Randomized Trial Comparing a Dual Action Pneumatic Compression System Against Multi-Layer Bandaging Systems: A Non-Inferiority Study
Phase: NA
Conditions: Venous Leg Ulcer
Sponsor: Tactile Medical

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Randomized Trial Comparing a Dual Action Pneumatic 
Compression System against Multi-Layer Bandaging Systems: A 
non-inferiority study 
 
Protocol# 6010 
 
27 September 2016 
 
Protocol Version 2.0 

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Investigator Signature 
 
 
 
Protocol Title: Randomized Trial Comparing a Dual Action Pneumatic Compression System 
against Multi-Layer Bandaging Systems: A non-inferiority study 
 
 
Protocol Number: 6010 
Version: 2.0; 27 September 2016 
 
 
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 Harmonization 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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SYNOPSIS 
 
Title of Study 
Randomized Trial Comparing A Dual Action Pneumatic Compression System 
against Multi-Layer Bandaging Systems: A non-inferiority study 
Protocol Date 
27 September 2016 
Protocol Version 
V 2.0 
Name of Sponsor 
Tactile Medical™ 
Investigational Product 
ACTitouch Adaptive Compression System 
Primary Endpoint 
Percentage of ulcer area reduction at 16 weeks, comparable 
Secondary Endpoint 
HRQOL; outpatient cost per subject 
Objectives: 
Demonstrate the following when comparing ACTitouch Adaptive Compression to multi-layer bandaging: 
• 
Comparable rate of healing 
• 
Greater improvement in QOL 
• 
Lower overall cost of care; lower resource utilization (in clinic time; clinic charges; patient treatment 
burden) 
METHODOLOGY 
Study Design 
Open label, non-inferiority, two arm, prospective, stratified, multi-center, 
randomized controlled trial (RCT) 
Treatments 
Daily ACTitouch usage; at least 12 hours sustained mode; two hours of Intermittent 
Pneumatic Compression (IPC) mode 
Multi-Layer Bandage (MLB): 24 hours except during clinic visits 
Treatment Duration 
Run-in – 2 Weeks 
Study treatment duration – 16 Weeks 
Follow Up – 3 months (Subjects in the ACTitouch arm who heal during the 
treatment period.) 
SUBJECT POPULATION 
Number Planned 
204 randomized subjects; 102 in each study arm 
Major Inclusion/ 
Exclusion Criteria 
Inclusion: 
• 
Subject must be ≥ 18 years of age or legal age at the time of enrollment. 
• 
Chronic venous insufficiency confirmed by ultrasound within previous 12 
months or prior to randomization. 
• 
Must have at least one of the following within the past 6 months: 
o 
Dorsalis Pedis (DP) systolic pressure ≥ 80mmHg for diabetic 
patients or ≥ 60mmHg for non-diabetic patients on study limb 
o 
Posterior Tibial (PT) systolic pressure ≥ 80mmHg for diabetic 
patients or ≥ 60mmHg for non-diabetic patients on study limb 
o 
Transcutaneous partial pressure oxygen (TcP02) > 30mmHg 
o 
Great toe systolic pressure > 40mmHg 
• 
Active ulceration (CEAP classification of C6). 
• 
Ulcer duration: Non healing VLU ≥ 1 month but not greater than 24 
months. 
• 
Ulcer size ≥ 2cm2 ≤ 50cm2. 
• 
Three or fewer separate full thickness ulcers on the study limb. 
o 
Sum  of  the  ulcer  areas  on  the  study  limb  must  be  ≤  50cm2  to 
participate in the study. 
• 
Must  be  able  and  willing  to  provide  informed  consent  prior  to  study 

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participation. 
Exclusion: 
• 
Target ulcer or any other ulcer on the study limb involves exposure of 
tendon, muscle, or bone. 
• 
Treatment of the target ulcer with living cellular therapy within 30 days of 
the time of projected randomization. 
• 
Endovenous ablation or other venous surgery within two weeks of 
enrollment. 
o 
Venous ultrasound must be completed after procedure to determine 
whether there is still venous insufficiency at the time of enrollment. 
• 
Acute deep vein thrombosis (DVT) or pulmonary embolism (PE) 
within the last 3 months. 
• 
Acute thrombophlebitis within the last 6 weeks. 
• 
History of pulmonary edema or decompensated congestive heart 
failure within 6 weeks of screening. 
• 
Currently has an active infection of the skin on target limb such as 
cellulitis requiring antibiotics. 
• 
History of target limb cancer within the last 2 years with the exception of 
treated non-melanoma skin cancer unless ulcer biopsy performed at 
screening is negative for neoplasia. 
• 
Active cancer receiving chemotherapy and/or radiation therapy. 
• 
Poorly controlled diabetes with an HbA1c value of > 12% within 
the past 3 months. 
• 
Changes to medications that affect edema  within the last 30 days. 
• 
Use of systemic corticosteroids requiring daily administration at 
doses greater than 5 mg of Prednisone per day or equivalent for 
greater than 2 weeks. 
• 
Currently pregnant or trying to become pregnant. 
• 
Inability or unwillingness to participate in all aspects of study 
protocol. 
Exclusions after a 2 week run-in: 
• 
If ulcer area has decreased by greater than 30% compared to 
baseline area, the subject will be removed from the study. 
• 
Ulcers measuring less than 1.5cm² after the run in. 
• 
Ulcers increasing in size greater than 50% after run. 
• 
Any ulcer appearing to have evidence of infection. 
• 
If the sum of the ulcer areas on the study limb is > 50cm2 the subject is not 
eligible to participate in the study. 
ASSESSMENTS 

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Efficacy [If applicable] 
Group 1: Multi-Layer Bandage 
• 
Will be seen in clinic once per week for: 
o 
Wound assessment 
o 
wound dressing changes, debridement, if necessary, as determined by 
the treating study investigator 
o 
wound tracing; photo 
o 
limb volume measurements 
• 
Subjects will be instructed to wear the MLB 24 hours daily, except upon 
removal and re-application during weekly clinic visits with debridement as 
determined necessary by PI 
Group 2: ACTitouch Adaptive Compression System 
• 
Will be seen in the clinic at weeks 1, 2, 4, 6, 9, 12, 16 during the treatment 
period. Subjects who experience complete healing of the study VLU will 
return to the investigational site 1, 2 and 3 months post heal. 
o 
wound assessment, as applicable 
o 
wound dressing changes, debridement, if necessary, as determined by 
the treating study investigator 
o 
wound tracing; photo, as applicable 
o 
limb volume measurements 
• 
Subject will be instructed to wear the AT in sustained mode for a minimum 
of 12 hours per day plus 2 hours IPC mode. 
Safety 
Adverse event monitoring 
Subject interview 
Physical examination 

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1.1 
Contact Information 
TABLE OF CONTENTS 
1.2 
Sponsor Contact Information 
1.3 
Study Principal Investigator Information 
2.0 
Abbreviations 
3.1 
Introduction 
3.2 
Background and Rationale 
3.3 
Device Descriptions 
4.0 
Study Objectives 
5.1 
Study Design 
5.2 
Study Endpoints 
5.2.1 Primary Endpoint 
5.2.2 Secondary Endpoint 
5.3 
Subject Selection 
5.3.1 Inclusion Criteria 
5.3.2 Exclusion Criteria 
5.3.3 Additional exclusions after 2 weeks run-in 
5.3.4 Subject Withdrawal or Early Termination 
5.4 
Dosage 
5.5 
Study Timetable 
6.1 
Study Visit Summaries 
6.2 
Screening Visit 
6.3 
Run in Visits 
6.4 
Randomization Visit 
6.5 
Treatment Visits (Weeks 1-16 or healed) 
6.6 
Compliance Call 
6.7 
Follow Up Visits (Months 1,2 & 3) 
6.8 
Unscheduled Visit 
6.9 
Recurrence 
7.1 
Study Procedures 
7.2 
Pre-screening 
7.3 
Informed Consent 
7.4 
Laboratory Testing 
7.5 
Randomization 
7.6 
Leg Volume Measurements 
7.7 
Wound Assessment 
7.8 
Wound Debridement 
7.9 
Wound Dressing 
7.10 Wound Photograph and Tracing 
7.11 Tissue/Skin Assessment 
7.12 Compression Application 

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7.13 Application Timing 
7.14 Compliance Assessment 
7.15 Costs 
7.16 Study Surveys/Questionnaires 
7.17 Study Schedule of Activities Table 
8.0 
Study Device Accountability 
9.1 
Risk Analysis and Adverse Events 
9.2 
Risk Analysis 
9.3 
Adverse Event Definition 
9.4 
Adverse Event Reporting 
10.0 
Deviation from Investigational Protocol 
11.1 
Quality Assurance Procedures 
11.2 Site Qualifications 
11.3 Data Collection Procedures 
11.4 Clinical Site Monitoring 
11.5 Data Safety Monitoring Board 
11.6 Investigator Reports and Records 
11.7 Changes to Study Plan 
12.1 
Statistical Methods and Determination of Sample Size 
12.2 Statistical Consideration 
12.3 Objectives 
12.4 Endpoints 
12.4.1 Primary Endpoints 
12.4.2 econd Endpoints 
12.4.3 xploratory Endpoints 
12.4.4 afety Endpoints 
12.5 Sample Size Assumptions 
12.6 Analysis Populations 
12.7 Analysis Plan 
12.7.1 eneral Analysis Issues 
12.7.2 Primary Endpoint Analysis 
12.7.3 econdary Endpoint Analysis 
12.7.4 xploratory Endpoint Analysis 
12.7.5 afety Endpoint Analysis 
12.8 Interim Analysis 
13.0 
Compensation 
14.0 
Publication Plan 
15.0 
References 
16.0 
Appendices 

