Physiologic Response to Varying Lymphoedema Compression Programs With the Flexitouch System
Phase: NA
Conditions: Lower Extremity Lymphoedema, Leg Lymphoedema
Sponsor: Tactile Medical

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 Physiologic responses to varying lymphoedema compression programs with 
the Flexitouch® System 
or 
“FlexDose” (Flexitouch Dosing Systemic Evaluation)  
 
 
Protocol # 4010 
 
 
 
Version 2.0 
13 March 2014 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Investigator Signature 
 
 
 
Title: Dosing Evaluation to Access Treatment Protocol for Lower Extremity 
Lymphoedema with Flexitouch® System 
 
 
Protocol Number: 4010 
 
 
I confirm that I have read this protocol.  I will comply with the protocol and the 
principles of Good Clinical Practices (GCP), the International Conference on 
Harmonisation Guidelines, Therapeutic Goods Act, institutional research policies and 
procedures and other appropriate regulatory requirements. 
 
 
 
_______________________________ 
Site Principal Investigator Name (Print) 
 
 
_______________________________ 
 
 __________________ 
Site Principal Investigator Signature   
 
Date 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
1.0 
Study Contact Information 
1.1 
Sponsor Contact Information 
1.2 
Investigator Contact Information 
2.0 
Common Abbreviations 
 
3.0 
Introduction 
3.1 
Background and Rationale 
 
 
 
 
 
 
3.2 
Device Description and Intended Use  
 
 
 
 
4.0 
Study Objective  
 
 
 
 
 
 
 
5.0 
Study Design 
 
 
 
 
 
 
 
 
 
5.1 
Overview of Study Design 
 
 
 
 
 
 
5.2 
Study Endpoints 
5.3 
Safety Endpoints 
6.0 
Study Population, Selection, Withdrawal/Early Exit 
6.1  Study Population 
 
        6.1.1  Inclusion Criteria 
 
        6.1.2   Exclusion Criteria 
 
     6.1.3   Exit/Discontinuation Criteria 
 
  6.2     Recruitment and Randomisation 
 
        6.2.1  Recruitment Plan 
 
        6.2.2   Randomisation Scheme 
 
  6.3     Study Timetable  
 
 
 
 
 
 
 
 
7.0 
Treatment Plan and Study Procedures  
 
 
 
 
 
 
7.1 
Dosage and Rationale  
7.2 
Subject Data Requirements 
 
 
 
 
 
 
7.3 
Laboratory Testing Procedures  
 
 
 
 
 
7.4 
Clinical Study Procedures 
 
7.4.1 Informed Consent 
 
7.4.2 Duplex Ultrasound 
7.4.3  Bioelectrical Impedance  
7.4.4 Limb Volume Measurement 
  7.4.5  Tonometry  
  7.4.6  Ultrasound 
  7.4.7  Other Measures 
  7.4.8 Screening Visit 
  7.4.9 Baseline Visit 
7.4.10 Treatment Visits 
7.4.11 Follow Up Visits 
7.5 Investigational Device Accountability  
 
 
 
8.0  Statistical Plan 
  8.1 Study Design 
  8.2 Efficacy Analysis 

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8.2.1 Analysis of Fluid Dynamic/Change 
 
8.2.2 Analysis of Subcutaneous Tissue Density/Fibrosis 
 
8.2.3 Analysis of Patient Reported Outcomes 
8.3 Adherence to Therapy 
9.0  Safety and Adverse Events 
 
  9.1 Risk Analysis 
 
  9.2   Adverse Event Reporting 
 
  9.3   Subject Withdrawal 
10.0  Deviations from the Clinical Protocol 
11.0 Subject Compensation 
12.0 General Study Information 
 
 12.1      Technical support 
 
 12.2      Discontinuation of the Study 
 
 12.3      Record Retention 
 
 12.4      Quality Assurance Procedures 
 
 12.5      Materials Provided by the Sponsor 
 
 12.6      Materials Provided by the Site 
 
 
 
 
 
13.0 Administrative Study Information 
 
 
 
 
 
 
 13.1      Pre-Study Site Visit  
 
 
 13.2      Ethics Committee Review 
 
 
 13.3      Clinical Site Monitoring 
 
 
 13.4      Investigator Records and Reports 
 
 13.5     Changes Necessary After Study Initiation 
 
 
 
 
 
14.0 References 
 
 
 
 
 
 
 
 
 
15.0 Appendices 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1.0 Study Contact Information 
 
1.1 
Sponsor Contact Information 
Tactile Systems Technology Inc. 
Sunday Hoy, Esq., Director of Clinical Resources and Research 
1331 Tyler Street NE, Suite 200 
Minneapolis, MN 55413   
USA 
+1.612.355.5121 Office 
+1.612.355.5104 Fax 
shoy@tactilesystems.com 
 
1.2 
Investigator Contact Information 
Vaughan Keeley, PhD, FRCP 
Consultant in Palliative Medicine 
Royal Derby Hospital 
Uttoxeter Road 
Derby DE22 3NE 
United Kingdom 
+441332783075 Office 
vaughan.keeley@nhs.net  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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2.0 Common Abbreviations/Acronyms: 
BMI 
Body Mass Index 
BIS 
Bioimpedance Spectroscopy 
CDT  
Complete Decongestive Therapy 
CE 
Conformité Européenne, meaning "European Conformity” 
CRF 
Case Report Forms 
DVT 
Deep Vein Thrombosis 
EC 
Ethics Committee 
FDA 
Food and Drug Administration 
FT   
Flexitouch® system 
LE  
Lower Extremity 
LTW 
Local Tissue Water 
MLD  
Manual Lymphatic Drainage 
MyMOP 
Measure Yourself Medical Outcome Profile 
PCD 
Pneumatic Compression Device 
TSTI  
Tactile Systems Technology, Inc 
U/S 
Ultrasound 
 
 
3.0 Introduction 
 
3.1 
Background and Rationale:  Lymphoedema is a chronic, progressive, 
and debilitating condition arising from congenital abnormalities (primary) 
or acquired damage (secondary) to the lymphatic system.1  A healthy 
lymphatic system works primarily to 1) drain a complex fluid called 
lymph from the tissues; 2) direct it to structures called lymph nodes which 
filter out cellular debris, bacteria, and toxins, and then; 3) return it to the 
major vessels of the venous system.1  The lymphatic system also serves 
vital immunological functions such as the production of lymphocytes to 
defend against infection and disease.  Approximately 2-3 liters of lymph is 
cycled daily from the bloodstream into bodily tissues and, via the 
lymphatic system, back into the general circulation.2 
 

