook 
and loop fasteners. A variety of upper and lower extremity treatment options are 
available. The pressure setting is variable between “decreased,” “normal,” and 
“increased.” Individual chamber pressures may also be individually adjusted. 
The novel FT-CC is identical to the Flexitouch Plus with the exception of an 
addition of a cellular communication module to the controller unit which transmits 
device usage data to a cloud-based database accessible to the study sponsor. This 
data will be used by the sponsor to send automated text messages to subjects 
randomized to the FT-CC ACTIVE group that have not used their device for 2 
consecutive days.   
The FT-CC will be labeled, “CAUTION – Investigational Device, Limited by 
Federal Law to Investigational Use” and each unit will have a unique serial number. 
The FT-CC is investigational only in that it has the cellular communication module; 
in all other aspects, including cleared intended use, FT-CC is the same as the 
currently marketed FT. 
 
Study Objective 
The objective of the study is to demonstrate the feasibility of using the FT-CC to actively 
monitor device use data to: 
• Determine if patient reminders impact the rate of compliance 
• Identify the impact device compliance has on arm girth, quality of life, and 
symptoms.  
 
Study Design 
This is a multi-center, on label, prospective, randomized, two-arm, feasibility study (Figure 
1) comparing the PASSIVE FT-CC to ACTIVE FT-CC. A multi-center design is used to 
expedite the enrollment period and provide a broader sample of the study population. 
Randomization was incorporated into the study to determine if ACTIVE FT-CC affects 
device use.  
 
   
 Figure 1. Study Design 
 
Endpoints  
5.1.1 
Primary Endpoint  
Compare the rate of compliance in patients treated with PASSIVE FT-CC 
and ACTIVE FT-CC  
Baseline 
(N=30)
Active FT-
C (N=15)
Passive FT-
C (N=15)

 
 
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5.1.2 
Exploratory Endpoints  
To assess the exploratory endpoints, subjects will be categorized as 
partially compliant and compliant (Table 1). These endpoints will be 
analyzed using the following compliance categories. 
    Table 1. Compliance Category Definitions 
Compliance Category 
Definition 
Partially Compliant 
FT-CC used on average 1-4 days per week  
Compliant 
FT-CC used on average 5-7 days per week 
• 
Assess the impact device compliance has on arm girth 
• 
Determine the impact device compliance has on measures of QoL and 
symptoms assessment: 
o Lymphedema Quality of Life Tool (LYMQOL ARM) 
o Short Form-36 (SF-36) 
o The Lymphedema Symptom Intensity and Distress Survey-ARM 
(LSIDS-A) 
5.1.3 
Outcome Measures 
Primary and exploratory endpoints will be based on the outcome measures 
as described in Table 2. 
    Table 2. Outcome Measures 
Endpoint 
Outcome Measure 
Compliance 
• Compare rate of compliance (# of days used/total study days) 
to prescribed treatment between FT-CC PASSIVE and FT-CC 
ACTIVE Subjects at 30 and 60 days 
Change in Arm Girth 
• Comparison between baseline and day 30/60 arm girth 
measurement 
Quality of Life 
• Comparison between baseline, 30 day, and 60 day surveys 
Symptom Assessment 
• Comparison between baseline, 30 day, and 60 day surveys 
 
Subject Selection 
The target population includes patients who have unilateral BCRL. Only patients 
who meet the criteria below will be considered for the study. A total sample of 30 
subjects will be randomized.  
5.2.1 
Inclusion Criteria 
1. Female 18 years of age or older 
2. Diagnosis of unilateral breast cancer-related lymphedema  
3. Willing and able to give informed consent (remotely or in person)  
4. Willing and able to comply with the study protocol requirements and all 
study-related visit requirements, including the ability to participate 
remotely 
5. Willing and able to receive text messages from sponsor  
5.2.2 
Exclusion Criteria 
1. In-home use of PCD within previous 3 months 

 
 