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Sunday Hoy, Esq., Director of Clinical Resources and Research 
1331 Tyler Street NE, Suite 200 
Minneapolis, MN 55413 
612-355-5121 
shoy@tactilemedical.com 
William Marston, MD 
Division of Vascular Surgery, CB #7212 
UNC Department of Surgery 
Chapel Hill, NC 27599-7212 
919-966-8596 
william_marston@med.unc.edu 
1.0  Contact Information: 
1.1 
Sponsor Contact Information 
Tactile Medical™ 
 
 
1.2 
Study Principal Investigator Information 
 
 
 
2.0 Abbreviations: 
ABI 
Ankle Brachial Index 
AE 
Adverse Event 
CEAP 
Clinical-Etiology-Anatomy-Pathophysiology 
CFR 
Code of Federal Regulations 
CRFs 
Case Report Forms 
CVD 
Chronic Vascular Disease 
CVI 
Chronic Venous Insufficiency 
DSMB 
Data Safety Monitoring Board 
DVT 
Deep Vein Thrombosis 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practices 
HRQOL Health-Related Quality of Life 
ICH 
International Conference on Harmonization 
IPC 
Intermittent Pneumatic Compression 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
MLB 
Multi-Layer Bandaging 
MITT 
Modified Intent-to-Treat 
QOL 
Quality of Life 
RCT 
Randomized Controlled Trial 
SAE 
Serious Adverse Event 
SD 
Standard Deviation 
U/S 
Ultrasound 
VLU 
Venous Leg Ulcer 
VSU 
Venous Stasis Ulcer 
IWRS 
Web-Based Randomization Process 
*The term ulcer and wound are used interchangeably throughout this document. 

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3.0 Introduction: 
3.1 1 Background and Rationale: 
Up to 1% of the adult population in developed countries will suffer from leg 
ulceration during their lifetime.1 The most severe form of CVI is when limb 
ulceration occurs due to chronic venous hypertension. It is estimated that the 
prevalence of venous leg ulceration (VLU) is between 1 and 1.5 million patients in 
the United States. 
 
It is important to address the underlying hemodynamic problem associated with 
chronic venous insufficiency rather than focusing solely on wound healing.2 
Treatment for chronic venous disease relies on provision of adequate external 
compression therapy to diminish venous hypertension, as these therapies diminish 
progressive dilation of incompetent veins, may help close the damaged valves, and 
diminish the accumulation of extravascular fluid.3 Compression is a key component 
of treatment guidelines for the management of VLU. 
 
The current standard of care in the treatment of VLUs is wound management in 
conjunction with compression therapy to promote venous return and reduction in 
edema.4,5  Options for limb compression treatment include compressive garments, use 
of multi-layer bandage systems, and paste bandage systems.2,3,6 Despite the inclusion 
of high strength compression in numerous VLU treatment guidelines, it is estimated 
that as many as 50% of VLUs never receive this type of therapy. In part, the reason 
for poor utilization of compression therapy is that most patients find the therapy 
difficult to use, due to difficulties in applying compression garments and/or pain or 
discomfort associated with use of the garment itself. To date, compression bandaging 
remains the most commonly used therapy in the treatment of VLUs.3,7 
 
Therefore, effective compression treatment must be easy to use (don and doff) and 
must be comfortable as key factors likely to increase patient compliance.8,9 
Intermittent pneumatic compression (IPC) treatment is one alternative.8   IPC was 
introduced as an adjunct treatment for VLU in 1981 which led to growing support for 
IPC as a treatment modality for patients with VLUs.10 IPC is a mechanical method of 
delivering compression that uses an air pump to periodically inflate/deflate bladders 
incorporated into sleeves which envelop the limb.11,12 
 
Published studies have demonstrated significant hemodynamic and hematologic 
improvement with IPC, as well as increases in ulcer healing rates when IPCs are used 
with standard compression therapy.8,13,14 
 
Harding et al. compared the efficacy and tolerability of the ACTitouch device to that 
of a conventional multi-layer bandaging system when treating VLUs.15 In this trial, 
the ulcer healing rate between the ACTitouch group and the conventional four-layer 
system group was similar. However, the ACTitouch performed significantly better in 
several key areas related to patient quality of life including, exudate management, 
skin protection, removal ease, bathing, and sleep comfort. 

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Medical, Minneapolis, MN, USA) is a dual treatment pneumatic compression 
device offering two operational modes: sustained compression mode and 
intermittent compression mode. The device is applied to the lower leg (calf, ankle, 
and foot) and consists of an under-sock worn against the skin, a compression sleeve 
containing four inflatable chambers and a controller unit. The controller provides the 
airflow to inflate the chambers and monitors and adjusts the chamber pressure to 
maintain the intended treatment pressures. 
In intermittent mode, the device provides cyclic inflation/deflation sequences to 
pre-set sequential gradient pressures. The pressure sequence starts at the foot and 
progresses up towards the knee until all chambers reach their intended pressure 
levels. Then all four chambers will deflate to the low pressure level. This cycle of 
inflation/deflation continues until the device is either unplugged or is turned off. 
The controller must be plugged into an AC outlet to operate in the intermittent 
mode. 
During “sustained compression mode” the chambers of the device are inflated to the 
target pressures and sustained compression is applied to the treatment area. The 
device monitors the pressure every 30 minutes and automatically adjusts to maintain 
the target pressure. In sustained mode, the electronic controller operates using its own 
rechargeable battery. This facilitates ambulatory use of the device. 
The ACTitouch has been cleared to market in the U.S. (K131193) for the following 
indications: enhancing venous return, reducing venous leg ulcer healing time, 
treatment and promotion of healing stasis dermatitis and venous stasis ulcers, 
treatment of chronic venous insufficiency, and reducing edema due to venous stasis 
(Appendix A). 
This study provides evidence to suggest that the ACTitouch system is as effective as 
four layer bandaging systems in healing venous leg ulcers, but is better accepted and 
achieves higher patient-reported quality-of-life scores in these challenging patients. 
 
3.2 2 Device Descriptions: 
ACTitouch – ACT - Adaptive Compression Therapy Delivery System (Tactile 
 
 
 
PROFORE (Smith & Nephew, Hull, United Kingdom) is a multi-layer compression 
bandaging system developed to apply sustained graduated compression for the 
management of venous leg ulcers and associated conditions. Four-layer compression 
bandaging is often the first choice in treatment for venous leg ulcers.16 
The four-layer system consists of a single layer of orthopedic wool applied in a spiral 
from toe to knee, followed by a crepe bandage applied in a spiral, an elastic long 
stretch bandage applied by the figure of eight method and finally a cohesive bandage 
applied in a spiral (Appendix B). PROFORE provides approximately 40mmHg 
pressure at the ankle decreasing to 17mmHg at the knee.17 
 
Coban™ 2 Compression System (3M Health Care, St. Paul, MN, USA)  is 
composed of two latex free layers that combine to create an inelastic sleeve 
conforming to the limb contour to provide a consistent proper pressure profile to 

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reduce edema. The Coban 2 compression system is indicated for patients with venous 
leg ulcers, lymphedema, and other conditions where compression therapy is 
appropriate. 
 
The two-layer system consists of an inner “comfort” layer made of a polyurethane 
foam and cohesive bandage. The outer layer is a cohesive bandage, designed to 
provide graduated compression. Inner and outer layer cohere to each other to reduce 
slippage. Application of the compression system should be done according to the 
manufactures instructions as outlined in the Instructions for Use (Appendix C). 
 
 
4.0  Study Objectives: 
The primary study objectives: 
Test non-inferiority of chronic VLU area reduction at 16 weeks with ACTitouch therapy 
compared to a standard regimen of multi-layer bandaging. 
The secondary study objectives: 
Assessment of the effect of the ACTitouch compared to a standard regimen of multi-layer 
bandaging at 16 weeks on health related quality of life (HRQOL) and outpatient costs. 
 
5.0  Study Design: 
The study is a two arm, open label, non-inferiority, prospective, stratified, multi-center, 
RCT. As part of screening there will be a two week run in period measuring the VLU 
initial treatment response. The study is designed to evaluate percentage of ulcer area 
reduction in venous leg ulcer patients comparing ACTitouch to multi-layer bandaging 
during the 16 week treatment phase. 