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A significant proportion of patients with lymphoedema experience a 
worsening, ultimately irreversible limb swelling arising from the 
accumulation of fluids normally regulated by the lymphatic system.  
Enlargement of extremity proportions may be dramatic and disfiguring.  
Many suffer impairments in mobility and function due to the weight and 
bulk of a lymphoedematous limb.  Complications include chronic pain, 
decreased range of motion, compromised immunological function and 
increased incidence of acute inflammatory episodes and infection.2,5,6,7  
Psychological complications include increased anxiety, depression, negative 
body image/loss of body confidence, anger, frustration, sexual dysfunction. 
8,9 
 
Lymphoedema is an incurable but treatable condition.  Growing awareness 
of the considerable health, economic and psychosocial consequences of this 
chronic disability has intensified the search for more effective management 
strategies.3,4,10-12 
 
The goals of lymphoedema therapy are 1) to reduce limb girth; 2) to 
reduce swelling by encouraging the development of collateral lymph 
drainage pathways and by stimulating function of intact routes (that is to 
improve lymph transport from the tissues); 3) to prevent re-accumulation 
of fluid in interstitial tissues; 4) to prevent or control infection and; 5) to 
reduce physical disability and psychological sequelae.1,13,14   
 
Pneumatic compression devices (PCDs) have been utilized for many years 
as an adjunct to home lymphoedema care.  PCD treatment is intended to 
assist with limb volume control for patients with lymphoedema.  In many 
cases, the aim is to simulate and potentially replace the conventional self-
manual lymphatic drainage (MLD) component during Phase II of 
Complete Decongestive Therapy (CDT) in patients suffering from 
lymphoedema.  The Flexitouch® system (FT) is an advanced PCD that 
was developed to aid in lymphoedema management at home.   
 
Though there have been a number of publications on the use of PCD for 
the treatment of lower extremity lymphoedema, none have had the aim to 
define the optimal treatment dose with regards to pumping pressure, 
frequency of treatment session, and duration of the treatment session.10  
Treatment duration in the literature can range from intensive treatment of 
6 to 8 hours per treatment session to a less time intensive treatment 
regimen of as little as 30 minutes to 1 hour per session.15,16 Additional 
studies are needed to further address the optimal dose including duration 
and pressure.16 Tactile Systems Technology, Inc (TSTI) the makers of the 
Flexitouch ® system (FT) is dedicated to improving the lives of patients 
with lymphoedema and chronic swelling conditions through ongoing 
clinical research to determine optimal treatment.   

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Compression garments are often part of standard care for patients with 
lymphoedema.  For the purposes of this study that is designed to evaluate 
the physiologic impact of pneumatic compression device dosing, the 
compression garment usage will not be formally evaluated.  However the 
compression garments will be standardized across all study patients, 
mandating knee high compression garments with a pressure of 30–40 
mmHg. If it is determined by data collection or clinical assessment that the 
garments variable is influencing the FT effect then the type and use of 
garment will be further controlled in future studies.  
 
3.2 Device Description and Intended Use:   
Flexitouch® system (Tactile Systems Technology, Inc., Minneapolis, 
MN, USA):  The FT is a programmable, segmental, gradient pneumatic 
compression device which has been cleared by the FDA for market in the 
US (K013061, K120972), by Heath Canada for market in Canada (88415) 
and by European Union for market in Europe (CE 0459) for the treatment 
of lymphoedema, primary lymphoedema, post mastectomy oedema, 
oedema following trauma and sports injuries, post immobilization oedema, 
and venous insufficiencies.   Additionally, the device has been cleared to 
market in the US by the FDA (K062818) for reducing wound healing time 
as well as the treatment and assistance in healing stasis dermatitis, venous 
stasis ulcers, arterial ulcers and diabetic leg ulcers (Appendix A).  
 
4.0 Study Objectives:  The study objectives have been selected in this proof of principle 
study in order to determine if there is a difference in treatment effect across the 3 
study groups when treating lower extremity lymphoedema using the Flexitouch® 
system.   
 
5.0 Study Design   
 
5.1 Overview of Study Design:  This study is a 3 arm, prospective, randomised, 
proof of principle clinical trial to determine the optimal treatment duration for 
achieving a measurable physiologic effect on lower extremity lymphoedema with the 
Flexitouch® system (FT) as determined by bioimpedance, perometry, tonometry, 
ultrasound, local tissue water assessment, symptom burden and subject interview..  
Each intervention arm will include 10 completed subjects for a total of 30 completed 
subjects. 
 
 
 
 
 
 
 

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5.2 
Endpoints The endpoints for this study include: 
• Intra/extra cellular fluid changes (bioimpedance) 
• Limb fluid volume changes (whole and segmental) 
(perometry and bioimpedance) 
• Superficial tissue characteristics (induration/depth and 
thickness of fascia) using ultrasound and tonometry.  
• Tissue water assessment utilizing Moisture Meter D and 
Ultrasound 
• Symptom assessment (MyMOP) 
• Qualitative interviews 
• Activity level between and post treatment (pedometer and 
patient log) 
 
Screening and Enrollment 
Randomisation 
Group A: Treatment 
once per day (1 hour)
 
 
Group C: Treatment 
twice per day consisting 
of 2 consecutive 1 hour 
treatments in the AM & 
PM (4 hours) 
• 5 Days in clinic treatment and measures 
Group B: Treatment 
twice per day (am 
and pm = 2 hours)
• 12 Days of treatment: 10 days in clinic 
treatment and measures and 2 days at home 
treatment only  

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5.3    Safety Endpoints: Safety endpoints will include incidence and 
severity of complications.  A clinician will assess any signs and 
symptoms of acute infection, DVT, cellulitis, pain or any other 
need for medical intervention and the possible need for a subject to 
discontinue the study.   
 
6.0 Study Population, Selection, Withdrawal/early exit 
 
6.1   Study Population: This is a community based trial.  The study population 
will be drawn from patients who are seeking or have previously sought 
treatment of primary or secondary lower extremity lymphoedema.  Only 
patients who meet the inclusion criteria listed below will be considered for 
participation.   
 
6.1.1   Inclusion Criteria:  Subjects may participate in this study if they 
meet all of the criteria described below:   
• Subjects must be ≥ 18 years old  
• Subjects must have a diagnosis of primary or secondary Stage 2 
unilateral or bilateral lower extremity lymphoedema.   
• Must currently be using adequate compression garment(s) as 
determined by the clinician: 
o Garments must be at least 20mmHg and no more than 3 
months old and must be worn upon rising and removed at 
bedtime.  
• Subjects must have clinically relevant excess limb swelling as 
determined by clinician “pitting test”.  
• Must be able to attend all required in-clinic treatment visits  
 
