A Registry to Evaluate the Flexitouch System and Flexitouch Plus for Treatment of Head and Neck Lymphedema
Conditions: Head and Neck Lymphedema
Sponsor: Tactile Medical

Protocol #4060 
Version 4.0; 24 January 2019 
 
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A Registry to Evaluate the Flexitouch System and 
Flexitouch Plus for Treatment of Head and Neck 
Lymphedema  
 
Protocol# 4060 
 
 
 
 
24 January 2019 
 
Protocol Version 4.0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol #4060 
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Investigator Signature 
 
 
 
Protocol Title: A Registry to Evaluate the Flexitouch System and Flexitouch Plus 
for Treatment of Head and Neck Lymphedema  
 
Protocol Number: 4060 
 
Version: 4.0; 24 January 2019 
 
 
I confirm that I have read this protocol. I will comply with the protocol and the 
principles of Good Clinical Practices (GCPs), institutional research policies and 
procedures, and other appropriate regulatory requirements. 
 
 
 
_______________________________ 
Site Principal Investigator Name (Print) 
 
 
_______________________________  
 __________________ 
Site Principal Investigator Signature   
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol #4060 
Version 4.0; 24 January 2019 
 
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SYNOPSIS 
 
Registry Title 
A Registry to Evaluate the Flexitouch System and Flexitouch Plus for 
Treatment of Head and Neck Lymphedema 
Protocol Date 
24 January 2019 
Protocol Version 
4.0 
Name of Sponsor 
Tactile Medical™ 
Device 
Flexitouch system or Flexitouch Plus with Head and Neck Garments 
Registry Objective 
To evaluate the long term effectiveness of the Flexitouch system and 
Flexitouch Plus in those with head and neck lymphedema. 
Primary Endpoint 
Symptom and function improvement 
Secondary Endpoints Changes in QOL, changes in pain, reduction in head and neck 
swelling, ease of use, treatment satisfaction 
Registry Design 
This registry is a multi-center, prospective, observational, registry 
designed to evaluate patients with head and neck lymphedema who 
receive the Flexitouch system or Flexitouch Plus.  
Treatment 
Flexitouch Head and Neck Treatment, as prescribed.  
Eligibility 
Inclusion Criteria: 
 
Age ≥ 18 years 
 
A diagnosis of head and/or neck lymphedema 
 
Must be able and willing to participate in all aspects of the 
registry and provide informed consent prior to registry 
participation 
 
Head and chest measurements within the following:  
o Crown of head circumference: ≤ 72 cm 
o Chest circumference: ≤ 158 cm 
 
Prescribed the Flexitouch system or Flexitouch Plus 
 
Exclusion Criteria: 
 
Uncontrolled hyperthyroidism or parathyroidism (for which 
endocrinologist recommends against neck compression)  
 
Carotid sinus hypersensitivity syndrome  
 
Symptomatic carotid artery disease, as manifested by a recent 
transient ischemic attack (within 30 days), ischemic stroke, or 
amaurosis fugax (monocular visual ischemic symptoms or 
blindness)  
 
Symptomatic bradycardia in the absence of a pacemaker  
 
Internal jugular venous thrombosis (within 3 months)  
 
Increased intracranial pressure or other contraindications to 
internal or external jugular venous compression  
 
Acute radiation dermatitis, unhealed surgical scar, unhealed or 
open wound(s), or surgical flap less than 6-8 weeks post-
operative  

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 
Facial or head and neck dermal metastasis  
 
Acute facial infection (e.g., facial or parotid gland abscess)  
 
Any condition in which increased venous and lymphatic return 
is undesirable  
 
Heart failure (acute pulmonary edema, decompensated acute 
heart failure)  
 
Subject is pregnant or trying to become pregnant  
 
Acute venous disease (acute thrombophlebitis, acute deep 
venous thrombosis, acute pulmonary embolism) 
Subject Participation 
Duration 
Approximately 6 months 
Sample Size 
Open 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
1.0 
Contact Information ............................................................................................................. 7 
 
Sponsor Contact Information ........................................................................................... 7 
2.0 
Abbreviations ....................................................................................................................... 7 
3.0 
Introduction .......................................................................................................................... 8 
 
Background and Rationale ............................................................................................... 8 
 
Device Description ........................................................................................................... 8 
4.0 
Registry Objective ............................................................................................................... 9 
5.0 
Registry Design .................................................................................................................... 9 
 
Endpoints .......................................................................................................................... 9 
 
Subject Selection ............................................................................................................ 10 
 
Registry Duration ........................................................................................................... 11 
6.0 
Registry Visit Summaries .................................................................................................. 11 
 
Screening/Baseline Visit #1 ........................................................................................... 11 
 
Device Training Visit #2 (Day 0) ................................................................................... 11 
 
Week 2 Phone Call Visit #3 (Day 14±3) ........................................................................ 12 
 
Month 1 Clinic Visit #4 (Day 28±5) .............................................................................. 12 
 