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Run In Period – Two Week Treatment Response 
 
 
 
 
 
Determine subject 
eligibilty 
Not Eligible 
Eligible 
Two Week Run In 
Phase 
Not Eligible: 
>30% decrease in 
ulcer area or >50% 
increase 
Eligible 
≤30% decrease in 
ulcer area 
Begin 
Treatment 

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Treatment Period (16 weeks) 
 
 
Eligible 
After Run-in 
Randomization 
Multi-Layer 
Bandaging 
ACTitouch 
Follow-up 
Weekly visits 16 weeks 
Follow-up 
Visits at weeks 1,2,4, 6, 9, 
12 & 16 
Non-healed 
Healed 
Healed 
Non-healed 

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Follow Up Period: 
 
 
 
 
 
 
 
5.1 1 Study Endpoints: 
5.1.1 Primary Endpoints: 
The primary clinical endpoint: 
• Percentage of ulcer area reduction at 16 weeks 
 
5.1.2 Secondary Endpoints: 
The secondary clinical endpoints will include the following: 
• Improvement in HRQOL 
• Outpatient costs per subject 
• Complications 
 
5.2 2 Subject Selection: 
This is a community based trial. The study population will be drawn from patients 
who have chronic non-healed VLUs of at least one (1) month prior to the start of 
the study. Only patients who meet the criteria listed below will be considered for 
participation. A minimum of 204 subjects will be enrolled at approximately 30 
centers in the United States. 
 
5.2.1 Inclusion Criteria: 
• Subject must be ≥ 18 years of age or legal age at the time of 
enrollment. 
VLU Free 
ACTitouch 
Subjects Healed 
Follow up Visits 
Months 1, 2 & 3 
Ulcer Recurrence 

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• Chronic venous insufficiency confirmed by ultrasound within 
previous 12 months or prior to randomization. 
o If a study subject has bilateral CVI, the limb that possess 
the largest ulcer meeting study criteria will be used as the 
study treatment limb for evaluation and documentation 
throughout the study. Non-study limbs will receive 
standard of care treatment as determined by the treating 
clinician. 
• Must have at least one of the following within the past six 
o months: 
o Dorsalis Pedis (DP) systolic pressure ≥ 80mmHg for 
diabetic patients or ≥ 60mmHg for non-diabetic 
patients on study limb 
o Posterior Tibial (PT) systolic pressure ≥ 80mmHg 
for diabetic patients or ≥ 60mmHg for non-diabetic 
patients on study limb 
o Transcutaneous partial pressure oxygen (TcP02) > 
30mmHg 
o Great toe systolic pressure > 40mmHg 
• Active ulceration (CEAP classification of C6) 
o VLU is defined by open skin lesion of the leg or foot that 
occurs in an area affected by venous hypertension. 
• Ulcer duration: Non healing VLU ≥ 1 month but not greater than 
24 months. 
• Ulcer size ≥ 2cm2  ≤ 50cm2 
o If there are multiple ulcers on the study limb, the largest 
ulcer will be used as the study treatment ulcer for 
evaluation and documentation throughout the study. If two 
ulcers are separated by no more than one centimeter of 
normal skin, their areas will be added together for study 
purposes. 
• Three or fewer separate full thickness ulcers on the study limb. 
o Sum of the ulcer areas on the study limb must be ≤ 50cm2 
to participate in the study. 
• Leg circumferences within the following range: 
Ankle – 12 to 44cm 
Calf – 22 to 60cm 
Below knee – 22 to 68cm 
• Must be able and willing to provide informed consent prior to 
study participation. 
 
5.2.2 Exclusion Criteria: Subjects will be ineligible for this study if they meet 
any of the criteria described below: 
• Target ulcer or any other ulcer on the study limb involves exposure 
of tendon, muscle, or bone. 
• Target ulcer is of non-venous etiology (sickle cell anemia, 

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necrobiosis lipoidica diabeticorum, pyoderma, malignancy). 
• Treatment of the target ulcer with living cellular therapy within 30 
days of the time of projected randomization. 
• Endovenous ablation or other venous surgery within two weeks of 
enrollment 
o Venous ultrasound must be completed after procedure to 
determine whether there is still venous insufficiency at the 
time of enrollment. 
• History of skin sensitivity to any of the components of AT, multi- 
layer bandages or compression garments. 
• History of an acute deep vein thrombosis (DVT) or 
pulmonary embolism (PE) within the last three (3) months. 
• Acute thrombophlebitis within the last six (6) weeks. 
• History of pulmonary edema or decompensated congestive 
heart failure within six (6) weeks of screening. 
• Currently has an active infection of the skin on the target 
limb such as cellulitis requiring antibiotics. 
• History of target limb cancer within the last two years with 
the exception of treated non-melanoma skin cancer unless 
ulcer biopsy performed at screening is negative for 
neoplasia. 
• Active cancer receiving chemotherapy and/or radiation 
therapy. 
• Poorly controlled diabetes with an HbA1c value of > 12% 
within the past three (3) months. 
• Changes to medications that affect edema within the last 30 
days prior to enrollment (e.g. diuretics, calcium channel 
blockers of the dihyropyridine class, pioglitazone, cox-1 
inhibitors, pregabalin, and gabapentin, diltiazem or 
fluctuating doses of systemic steroids). 
• Use of systemic corticosteroids requiring daily 
administration at doses greater than 5mg of Prednisone per 
day or equivalent for greater than two weeks. 
o 
Low dose steroid administration (Prednisone up to 
5mg per day or equivalent) is allowable for an 
unlimited period of time. Topical steroid 
administration to peri-ulcer area or other skin is 
allowable but cannot be applied to the ulcer itself. 
• Currently pregnant or trying to become pregnant. 
• Inability or unwillingness to participate in all aspects of 
study protocol. 
• Exhibit any condition which, according to the Investigator, 
justifies the subject’s exclusion from the study, such as a 
medical condition where an increase in venous or lymphatic 
return is undesirable. 
• Currently participating in another clinical trial. 

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5.2.3 Additional Exclusions after two week run-in: Subjects will exit the 
study if they meet any of the following criteria: 
• Subject’s target ulcer has decreased in size by greater than 
30% compared to the baseline area. 
• Subject’s target ulcer has increased in size by greater than 
50% compared to the baseline area. 
• Subject’s target ulcer measures less than 1.5cm² at the 
Randomization Visit. 
• Subject appears to have evidence of infection in any ulcer. 
• The sum of the ulcer areas on the subject’s study limb is > 50cm2. 
 
5.2.4 Subject Withdrawal or Early Termination: 
Subjects will exit the study if they meet any of the following criteria: 
• Subject death 
• Subject voluntarily withdraws or investigator’s decision 
• Subject experiences an adverse event that in the investigator’s 
clinical judgment necessitates study discontinuation 
• Ulcer recurrence during the 3 month follow up period 
• Subject acquires any of the exclusion criteria, except 
o If subject acquires an infection, they may be treated for the 
infection and continue in the trial in the investigator’s 
discretion. The investigator can instruct the subject to cease 
sustained or IPC treatment for up to two (2) consecutive 
weeks but no more than four (4) weeks total. If the subject 
is required to abstain from study treatment for greater than 
the amount described above, the subject will be removed 
from the study. 
 
5.3 Dosage: 
Run-in 
All subjects will participate in a two week run-in phase. The treatment will include 
multi-layer compression bandaging which must be worn 24 hours a day except 
during clinic visits. The run-in phase is intended to assess the subject’s initial 
response to standard of care treatment using multi-layer bandaging before receiving 
treatment with the investigational device. 
 
VLU Treatment Period 
All subjects enrolled will be randomized into either treatment using the ACTitouch 
system or multi-layer bandaging which consists of either PROFORE or Coban 2. 
 
Investigational Group: Subjects assigned to the ACTitouch system must wear the 
device in sustained mode during all wakeful hours (at least 12 hours each day) and 
IPC mode for a minimum of 2 hours each day.  Subjects will be instructed to 
remove the ACTitouch for bathing and when driving or operating machinery, and 
reapply immediately after these activities. 

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At each visit the subject’s compliance will be evaluated via the compliance tracker 
on the ACTitouch device. 
 
Subjects randomized to the ACTitouch arm of the study will also be contacted 
weekly between study visits by study personnel to support device compliance and 
answer questions as outlined in Section 7.16. 
 
Control Group: Subjects assigned to multi-layer bandaging must wear the 
bandaging 24 hours a day except during clinic visits when the limb is being 
assessed by the study staff. 
 
Follow Up Period 
All subjects assigned to the ACTitouch arm who heal during the 16 week treatment 
period will be followed for 3 months post VLU healing. These subjects will be 
instructed to continue to use the ACTitouch device as outlined in the 16 week 
treatment period [sustained mode during all wakeful hours (12 hours each day) and 
IPC mode for 2 hours daily].  Subjects will be instructed to remove the ACTitouch 
for bathing and when driving or operating machinery, and reapplied immediately 
after these activities. 
 
5.4 Study Timetable: 
 
Task 
Months 
1-6 
7-12 
13-18 
19-24 
24-30 
Identify Sites 
X 
IRB/Regulatory 
X 
Enrollment 
X 
X 
Treatment 
X 
X 
X 
X 
Data Entry 
X 
X 
X 
X 
Data Analysis 
X 
 
 
6.0 Study Visit Summaries: 
6.1 
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 the Study Schedule of Activities section 7.17 for visit 
activities. After the informed consent process is complete, the subject will begin 
the run-in phase of the study. 
 