6.1.2 Exclusion Criteria:  Subjects will be ineligible for this study if 
they meet any of the criteria described below: 
• Diagnosis of active or recurrent cancer, or less than 3 months at the 
time of initial evaluation from the completion of chemotherapy, 
radiation therapy or primary surgery for the treatment of cancer. 
• Active infection or inflammation   
• Active thrombophlebitis (within the last 2 months) 
• History of  pulmonary embolism (within the last 2 months) 
• Documented history of deep chronic venous insufficiency or deep 
venous obstruction with  a reflux duration of > 2 second in the deep 
system, and any history of deep vein thrombosis (DVT) 
• History of pulmonary edema  
• History of congestive heart failure  
• History of chronic kidney disease with a glomerular filtration rate 
(GFR) of less than 30 mls per minute. 
• Patients with poorly controlled asthma (i.e. those with severe 
persistent symptoms throughout the day, night time awakenings 

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several times per week, use of a beta2 agonist inhaler several times 
per day and those whose normal activity is extremely limited). 
• Symptomatic or severe peripheral artery disease, defined by current 
lifestyle-limiting claudication or critical limb ischemia  
• Presence of an open wound or ulcer of any etiology 
• Diagnosis of lipoedema and lipolymphoedema*  
• Currently using an in home pneumatic compression device  
• Metal implants that would interfere with bio impedance equipment 
• Individual with pacemaker or other implanted electronic devices 
• Inability or unwillingness to remove bandaging from treatment 
regimen while participating in the study.   
• Pregnancy  
• Any condition where increased venous and lymphatic return is 
undesirable 
• Inability or unwillingness to participate in all aspects of study 
protocol and/or inability to provide informed consent 
• Currently participating in another clinical trial 
• Currently using diuretics 
• BMI > 40 
 
6.1.3 Exit/Discontinuation Criteria:  Subjects may exit the study prior 
to completion of all study visits if they meet any of the following 
criteria.  The data collected as part of the study will be included in 
the intent to treat analysis.  
• Subject death 
• Subject voluntarily withdraws 
• Subject experiences a serious adverse event that in the 
investigator’s clinical judgment necessitates study discontinuation 
• Subject acquires any of the exclusion criteria during treatment 
phase of the study 
 
* Clinical assessment of lipoedema and lipolymphoedema will be completed to 
assure that the subject meets enrollment criteria. Lipoedema is a type of 
lipodystrophy, which can cause enlargement of the legs and be confused with 
lymphoedema.  It is a clinical diagnosis with no specific diagnostic tests 
available.  The typical pattern of lipoedema is excess fat deposition in the lower 
part of the body from the hips to the ankles, commonly with a history of bruising 
and tenderness.  Patients also exhibit asymmetrical weight loss on dieting with 
weight being lost in the upper part of the body rather than the legs.  Pure 
lipoedema is non pitting. 
 
Lipolymphoedema is the term used when patients with lipoedema develop 
superadded oedema.  This typically forms around the ankles and feet and is 
pitting in nature.  The diagnosis of lipolymphoedema is made by applying the 

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diagnostic criteria for lipoedema but with the presence of pitting oedema in the 
ankles and feet.   
 
6.2 Recruitment and Randomisation  
 
6.2.1 Recruitment Plan:  Subjects will be recruited from patients 
either seeking or who have previously sought treatment at a clinic 
for lymphoedema.  Desired enrollment/follow-up time (first 
subject in to last subject out) is 20 weeks.  If additional recruitment 
is required to meet enrollment, referring general practitioners and 
potential reference clinics may be solicited for subjects.  Patient 
advocacy/support groups may also be notified of the study 
opportunity.  Subject recruitment materials may be provided for 
referring physicians’ waiting rooms including posters, flyers, 
brochures, etc.  If additional recruitment is required, direct to 
public advertisements in local newspapers may be utilized.   
 
 
6.2.2 Randomisation Scheme:  After completing the informed 
consent, subjects will be randomly assigned equally to one of three 
groups.  Randomisation will follow the computer generated 
scheme.  A master copy of the scheme will be kept at TSTI.  
 
 
The site(s) will be provided with sealed envelopes containing the 
device assignment for each potential subject.  Each envelope will 
be numbered sequentially from 01 to 030.  Randomisation 
envelopes and/or subject IDs cannot be used more than once.  
After the subject signs the informed consent agreeing to participate 
in the study, the appropriate study staff will obtain the next 
sequential sealed randomisation envelope and open it while the 
subject is present.   
 
 
The randomisation assignment cannot be changed or chosen by the 
subject or the investigator.  The randomisation envelope should be 
placed in the subject binder. 
  
6.3 Study Timetable:  
 
Task 
 
 
 
 
           25 Weeks 
 
1-5 
6-10 
10-15 
15-20 
21-25 
EC/Regulatory 
X 
X 
 
 
 
Enrollment 
 
X 
X 
X 
 
Treatment 
 
X 
X 
X 
X 
Data Entry 
 
X 
X 
X 
X 
Data Analysis 
 
 
 
X 
X 
  

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7.0 Treatment Plan and Study Procedures:  
 
 
7.1 Dosage and Rationale: All subjects enrolled will receive treatment to the 
study leg using the FT study device.  The treatment will be received in clinic 
and the garments applied by a trained clinician with the exception of Group 
A’s weekend treatment which will be done by the patient in their home.  
 
Subjects will be randomised into one of three groups.  Following 
randomisation and study arm assignment the subjects will receive treatment 
according to study arm assignment: 
Group A:  subjects will receive 12 consecutive days of treatment 
utilizing the following treatment regimen. The first 5 days will be 
in clinic (Monday through Friday) followed by self administered at 
home treatment for 2 days (Saturday and Sunday).  The last 5 days 
of treatment will be in clinic ending the treatment phase on day 12 
(Monday through Friday).  
o One lower extremity treatment per day using program L1 
with the pressure set to “normal” applying the full garment 
set.   
 
Groups B & C subjects will receive 5 consecutive days of 
treatment in clinic (Monday through Friday) utilizing the following 
treatment regimens.   
o Group B: Two lower extremity treatments per day (am and 
pm) using program L1 with pressure set to “normal” 
applying the full garment set.  
o Group C: Two consecutive treatments 2 times a day (am 
and pm) using program L1 with pressure set to “normal” 
applying the full garment set.  
 
In the case of bilateral lymphoedema, the leg with the largest volume will be 
considered the study leg.  The contralateral (non study) leg will be treated in 
the same manner that it was being treated prior to entering the study. Limb 
volume measures for both legs will be collected.   
 
 
At the screening visit, each subject’s compression garment(s) will be 
assessed for clinical adequacy (Class: ≥ 20mmHg; Age: 3 months or less) by 
the Principal Investigator. Subjects will be instructed to wear the 
compression garment(s) every day during wakeful time.  Garments may be 
remove while bathing and overnight.  The clinician will remove the 
subject’s compression garment during device treatment.  This treatment 
regimen is consistent with standard home care compression garment(s) 
treatment. 

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7.2 Subject Data Requirements:  The following data will collected from all 
subjects: 
*Group C: Will have moisture meter done before the first treatment session, after the first 
treatment session, and then after the final treatment session of the day = 3 times total 
during treatment visits.  
 