Month 2 Phone Call Visit #5 (Day 56±5) ...................................................................... 12 
 
Month 3 Clinic Visit #6 (Day 84±5) .............................................................................. 12 
 
Month 6 Clinic Visit #7 (Day 168±14) .......................................................................... 13 
 
Registry Exit ................................................................................................................... 13 
7.0 
Registry Schedule of Activities ......................................................................................... 14 
8.0 
Registry Procedures ........................................................................................................... 14 
 
Laboratory Testing Procedures ...................................................................................... 14 
 
Vital Signs & Lymphedema Evaluation ......................................................................... 15 
 
Function Assessment ...................................................................................................... 15 
 
Swelling Assessment ...................................................................................................... 15 
 
Symptom Assessment .................................................................................................... 15 
 
Quality of Life & Pain Assessment ................................................................................ 15 
 
Device Use Evaluation ................................................................................................... 15 
 
Ease of Use and Treatment Satisfaction ......................................................................... 16 
 
Compliance Assessment ................................................................................................. 16 
 
Adverse Event Reporting & Device Observations ..................................................... 16 
9.0 
Subject Withdrawal or Early Termination ......................................................................... 17 
10.0  Device Accountability ....................................................................................................... 17 

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11.0  Risk Analysis and Adverse Events .................................................................................... 18 
12.0  Provisions to Protect the Privacy of Registry Participants/Information Security Plan ...... 18 
13.0  Deviation from Registry Plan ............................................................................................ 19 
14.0  Quality Assurance Procedures ........................................................................................... 19 
 
Site Qualification ........................................................................................................ 19 
 
Site Initiation .............................................................................................................. 19 
 
Data Collection Procedures ........................................................................................ 19 
 
Onsite Monitoring ...................................................................................................... 20 
 
Data Safety Monitoring .............................................................................................. 20 
 
Reports and Records ................................................................................................... 20 
15.0  Statistical Methods ............................................................................................................. 22 
16.0  Compensation .................................................................................................................... 23 
17.0  Publication Plan ................................................................................................................. 23 
18.0  References .......................................................................................................................... 23 
19.0  Appendices ......................................................................................................................... 24 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1.0 
Contact Information 
 
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 
 
2.0 
Abbreviations 
AE 
Adverse Event 
CDT 
Complete Decongestive Therapy 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
EDC 
Electronic Data Capture 
FDA 
US Food and Drug Administration 
GCP 
Good Clinical Practice 
HNC 
Head and Neck Cancer 
HNL 
Head and Neck Lymphedema 
ICH 
International Conference on Harmonization 
IRB 
Institutional Review Board 
MLD 
Manual Lymph Drainage 
QOL 
Quality of Life 
ROM 
Range of Motion 
SAE 
Serious Adverse Event 
VAS 
Visual Analog Scale 
 
 
 

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3.0 
Introduction 
 
Background and Rationale  
Secondary head and neck lymphedema (HNL) is a frequent late effect in patients 
treated for head and neck cancer (HNC) as the primary cancer or factors related to 
treatment (surgery, radiation, or chemotherapy) either destroy or obstruct lymphatic 
vessels and damage adjacent soft tissue.1,4  HNL occurs in over 50% of patients 
receiving radiation and/or surgery for HNC.2 HNL may involve external structures 
(soft tissues of the face, neck, and eyes) or internal structures (oral cavity, mucous 
membranes, larynx, and pharynx), but most often both are involved 
simultaneously.3  The resultant clinical impact is dependent on the anatomic sites 
involved and the extent of associated lymphatic dysfunction. These symptoms can 
range from mild to severe. The most common areas of external swelling and 
fibrosis are in the submental region and the neck.2,4  In severe cases, HNL may 
impact critical physical functions (e.g., respiration, mastication, swallowing, 
communication, and vision). HNL, comparable to lymphedema at other sites, is 
often associated with psychological distress and degradation to quality of life.3,4  In 
a recent study of 1,202 HNC patients, the majority of patients reported cosmetic 
concerns and discomfort. More than one third reported functional complaints, 
including difficulty swallowing (68%) and difficulty breathing (39%).2 The most 
common functional complaint among patients who underwent total laryngectomy 
was difficulty breathing, often related to tracheostomal obstruction from submental 
edema.2  
Damaged lymphatics result in high-protein fluid collection in the affected tissues. 
Lymphedema is associated with chronic inflammation, which may lead to a self-
perpetuating and progressive course.5 HNL patients often experience tightness and 
discomfort in the muscles of the neck and shoulders which may impede range of 
motion and function of these muscular groups.3 Damage to the muscles in the 
affected region may also occur after radiation, resulting in atrophy, weakness, and 
altered sensation. 
The treatment of HNL utilizes modified techniques of in-clinic complete 
decongestive therapy (CDT), including manual lymph drainage (MLD). Currently, 
some patients are able to continue simplified versions of these techniques at home, 
yet, many patients with HNL experience difficulty performing the treatment and/or 
find the treatment is insufficient in effectively managing their symptoms long-term. 
Clinicians and patients have therefore identified a need for additional effective 
options for at home treatment of HNL. In response, Tactile Medical has developed 
a garment for the treatment of HNL utilizing the Flexitouch system or Flexitouch 
Plus pneumatic compression device. Tactile Medical seeks to evaluate the long term 
effectiveness of the Flexitouch system and Flexitouch Plus. 
 