Subjects may be enrolled if they are on a current Pentoxifylline regimen, 
but Investigators should not start patients on Pentoxifylline during the trial 
if the patient is not taking the drug at enrollment. 

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6.2 
Run-in Visit: 
There could be up to 4 visits during the run in phase, 3 visits if the Screening and 
Baseline visits occur on the same day. The visit schedule is as follows 
Screening/Baseline; Run-in Week 1 and Randomization (±2 days). The subjects 
will follow the treatment regimen outlined in section 7.17. At each visit the study 
staff will access the ulcer. If the subject meets any of the exclusion criteria listed in 
section 5.2.3 at the Randomization Visit the subject will be excluded from the 
study. 
 
6.3 
Randomization Visit: 
At the randomization visit the subject will undergo procedures as outlined in the 
Study Schedule of Activities table in section 7.17. 
 
The subject will leave the randomization visit with: 
• Schedule for the next study visit (if possible, follow-up visits should be 
scheduled at the same time of day) 
• Instructions on use and application of the assigned study apparatus, as applicable 
• Diary and instructions to record daily activity 
• Contact information and instructions to call if any problems arise 
 
6.4 
Treatment Visits (Weeks 1-16 or healed): 
Investigational Group: Subjects will be seen in clinic at weeks 1, 2, 4, 6, 9, 12, 16 
(±2 days) for 16 weeks or until the VLU is completely healed, as defined by 
complete closure with no open area or exudate. At the visits the subject will 
undergo the procedures as outlined in the Study Schedule of Activities table in 
section 7.17. 
 
Control Group: Subjects will complete weekly visits for 16 weeks or until the VLU 
is completely healed, as defined by above. At the weekly visits the subject will 
undergo procedures as outlined in the Study Schedule of Activities table in section 
7.17. 
 
The study staff will review the subject diary with the subject during each visit to 
ensure that all entries are complete and understood by the study staff. Any 
corrections must be made by the subject, and initialed and dated by them. 
 
6.5 
Support Contact: 
Subjects randomized to the ACTitouch arm of the study will be contacted by study 
personnel (via text or phone call). The first follow up contact will occur 3 days (±1 
day) after the Randomization Visit and the second follow up contact will occur 3 
days (±1 day) after the Treatment Week 1 Visit. 
 
For the remainder of the VLU treatment period, follow up contact will occur on 
weeks that the subject is not returning to the clinic for a study visit. The subject 
will be contacted during treatment weeks 3, 5, 7, 8, 10, 11, 13, 14, and 15 (±2 days 
from optimal date). If an ACTitouch subject is seen for an unscheduled study visit 

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Page 20 of 41 
 
within one of these windows, this will take the place of the support contact for that 
week. 
 
6.6 Follow Up Visits (Months 1, 2 &3): 
Subjects who are assigned to the ACTitouch device and heal during the 16 week 
treatment period will continue to be seen monthly for 3 months (±7 days) post 
healed visit.  At the visit the subject will undergo the procedures outline in the 
Study Schedule of Activities table in section 7.17. 
 
The study staff will review the subject diary with the subject during each visit to 
ensure that all entries are complete and understood by the study staff. Any 
corrections must be made by the subject, and initialed and dated by them. 
 
6.7 Unscheduled Study Visit: 
The subject may return to the investigational site for unscheduled visits during the 
study. At this unscheduled study visit the subject will complete all study procedures 
as outlined in the Study Schedule of Events Section 7.17. 
 
6.8 Recurrence Visit: 
If the subject’s VLU recurs during the 3 month follow up period the subject will be 
instructed to return to the investigational site to be assessed. At the visit the subject 
will undergo the procedures outlined in the Study Schedule of Activities table in 
section 7.17. 
 
7.0 Study Procedures: 
7.1 Pre-screening: 
Pre-screening of potential subjects will be conducted by study staff either by phone 
or in person. Potential subjects who are interested in participating in the study will 
meet with study staff in-person for the consent process. 
 
7.2 Informed Consent: 
Informed consent must be obtained from all subjects prior to participation in 
clinical studies as mandated by Federal Regulations and/or the qualifying 
Institutional Review Board/Ethics Committee (IRB/EC). A blank copy of the 
IRB/EC-approved informed consent form must be kept on-site and by Tactile 
Medical. The signed original for each subject must be kept in the subject’s medical 
records. 
 
A copy of the consent will be given to the subject to read and take home to consider 
if they prefer. All questions must be answered prior to signing the informed consent 
form. Clinical study procedures cannot be performed until subject signs the consent. 
A signed copy of the consent should be provided to the subject. 
 
7.3 Laboratory Testing: 
After providing informed consent, women of child bearing potential will be tested 
for pregnancy at the site specific clinical laboratory according to site standard 

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procedures. If the pregnancy test is positive, subjects will be excluded from the 
study. 
 
Subjects with diabetes must have a HbA1c value ≤ 12% within the past three 
(3) months.  If the subject does not have a documented HbA1c at the time of 
consent then one must be completed after providing informed consent but 
before randomization.  If the HbA1c is > 12% the subject will be excluded 
from the study. 
 
All potential subjects must have a dorsalis pedis (DP), posterior tibial (PT), 
TcP02, or great toe pressure as outlined in the criteria within the last six 
months to meet study eligibility, unless approval is obtained from the 
Sponsor Chief Medical Officer. If the aforementioned tests are > 6 months or 
the subject hasn’t undergone one of the required tests one will need to be 
completed to determine eligibility. 
 
7.4 Randomization: 
After completing the informed consent process, subjects who meet the entrance 
criteria will complete the Run-in Phase before being randomly assigned into either 
the multi-layer bandage or ACTitouch group. The scheme will be generated 
randomly, electronically by Clindex, and will be stratified based on ulcer size and 
duration at time of randomization. 
 
For the purpose of this study, multi-layer bandages include PROFORE and Coban 2 
only. The use of multi-layer bandaging other than the pre-specified bandages will 
be considered a deviation from the protocol and must be reported to the sponsor 
immediately. This deviation could result in termination of the study subject. 
 
7.5 Leg Volume Measurements: 
Circumferential measures of both legs will be taken at 4cm intervals starting at 
10cm up from the bottom of the subject’s heel, flexed at 90 degrees to the leg and 
continue to the knee at the popliteal fold (Appendix D). If possible, the same 
clinician will be asked to take the measurements for each patient visit. 
 
7.6 
Wound Assessment: 
At each study visit (if applicable) the ulcer will be assessed by qualified study 
personnel. The ulcer features that will be assessed will include ulcer drainage, type 
and amount, ulcer bed features, wound margin, and periwound areas; and other 
aspects including but not limited to odor, pain, and debridement. 
 
Ulcer closure/healing is defined by 100% epithelialization and no drainage. 
 
7.7 
Wound Debridement: 
Ulcer debridement will be undertaken as needed per the investigator’s clinical 
decision. The methods of debridement may include enzymatic, sharp, surgical, and 
mechanical debridement and/or pulse lavage. 

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7.8 
Wound Dressings: 
All subjects will undergo wound dressing changes, either in the clinic or at home. 
Wound dressing will be selected by the investigator. Generally, “dry ulcers” will 
require hydrocolloid dressings and “wet ulcers” will require foam or alginate. 
 
7.9 
Wound Photograph and Tracing: 
At each study visit, (if applicable) the study ulcer will be photographed and the 
wound will be traced using the Silhouette™ system (Appendix E). 
 
In addition, at the initial visits all ulcers on the study limb will be photographed 
and traced to ensure that the sum of the areas is not greater than 50cm2. Any ulcers 
that form on the study limb during the course of the study will also be 
photographed and traced for AE documentation. 
 
The initial visit, enrollment visit, and healed visit image and tracing will be 
evaluated by a single independent adjudicator to increase integrity and to provide a 
blinded analysis. Ulcer surface areas that fall on or near the minimum or maximum 
ulcer surface area allowed for study inclusion will be adjudicated in a timely 
manner. Study staff will have access to the adjudication results by a time no later 
than the next scheduled subject visit. 
 
7.10 Tissue/Skin Assessment: 
The subject’s legs will be examined for irritation, trauma and ulceration at each 
study visit. At any time during the study the investigator may determine that a 
tissue/skin change requires the subject to be withdrawn from the study. 
 
7.11 Compression Application: 
Application of ACTitouch System: 
The ACTitouch system will be applied by the trained study staff. First the 
ACTitouch under-sock will be applied. The sock will be in direct contact with the 
skin and wound dressings and the ACTitouch sleeve will wrap around the pre- 
covered leg. The ACTitouch will be applied while the subject is seated, with the 
feet lightly resting on the floor. 
 
Application of Multi-Layer Bandaging: 
The trained study staff will apply the multi-layer bandaging according to 
manufacturer’s instructions. The multi-layer bandaging will be in direct contact 
with the skin and the wound dressings. 
 