7.3 Laboratory Testing Procedures:  After provision of informed consent, 
women of child bearing potential will be tested for pregnancy at the site 
specific clinical laboratory according to site standard procedures.  If the 
pregnancy test is positive, subjects will be excluded from the study.  
Potential subjects suspected to have renal dysfunction will undergo a blood 
test to determine the glomerular filtration rate (GFR).  Those subjects with a 
GFR of less than 30mls per minute would be excluded from the study.  
7.4 Clinical Study Procedures:  Pre-screening of subjects will be conducted by 
study staff either by phone or in person. Potential subjects will meet with 
study staff in-person for the consent process.  
 
7.4.1 Informed Consent: Informed consent must be obtained from all 
subjects prior to randomisation and participation in clinical studies 
as mandated by Federal Regulations and/or the qualifying Ethics 
Committee (EC).  A blank copy of the EC-approved informed 
consent form must be kept on-site and by the sponsor.  The signed 
original for each subject must be kept in the subject’s medical 
Key: 
B = Before Treatment 
A= After Treatment 
D = During Visit 
Screening  
Baseline/ 
Initial Treatment  
 (D1)   
Treatment  
(≠ D1, 5 & 
12)  
Day 5(All 
Groups) and 
Day 12 
(Group A) 
Medical History 
D 
 
 
 
Bio Impedance 
 
B A 
B A 
B A 
Perometer 
 
B A 
B A 
B A 
Duplex U/S 
B 
 
 
 
Interface Pressure 
 
B 
B 
B 
Ultrasound 
 
B 
 
A 
Tonometry 
 
BA  
BA 
BA 
Moisture Meter D 
 
B A* 
B A* 
B A* 
Subject Interview 
 
 
 
D 
MyMOP 
 
D 
 
D 
Activity Level 
 
D 
D 
D 
BMI 
 
D 
D 
D 
Adverse effects 
 
A 
A 
A 
Compliance  
 
D 
D 
D 

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records and copy of the signed informed consent will be provided 
to the subject.   
 
A copy of the consent will be given to the subject to read and take 
home to consider if they prefer.  All the subject’s questions will be 
answered, prior to signing the informed consent.  No research 
procedures will be performed until subject signs the consent.  A 
signed copy of the consent will be provided to the subject. After 
completing the informed consent, subjects will be randomly 
assigned equally to one of 3 groups. 
 
7.4.2 Duplex Ultrasound: This test will be done at the time of the 
screening visit to rule out a significant deep vascular obstruction or 
venous insufficiency as determined by a reflux of > 2 second.  If 
the subject had a duplex U/S done within the last two months the 
results may be reviewed and utilized for inclusion or exclusion into 
the study.   The test has no associated risks.  A water soluble gel is 
placed in a handheld transducer, which directs high-frequency 
sound waves to the arteries or vein being tested.  Subject should 
experience no pain or discomfort.  
 
7.4.3  Bioelectrical Impedance:  A Bioimpedance Spectroscopy (BIS) 
device will also be used to quantify changes in intra- and extra- 
cellular fluid at each visit.  BIS utilizes the characteristics of 
frequency dependent current flow to detect fluid changes.  
Measurements are generated by a low frequency electrical signal 
transmitted to the patient from the device through skin surface 
electrodes.  The measurement is imperceptible to the subject and is 
not confounded by weight or muscle changes that may occur in the 
limbs. Appendix B contains the study procedure for bioimpedance. 
 
7.4.4    Limb Volume Measurement:  Limb volume measures will be 
taken at each visit for both legs of the subject.  The site will 
conduct limb volume measurements using an optoelectronic 
system (Pero-System, Perometer, Appendix C).  The perometer 
utilizes infra red light beams to measure limb volume more rapidly 
than the circumferential tape measure method.  These systems have 
been validated against circumferential measures to a correlation 
coefficient of .977 in leg subjects.17 The perometer can be used for 
whole leg or segmental (upper/lower) measurements. Perometer 
measurement will be taken twice on each leg and the average used.  
 
7.4.5   Tonometry: Tissue assessment/fibrosis will be evaluated with use 
of a tonometer at anatomically defined locations on the affected leg 
and on the trunk.  The Tonometer is a mechanical device that gives 

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an indication of the resistance of tissue to compression.  It is used 
in lymphoedema to give an estimate of the extent of pitting and 
fibrotic induration.  Tonometry readings of the affected areas will 
be compared to readings taken pre-treatment intervention. 
Appendix D contains the Tonometer operating instructions and the 
body points for this trial.  
 
7.4.6  Tissue Ultrasound (U/S): Tissue ultrasound will be used to 
measure skin thickness and oedema in fixed areas of the limb and 
trunk at Day 1 (pre-treatment) and at the day 5 (All Groups) and 
day 12 (Group A) post FT treatment.  Measurements will be 
obtained at defined anatomic locations.  The aim of this is to 
measure and assess for changes in the tissue in the treated limb and 
trunk.  A positive correlation has been observed between skin 
thickness and oedema in the affected lymphoedema arm.  In 
addition, increases in skin thickness may also be related to 
development of fibrosis or other skin changes.  The use of 
ultrasound has been suggested in the literature as another simple, 
reliable means to evaluate therapeutic outcomes.18  
 
7.4.7  Other Measures:  
Local tissue water (LTW) measures will be obtained with a 
Moisture Meter D™ (Delfin Technologies, Finland).  This device 
and technology has been demonstrated to provide a measure of 
LTW and its change based on measurements of the skin’s tissue 
dielectric constant at a frequency of 300 MHz. The method has 
been widely used in clinical studies to evaluate LTW and its 
change under a variety of conditions.19-22 (Appendix E) 
 
Interface pressure will be obtained with the PicoPress®.  This 
technology was designed to be used to determine the pressure 
exerted under both static and dynamic compression. The 
PicoPress® transducer allows for dynamic pressures readings.23 
Appendix F    
 
Symptom assessment will be obtained by using the Measure 
Yourself Medical Outcome Profile (MyMOP).  This questionnaire 
was created to be a patient-generated or individualized outcomes 
questionnaire.  It was designed to be problem specific but also 
include general wellbeing questions.  Patient symptoms can be 
emotional, social or physical (Appendix G).  At the conclusion of 
study treatment visits the subject-reported treatment comfort and 
effectiveness will be assessed by asking the subject targeted 
questions. (Appendix H) 
 

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Activity level will be monitored through the use of a pedometer 
and a subject diary.  The subject wear a pedometer during the 
treatment phase of the study to record the number of steps 
accumulated throughout the day.  The diary is intended to capture 
additional information regarding the subject’s activity level such as 
type of activity.   
 
7.4.8    Screening Visit: At this visit, the patient will be asked to provide 
written informed consent and inclusion and exclusion criteria will 
be evaluated to ensure that the patient meets all entrance criteria. 
See section 7.2 for a schedule of events.   
 