 
Device Description  
The Flexitouch system and Flexitouch Plus (Tactile Medical™, Minneapolis, MN, 
USA) are pneumatic compression devices which have been cleared by the Food and 
Drug Administration (FDA) for market in the US (K153311 and K170216, 
respectively; US HCPCS code E0652).  

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The Flexitouch® Head and Neck Garment is constructed of nylon and has up to 16 
pneumatic chambers covering part of the head, neck, and chest. The device applies 
brief applications of dynamic pressure in a wave-like manner to the treatment area. 
Used in conjunction with the Flexitouch controller, the Head and Neck Garment is 
intended to treat lymphedema affecting the head and neck by stimulating the 
adjacent axillary lymphatic tributary regions and directing fluid from the affected 
area to healthy, functioning regions. 
 
4.0 
Registry Objective 
The objective of this registry is to evaluate the long term effectiveness of the Flexitouch 
system and Flexitouch Plus in those with head and neck lymphedema. This outcome data 
will include information regarding each subject’s medical history, symptoms, quality of 
life, pain, range of motion (ROM), swelling, ease of use, treatment satisfaction, treatment 
compliance, and device-related adverse events. 
 
5.0 
Registry Design 
This multi-center, prospective, observational, registry will follow patients with head and 
neck lymphedema who are using the Flexitouch system or Flexitouch Plus. Data collection 
will occur at Baseline and Days 14, 28, 56, 84, and 168. 
 
 
    
 
Endpoints  
5.1.1 Primary Endpoints  
To evaluate symptom and function improvement after 168 days 
(approximately 6 months) of treatment with the Flexitouch system or 
Flexitouch Plus based upon:   
 Symptom survey (EORTC H+N35); and 
 Range of motion measures (neck, mouth, and shoulder).  
 
Approach to 
Participate
Assess 
Eligibility/ 
Consent
Complete F/U 
Visits

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5.1.2 Secondary Endpoints 
To evaluate quality of life (QOL), pain, swelling, ease of use, and 
treatment satisfaction after 168 days (approximately 6 months) of 
treatment with the Flexitouch system or Flexitouch Plus based upon:  
 
Change in the QOL (EORTC C30); 
 
Change in pain (VAS); 
 
Change in swelling (upper neck, lower neck, and ear to ear 
measurements); and  
 
Ease of use and treatment satisfaction (survey). 
 
 
Subject Selection 
The registry population will be drawn from patients who have head and neck 
lymphedema and are prescribed the Flexitouch system or Flexitouch Plus for in-
home treatment of their head and neck lymphedema. Only patients who meet the 
criteria listed below and have provided informed consent will be considered for 
participation. Subjects will be considered enrolled in the study after they have 
signed the Informed Consent Form, met all inclusion/exclusion criteria, and 
completed the device training visit. Any subjects who do not meet 
inclusion/exclusion criteria, or do not ultimately receive the device, will be 
considered screen failures.    
5.2.1 Inclusion Criteria  
Patients must meet the following criteria: 
 Age ≥ 18 years 
 A diagnosis of head and/or neck lymphedema 
 Must be able and willing to participate in all aspects of the registry 
and provide informed consent prior to registry participation 
 Head and chest measurements within the following:  
o Crown of head circumference: ≤ 72 cm 
o Chest circumference: ≤ 158 cm 
 Prescribed the Flexitouch system or Flexitouch Plus 
 
5.2.2 Exclusion Criteria  
Patients must not meet any of the following criteria: 
 Uncontrolled hyperthyroidism or parathyroidism (for which 
endocrinologist recommends against neck compression)  
 Carotid sinus hypersensitivity syndrome  
 Symptomatic carotid artery disease, as manifested by a recent 
transient ischemic attack (within 30 days), ischemic stroke, or 
amaurosis fugax (monocular visual ischemic symptoms or 
blindness)  
 Symptomatic bradycardia in the absence of a pacemaker  
 Internal jugular venous thrombosis (within 3 months)  
 Increased intracranial pressure or other contraindications to 
internal or external jugular venous compression  
 Acute radiation dermatitis, unhealed surgical scar, unhealed or 
open wound(s), or surgical flap less than 6-8 weeks post-operative  

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 Facial or head and neck dermal metastasis  
 Acute facial infection (e.g., facial or parotid gland abscess)  
 Any condition in which increased venous and lymphatic return is 
undesirable  
 Heart Failure (acute pulmonary edema, decompensated acute 
heart failure)  
 Subject is pregnant or trying to become pregnant  
 Acute venous disease (acute thrombophlebitis, acute deep venous 
thrombosis, acute pulmonary embolism) 
 
 
Registry Duration 
Enrollment will occur at centers throughout the United States. Subjects will remain 
active in the registry for a period of 168 days (approximately 6 months), and after 
that time, no additional information will be collected. The duration of the registry 
has not been specified; however, enrollment will be open for the duration of the 
registry. Registry analyses will be completed at various times throughout the 
lifecycle of the project.   
 