7.12 Application Timing: 
The time to apply compression by study personnel on the subject’s limb in clinic 
will be recorded throughout the study as specified (section 7.16). Both treatment 
application methods will be timed and recorded. The study personnel will lay out 
all required materials to be applied. Immediately after the timing starts either the 
first contact layer in the multi-layer bandaging group or the under-sock of the 

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Page 23 of 41 
 
ACTitouch group will be applied. The timer will be stopped once the final layer 
has been completely applied in the multi-layer bandaging group or the last piece of 
Velcro is properly secured for the ACTitouch group. 
Short Form-36 (SF-36): Functional status and quality of life will be assessed via 
the SF-36, a validated quality of life tool that has been widely utilized and has 
been found to be appropriate for use in evaluating health related quality of life 
impacts. (Appendix I) 
EuroQol 5D (EQ-5D) Health Questionnaire: Applicable to a wide range of health 
conditions and treatments, the EQ-5D provides a simple descriptive profile and a 
single index value for health status that can be used in the clinical and economic 
evaluation of health care as well as in population health surveys. (Appendix K) 
Work Productivity and Activity Impairment Questionnaire-Specific Health Problem 
(WPAI-SHP) is a brief instrument that measures work and activity impairment related 
to a specific health problem with a recall period of seven days. (Appendix L) 
Tolerance and Comfort Survey: Tolerance and comfort will be assessed as outlined 
in the study schedule of activities, section 7.16. If the subject terminates the study 
early the subject should be asked to complete the survey evaluating their assigned 
treatment. (Appendix M) 
 
 
7.13 Compliance Assessment: 
Subject compliance will be evaluated through the support call, subject diary, 
interview, and ACTitouch Compliance Tracker (for the subjects randomized to 
ACTitouch) at each study visit. 
 
7.14 Cost: A sub-study evaluating economics will also be included in this study.  The 
economic sub-protocol outlines the collection of essential health economic items 
concerning visits, procedures and lab tests, QOL and work productivity. (Appendix 
G). 
 
7.15 Study Surveys/Questionnaires: Subjects and study clinicians will complete 
survey/questionnaires to assess symptoms, quality of life, acceptance/tolerability, 
and ease of use of their assigned device. 
 
Charing Cross Venous Ulcer Questionnaire: Consists of 21 items for the 
assessment of patients’ perception of their health when venous ulceration is 
present, to be used in conjunction with the SF-36. (Appendix H) 
 
 
Venous Clinical Severity Score (VCSS): A disease severity measurement tool 
including clinical descriptors that have the ability to change over time which 
allows for improvements to be captured. (Appendix J) 
 
 

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Tr 
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Tr Tr 
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Medical History 
X 
Pregnancy Test (women of 
childbearing  potential) 
X 
Venous  Ultrasound 
X**    X**    X** 
Arterial Pressure Test 
(if > 6 months) 
X 
Ulcer Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X* 
Ulcer Photograph & Tracing 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X* 
Tissue/Skin  Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Limb Vol. Measurements 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weekly Phone Call 
(ACTitouch arm only) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Application  Timing 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
EQ-5D-3L 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Charing Cross 
X 
X 
SF-36 
X 
X 
VCSS 
X 
X 
Work Productivity Survey 
X 
X 
Tolerance/Comfort  Survey 
X 
Compliance 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Cost Data 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Complications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
* Active Ulcer 
** 12 months prior to screening or before randomization 
7.16 Study Schedule of Activities 
Run In / Treatment Periods: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Ulcer Assessment 
X* 
X* 
X* 
X 
Ulcer Photograph & Tracing          X* 
X* 
X* 
X 
Tissue/Skin Assessment 
X 
X 
X 
X 
Limb Vol. Measurements 
X 
X 
X 
X 
Application Timing 
X 
X 
X 
X 
EQ-5D-3L 
 
 
X 
X 
Charing Cross 
X 
X 
SF-36 
X 
X 
VCSS 
X 
X 
Tolerance/Comfort Survey 
X 
X 
Work Productivity Survey 
X 
X 
Compliance 
X 
X 
X 
X 
Cost Data 
X 
X 
X 
X 
Complications 
X 
X 
X 
X 
 
Follow Up Period: 
 
Key: 
*Active Ulcer 
Follow Up 
Month 1 
Follow Up 
Month 2 
Follow Up 
Month 3 
VLU 
recurrence 
visit 
 
8.0 Study Device Accountability: 
Site personnel must maintain device accountability log(s). Completion of these log(s) will 
ensure that all ACTitouch Control Units and Sleeves 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 Tactile Medical. Device location, Subject ID assigned, date, and final 
disposition (e.g., returned to Tactile Medical, garments discarded, garments retained by 
subject) of all ACTitouch Control Units and Sleeves will be documented. Tactile Medical 
must also maintain device accountability documenting all shipments and returns of Control 
Units by serial number, date, and person completing the log. Storage locations for the 
Control Units and Sleeves 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 the study, the subject must return the ACTitouch controller to the 
investigational site. The site personnel will disinfect the Control Unit by thoroughly 
cleaning it with a disinfectant before it can be reassigned to a subject or returned to the 
Tactile Medical. The subjects may keep the sleeve and under-socks. If sleeve and under- 
socks are returned to the site they CANNOT be reused on multiple subjects and should be 
appropriately discarded upon study return. 
 
9.0 Risk Analysis 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 IPC 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 

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Page 27 of 41 
 
shock if the device is immersed in water or if the housing is broken and subject 
attempts to service the unit. 
 
IPC devices are contraindicated for use in the presence of pulmonary edema, acute 
thrombophlebitis, congestive heart failure, acute deep vein thrombosis, episodes of 
pulmonary embolisms, acute infection, and inflammation or other conditions 
where increased venous or lymphatic return in undesirable. 
 
There are minimal side effects expected from either treatment subjects will 
receive in this study and the study uses only currently FDA cleared interventions. 
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 CVI or 
VLUs can be serious, long lasting, or may be permanent. The risks listed below 
are symptoms of CVI and/or VLUs and may be experienced by all subjects: 
• Pain or discomfort 
• Swelling of the lower legs/ankles 
• Aching or tiredness in the legs 
• Leathery looking skin 
• Flaking or itching of the skin 
• Stasis ulcers 
 
9.2 Adverse Event Definition: 
An adverse event (AEs) includes any complication whose clinical significance is 
greater than anticipated, or which occurs with a frequency greater than that 
which is usually seen for this type of device. A serious adverse event (SAE) is 
defined as an event that, 
• results in death 
• is life-threatening (places the subject at immediate risk of death from 
the experience as it occurred) 
• results in a persistent or significant disability/incapacity 
(substantial disruption of one’s ability to carry out normal life 
functions) 
• results in medical or surgical intervention 
• results in or prolongs an existing hospitalization (even if the 
hospitalization is a precautionary measure for observation) 
 
An unanticipated adverse device effect (UADE) is any serious adverse effect 
related to the device that meets the definition above or any other unanticipated 
serious problem associated with a device that relates to the rights, safety, or 
welfare of subjects. Investigators must report all SAE and/or UADE to Tactile 
Medical within 72 hours of first learning of the event. SAE and/or UADE will be 
reported in writing to the appropriate IRB in accordance with their policy. 
 
9.3 Adverse Event Reporting: 
Investigators will be responsible for reporting the following pre-defined adverse 
events regardless of severity, to Tactile Medical in a timely manner: 
• New or worsening ulceration 

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• Clinically worsened or new onset heart failure 
• Increase in leg swelling greater than 20% 
• Skin irritation/blistering 
• Infection of the study limb(s) 
• Other – an AE that according to the investigator’s opinion is significant 
and requires reporting to Tactile Medical but doesn’t necessarily meet the 
definition of the pre-defined AEs or an SAE 
 
10.0 
Deviation from Investigational Protocol: 
Any deviation from this protocol undertaken to protect the life or physical well-being of a 
subject in an emergency situation must be reported to Tactile Medical and the respective 
IRB as soon as possible, but in no event later than five (5) working days after the 
emergency occurred. Anticipated deviations from the protocol in a non-emergency 
situation must be pre-approved by Tactile Medical via telephone, email, fax, or mail. It is 
preferred that deviations scheduled to be performed in a nonemergency situation not be 
conducted until authorized by Tactile Medical. All protocol deviations must be 
documented. Deviation that may affect the scientific soundness of the study, or the rights, 
safety or welfare of the subject must also be reported to the reviewing IRB according to 
their reporting requirements. Protocol deviations may necessitate the discontinuation of 
the subject or the investigational site from the study. 
 
11.0 
Quality Assurance Procedures: 
This study will be conducted in accordance with Good Clinical Practice and International 
Conference on Harmonization (ICH) Guidelines, Code of Federal Regulations (CFR), 
institutional research policies and procedures and other appropriate regulatory 
requirements to ensure subject safety and quality of clinical procedures related to the 
conduct of the clinical trial. The investigators will permit regular monitoring, audits and 
site inspections by the IRB, 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. Clinical trial monitoring may be conducted to ensure compliance to this 
protocol. 
 
11.1 
Site Qualifications: 
Tactile Medical may conduct onsite visits or telephone qualification (pre-study 
audit) prior to study initiation to verify adequate resources, qualified staffing and 
a sufficient subject pool. 
 