After the informed consent process is complete, the subject will be 
randomised into one of 3 study groups.  The baseline visit must 
occur on a Monday.  Study staff and the subject will make every 
attempt to schedule all study visits at the same time of day. 
 
At this visit, the subject will withdraw all at home lymphoedema 
treatments with the exceptions of wearing appropriate compression 
garments and maintaining proper skincare.  Subjects cannot use 
limb bandaging at any time during the study.    
 
The subject will leave the screening visit with: 
• Schedule for all study visits with the first treatment visit 
starting on a Monday.   
• Pedometer and instruction to start wearing the morning of 
the first treatment visit 
• Diary to record daily activity and instructions to start 
documenting the morning of the first treatment visit 
• Contact information and instructions to call if any problems 
arise 
 
7.4.9    Baseline Visit/Initial Treatment: At the time of the 
baseline/initial treatment visit the subject will undergo the study 
procedures according to the table in section 7.2.   
 
During the visit the subject will undergo treatment according to 
which group they were randomised.  For Groups B and C which 
receive FT treatment twice a day the subject must have at least 2 
hours and no more than 6 hours between the am and pm treatment 
sessions. The compression garment must be worn between the am 
and pm treatment sessions. 
 
7.4.10    Treatment Visits (Group A: Day 2  to 5; 8 to 12; Group B & 
C: Day 2 to 5):   The subject will be examined, receive FT 

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treatment according the treatment group assigned and the study 
parameters according to the table in section 7.2 will be completed 
and recorded by appropriately trained study staff.   
 
 
7.5  Investigational Device Accountability 
The site must maintain a device accountability log.  Completion of this log 
will ensure that all investigational devices are properly tracked and 
accounted for throughout the study from the time they are received by the 
institution to the time they are returned to the study sponsor or other 
designated site.  Device location, Subject ID assigned, date Subject returned 
to site (if assigned to Group A subject), controller disinfected, and final 
disposition (e.g., returned to sponsor, garments discarded) of all pneumatic 
compression devices and garments will be documented.  The sponsor must 
also maintain device accountability documenting all shipments and returns 
of investigational devices by serial number, date, and person completing the 
log.  Storage locations for the investigational devices and garments will be 
secure (i.e., locked and away from other devices) with access restricted only 
to investigators and authorized research personnel. 
 
Sanitation Procedure: 
At the conclusion of each treatment session the clinic will disinfect the 
controller and store the subject’s garments which must be clearly labeled 
with subject identification information until the next treatment to ensure that 
the garments are not used on other study subjects. Group A will be taking a 
controller and their FT garments home for the weekend.  Upon return that 
site must disinfect the controller before using in clinic.  The subject 
garments should be stored like all other subject assigned study garments. 
The garment(s) CANNOT be reused on multiple subjects and should be 
appropriately discarded upon study completion.   
 
8.0 Statistical Plan 
 
8.1 Study Design: This study is a prospective, randomised, proof of principle 
clinical trial to determine the optimal treatment duration and frequency 
between three options for treating lower extremity lymphoedema with the 
Flexitouch® system (FT).  Optimal treatment duration will be determined by 
a nested series of physiologic and clinical changes induced by FT treatment 
within three key outcomes categories: (a) fluid dynamics (as assessed by 
bioimpedance, perometry, and local tissue water assessments); (b) tissue 
characteristics/fibrosis (by ultrasound and tonometry measurements); and (c) 
patient-reported outcomes (quantified by symptom assessment tools, 
treatment assessments, treatment adherence, and subject interview.) Patient 
demographics will be summarized and compared between the randomised 
groups. 
 

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8.2 Efficacy Analysis 
Analysis will be undertaken for the following groups:   
 
Group A: One lower extremity treatment per day using program L1 
with the pressure set to “normal” utilizing the full garment set over 12 
days.  Total number of treatment hours=12. 
 
Group B: Two lower extremity treatments per day (am and pm) using 
program L1 with pressure set to “normal” utilizing the full garment set 
over 5 days. Total number of treatment hours=10. 
 
Group C: Two consecutive treatments 2 times a day (am and pm) 
using program L1 with pressure set to “normal” utilizing the full 
garment set over 5 days.   Total number of treatment hours=20.  
 
 
This study is planned to have a maximum of 30 completed subjects, 10 in 
each group with unilateral or bilateral primary or secondary leg 
lymphoedema.  Each subject will receive the FT as per the groups described 
above. This small sample size will not offer a powered statistical analysis 
for any single outcome measurement, but is designed to estimate treatment 
effects for each proposed endpoint for evaluation in a subsequent clinical 
trial.  This study is designed to determine both which measurement 
endpoints are most sensitive to the variable dosing protocols and to 
determine which endpoint should be defined as the primary end-point in a 
larger investigation of compression “dosage”. The study will be used to find 
the effect size for comparisons between the doses and from this to estimate a 
suitable sample size for a definitive study.  
 
Subjects with missing data for the study outcomes will be included in the 
intention to treat analysis.  However, the study will continue to enroll until 
there are 10 subjects in each arm that complete all study visits.  After 30 
patients have been randomised, those patients who fail to complete all 
treatment visits will be replaced until all data are available for 10 subjects in 
each study group.  Data from the subjects who fail to complete will be used 
to determine the adherence to therapy in each randomised group. 
 
Study analysis will be conducted for “within day” change as well as 
“between day” change.  “Within day” change is defined as a comparison of 
pre-treatment measures against post-treatment measures following the last 
treatment of the day. “Between day” change is defined as a comparison of 
pre-treatment outcomes on treatment day 1 compared to post-treatment 
outcome measures on the final treatment day (day 12 for group A, day 5 for 
groups B and C).  
 

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This study will evaluate FT-induced changes in three types of outcome 
measurements categorized as:  
(a) fluid dynamics (measured via bioimpedance; moisture meter; and 
perometry);  
(b) subcutaneous tissue density (a presumed surrogate marker of tissue 
fibrosis measured via tonometry) 
(c) patient reported outcomes addressing symptoms, treatment 
satisfaction; and treatment adherence (measured via MYMOP; patient 
survey and adherence diary). 
 
Although this is a pilot study with multiple outcomes, the outcome 
measurement order as listed above indicates a pre hoc identification of the 
order of significance of the outcome measures (change in fluid dynamics > 
change in tissue fibrosis > change in patient outcomes) in this short-term 
dose-finding trial.  
 
8.2.1 Analysis of Fluid Dynamics/Change 
 
Bioimpedance measurement 
It is hypothesized that changes in the intracellular and extracellular fluid 
ratios as measured by multifrequency bioimpedance will yield the most 
relevant pilot data indicative of treatment success. At present there is no 
indication of the magnitude of the effect expected using bioimpedence.  
However, since this is a comparative study, any difference in ECF/ICF 
change will be evaluated between the three groups.  This will be 
determined using a linear mixed model with repeated measures. 
 