6.0 
Registry Visit Summaries  
 
Screening/Baseline Visit #1 
All potential subjects will be screened to ensure compliance to general inclusion 
and exclusion criteria. If subjects appear eligible to participate based on their 
medical history, they will be consented to participate in the registry. All consented 
subjects will undergo the following procedures: 
 Obtain Informed Consent;  
 Obtain Medical History and Current Medications; 
 Administer a pregnancy test for all female subjects of child-bearing potential; 
 Complete lymphedema evaluation;  
 Complete the Clinical Intake Form (Appendix A); 
 Obtain vital signs (if collected as part of standard of care); 
 Obtain baseline ROM measurement (Appendix B); 
 Obtain baseline swelling measurements (Appendix C); 
 Have subject complete the EORTC C30 (Appendix D), EORTC H+N35 
(Appendix E), and VAS (Appendix F); 
 Instruct the subject on the methods to track compliance;  
 Instruct subject on device prescription and training procedures at home or at 
the clinic; and 
 Ensure a clinical research coversheet is submitted with the device order to 
Tactile Medical when ordering the Flexitouch system or Flexitouch Plus. 
 
 
Device Training Visit #2 (Day 0) 
All subjects will be instructed to conduct head and neck lymphedema treatment as 
prescribed by their treating clinician. Prior to using the Flexitouch system or 
Flexitouch Plus in-home, Tactile personnel will perform device training either in-
home or at the clinic, per standard practice. The date of training (Day 0), which will 

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take place approximately 1-3 weeks after the device order is placed, will be used to 
determine the timing of the follow-up schedule. 
  
 
Week 2 Phone Call Visit #3 (Day 14±3)  
Approximately 14 days after the subject receives training and begins using the 
prescribed treatment, clinic personnel will call the subject to assess the following at 
Visit 3: 
 Changes to medical history; 
 Device-related adverse events (NOTE: Compare events to pre-existing 
conditions documented in Medical History to determine if the event is a new 
event, a worsening of a pre-existing event, or just a reoccurrence of a pre-
existing event); and 
 Any questions/concerns the subject has regarding device use and/or 
compliance. 
 
 
Month 1 Clinic Visit #4 (Day 28±5) 
Approximately 28 days after the subject begins using the prescribed treatment, he 
or she will return to the clinic and undergo the following procedures at Visit 4: 
 Changes to medical history; 
 Obtain vital signs (if collected as part of standard of care); 
 Obtain ROM measurement (Appendix B); 
 Obtain swelling measurements (Appendix C); 
 Have subject complete the EORTC C30 (Appendix D), EORTC H+N35 
(Appendix E), and VAS (Appendix F); 
 Record device-related adverse events (NOTE: Compare events to pre-existing 
conditions documented in Medical History to determine if the event is a new 
event, a worsening of a pre-existing event, or just a reoccurrence of a pre-
existing event); and 
 Review treatment compliance with subject. 
 
 
Month 2 Phone Call Visit #5 (Day 56±5) 
Approximately 56 days after the subject begins using the prescribed treatment, 
clinic personnel will call the subject to assess the following at Visit 5: 
 Changes to medical history; 
 Device-related adverse events (NOTE: Compare events to pre-existing 
conditions documented in Medical History to determine if the event is a new 
event, a worsening of a pre-existing event, or just a reoccurrence of a pre-
existing event); and 
 Any questions/concerns the subject has regarding device use and/or 
compliance. 
 
 
Month 3 Clinic Visit #6 (Day 84±5) 
Approximately 84 days after the subject begins using the prescribed treatment, he 
or she will return to the clinic and undergo the following procedures at Visit 6: 
 Changes to medical history; 

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 Obtain vital signs (if collected as part of standard of care); 
 Obtain ROM measurement (Appendix B); 
 Obtain swelling measurements (Appendix C); 
 Have subject complete the EORTC C30 (Appendix D), EORTC H+N35 
(Appendix E), and VAS (Appendix F); 
 Record device-related adverse events (NOTE: Compare events to pre-existing 
conditions documented in Medical History to determine if the event is a new 
event, a worsening of a pre-existing event, or just a reoccurrence of a pre-
existing event); and 
 Review treatment compliance with subject. 
 