11.2 
Data Collection Procedures: 
Raw data will be collected on appropriate Source Document Worksheets, or site- 
specific appropriate forms which include but are not limited to, clinic charts and 
site-generated Source Document Worksheets. Data collected shall be entered into 
the validated and secure Clindex electronic data capture system. 
 
11.3 
Clinical Site Monitoring: 

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Clinical sites will be monitored for compliance with the clinical protocol, 
investigator agreement, and applicable regulatory requirements. Regular contact 
will be maintained to ensure: 
• Subject safety 
• That clinical site staff is well informed of regulations and sponsor 
requirements 
• That the clinical protocol is followed 
• That data is gathered in 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, IRB 
review, and regulatory inspection(s), providing direct access to source data and 
documents as appropriate. Monitoring will be performed by study sponsor and/or 
designee. Monitoring will review subject source documentation and Case Report 
Forms (CRFs) for accuracy, completeness, and compliance with Good Clinical 
Practice procedures. 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. 
 
11.4 
Data Safety Monitoring Board: 
An independent data safety monitoring board (DSMB) will be established by the 
sponsor to review and monitor any serious adverse events, review safety data and 
may be called upon to review interim analysis data. The frequency of the review 
is expected to be quarterly but may be dependent on a number of parameters 
including but not limited to; the rate of enrollment, number of AEs and/or SAE, 
number of significant deviations from the protocol. At the conclusion of the 
review the DSMB may provide recommendations pertaining to study 
continuation, modification, or termination of the trial or a specific investigational 
site. 
 
11.5 
Investigator Reports and Records: 
Records to be maintained by the investigator in a designated study file include: 
• Investigational plan and all amendments 
• Signed Investigator Agreement 
• IRB approval letter, including a copy of the approved consent forms, 
progress reports, Adverse Event Report 
• IRB roster or Assurance number, if applicable 
• All correspondences relating to the conduct of this study between the site 
and sponsor, IRBs, and study monitor 
• Curriculum Vitae and professional license for all study personnel, if 
applicable 
• Site personnel signature and documentation regarding the Investigator’s 
delegation of responsibility 
• Clinical Site Visit log 

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• 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 
• Reports (see Table 3) 
 
The following records must be maintained for each subject enrolled: 
• Signed and dated informed consent form 
• Completed CRFs, queries and source document worksheets (if applicable) 
• Complete medical records including procedure reports, lab reports (if 
applicable), etc. 
 
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 3. 
 
Table 3: Investigator Reports 
Reports 
Submit To 
Timeframe 
Unanticipated 
Adverse 
Device Event 
Sponsor and 
Reviewing IRB 
DSMB 
As soon as 
possible but no 
later than 10 
working days 
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 
 
Subject study records, correspondence files, all supporting study documentation, 
and reports must remain on file at the investigational site for a minimum of ten 
years after the conclusion of this study. All investigators must contact Tactile 
Medical prior to destroying or archiving off-site any records and reports pertaining 
to this study to ensure that they no longer need to be retained on-site. 
 
Additionally, Tactile Medical 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. 
 
11.6 
Change to Study Plan: 
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 IRB 

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approval obtained before the changes are implemented. All changes must be 
documented. 
 
12.0 
Data Analysis and Statistical Considerations 
 
12.1 
Statistical Considerations: 
This is a prospective, randomized, stratified, open label, parallel-group, multi- 
center trial designed to assess the clinical non-inferiority with respect to the 
percentage of wound area reduction at 16 weeks with the ACTitouch® Adaptive 
Compression System compared to the Multi-layer Bandaging system in subjects 
with venous leg ulcer (VLU). Secondary endpoints include health-related quality 
of life (HRQOL) and Cost of the ACTitouch® Adaptive Compression System 
compared to the Multi-layer Bandaging system in subjects with VLU. Two 
hundred and four (204) subjects will be randomized 1:1 into 2 arms, ACTitouch® 
and Multi-layer Bandaging Systems. Subjects will receive follow-up evaluations 
at regularly scheduled clinic visits during 16 weeks of follow-up. Subjects will be 
randomized to 4 strata based on ulcer size and duration (age): 
 
Size of Ulcer 
⋅ 
1.5cm<=size<=12cm 
  
12cm<size<= 50cm 
 
Age of Ulcer 
  
1<=age<=6 months 
  
6<age<= 24 months 
Subjects will be randomized to treatment groups within strata using a web-based 
randomization process. 
 
Unless otherwise specified, all safety data, efficacy data, demographic data, and 
other baseline characteristics will be summarized by treatment group. Continuous 
data will be summarized by reporting the number of observations, mean, standard 
deviation, median, minimum and maximum values. Categorical data will be 
described using frequency tables showing the number and percentage of subjects 
falling within a particular category. 
 
Efficacy analysis and associated p-value calculation are described below and will 
be further elaborated in the Statistical Analysis Plan (SAP) issued prior to 
database lock. Statistical tests will be performed at a one-sided alpha of .025 for 
non-inferiority and two-sided alpha level of 0.05 for all other comparisons, unless 
otherwise specified. Between-group analyses will employ analysis of covariance 
(ANCOVA) with stratum and treatment group as covariates for continuous data, 
and chi-square or Cochran-Mantel Haenzel (CMH) methods for stratified 
categorical data. Kruskal-Wallis tests will be used to compare ordinal variables 
stratified by ulcer age, wound area and treatment group. If serious departures in 
the assumptions of normality and homogeneity of variance occur, nonparametric 
methods will be used for continuous data. 
 
12.2 
Objectives: 

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The primary efficacy objectives are: 
• Assess the non-inferiority of chronic VLU closure at 16 weeks with 
ACTitouch® therapy compared to a standard regimen of multi-layer 
bandaging. 
The  secondary and  exploratory efficacy objectives  include  assessment of  the 
effect of ACTitouch® compared with multi-layer bandaging treated subjects on: 
• HRQOL 
• outpatient cost per patient 
• incidence of 100% healed VLU 
• ulcer free days 
• outpatient cost per patient healed 
• outpatient cost per patient not healed 
• time-to-100% healed 
• cumulative incidence of 100% healed 
• total cost per patient (including inpatient costs) 
 
The safety objective is to compare ACTitouch® treated subjects to multi-layer 
bandaging treated subjects at 16 weeks in terms of the incidence of ulcer-related 
adverse events including infections, maceration, allergic reaction to dressing, 
hospitalization for worsening VLU. 
 
12.3 
Endpoints: 
12.3.1 Primary Endpoints 
The percentage of ulcer area reduction at 16 weeks. 
12.3.2 econdary Endpoints 
The secondary endpoints in clinical order of prioritization are as follows: 
• the difference in changes in HRQOL at 16 weeks using the overall 
score of the Charing Cross Venous Ulcer Questionnaire. 
• outpatient cost per subject at 16 weeks 
12.3.3 xploratory Endpoints 
• the incidence of subjects with 100% healed VLUs at 16 weeks 
• ulcer-free days at 16 weeks 
• HRQOL at 16 weeks using the overall and physical scores of the SF- 
36. 
• outpatient cost per subject for subjects with 100% healed VLU at 16 
weeks 
• outpatient cost per subject for subjects without 100% healed VLU at 
16 weeks 
• time-to-100% healed VLU 
• cumulative incident of 100% healed 
• total cost per patient (including inpatient costs) 
• ease of use 
• treatment satisfaction 
• limb volume changes 
• compliance 

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The primary hypothesis of interest is: 
H0: 𝝁𝝁 − 𝝁𝝁ﰀ =  δ ≤ - |Mni| 
vs. 
H1: δ > - |Mni| 
where 𝝁𝝁 represents the mean percentage of ulcer area reduction in the 
ACTitouch® group, 𝝁𝝁ﰀ = mean percentage of ulcer area reduction in the multi- 
layer bandaging treated group, δ = difference in the mean percentage of ulcer area 
reduction, and Mni  =  the non-inferiority margin. 
Under the assumptions that δ = 0%, Mni = 12.5%, and that the standard deviation 
of the ulcer area reduction in each group is 30%, then a sample size of 92 
evaluable subjects per group will yield at least 80% power to detect non- 
inferiority of ACTitouch® group versus multi-layer bandaging treated group, 
using the two-sample t-test at a one-sided 0.025 level of significance. The 
specification of a 12.5% non-inferiority margin and 30% standard deviation are 
based on similar studies of VLUs.18,19   The sample size is set at 102 subjects per 
treatment group to account for approximately 10% withdrawals. 
 
12.3.4 afety Endpoints 
The safety endpoints are as follows: 
• the incidence of ulcer-related adverse events at 16 weeks 
• the incidence of ulcer infections at 16 weeks 
• the incidence of hospitalization for worsening VLU at 16 weeks 
 
12.4 
Sample Size Assumptions: 
 
12.5 
Analysis Populations: 
Intent-to-Treat (ITT):  All randomized subjects. 
 
Modified-intent-to-treat (MITT): All randomized  subjects  who  received  the 
investigational procedure per protocol. This is the primary analysis population. 
 