For the within day measures the change in ECF/ICF will be calculated, 
and used as the dependent variable.  Assigned group and day of visit will 
be forced into the model to allow for comparisons between groups and 
changes over time ECF/ICF ratio at baseline, BMI, time of day 
measurements are taken, activity level (number of hours upright and 
ambulatory), age, number of hours utilizing compression garment, will be 
tested for inclusion in the model.  
 
To evaluate the between day outcome the change in ECF/ICF from 
baseline (pre-treatment) will be calculated for each follow up visit (post-
treatment), with assigned group and day of visit forced into the model.  
Identical confounding variables will be used as for the within day analysis. 
 
Final analysis will examine the change in ECF/ICF ratio from baseline to 
end of final treatment using the same model as above. 
 
Local Tissue Water 

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Local Tissue Water (LTW) will be assessed prior to and post-treatment at 
each visit as for the bioimpedance data.  The analysis will therefore be 
undertaken in a similar way to the bioimpedance data. 
 
Perometry 
Perometry will used to estimate limb volume pre and post treatment.  The 
analysis will therefore be undertaken in an identical way as for the 
bioimpedance measurements.   
 
8.2.2 Analysis of Subcutaneous Tissue Density/Fibrosis 
 
Subcutaneous tissue density and fibrosis are being assessed using one 
method, namely tonometry. Tonometry will be assessed at two or 3 time 
points depending on study group, at baseline (prior to first treatment), and 
after the final treatment on day 5 and day 12 if applicable.   A repeated 
measures mixed linear model will be used to determine the changes in 
subcutaneous density at these time points.  Randomised group will be 
forced into the model.  Other covariates considered for inclusion in the 
model will include BMI, time of day measurements are taken, activity 
level (number of hours upright and ambulatory), age and number of hours 
utilizing compression garments. 
 
8.2.3.  Analysis of Patient Reported Outcomes. 
 
Patients’ self-reported symptoms and change in symptoms are recorded 
using the MYMOP questionnaire.  Analysis will be undertaken to compare 
the intensity of the self-reported symptoms using a repeated measures 
analysis, with BMI, activity level (number of hours upright and 
ambulatory), age and number of hours utilizing compression garments. 
 
8.3 Adherence to Therapy 
 
Adherence will be evaluated by investigating the number and reasons for 
withdrawal for patients who fail to complete the pre-specified number of 
treatments and visits along with compression garment compliance and at 
home device usage for Group A.   
 
9.0 Safety and Adverse Events 
 
9.1 Risk Analysis:  The subjects enrolled in the study are not expected to be at 
any higher or additional risk than those who use non-study pneumatic 
compression devices.  There is risk with using any pneumatic compression 
device.  These may include, but are not limited to risk of explosion if the 
device is used in the presence of flammable gases, risk of electrical shock if 

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the device is immersed in water or if the housing is broken and subject 
attempts to service the unit.   
 
Pneumatic compression devices are contraindicated for use in the presence of 
pulmonary edema, thrombophlebitis, congestive heart failure, deep vein 
thrombosis, episodes of pulmonary embolisms, acute cancer, acute infection, 
and inflammationor other conditions where increased lymphatic return in 
undesirable.  Clinical trials have not been completed to show the safety of 
using the FT garments during pregnancy and therefore should not be used.  
 
There are minimal side effects expected from the treatment subjects will 
receive in this study.  The expected risks are often a failure to respond to the 
treatment intervention and are not related to the treatment itself.  In some 
cases, side effects due to lymphoedema can be serious, long lasting, or may be 
permanent.  The risks listed below are symptoms of lymphoedema and may be 
experienced by all subjects with lymphoedema: 
Likely: 
• Pain or discomfort 
• Increased swelling 
 
Less Likely: 
• Cellulitis – Infection of the skin which may include swelling, 
redness, and tenderness of the infected tissue 
• Development of or increased edema in the truncal and/or genital 
region. 
 
Ultrasound, bio-impedance and moister meter are procedures with minimal 
risk involved.   
 
9.2 Adverse Events Reporting:  All adverse events (related or not related to the 
device treatment) that occur throughout the conduct of the study will be 
reported. An adverse event is defined as any undesirable experience 
associated with the use of a medical product. 
 
Anticipated Adverse Events 
Adverse events associated with lymphoedema may include, but are not limited 
to: cellulitis, deep vein thrombosis, increased swelling.  
 
All adverse events are to be reported to TSTI at the time of occurrence or 
when the Investigator becomes aware of the adverse event (e.g., at the follow-
up evaluation). 
 
TSTI may request that additional information such as operative notes, 
discharge summaries, lab reports, and a physician’s summary of the event, be 
provided to TSTI as supporting documentation for any reported adverse event.  

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In the event of a subject death, a death summaries and autopsy reports will be 
provided to TSTI. 
 
Serious Adverse Events 
A serious adverse event is any adverse event that affects subject health or 
safety, that is life threatening, results in disability or permanent damage, or 
requires intervention to prevent permanent impairment/damage, or an event 
that results in hospitalization (initial or prolonged) or causes congenital or 
anomaly/birth defect, or results in death.   
 
It is the responsibility of the Principal Investigator to notify their EC of any 
adverse events, as required.  Serious adverse events will be reviewed by TSTI 
and the final determination as to whether or not an event is related to the 
device or treatment will be made by TSTI.  If a serious adverse event is 
deemed related by TSTI, TSTI will report the event to the appropriate 
regulatory body and to all reviewing EC and participating investigators within 
10 working days after TSTI first receives notice of the event, as required. 
 
The protocol is specifically designed to minimize risks through careful subject 
selection (reference section 5.1.1 Inclusion Criteria and 5.1.2 Exclusion 
Criteria), rigorous adherence to a standardized schedule of treatment visits and 
routine clinical monitoring by TSTI representatives. 
 
9.3   Subject Withdrawal:  Subjects may voluntarily withdraw at any time, for 
any reason.  Reasons for withdrawal will be recorded if the subject is willing 
to share this information.  Subjects will be withdrawn from the study if they 
experience a serious adverse event or for any other reason set forth in 
section 5.1.3 or if in the investigator’s judgment the subject develops an 
unrelated illness which will significantly affect assessment of the subject’s 
clinical condition.  The data from the withdrawn subjects will be included in 
the intent to treat analysis.   
 
Withdrawn subjects will be replaced according to the following process: 
• After all randomisation assignments have been assigned via the 
randomisation scheme. The site will review the subject withdrawal 
list and replace the subject according the sequence of subject 
withdrawal.  For example:  If first subject withdrawal is from Group 
A then the second from Group C.  The next eligible subject would be 
enrolled in Group A followed by Group C.  This will continue until 
there are 10 subjects completed in each study group for a total of 30 
completed subjects.  
  