 
Month 6 Clinic Visit #7 (Day 168±14)  
Approximately 168 days after the subject begins using the prescribed treatment, or 
upon early termination of a subject (if possible), he or she will return to the clinic 
and undergo the following procedures at Visit 7:  
 Changes to medical history; 
 Obtain vital signs (if collected as part of standard of care); 
 Complete lymphedema evaluation; 
 Obtain ROM measurement (Appendix B); 
 Obtain swelling measurements (Appendix C); 
 Have subject complete the EORTC C30 (Appendix D), EORTC H+N35 
(Appendix E), VAS (Appendix F), and Ease of Use and Treatment 
Satisfaction Survey (Appendix G); 
 Record device-related adverse events (NOTE: Compare events to pre-existing 
conditions documented in Medical History to determine if the event is a new 
event, a worsening of a pre-existing event, or just a reoccurrence of a pre-
existing event); and 
 Review treatment compliance with subject. 
 
 
Registry Exit 
Once a subject completes all required visits, or chooses to withdraw from 
participation prior to Clinic Visit #7, ensure the following has been recorded:  
 Date and reason for registry exit; 
 Changes to medical history; 
 Device-related adverse events (NOTE: Compare events to pre-existing 
conditions documented in Medical History to determine if the event is a new 
event, a worsening, of a pre-existing event or just a reoccurrence of a pre-
existing event); and 
 Treatment compliance. 
 

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7.0 
Registry Schedule of Activities  
 
Procedures 
Visit 1 
(in 
clinic) 
Visit 2 
(in home 
or clinic) 
Visit 3 
(phone 
call) 
Visit 4 
(in 
clinic) 
Visit 5 
(phone 
call) 
Visit 6 
(in 
clinic) 
Visit 7 
(in 
clinic) 
Screen/ 
Baseline  
Day 0 
Week 2  
(Day 14 
± 3 
Days) 
Month 1 
(Day 28 
± 5 
Days) 
Month 2 
(Day 56 
± 5 
Days) 
Month 3 
(Day 84 
± 5 
Days) 
Month 6 
(Day 168 
± 14 
Days) 
Informed Consent 
X 
 
 
 
 
 
 
Device Training 
 
X 
 
 
 
 
 
Pregnancy Test (if 
applicable) 
X 
 
 
 
 
 
 
Medical History 
X 
 
X* 
X* 
X* 
X* 
X* 
Vital Signs (if 
applicable) 
X 
 
 
X 
 
X 
X 
Lymphedema 
Evaluation  
X 
 
 
 
 
 
X 
Range of Motion 
(Neck, mouth, 
shoulders) 
X 
 
 
X 
 
X 
X 
Assess Swelling  
X 
 
 
X 
 
X 
X 
QOL (EORTC 
C30) 
X 
 
 
X 
 
X 
X 
Symptoms 
(EORTC H+N35) 
X 
 
 
X 
 
X 
X 
Assess Pain (VAS) 
X 
 
 
X 
 
X 
X 
Ease of Use and 
Satisfaction Survey 
 
 
 
 
 
 
X 
Complications/ 
AEs/SAEs 
 
 
X 
X 
X 
X 
X 
Device Use 
Evaluation 
 
 
X 
 
X 
 
 
Compliance 
 
 
X 
X 
X 
X 
X 
* Change in medical history. 
 
 
8.0 
Registry Procedures 
 
Laboratory Testing Procedures 
Women of childbearing potential will be tested for pregnancy according to the site 
specific procedures at the baseline visit. If the pregnancy test is positive, the subject 
will not be enrolled in the registry. 
If the subject becomes pregnant at any time during the registry, the subject will be 
withdrawn from registry participation and followed at the Investigator’s discretion.  
  
 

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Vital Signs & Lymphedema Evaluation 
Research personnel will assess vital signs at each clinic visit (if collected as part of 
standard of care).  
The clinical stage of lymphedema will be evaluated by a clinician at Baseline and 
Visit 7 using the following definitions: 
 Stage 0: No visible edema but patient reports heaviness 
 Stage 1a: Soft visible edema; no pitting, reversible 
 Stage 1b: Soft pitting edema; reversible 
 Stage 2: Firm pitting edema; not reversible; no tissue changes 
 Stage 3: Irreversible; tissue changes 
The evaluation will also document the presence or absence of issues with speech, 
edema, wounds, facial asymmetry, and skin changes. 
 
 
Function Assessment 
Cervical, mouth, and shoulder range of motion measurements will be taken at each 
in-clinic visit (Appendix B). The measurements will be completed by research 
personnel with documented training showing the individual was able to 
independently and accurately conduct the measurements on 2 occasions.  
 
 
Swelling Assessment 
Swelling measurements will be taken at each in-clinic visit (Appendix C). The 
measurements will be completed by research personnel with documented training 
showing the individual was able to independently and accurately conduct the 
measurements on 2 occasions.  
 
 
Symptom Assessment 
Symptoms will be assessed at each in-clinic visit using the EORTC H+N35 
(Appendix E). The survey will be completed by the subject. 
 