Per-Protocol (Completers): All randomized subjects who have received the 
investigational procedure per protocol and who completed the 16 week follow-up 
visit. 
 
The Primary and Secondary Efficacy analyses will be performed on the ITT, 
MITT and Completer populations. Safety analyses will be performed on the 
MITT population. 
 
12.6 
Analysis Plan: 
12.6.1 eneral Analysis Issues: 
Statistical analysis will be performed using SAS Version 9.4 or higher. 
Non-inferiority analyses will be considered statistically significant at the 

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one-sided α=.025 level. All other p-values presented will be two-sided and 
will be considered statistically significant at the two-sided α=.05 level of 
significance unless otherwise noted. Statistical testing of the primary and 
secondary endpoints (Stage I) will be performed in hierarchical fashion. 
The primary efficacy analysis will be performed at the one-sided α=.025 
level. If the primary efficacy analysis is statistically significant then the 
first secondary end point will be analyzed at the two-sided α=.05 level. If 
this analysis is statistically significant, then the second secondary end 
point will be analyzed at the two-sided α=.05 level. Otherwise, testing on 
secondary endpoints will cease and the treatment will not be considered 
beneficial on either secondary endpoint. P-values for exploratory 
endpoints will not be adjusted for multiple comparisons. 
 
 
Baseline demographic and background variables will be summarized by 
treatment group and strata. For categorical variables, frequencies and 
percentages will be presented. For continuous variables, descriptive 
statistics including: sample size, mean, standard deviation, minimum, and 
maximum, will be presented. Continuous variables will be compared 
between treatment and control groups using ANCOVA. Categorical 
variables will be compared between treatment and control groups using 
the Kruskal-Wallis tests. 
 
12.6.2 Primary Endpoint Analysis: 
The percentage of each subject’s ulcer area reduction at 16 weeks will be 
assessed using a specialized ulcer camera and ulcer imaging system. 
Images will be centrally read by a qualified independent adjudicator. The 
percentage of ulcer area reduction for the ACTitouch® treated subjects 
will be compared with multi-layer bandaging treated subjects using 
analysis of covariance (ANOCOVA) with the following covariates: 
treatment group; duration of VLU ([1,6]; (6,24] months); baseline size of 
VLU, [1.5,12cm], (12,50cm]; history of diabetes; age. The analysis will be 
conducted on the ITT, MITT and Completer populations. The covariate 
adjusted one-sided lower bound 97.5% confidence interval of the 
treatment difference in mean percent ulcer area reduction (calculated as 
mean of ACTitouch® group minus mean of multi-layer bandaging treated 
group) is compared to the non-inferiority margin (-.125) . If the lower 
bound exceeds the margin, the null hypothesis is rejected, and 
ACTitouch® system is deemed non-inferior to multi-layer bandaging. 
 
A treatment-by-study center interaction will be assessed at the 0.10 level 
of significance using analysis of covariance with effects for treatment, 
study center and treatment-by-study center interaction. A non-significant 
interaction or any significant interaction deemed only quantitative in 
nature will not preclude study centers from being pooled for the final 
analysis. A significant qualitative interaction will be further inspected to 

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assess the study centers causing the interaction. Study centers with less 
than 15 subjects will be pooled by geographic region prior to carrying out 
the analysis. 
 
A qualitative interaction between center and treatment group is defined as 
directionally inconsistent estimated coefficients for the treatment group 
parameter in a subgroup analysis of treatment group by center – i.e., 
analysis of covariance model with stratification by center specified as 
subgroups. Any study center with a qualitatively different treatment group 
effect by subgroup will be compared with other centers in terms of a 
number of variables including: enrollment rate, adverse event rate, rate of 
data queries generated by clinical data management, confirmation of 
correct drug assignment and randomization at the site, number and 
seriousness of protocol deviations. If a center is deemed to be qualitatively 
different from the other centers in terms of their interaction with treatment 
group, then the primary efficacy analysis will be stratified by center (i.e., 
those centers with a qualitative a difference versus all others). If only one 
or two centers are qualitatively different, then analyses will be conducted 
with and without the centers, and the results will be compared. 
 
Several imputation approaches will be used for missing data due to 
subjects prematurely withdrawing prior to the 16 week time point. The 
results will be descriptively compared across approaches to assess the 
sensitivity of results to the various techniques. 
• Complete case analysis 
• Multiple imputations via the linear regression technique, where the 
imputation model will include treatment group and all covariates 
discussed in the Analysis Plan. 
• Available data analysis (include any available measurements) using 
the general linear mixed models. 
 
12.6.3 econdary Endpoint Analysis 
The following analyses will be carried out on all three analysis 
populations defined above. ACTitouch® treated subjects will be compared 
with multi-layer bandaging treated subjects in terms of: 
• the difference in changes in HRQOL at 16 weeks assessed by the 
overall score of the Charing Cross Venous Ulcer Questionnaire using 
a similar ANCOVA model as used in similar to the  Primary 
Endpoint Analysis. If the primary efficacy analysis was significant, 
then the difference will be tested at the two-sided α=.05 level. 
the difference in VLU-related outpatient cost per subject at 16 weeks 
between ACTitouch® treated subjects with multi-layer bandaging 
treated subjects using non-parametric rank-order, Wilcoxon rank 
sum tests.  If the prior secondary efficacy analysis was significant, 
then the difference will be tested at the α=.05 level. 
12.6.4 xploratory Endpoint Analysis 

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• To compare the difference in the incidence of subjects with 100% 
healed VLUs at 16 weeks between ACTitouch® treated subjects 
with multi-layer bandaging treated subjects based on logistic 
regression with the same covariates as used in the Primary Endpoint 
Analysis. 
• To compare the difference in ulcer-free days at 16 weeks between 
ACTitouch® treated subjects with multi-layer bandaging treated 
subjects based on non-parametric analysis of covariance using the 
same covariates. 
• To compare the difference in changes in HRQOL at 16 weeks 
compared to baseline between ACTitouch® treated subjects with 
multi-layer bandaging treated subjects using the physical component 
score of the SF-36 using the same method as the Primary Endpoint 
Analysis. 
• To compare the difference in VLU-related outpatient cost per subject 
for subjects with 100% healed VLU at 16 weeks between 
ACTitouch® treated subjects with multi-layer bandaging treated 
subjects using non-parametric rank-order, Wilcoxon rank sum tests. 
• To compare the difference in outpatient cost per subject for subjects 
without 100% healed VLU at 16 weeks between ACTitouch® 
treated subjects with multi-layer bandaging treated subjects using 
non-parametric rank-order, Wilcoxon rank sum tests. 
• To compare the difference in the time-to-100% healed VLU between 
ACTitouch® treated subjects with multi-layer bandages treated 
subjects using a Cox Proportional Hazard model with the same 
covariates as above. 
• To compare the cumulative incidence graphs of subjects with 100% 
percent healed VLU between ACTitouch® treated subjects with 
multi-layer bandaging treated subjects using Kaplan-Meier product- 
moment estimates. 
• To compare total VLU-related cost per subject (including cost of 
scheduled 
VLU-related 
study 
visits, 
VLU-related 
inpatient 
admissions, non-study ACTitouch® treated subjects with multi-layer 
bandaging treated subjects using non-parametric rank-order, 
Wilcoxon rank sum tests. 
• Subjects who are assigned to the ACTitouch device and heal during 
the 16 week treatment period will continue to be seen monthly for 
each of 3 months (±7 days) post healed visit. At the visit the subject 
will undergo the procedures outline in the Study Schedule of 
Activities table in section 7.17. For such subjects, the recurrence 
rate (percent of subjects who are no longer 100% healed) at months 
1, 2 and 3 will be tabulated. Descriptive statistics of the percentage 
of wound area reduction will be tabulated at each of the 3 monthly 

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]
visits. 
The  percentage  of  non-compliant  patients  will  also  be 
presented at each month. 
 
12.6.5 afety Endpoint Analysis 
The following analyses will be carried out on the Safety Populations. 
ACTitouch® treated subjects will be compared with multi-layer 
bandaging treated subjects in terms of: 
• the difference in the incidence of ulcer-related adverse events 
(defined as  ulcer infections, maceration, allergic reaction to 
dressing, or hospitalization for worsening VLU) at 16 weeks using 
the Kruskal-Wallis test. 
• the difference in the incidence of ulcer infections at 16 weeks using 
the Kruskal-Wallis test. 
• the difference in the incidence of ulcer maceration at 16 weeks using 
the Kruskal-Wallis test. 
• the difference in the incidence of allergic reactions to dressing at 16 
weeks using the Kruskal-Wallis test. 
• the difference in the incidence of hospitalization for worsening VLU 
at 16 weeks using the Kruskal-Wallis test. 
 