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2. Phase-one CDT within previous 1 month or planned phase-one CDT 
during study participation 
Phase-one CDT defined as professionally administered MLD and/or 
multi-layer short stretch compressive bandaging. 
3. Inability to be fit for PCD garments 
4. Heart failure (acute pulmonary edema, decompensated acute heart 
failure) 
5. Acute venous disease (acute thrombophlebitis, acute deep venous 
thrombosis, acute pulmonary embolism) 
6. Active skin or limb infection/inflammatory disease (acute cellulitis, 
other uncontrolled skin or untreated inflammatory skin disease) on the 
arms or trunk 
7. Currently receiving treatment for cancer with curative intent. 
8. Any circumstance where increased lymphatic or venous return is 
undesirable 
9. Currently pregnant or trying to become pregnant 
10. Known inability to receive cell phone connection where FT-CC therapy 
will be administered 
 
Point of Enrollment and Randomization 
Subjects will be considered enrolled in the study once the Informed Consent Form 
(ICF) 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 electronic data capture (EDC) database and assigned sequentially as soon as a 
subject is considered enrolled.  
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 treatment, the Investigator 
should inform Tactile Medical immediately. 
 
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. 
• 
Discretion of the Principal Investigator 

 
 
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Subjects may be withdrawn at the investigator’s discretion in the event of 
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 recorded. 
 
Randomization Assignment and Treatment Duration 
Eligible patients will be randomized (1:1) to one of the following groups for 60 
days:   
• 
ACTIVE FT-CC – Text message reminders will be sent if subject does not 
use device for 2 consecutive days 
• 
PASSIVE FT-CC – Text message reminders will not be sent to subjects 
The FT-CC prescription will be a daily 60-minute U1 unilateral treatment at normal 
pressure. Settings and programs may be modified by the discretion of the 
investigator, if needed, and these modifications will be documented. If subjects are 
assigned to the ACTIVE FT-CC group and their device is not used for 2 
consecutive days, they will receive a text message reminding them to use their 
device. If subjects are assigned to the PASSIVE FT-CC group, they will not receive 
text message reminders. 
If subjects assigned to the ACTIVE FT-CC group are not able to receive text 
messages due to cellular connectivity or text transmission issues, alternate methods 
may be used to remind the subject to use their device and will be documented on 
the Case Report Form (CRF). 
 
Study Timeline  
The expected study duration is approximately 10 months with 2-3 months spent on 
activation, 5 months enrolling and following subjects, and 2 months completing the 
data analysis.  
 
Study Assessments 
In an effort to reduce potential exposure to COVID-19, all study assessments are intended 
to be performed in a contactless manner (i.e., telephone, video conference, etc). If an 
assessment is done in-person, the reason will be documented, (e.g., required for adverse 
event assessment, requested by subject, risk for COVID-19 eliminated, assessment 
performed in conjunction with another clinic visit, etc.).  
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).   
All data entry, storage, transmission, and management will be conducted using iMedNet, a 
21 code of federal regulations (CFR) Part 11 compliant EDC system. When all data have 
been validated, signed, and locked, the database will be locked and available for analysis. 

 
 
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All devices and testing procedures outlined are standard of care or approved/cleared for use 
by the Food and Drug Administration (FDA) with the exception of FT-CC. Tactile Medical 
will provide qualified trainers to train the subject on how to use the FT-CC.  
 
Screening/Baseline Visit 
If a patient appears eligible to participate based on medical history, they  will be 
contacted or approached to assess interest. If the subject is interested in learning 
more, an ICF will be provided to them (in-person, electronically, or via mail) and 
the subject will be given adequate time to review and ask questions. If the subject 
decides to participate and provides documented informed consent, they will 
undergo the following assessments: 
• 
Obtain medical history 
• 
Administer a serum or urine pregnancy test for all female subjects of child-
bearing potential (if this is required, it will be done at the clinic) 
• 
Height and weight  
• 
Medication Review 
• 
Lymphedema evaluation 
• 
Lymphedema treatment review 
• 
Arm Girth 
• 
Randomization 
• 
LYMQOL ARM 
• 
SF-36 
• 
LSIDS-A 
• 
FT-CC Garment Measurements 
 
Day 0 – Training  
FT-CC training should occur within 21 days of the Screening/Baseline visit. The 
training may occur remotely using electronic means (i.e., telephone, video 
conference, etc), or in-person. Training will be performed by qualified Tactile 
Medical personnel.   
 