 
Quality of Life & Pain Assessment 
Quality of Life will be assessed at each in-clinic visit using the EORTC C30 
(Appendix D). The survey will be completed by the subject. 
Pain will be assessed at each in-clinic visit using the VAS (Appendix F). The 
assessment will be completed by the subject. 
 
 
Device Use Evaluation 
During the phone follow-up at Visit 3 and 5, site research personnel will ask the 
subject questions about device use to evaluate if additional device training by 
Tactile personnel is warranted. 
 
 

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Ease of Use and Treatment Satisfaction 
Ease of use and treatment satisfaction will be assessed by survey (Appendix G). 
The survey will be completed by the subject. 
 
 
 
Compliance Assessment 
Compliance with device treatment may be assessed at each in-clinic and phone 
follow-up visit. The subject may be asked to record compliance in a diary 
(Appendix H), or device use data may be downloaded periodically for subjects 
using the Flexitouch Plus. 
 
 Adverse Event Reporting & Device Observations   
Reportable events, as defined below, will be recorded in the subject’s medical 
record and on the Adverse Event (AE) Log.  
 
8.10.1 Device-Related Adverse Event (AE) 
This registry will only collect device-related adverse events. A device-
related adverse event is defined as any untoward medical occurrence in the 
subject that is associated with the use of the Flexitouch system or 
Flexitouch Plus.   
Adverse events will be reported to the IRB in accordance with IRB policy. 
 
8.10.2 Serious Adverse Event (SAE) 
A serious adverse event is an untoward medical occurrence where the 
outcome is:  
 Death; 
 Life-threatening event (places the subject at immediate risk of death 
from the experience as it occurred);  
 Hospitalization (initial or prolonged) if admission to hospital was 
warranted as a result of an adverse event; 
 Disability or permanent damage (substantial disruption of one’s 
ability to carry out normal life functions);  
 Congenital anomaly or birth defect; 
 Required intervention to prevent permanent impairment or damage; 
or 
 Important medical event that required medical or interventional 
treatment to prevent one of the previous outcomes. 
Investigators must report all device-related, Serious Adverse Events 
(SAEs) to Tactile Medical within 10 work days of becoming aware of the 
event. Device-related SAEs will be summarized in writing and reported to 
the IRB in accordance with IRB policy. 
 
8.10.3 Device Observations 
Device observations will be recorded and reported to Tactile Medical. 
Device observations include device failures, device malfunctions, use 
errors, device issues, and user preferences, as defined below:  

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 Device Failure: A device failure has occurred when the device is 
used in accordance with the IFU, but does not perform as described 
in the IFU and also negatively impacts treatment of the study 
subject. 
 Device Malfunction: A device malfunction occurs when an 
unexpected change to the device that is contradictory to the IFU is 
observed, which may or may not affect device performance.  
 Use Error: A device use error is an act or omission of an act that 
results in a different medical device response than intended by the 
manufacturer or expected by the user. Use error includes slips, 
lapses, and mistakes. An unexpected physiological response of the 
subject does not itself constitute a use error. 
 Device Issue: Any other issue with the device that does not fall 
into one of the above categories.  
 User Preference: Information on user expectations, likes, dislikes, 
motivations, and inclinations that drive subject satisfaction with 
the device.  
 
9.0 
Subject Withdrawal or Early Termination  
Subject participation may be terminated prior to completing the registry 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. 
 Lost to Follow-up  
A certified, return-receipt letter must be sent to the subject after 2 attempts to reach 
the subject by telephone have failed. The subject will be considered lost to follow-up 
if this communication is unsuccessful. 
 Adverse Event  
 
Subject experiences an adverse event that in the investigator’s clinical judgement 
necessitates discontinuation of their participation in this registry.  
 Discretion of the Principal Investigator 
Subjects may be withdrawn at the investigator’s discretion in the event of subject 
noncompliance, changes in the subject’s health, or other reasons based on the 
investigator’s clinical judgment. 
 
When a subject withdraws prior to completing the registry, all effort should be made to 
complete Visit 7 prior to documenting the reason for withdrawal in the subject’s medical 
record.   
 
10.0 Device Accountability  
To participate in the registry, the Flexitouch system or Flexitouch Plus must be prescribed 
by a clinician and paid for by the subject or their payer. The Flexitouch system or 
Flexitouch Plus will be provided to the subject and tracked according to normal business 
practices at Tactile Medical.   
 