 
10.0 Deviations from the Clinical Protocol:  Any deviation from this Clinical Protocol 
undertaken to protect the life or physical well-being of a subject in an emergency 

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situation must be reported to the sponsor and the respective EC as soon as possible, 
but in no event later than five (5) working days after the emergency occurred.  
Anticipated deviations from this plan in a non-emergency situation must be pre-
approved by the sponsor via telephone, e-mail, fax, or mail.  It is preferred that 
deviations scheduled to be performed in a nonemergency situation not be conducted 
until written authorization via fax, mail, or e-mail is provided by the sponsor.  All 
protocol deviations must be documented. Deviations that may affect the scientific 
soundness of the study, or the rights, safety or welfare of the subjects must also be 
reported to the reviewing EC according to their reporting requirements.  Protocol 
deviations may necessitate the discontinuation of the subject from the study. 
 
11.0 Subject Compensation:  The sponsor agrees that it is responsible for the reasonable 
and necessary costs of diagnosis, care and treatment of any undesirable side effects, 
adverse reactions, illness or injury to a subject in the Investigation which are 
determined to result from participation in the Investigation, except for cost as a 
result of (i) any failure of Institution, Site Principal Investigator or any of the 
employees or agents of the Institution, Principal Investigator or Co-Investigator, to 
conduct the investigation in compliance with the clinical protocol, (ii) violation of 
any law, including the Health Insurance and Portability Act (HIPAA) (iii) any 
negligent or willful acts or omissions of Institution, Site Principal Investigator or 
Co-Investigator (iv) any misuse of the device by the Institution, or Site Principal 
Investigator or any Co-Investigator or any of the employees or agents of the 
Institution, Site Principal Investigator or Co-Investigator or (v) medical problems 
caused by failure of the subject to follow study instructions.  Subjects may be 
provided reasonable reimbursement for time and/or parking/travel costs arising out 
of their participation in the trial.  Subjects will not be otherwise compensated for 
their participation in the study.  
 
12.0 General Study Information 
 
 
 
 
 
 
 
 
12.1 Technical Support:  Training and support for study procedures will be 
provided by the Sponsor contact listed in Section 1.1 or designee.   
 
12.2 Discontinuation of the Study:  The study may be terminated if: 
• That the rate of severe adverse events in any arm of the study is such 
that the Ethics Committee decides continued participation would 
compromise subject safety.  If deemed necessary by the Ethics 
Committee, a follow-up safety analysis will be performed for all 
subjects. 
• Target subject accrual has not met, and cannot meet subsequent trial 
objectives. 
Upon study termination by Sponsor, Sponsor will compensate Institutions 
for actual Study costs incurred through the close out of the Study, in 
accordance with the terms of the study contract.  
 

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12.3 Record Retention:  Records must be maintained for a period of at least ten 
years after the date on which the study is completed or terminated.  
Investigator or Institution shall notify Sponsor at least thirty (30) days prior 
to any planned archiving or destruction of records related to this study. The 
recordings from the patient interviews will be transcribed and the recording 
then deleted. The transcription will be maintained with the study records. 
 
12.4 Quality Assurance Procedures:  This study will be conducted in 
accordance with Good Clinical Practice and International Conference on 
Harmonization Guidelines, NHS Trusts, institutional research policies and 
procedures and other appropriate regulatory requirements to ensure subject 
safety and quality of clinical procedures related to the conduct of the clinical 
trial.  The investigators will permit regular monitoring, audits and site 
inspections by the EC, the sponsor, government regulatory bodies and any 
institution compliance and quality assurance groups of all study related 
documents (e.g. source documents, regulatory documents, data collection 
instruments, study data, etc.).  The investigator will ensure the capability for 
inspection of applicable study related facilities. Regular trial monitoring will 
be conducted to ensure compliance to this protocol.   
 
12.5 Materials Provided by the Sponsor:  Sponsor will provide administrative 
study materials along with the FT controllers and garments, PicoPress® and 
pedometers. 
 
12.6 Materials Provided by the Site:  Institution will provide assessment 
equipment (scales, lab tests, perometer, bio impedance equipment, 
tonometer,  clinical and support staff) needed to complete the trial.   
 
13.0 Administrative Study Information 
 
 
 
 
 
 
 
13.1 Pre-Study Site Visit:  The study sponsor may conduct onsite visits or 
telephone qualification (pre-study audit) prior to study initiation to ensure to 
verify adequate resources, staffing and a sufficient subject pool.  
 
13.2 Ethics Committee Review:  Prior to subject enrollment and study initiation, 
the appropriate Ethics Committee and National Competent Authority (if 
applicable) must approve the clinical study.  It is the responsibility of the 
investigator to provide the Ethics Committee with all necessary information 
to satisfy the individual institution’s requirements. 
 
13.3 Clinical Site Monitoring:  Clinical sites will be monitored for compliance 
with the clinical protocol, investigator agreement, and applicable regulatory 
regulations.  Regular contact will be maintained to ensure: 
• Subject safety,  

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• That clinical site staff is well informed of regulations and sponsor 
requirements,  
• That the clinical protocol is followed, 
• That data is gathered in a complete and timely way, 
• That problems with data or data collection are addressed appropriately 
and in a timely manner, 
• That adverse events are properly reported in a timely manner.  
• Investigator and Institution will permit trial related monitoring, audits, EC 
review, and regulatory inspection(s), providing direct access to source 
data and documents as legally appropriate.  Monitoring will be performed 
by study sponsor and/or local study monitor.  Monitoring will review 
subject source documentation and Case Report Forms for accuracy, 
completeness, and compliance with Good Clinical Practice procedures.  
Monitoring site visits will be performed at approximately quarterly 
intervals.  Additional site visits may be scheduled at the discretion of the 
Sponsor upon review of the monitoring reports.  In addition to site visits, 
a screening log will be submitted to Sponsor or designee by the sites as 
requested (by fax or e-mail).  This screening log will be reviewed with 
the site for plan vs. actual recruitment purposes. 
 
13.4  Investigator Records and Reports:  Records to be maintained by the 
investigator in a designated study file include: 
• Investigational plan and all amendments 
• Signed Investigator Agreement 
• EC approval letter, including a copy of the approved consent forms, 
progress reports, Adverse Event Report 
• EC roster or Assurance number, if applicable 
• All correspondences relating to the conduct of this study between the site 
and sponsor, ECs, and study monitor 
• Curriculum Vitae and professional license for all study personnel, if 
applicable 
• Site personnel signature and documentation regarding the Investigator’s 
delegation of responsibility  
• Clinical Site Visit log 
• Protocol/device related training records for all applicable study personnel 
• Investigational device inventory information including the date, quantity 
and serial number of all devices and received identification of all subjects 
who received treatment, and final disposition of the devices. 
• Screening log  
• Financial Disclosure documentation for the Investigator and Co-
Investigators, if applicable 
• Reports (see Table 1) 
 
The following records must be maintained for each subject enrolled: 

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• Signed and dated informed consent forms 
• Completed CRFs,  queries and source document worksheets (if applicable)   
• Complete medical records including procedure reports, lab reports (if 
applicable), etc. 
• Records pertaining to a subject’s death during the investigation 
 
Investigators are required to prepare and submit to the sponsor or its designees complete 
accurate and timely reports on this investigation as required by regulations.  The types of 
reports to be submitted are summarized in Table 1. 
 