Day 30 (±7 days) Follow-Up Visit 
The subject will be contacted for the following assessments: 
• Weight (only required if they have access to a scale and can self-report) 
• Medication Review 
• Lymphedema Treatment Review 
• Arm Girth 
• LYMQOL ARM 
• SF-36 
• LSIDS-A 
• Adverse Event (AE) & Device Observation Assessment 
 
Day 60 (±7 days) Follow-Up Visit 
The subject will be contacted for the following assessments: 
• Weight (only required if they have access to a scale and can self-report) 

 
 
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• Medication Review 
• Lymphedema Treatment Review 
• Arm Girth 
• LYMQOL ARM 
• SF-36 
• LSIDS-A 
• AE & Device Observation Assessment  
After the subject has completed their Day 60 follow-up visit, they will be exited 
from the study and the FT-CC device will be collected. Return of the FT-CC may 
be done by the subject returning the controller to the clinic or by shipping it back 
from their home in a box provided by Tactile Medical.  
 
Study Schedule of Activities  
The study schedule of activities is shown below (Table 3). 
Table 3. Schedule of Study Activities 
Assessments 
Screening/Baselin
e 
Day 0 - Training 
Day 30 
Day 60 
Visit Window 
N/A 
Within 21 days 
after 
Screening/Baseline 
±7 Days 
±7 Days 
Informed Consent 
X 
 
 
 
Demographics & Medical History 
X 
 
 
 
Pregnancy Test (if applicable)1 
X 
 
 
 
Inclusion/Exclusion Assessment 
X 
 
 
 
Height and Weight 
X2 
 
X3 
X3 
Medication Review 
X 
 
X 
X 
Lymphedema Evaluation 
X 
 
 
 
Lymphedema Treatment Review 
X 
 
X 
X 
Arm Girth 
X 
 
X 
X 
Randomization 
X 
 
 
 
Quality of Life Assessments 
(LYMQOL ARM, SF-36) 
X 
 
X 
X 
Symptom Assessment (LSIDS-A) 
X 
 
X 
X 
FT-CC Garment Measurements 
X 
 
 
 
FT-CC Training  
 
X 
 
 
AE & Device Observation 
Assessment  
 
 
X 
X 
1If pregnancy test is required, it will be performed in the clinic 
2Height collected at Screening/Baseline visit only; height and weight collected via self-report for subjects with 
access to scale or from subject’s most recent medical history  
3Weight collected via self-report if subject has access to a scale at home 

 
 
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Study Procedures 
 
Informed Consent  
Subjects will sign an ICF 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 all 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 medical record, including if the process was performed in-
person or remotely. 
 
Demographics & Medical History 
Demographics will be collected including the date of birth, 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 during the Screening/Baseline visit. If the pregnancy test is 
positive, the subject will not be enrolled in the study. 
 
Height and Weight 
Height and weight will be collected during the Screening/Baseline visit via self-
report for subjects who have access to a scale or from the subject’s most recent 
medical history. Weight will be collected during follow-up visits via self-report if 
the subject has access to a scale. 
 
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) 
 
Lymphedema Evaluation 
Research personnel will confirm a diagnosis of unilateral breast cancer-related 
lymphedema by review of the subject’s medical records. 
 
Lymphedema Treatment Review 
During each visit, with the exception of the training visit, the subject will also be 
asked questions regarding their use in the last 7 days of the FT-CC (Day 30 and 60 
only), compression garments, and other prescribed lymphedema treatment. 
 