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11.0 Risk Analysis and Adverse Events   
Pneumatic compression is a minimal risk therapy with minimal known complications or 
adverse events. However, as with any treatment, there is the possibility of undesirable 
events such as a local skin reaction to the device materials. The subject will be made aware 
of known complications and adverse events at the time of consent, and monitored closely 
throughout the registry.   
There are nominal possible adverse effects associated with the therapy. The expected 
adverse effects that are experienced by patients using this device are often due to the 
natural history of the primary disease, or a failure to achieve an adequate response to the 
compressive therapeutic intervention, and are thus not related to the therapy itself. In some 
cases, lymphedema adverse events can be serious, long lasting, or may be permanent. The 
risks listed below are symptoms or signs of lymphedema and may be experienced by all 
subjects with lymphedema: 
Likely: 
• 
Pain or discomfort 
• 
Increased swelling 
Less Likely: 
• 
Cellulitis – Infection of the skin which may include swelling, redness, and 
tenderness of the infected tissue 
• 
New or increased edema in the trunk and/or genital region 
Registry subjects will be informed of any significant new findings that develop during the 
course of this registry that may affect their willingness to continue participation. The 
Principal Investigator will oversee all safety aspects of the registry and report all adverse 
events to the IRB. Should a subject choose to terminate his or her participation in the 
registry, he or she will be treated according to the standard of care that applies at the point 
of withdrawal. 
 
12.0 Provisions to Protect the Privacy of Registry Participants/Information Security Plan 
This research represents a registry documenting head and neck lymphedema. 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 password protected electronic database and the use of subject codes to de-
identify data). 
Precautions will be taken to make sure that only authorized individuals will be accessing 
subject research records. The collection of sensitive information about subjects is limited to 
the amount necessary to achieve the aims of the research registry, so that no unneeded 
sensitive information is being collected. The Information Security Plan, per the 
requirements of VHA Handbook 1200.05 include, but are not limited to, the following 
provisions: 
a. Individually identifiable information will be collected and used in accordance with 
ICH GCP 
b. Data are to be collected via clinical research forms 

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c. Data will be stored at the Investigation Site and at the Company in accordance 
with ICH GCP and retained in accordance with the Company’s Policy 30 (Record 
Retention Policy) 
d. Data will be transported or transmitted from one location to another via Federal 
Express or secure email in accordance with the Company’s internal Policy 45 
(Confidentiality and Privacy of Patient Information) and Policy 91 (Data 
Transmission) 
e. The PI, Company clinical research team, and authorized Site personnel will have 
access to the data and thus are responsible for its security 
f. Company will abide by all HIPAA regulations when considering Business 
Associates or downstream entities that may have access to data 
g. The Coordinating Center, Investigation Site, PI, and Company clinical research 
team will have access to and be responsible for the security of the information. 
Company will abide by its internal Policy 45 (Confidentiality and Privacy of 
Patient Information) 
h. Medical records, verbal reports, and clinical research forms will account for the 
information 
i. Company will follow guidelines established by the Company (Policy 45), ICH 
GCP, and HIPAA to ensure security measures are in place to protect individually 
identifiable information 
j. If VA information is suspected or confirmed lost, a report will be filed with the 
Department of Veterans Affairs, Office of the Inspector General at 
https://www.va.gov/oig/hotline/ 
 
13.0 Deviation from Registry Plan  
All deviations will be documented on the Deviation Log and reported to the IRB as 
required by IRB policies.   
 
14.0 Quality Assurance Procedures  
This registry will be conducted in accordance to all applicable regulations. Good Clinical 
Practice (GCP) (GCP E6 R2) will be used as a guidance for the preparation and conduct of 
the clinical registry.  
 
 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 registry completion. 
 
 Site Initiation  
Tactile Medical personnel will conduct a Site Initiation Visit onsite or by telephone 
to ensure all required regulatory documents are accurate and complete, and site 
personnel has been adequately trained on the registry protocol. An activation letter 
will be sent to the Principal Investigator once the site is approved to enroll subjects. 
 Data Collection Procedures  
Raw data will be collected on appropriate source document worksheets and CRFs 
will be submitted to Tactile Medical for data entry. Alternatively, at some point 

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during the registry, source document data may be entered directly into a validated 
and secure electronic data capture (EDC) system by trained site personnel. 
 
 Onsite Monitoring  
Clinical sites will be monitored for compliance with the clinical protocol, 
investigator agreement, and applicable regulations throughout the registry. Prior 
to each visit, the investigator will receive a confirmation letter outlining the 
scheduled dates and activities.  
 
Regular site contact will be maintained to ensure: 
 Subject safety; 
 Clinical  site  staff  are  well  informed  of  regulations  and  sponsor 
requirements; 
 The clinical protocol is followed; 
 Data are 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 site visits, a screening log must be submitted to Tactile Medical as 
requested (by fax or e-mail). This screening log should be reviewed with site staff 
to assess planned versus actual recruitment.   
The Principal Investigator and Institution agree to permit trial related monitoring, 
audits, IRB review, and regulatory inspection(s); providing direct access to source 
data and documents, as appropriate. Monitoring and source verification will be 
performed by a Tactile Medical CRA and/or designee. Source verification includes 
reviewing subject source documentation and Case Report Forms (CRFs) for 
accuracy, completeness, and compliance with GCP.  
 