 
 
Table 1: Investigator Reports 
Reports 
Submit To 
Timeframe 
Unanticipated 
Adverse 
Device Event 
 
Sponsor and 
Reviewing EC 
 
As soon as 
possible but no 
later than 10 
working days 
Withdrawal of EC 
Approval 
Sponsor  
Within 5 working 
days 
Progress  
Sponsor, Monitor 
and Reviewing EC 
Annually, at a 
minimum 
 
Final  
 
Sponsor and 
Reviewing EC 
 
Within 3 months 
following the 
completion or 
termination of the 
Investigator’s part 
 
Subject study records, correspondence files, all supporting study documentation, and 
reports must remain on file at the investigational site for a minimum of ten years after the 
conclusion of this study or when it is no longer needed to support a marketing 
application, whichever is later.  All investigators must contact Tactile Systems 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 Systems 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.  
 
13.5 Changes Necessary After Study Initiation:  Should changes in the study 
plan or protocol become necessary in the course of the clinical trial, those 
specific changes will be discussed and agreed upon by the Sponsor, its 
acting representative if appropriate, Investigator, and appropriate EC 

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approval obtained before the changes are implemented.  All changes must 
be documented. 
 
 
14.0 References 
1. Szuba A, Rockson SG. Lymphedema; Classification, diagnosis and therapy. Vasc Med 1998; 3: 
145-156. 
2. Moffatt CJ, Franks PJ, Doherty DC, Williams AF, Badger C, Jeffs E, Bosanquet N, Mortimer PS. 
Lymphedema: an underestimated health problem. Q J Med 2003; 96: 731-738. 
3. Tiwari A, Cheng KS, Button M, Myint F, Hamilton G. Differential diagnosis, investigation, and 
current treatment of lower limb lymphedema. Arch Surg 2003; 138 (2): 152-161. 
4. Gomide LB, Matheus JPC, Candido dos Reis FJ. Morbidity after breast cancer treatment and 
physiotherapeutic performance. [Review Article]. Int J Clin Pract 2007; 61 (6); 972-982.  
5. Fleissig A, Fallowfield LJ, Langridge CI, Johnson L, Newcombe RG, Dixon JM, Kissin M, 
Mansel RE. Post-operative arm morbidity and quality of life. Results of the ALMANAC 
randomized trial comparing sentinel node biopsy with standard axillary treatment in the 
management of patients with early breast cancer. Breast Cancer Res and Treatment 2006; 95: 279-
293. 
6. Velanovich V, Szymanski W. Quality of life of breast cancer patients with lymphedema. Am J 
Surg 1999; 177: 184-188. 
7. Morgan, Franks, & Moffatt, (2005).Health related quality of life with lymphedema: a review of 
the literature. International Wound Journal, 2 (1), 47-62. 
8. Williams A.F., Moffatt C.J., Franks P.J. (2004) A phenomenological study of the lived 
experiences of people with lymphedema.  International Journal of Palliative Nursing, 10, 279-
286. 
9. Ridner, S.H., MKcMahon, E., Dietrich, M.S., Hoy S. (2008) Home-Based lymphedema treatment 
in patients with cancer-related lymphedema or non cancer-related lymphedema. Oncology Nursing 
Forum, 35, 671-680.   
10. Brennan MJ, Miller LT. Overview of treatment options and review of the current role and use of 
compression garments, intermittent pumps, and exercise in the management of lymphedema. 
Cancer 1998; 83 (12 Suppl American): 2821-2827. 
11. Kligman L, Wong RK, Johnston M, Laetsch NS. The treatment of lymphedema related to breast 
cancer: a systematic review and evidence summary. Support Care Cancer. 2004 Jun; 12(6):421-
31. 
12. Harris SR, Hugi MR, Olivotto IA, Levine M. Steering Committee for Clinical Practice Guidelines 
for the Care and Treatment of Breast Cancer Clinical practice guidelines for the care and treatment 
of breast cancer: 11. Lymphedema. CMAJ. 2001; 164(2):191-199. 
13. Badger C, Preston N, Seers K, Mortimer P. Physical therapies for reducing and controlling 
lymphedema of the limbs. The Cochrane Database of Systematic Reviews 2004, Issue 3. Art NO: 
CD003141.pub2. DOI: 10.1002/14651858.CD003141.pub2. 
14. Cohen SR, Payne DK, Tunkel RS. Lymphedema: Strategies for Management. Cancer 2001; 92 (4) 
(Suppl): 980-987. 
15. Cheville A, McGarvey CL, Petrek JA, Russo SA, Taylor ME, Thiadens SR. Lymphedema 
Management. Seminars in Radiation Oncology. 2003:13 (3) 290-301 
16. Comerota A, Aziz. The Case For Intermittent Pneumatic Compression. Journal of Lymphoedema 
2009; 4(2):57-64.  
17. Mayrovitz HN, Sims N, Macdonald J. Assessment of limb volume by manual and automated 
methods in patients with limb edema or lymphoedema. Adv Skin Wound Care 2000;13(6):272-
276. 
18. Mellor RH, Bush NL, Stanton AWB, Bamber JC, Levick JR, Mortimer PS. Dual-frequency 
ultrasound examination of skin and subcutis thickness in breast cancer-related lymphoedema. The 
Breast Journal 2004;10(6):496-503. FH 

Form – 038-7; 12/2009 
Tactile Systems Technology 
 
Page 29 of 29 
 
 
 
19. Nuutinen J, Ikaheimo R, Lahtinen T. Validation of a new dielectric device to assess changes on 
tissue water in skin and subcutaneous fat. Physiol Meas. 2004, 25: 447-454. 
20. Laaksonen DE, Nuutinen J, Lahtinen T, Rissanen A, Niskanen LK. Changes in abdominal 
subcutaneous fat water content with rapid weight loss and long-term weight maintenance in 
abdominally obese men and women. Int J Obes Relat Metab Disord. 2003, 27: 677-683. 
21. Mayrovitz HN. Assessing local tissue edema in postmastectomy lymphoedema. Lymphology. 
2007. 40:87-94. 
22. Mayrovitz HN, Davey S, Shapiro E. Local tissue water assessed by tissue dielectric constant: 
anatomical site and depth dependence in women prior to breast cancer treatment related surgery. 
Clin Physiol Funct Imaging. 2008. 28: 337-342. 
23. Partsch H, Mosti G. Comparison of three portable instruments to measure compression pressure. 
International Angiology. 2010. 29:426-430. 
15.0 
Appendices