Arm Girth 

 
 
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The subject will be provided with a tape measure to make an arm girth 
measurement on the anterior forearm 6 cm below the midline of the antecubital 
fossa on the affected arm (see Figure 2). If a family member or care provider is able 
to do this measurement for the subject, the same person should perform the 
measurement at all visits. 
 
Figure 2. Arm girth to be measured on 
the anterior forearm 6 cm below (distal 
to) the midline of the antecubital fossa. 
      
 
Randomization 
If the subject meets all of the inclusion criteria and none of the exclusion criteria, 
they will be randomly assigned to ACTIVE FT-CC or PASSIVE FT-CC.  
Randomization will occur via entering the randomization CRF in the EDC system. 
The randomization assignment should not be shared with the research subject.  
The randomization assignment cannot be changed or chosen by the subject or the 
investigator.  
 
Quality of Life Assessments 
7.10.1 LYMQOL ARM 
The LYMQOL ARM is an assessment tool designed for measuring quality 
of life (QoL) in patients with upper limb lymphedema. It is a 21-item 
questionnaire which has been designed and validated in patients with 
chronic edema and covers four domains: function, appearance, symptoms, 
and mood, and in addition, has an overall QoL score (11). The subject will 
have a unique user account and can complete the assessment online via 
secure connection to the study database. If subject is not able to complete 
the questionnaire electronically, they can also be mailed to them for 
completion.  
7.10.2 SF-36 
The SF-36 is an assessment of functional status and quality of life. This 
questionnaire is a validated QoL tool that has been widely utilized and has 

 
 
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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. 
 
Symptom Assessment 
The LSIDS-A is a 30-item validated assessment tool designed for measuring arm 
lymphedema and its associated symptoms in patients with breast cancer-related 
lymphedema (12). The subject will have a unique user account and can complete 
the assessment online via secure connection to the study database. If a subject 
cannot complete the questionnaire electronically, a paper version may be mailed to 
them for completion. 
 
FT-CC Garment Measurements 
The subject’s chest, arm inseam, biceps, and hips will be measured to determine the 
appropriate size for the arm-shoulder and trunk garment. 
 
FT-CC Training 
After all baseline assessments have been performed, the subject will be contacted 
by a Tactile Medical trainer to schedule a training visit on how to use the FT-CC. 
This training may occur virtually, at the clinic, or in the subject’s home. Training 
may be conducted up to 21 days after the baseline visit.  
 
AE & Device Observation Assessment 
AE assessment will occur after randomization and continue throughout the study. 
Reportable events, as defined below, will be recorded in the subject’s medical 
record and on the CRFs. All device related AEs will be assessed by the Tactile 
study team for reporting through the Tactile Medical Complaint System.   
7.14.1 AE 
An adverse event is any untoward medical occurrence in a clinical research 
study subject which may or may not be related to the use of the medical 
device under investigation.  
Adverse events will be reported to the IRB in accordance with IRB policy. 
7.14.2 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; 

 
 
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• 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 working days of becoming aware of the event. SAEs 
will be summarized in writing and reported to the IRB in accordance with 
IRB policy. 
7.14.3 Unanticipated Adverse Device Effect (UADE) 
A UADE is 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 UADEs to Tactile Medical within 10 working 
days of becoming aware of the event. UADEs will be summarized in 
writing and reported to the IRB in accordance with IRB policy. 
7.14.4 Device Observations 
Device observations will be recorded and reported to Tactile Medical and 
assessed by the Tactile study team for reporting through the Tactile 
Medical Complaint system. 
7.14.5 Adverse Event Severity 
Severity will be assessed by the investigator using the following 
definitions: 
• Mild: Subject aware of sign of symptom, but easily tolerated. 
• Moderate: Interferes with normal activities. 
• Severe: Incapacitating, with inability to perform normal activities. 
 