 Data Safety Monitoring  
A periodic review may be completed by a designated member of the Scientific 
Advisory Board or the Chief Medical Officer at Tactile Medical. The frequency of 
the review will be determined based 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 registry continuation, 
modification, or termination of the trial or investigational site.  
 
 Reports and Records   
Records to be maintained by the investigator in a designated registry file include: 
 Investigational plan and all amendments; 
 Signed Investigator Agreement/Research Contract; 

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 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 registry between the site 
and sponsor, IRB, and registry monitor; 
 Curriculum Vitae and professional license for all registry personnel, 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 registry personnel; 
 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. These reports include: 
 
Reports 
Submit To 
Timeframe 
Device-Related AE 
Sponsor and 
Reviewing IRB 
Sponsor: Within 15 working 
days of becoming aware of the 
event; 
IRB: In accordance with 
IRB procedure. 
SAE  
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 
Progress 
Sponsor and Reviewing IRB 
Annually, at a 
minimum 
Final 
Sponsor and 
Reviewing IRB 
Within 3 months 
following the completion 
or termination of the 
Investigator’s part 
 
The following records must be maintained for each subject enrolled: 
 Original, signed and dated informed consent form, as well as documentation 
of the process of consent; 
 Completed CRFs, queries, and source document worksheets, as applicable; 
and 

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 Complete medical records including procedure reports, lab reports, etc., as 
applicable. 
 
Subject registry records, correspondence files, all supporting registry 
documentation, and reports must remain on file at the site for a minimum of ten 
years after the conclusion of this registry. All investigators must contact Tactile 
Medical personnel prior to destroying or archiving off-site any records and reports 
pertaining to this registry to ensure that they no longer need to be retained on-site. 
Additionally, Tactile Medical personnel must be contacted if the investigator plans 
to leave the investigational site to ensure that arrangements for a new investigator 
or records transfer are made prior to the investigator’s departure.  
 
15.0 Statistical Methods   
For continuous variables, descriptive statistics will include the number of subjects (n), 
mean, standard deviation, median, inter-quartile range, minimum, and maximum, based 
upon subjects with reported data for the variable being analyzed.  
 
Frequencies (numerator and denominator), percentages, and 95% confidence intervals will 
be displayed for categorical data. Percentages by categories will be based on the number of 
subjects with no missing (unreported) data for the specific variable being analyzed and the 
count of the patients for each individual level of the categorical variable (the level specific 
numerators). Percentages will add up to 100%, unless otherwise indicated. 
 
There are no plans to impute missing data and there are no plans to explicitly report 
missing data (counts and/or percentages) in the tables for all variables as part of the 
planned study report content. Variations in the reported sample sizes within and/or between 
relevant tables can be used to ascertain insights into unreported data. In some cases, 
unreported data may be due to 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 observational nature of the study suggests that the statistical focus will be on 
estimation and hypothesis generation and not hypothesis testing. Though p-values will be 
reported as apropos, point estimates, and 95% confidence intervals will be used to guide 
exploratory analyses for potentially clinically meaningful differences or changes to be 
discussed and evaluated. 
 
Inter-group (e.g., bivariate) comparisons, when performed, will utilize chi-square, 
ANOVA, t-test, and appropriate non-parametric tests, unless otherwise specified. 
 
Multivariable models (e.g., linear regression or logistic regression) may be used to assess 
the predictive relationships and control for possible confounding imbalances of selected 
multiple variables to specific outcome measures of interest. 
 
Any formal null hypothesis-based statistical comparisons will be made using two sided 
tests at the α=0.05 significance level unless specifically stated otherwise. All null 
hypotheses will be of no inter-group difference, all alternative hypotheses will be two-
sided, unless specifically stated otherwise. 

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All data processing, summarization, and analyses will be performed using R Version 3.4.0 
or higher.  
 
16.0 Compensation 
Registry subjects may be compensated for their time and travel for participating in this 
registry. 
 
17.0 Publication Plan 
All information obtained during the conduct of the registry 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 registry. All publications 
(e.g., manuscripts, abstracts, and slide presentations) based on this registry must be 
submitted to Tactile Medical for review and approval before submission or according to the 
individual site clinical trial agreement. 
 
18.0 References 
1. Jensen MR, Simonsen L, Karlsmark T, Bulow J. Lymphoedema of the lower 
extremities--background, pathophysiology and diagnostic considerations. Clin Physiol 
Funct Imaging. 2010 Nov;30(6):389-98. 
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. 
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). 
 
 

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19.0 Appendices 
Appendix A – Clinical Intake Form (Rev B) 
Appendix B – Range of Motion Booklet (2010) 
Appendix C – Swelling Measurements (ALOHA Protocol) (April 2018) 
Appendix D – EORTC C30 (Version 3) 
Appendix E – EORTC H+N35 (Version 1) 
Appendix F – VAS (2001) 
Appendix G – Ease of Use and Treatment Satisfaction Survey (April 2018) 
Appendix H – Compliance Diary (April 2018)