12.7 
Interim Analysis: 
There will be a formal interim analysis of the primary endpoint when 50% of the 
subjects have completed the 16 week treatment phase, defined as completing all 
16 weeks, healed or withdrew prior to the 16 week visit or healing. At this 
interim visit, comparison of the percentage ulcer area reduction between 
ACTitouch® treated subjects with multi-layer bandaging treated subjects will be 
made using the same ANOCOVA model as above. The DSMB will not 
recommend stopping the study for overwhelming efficacy based on the 
comparison of the ACTitouch® doses versus control (multi-layer bandaging). 
Nevertheless, due to the interim look, an O’Brien-Fleming-type alpha-penalty for 
the final analysis will be taken; and the final one-sided alpha will be 0.0249 
 
The DSMB will be provided with conditional power of obtaining non-inferiority 
of ACTitouch to control with respect to mean percent ulcer healing by the end of 
the study. This conditional power is calculated according to the following 
formula: 
 
  
 
CPδ(n2,zα|z1) =1 − ∅ [ 
Zα √2(n1+n2 − Z1√2n1  −  n2(δ−δ∆) 
√2n2 
where: 
n1 – sample size per arm at interim; 
n2  – sample size per arm in second stage (from interim to final analysis) as 
originally planned; 
Δ – non-inferiority margin; 
δ∆ = Δ/σ ; 

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σ2   –  assumption  of  true  variance  of  treatment  effects  pooled  across  arms 
(estimated from the interim data); 
δ – assumption of true effect size=(µC - µT)/σ (this will be set to 0); 
z1 – non-inferiority test statistic calculated at the interim analysis; 
zα – α percentile of the standard normal distribution (α = one-sided 0.0249); 
zβ – β percentile of the standard normal distribution; 
Φ[] – the standard normal cumulative distribution function. 
 
The Data Safety Monitoring Board (DSMB) and Statistical Analysis Plan (SAP) 
will outline the various recommendations the DSMB may make regarding the 
continuation of the study based on the conditional power calculated at the interim 
analysis. Each recommendation depends on the pattern of conditional power 
calculated under the assumption that the true population treatment difference is 
the original point estimate in excess of the non-inferiority margin. The following 
table, which will be included in the DSMB Charter, outlines the various 
recommendations the DSMB may make regarding the continuation of the study 
based on the conditional power calculated at the interim analysis. 
 
Conditional 
Power 
Possible DSMB Recommendations 
< 10% 
Stop study for futility20 
10%-30% 
Continue randomization into 
ACTitouch and multi-layer 
bandaging arms. 
30%-80% 
Continue randomization into 
ACTitouch and multi-layer 
bandaging DSMB may recommend 
an increase in randomized sample 
size in order to achieve conditional 
power of 80% for a significant non- 
inferiority effect 
> 80% 
Continue randomization into 
ACTitouch and multi-layer 
bandaging arms using the originally 
planned sample size. 
 
 
In the event the DSMB recommends a sample size increase for the final analysis 
to achieve 80% conditional power, the critical value to be used for the final 
analysis will be: 
 
C2 - new final critical value (maintaining the overall 0.025 level of significance) 
to be used when sample size is increased from n1 to n2 

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1 
1
 
 
𝑛𝑛1 
2 𝑍𝑍2 
(𝑍𝑍  +  𝑍𝑍1 )𝑍𝑍  +   √ 2 
(√ 
C2   = 
  
𝑛𝑛1 − 𝛿𝛿∆) 𝑍𝑍1 
2 
2 𝑍𝑍2 
√𝑛𝑛1 ⌈√ 𝑛𝑛1 −  𝛿𝛿∆⌉ + (𝑍𝑍  +   𝑍𝑍ﰀ )2 
Computer simulations show that this approach to sample size increase maintains 
Type I error at the desired nominal level. 
 
There is no stopping the study for overwhelming efficacy of the experimental 
arm. However, note that the DSMB can recommend stopping the study for safety 
issues at any time, regardless of interim results. 
 
13.0 
Compensation: 
Study subjects may be compensated for their time and travel associated with participation 
in this study. 
 
14.0 
Publication Plan: 
All information obtained during the conduct of the study will be considered to be 
confidential and is property of Tactile Medical. Written permission from the Sponsor is 
required before disclosing any information related to this study. All publications (e.g. 
manuscripts, abstracts, and presentations) based on this study must be submitted to the 
Sponsor for review and approval before submission or according to the individual site 
clinical trial agreement. 
 
15.1 
References 
1. Gottrup, F. (2004). A specialized wound-healing center concept: importance of a 
multidisciplinary department structure and surgical treatment facilities in the treatment of 
chronic wounds. The American Journal of Surgery, 187(5A), 38S-43S. 
2. Smith, P.C., Sarin, S., Hasty, J., & Scurr, J.H. (1990). Sequential gradient pneumatic 
compression enhances venous ulcer healing: A randomized trial. Surgery, 8, 871-875. 
3. Kantor, J., & Margolis, D.J. (2003). Management of leg ulcers. Seminars in Cutaneous 
Medicine and Surgery, 22(3), 212-221. 
4. Partsch, H., Menzinger, G., & Mostbeck, A. (1999). Inelastic leg compression is more 
effective to reduce deep venous refluxes than elastic bandages. Dermatologic 
Surgery, 25(9), 695-700. 
5. Cullum, N., Nelson, E.A., Fletcher, A.W., & Sheldon, T.A. (2001). Compression for 
venous leg ulcers. Cochrane Database of Systematic Reviews, 2. DOI: 
10.1002/14651858.CD00265. 
6. Meissner, M.H., Eklof, B., Gloviczki, P., Lohr, J.M., Lurie, F., Kistner, R., Wakefield, 
T.W. (2007). Mapping the future: Organizational, clinical, and research priorities in 
venous disease. Journal of Vascular Surgery, 46, 84S-93S. 

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Appendix A: ACTitouch User Guide 
Appendix B: Profore User Guide 
Appendix C: Coban™ 2 Layer Compression System Package Insert 
Appendix D: Lower Extremity Measuring Guide 
Appendix E: Silhouette User Guide 
Appendix F: Eco Sub Protocol 
Appendix G: Charing Cross Venous Ulcer Questionnaire 
7. Comerota, A.J. (2011). Intermittent pneumatic compression: Physiologic and clinical 
basis to improve management of venous leg ulcers. Journal of Vascular Surgery, 53, 
1121-1129. 
8. Kalodiki, E. (2007). Use of intermittent pneumatic compression in the treatment of 
venous ulcers. Future Cardiology, 3(2), 185-191. 
9. Nelson, E.A., Mani, R., & Vowden, K. (2008). Intermittent pneumatic compression for 
treating venous leg ulcers. Cochrane Database of Systematic Reviews, 2, CD001899 
10. McCollugh, J.M. (1981). Intermittent compression for the treatment of a chronic stasis 
ulceration: A case report. Physical Therapy, 61, 1452-1453. 
11. Nelson, E.A., Mani, R., Thomas, K., & Vowden, K. (2011). Intermittent pneumatic 
compression for treating venous leg ulcers (Review). Cochrane Database of Systematic 
Reviews, 2. DOI: 10.1002/14651858.CD001899.pub.3. 
12. Mani, R., Vowden, K., & Nelson, E.A. (2001). Intermittent pneumatic compression for 
treating venous leg ulcers. Cochrane Database of Systematic Reviews, 4. DOI: 
10:1002/14651858.CD001899. 
13. Mellor, R.H., Bush, N.L., Stanton, A.W.B., Bamber, J.C., Levick, J.R., & Mortimer, P.S. 
(2004). Dual-frequency ultrasound examination of skin and subcutis thickness in breast 
cancer-related lymphoedema. The Breast Journal, 10(6), 496-503. 
14. Partsch, H., & Mosti, G. (2010). Comparison of three portable instruments to measure 
compression pressure. International Angiology, 29, 426-430. 
15. Harding, K.G., Vanscheidt, W., Partsch, H., Caprini, J.A., & Comerota, A.J. (2014). 
Adaptive compression therapy for venous leg ulcers: A clinically effective, patient- 
centered approach. International Wound Journal, 60(2), 71-90. 
16. Smith JJ, Guest MG, Greenhalgh RM, Davies AH. Measuring the quality of life patients 
with venous ulcers. Journal of Vascular Surgery 2000; 31(4):642-649. 
17. Blair SD, Wright Dl, et al. Sustained compression and healing of chronic venous ulcers. BMJ 
1998: 297: 1159-1161 
18. Armstrong DG, Marston WA, Reyzelman AM, Kirsner RS. Comparative effectiveness of 
mechanically and electrically powered negative pressure wound therapy devices: a 
multicenter randomized controlled trial. Wound Repair and Regeneration 2012:20;332- 
341. 
19. Armstrong DG, Marston WA, Reyzelman AM, Kirsner RS. Comparison of negative 
pressure wound therapy with an ultraportable mechanically powered device vs. 
traditional electrically powered device for the treatment of chronic lower extremity 
ulcers: a multicenter randomized-controlled trial. Wound Repair and Regeneration 
2011:19;173-180 
20. Mehta CR, Pocock SJ. Adaptive increase in sample size when interim results are 
promising: a practical guide with examples. Statistics in Medicine. 2011:30;3267-3284. 
 
16.0 
Appendices 

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Appendix H: SF-36 V.2 Questionnaire 
Appendix I: VCSS 
Appendix J: EQ-5D QoL Questionnaire 
Appendix K: WPAI-SHP 
Appendix L: Tolerance and Comfort Survey