Accountability  
The FT-CC and FT garments will be provided at no cost to the subject and be utilized with 
the assistance of study personnel. The FT-CC and FT garments will be shipped directly to 
the subject and will be returned to Tactile Medical upon study exit. The subject may ship 
the controller back to Tactile Medical (Tactile Medical will provide a box and label) or 
return the FT-CC to the site. Tactile Medical will provide all shipping records to the site to 
enable appropriate accountability of study devices. The record will include the receipt, 
location, use, and final disposition of all controllers and garments. Subjects may keep the 
FT garments at the end of the study. Study devices will be stored in a secure area with 

 
 
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restricted access. At the conclusion of the study all FT-CCs will be returned to Tactile 
Medical.  
 
Risk Analysis  
This study does not present risks above and beyond those normally associated with the use 
of the Flexitouch Plus.  
Theoretically, massage and mechanical compression could mobilize dormant tumor cells in 
some patients; however, this is expected to have limited impact on prognosis such that the 
benefits of reduction in morbid edema will likely outweigh those theoretical risks. 
Pneumatic compression is a minimal risk therapy with nominal complications or adverse 
events. Known reactions to sequential pneumatic compression therapy include: 
Likely: 
• Local skin irritation 
• Pain or discomfort 
• Increased swelling 
Less Likely: 
• Cellulitis  
• New or increased edema in the trunk and/or genital region 
Highly Unlikely: 
• Electric shock (if device is not maintained or used properly) 
Risk analysis assessments determined the probability of occurrence for these potential 
device risks are at the lowest level. Thus, the residual risks for these types of hazards is 
acceptable with the benefits to treating patients outweighing the risks. 
Use of the Flexitouch Plus may not improve lymphedema symptoms, such as: 
• Increased edema 
• Pain or discomfort 
• Redness, swelling/inflammation, and blistering 
• Skin breakdown, including pressure ulcers 
• Cellulitis infection 
• Stasis dermatitis 
The addition of cellular connectivity does not introduce any new risks to the patient 
regarding treatment. Risk is limited to a potential cybersecurity breach given its cellular 
connection; however, the device data that is being transmitted does not contain any 
protected health information (PHI).  
If the subject is randomized to the FT-CC arm, they must consent to receiving text 
messages from Tactile Medical. The text messages will not include any of the subject’s 
PHI. 
Subjects will be made aware of known complications and adverse events at the time of 
consent and monitored closely throughout the study. Subjects will be informed of any 
significant new findings that develop during the course of the study that may affect their 
willingness to continue participation. Should a subject choose to terminate his or her 

 
 
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participation in the study, he or she will be treated according to the standard of care that 
applies at the point of withdrawal. 
The Principal Investigator and the study team will oversee all safety aspects and report 
adverse events to the IRB, as required. Should a subject choose to terminate his or her 
participation, he or she will be treated according to the standard of care that applies at the 
point of withdrawal. 
 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.  
There are security measures in place to prevent a breach of confidentiality from happening 
including a 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 study, so that no unneeded 
sensitive information is being collected.   
 Deviations from Study Plan  
All deviations will be documented and reported to the IRB as required by IRB policies.   
 Regulatory Assessment 
The investigational device used in this study meets the requirements of a nonsignificant 
risk (NSR) device given the FT-CC is used for its intended purpose and: 
• Is not an implant 
• Is not used to support or sustain human life  
• Is not of substantial importance in diagnosing, curing, mitigating, or treating disease 
or otherwise preventing impairment of human health 
• Does not otherwise present a potential for serious risk to the health, safety, or 
welfare of a subject  
Per 21 CFR 812, an NSR study is not required to follow all IDE regulations nor have an 
IDE application approved by FDA before proceeding. An NSR study must follow the 
abbreviated requirements at 21 CFR 812.2(b) which address labeling, IRB approval, 
informed consent, monitoring, records, reports, and prohibition against promotion. There is 
no need to make progress reports or final reports to FDA. In addition, Sponsors and IRBs 
do not have to report the IRB approval of an NSR device study to FDA. The IRB serves as 
the FDA’s surrogate for review, approval, and continuing review of the NSR device 
studies. The IRB application should state that the study is NSR and be supported with the 
rationale in the preceding paragraph. An NSR device study may start as soon as the IRB 
reviews and approves the study, without prior approval by FDA. 
Importantly, the investigational software present on the FT-CC was built in accordance 
with 820.30 Design Controls, with the controller and garments being manufactured in full 
compliance with 21 CFR 820. 
 Quality Assurance Procedures  

 
 
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This study will be conducted in accordance with Good Clinical Practice (GCP), 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 study. As required by 21 CFR 56 and the Declaration of Helsinki, 
the protocol, amendments, and ICF 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 have been adequately trained on the protocol. An activation letter will be 
sent to the Principal Investigator once the site is approved to enroll subjects. 
 
Monitoring  
Clinical sites will be monitored, remotely or onsite, 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 staff are 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;  
• 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 monitoring 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 study 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. 

 
 
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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 (PI) 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. 
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 study 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; 
• 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 6).  
Table 6. Required Reports 
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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 ICF, 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 
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. 
 Changes 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.  
 Statistical Methods   
 
Sample Size Determination 

 
 
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No power calculations were used to derive a sample size for this study given this 
study seeks to identify which health outcomes should be used for a larger 
randomized controlled trial in the future. The desired target sample size for this 
feasibility study is 10 analyzable data sets for each group. It is estimated that up to 
30 subjects will need to be enrolled to achieve 60 day follow-up data on 20 
subjects.  
 
Statistical Analysis 
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 3.6.0 or higher.  
 Publication Plan 
All information obtained during the conduct of the study will be considered confidential 
and 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 and Publication Plan. 
 References 
1  
Perdomo M, Davies C, Levenhagen K, Ryans K. Breast cancer edge task force 
outcomes: Assessment measures of secondary lymphedema in breast cancer 
survivors. Rehabilitation Oncology. 2014; 32:22-35. 

 
 
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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. Lymphatic 
Research Biology. 2014; 12:103-9. 
3 
Langbecker D, Hayes SC, Newman B, Janda M. Treatment for upper-limb and 
lower-limb lymphedema by professionals specializing in lymphedema care. 
European Journal of Cancer Care. 2008; 17:557-64. 
4 
Fife CE, 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; 20:3279-86.  
5 
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. Lymphatic Research Biology. 2015; 
13:208-14.  
6 
Blumberg SN, Berland T, Rockman C, et al. Pneumatic compression improves 
quality of life in patients with lower-extremity lymphedema. Annals of Vascular 
Surgery. 2016; 30:40-4. 
7 
Muluk SC, Hirsch AT, Taffe EC. Pneumatic compression device treatment of 
lower extremity lymphedema elicits improved limb volume and patient-reported 
outcomes. European Journal of Vascular Endovascular Surgery. 2013; 46:480-7. 
8 
Ridner SH, McMahon E, Dietrich MS, Hoy S. Home-based lymphedema treatment 
in patients with cancer-related lymphedema or noncancer-related lymphedema. 
Oncology Nursing Forum. 2008; 35:671-80. 
9 
Palmer S. Barriers and facilitators to successful lymphedema therapy: the role of 
adherence. Lymph Link. 2006; 18:1-5. 
10 Brown JC, Cheville AL, Tchou JC, Harris SR, Schmitz KH. Prescription and 
adherence to lymphedema self-care modalities among women with breast cancer-
related lymphedema. Support Care Cancer. 2014; 22:135-43. 
11 Keeley V, Crooks S, Locke J, et al. A quality of life measure for limb lymphedema 
(LYMQOL). Journal of Lymphoedema. 2010; 5:26-37. 
12 Ridner SH, Dietrich MS. Development and validation of the lymphedema symptom 
and intensity survey-arm. Support Care Cancer. 2015; 23:3103-12.