Efficacy and Safety of Vascular Boot Warming Program After Acute DVT±PE for Earlier Resolution of Venous Thromboembolism (VTE) and Prevention of Post Thrombotic Syndrome: A Pilot Study.
Phase: NA
Conditions: Acute DVT of Lower Extremity
Sponsor: Mayo Clinic

 
 
Efficacy and Safety of Vascular 
Boot Warming Program after 
Acute DVT +/- PE for Earlier 
Resolution of VTE and 
Prevention of Post Thrombotic 
Syndrome: A pilot study. 
 
NCT# NCT03465735 
 
Date: 1/29/2018 

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IRB Minimal Risk Protocol Template 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
General Study Information 
 
Principal Investigator: Waldemar E. Wysokinski, M.D., Ph.D.  
Co-Investigators: Thanila Macedo, M.D.; Mathew Urban, PhD.; and Thom Rooke, M.D.      
 
 
 
 
 
 
 
 
Study Title:    Efficacy and Safety of Vascular Boot Warming Program after Acute DVT±PE for Earlier 
Resolution of VTE and Prevention of Post Thrombotic Syndrome: A pilot study.  
 
Short Title:  Vascular Boot Warming Program After Acute DVT ±PE  
 
Protocol version number and date:    Version4.0, 01/29/2018   
 
Purpose 
 
Hypothesis: Early use of a vascular boot warming program plus standard anticoagulation can be a safe and 
effective method to resolve DVT±PE earlier and prevent development of post-thrombotic syndrome. 
 
Note: If this study establishes a human specimen repository (biobank) for research 
purposes, do not use this template. Use the Mayo Clinic Human Specimen Repository 
Protocol Template found on the IRB home page under Forms and Procedures at 
http://intranet.mayo.edu/charlie/irb/ 
 
First-time Use: Use this template to describe your study for a new IRB submission. 
1. Complete the questions that apply to your study. 
2. Save an electronic copy of this protocol for future revisions.    
3. When completing your IRBe application, you will be asked to upload this template to the protocol 
section. 
Modification:  To modify this template after your study has been approved: 
1. Open your study in IRBe. Click on the study ‘Documents’ tab and select the most recent version of the 
protocol. Save it to your files. 
2. Open the saved document and activate “Track Changes”.  
3. Revise the protocol template to reflect the modification points , save the template to your files 
4. Create an IRBe Modification for the study and upload the revised protocol template. 

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Aims, purpose, or objectives: 
Primary Objective 
1. The primary objective is to demonstrate whether a vascular boot warming program plus standard 
anticoagulation over standard anticoagulation can improve resolution of DVT±PE and functional 
performance in patients with deep vein thrombosis of the lower extremity ± pulmonary embolism.  
Secondary Objectives 
1. Determine if early vascular boot warming plus standard anticoagulation (after 24 hours of anticoagulation 
therapy from time of diagnosis) is a safe intervention after diagnosis of acute DVT±PE. 
2. Determine if vascular boot warming plus standard anticoagulation improves or accelerates the resolution of 
the clot among those with DVT±PE. 
3. Determine if vascular boot warming plus standard anticoagulation improve the venous functional study 
measures of calf pump ejection fraction, VFR, PDR T90, and overall venous performance score. 
4. Determine whether a vascular boot warming plus standard anticoagulation can improve the quality of life in 
patients with venous insufficiency or previous history of deep vein thrombosis of the lower extremity ± PE. 
5. Identify difference in activity level between those who underwent a vascular boot warming program/activity 
plus standard anticoagulation versus standard anticoagulation only. 
6. Analyze whether shear wave elastography will provide a more accurate and reliable method to assess the 
age of thrombosis and better quantification of thrombosis resolution. 
7.   Collect natural history data of post-thrombotic syndrome.  
 
Background:   
 
Venous thromboembolism (VTE) is a major public health problem with over 500,000 incident or 
recurrent VTE events occur in the US annually.1-3  Survival after VTE is reduced, especially after pulmonary 
embolism (PE). 4  The incidence of VTE in Olmsted County, MN increased by ~5% per decade over the 30-year 
period, 1981-2010.5 Anticoagulation for VTE has been the mainstay treatment with little advancement.  
Unfortunately, acute and chronic venous disorders are extremely common in those that experience VTE.  Post-
thrombotic syndrome (PTS) is one of the dreaded long-term complications of deep venous thrombosis (DVT). 
It’s been estimated that 1 to 3 of 1000 people in general population is affected by DVT and 25% to 50% 
patients of patients with DVT develop PTS.6 The manifestations of PTS can vary from minor leg swelling at the 
end of the day to severe complications of debilitating limb pain, intractable edema, and leg ulcerations requiring 
extensive nursing and medical care.7 It can reduce the patient’s quality of life in addition to being a significant 
financial burden. It is estimated that annually we spend over a billion dollars (up to 2% of the total healthcare 
budget in all Western countries) on the treatment of chronic wounds.  There are still huge gaps in understanding 
the underlying mechanism and progression of the condition.   
Expedient resolution of thrombosis may have a significant impact on PTS.  Resolution and 
recanalization of venous thrombosis generally begins within 1 week of the acute episode.10 Studies have shown 
that at least 5% of thrombosed venous segments completely clear within 1 week and 16% to 51% of the cases 

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resolved within 6 months.8-10 Killewich et al9 demonstrated thrombus regression was evident at 1 to 2 weeks 
and progressed such that only 26% of residual thrombus remained at 24 to 36 weeks. Complete resolution of 
thrombus occurred in 10 of 18 patients (56%) who completed the 9-month study.  
O'Shaunessy et al8 reported that 60% of their patients had completely resolved their thrombus by the end 
of 1 year. This study examined 63 above-knee DVT anatomic segments with duplex scanning at 1 week, 1 
month, 6 months, and 1 year after the acute event. The segments under investigation were the external iliac vein 
(EIV), common femoral vein (CFV), superficial femoral vein (SFV), and popliteal vein (PV). Initially, a greater 
number of segments were occluded (71%) than partially thrombosed (29%). The occluded segments were 
predominantly in the SFV and PV. At 1 year the thrombi had fully resolved in 60% of the venous segments, 
27% remained partially recanalized, and 13% were occluded. At 1-year follow-up the thrombus had fully 
resolved in 103 segments: 94% of the EIVs, 78% of the CFVs, 42% of the SFVs, and 54% of the PVs. Of these, 
61% of the segments were found to be competent without reflux flow, and 39% were incompetent with reflux 
flow of greater than 1 second. The time involved for individual segments to fully recanalize varied from 1 week 
to 1 year. Segments that resolved within the first 6 months had a higher frequency of valvular competency than 
incompetency (P > .006). The segments that resolved after 6 months had a higher incidence of incompetency to 
competency (31:13), but this was not statistically significant. The SFV and PV had a higher incidence of 
valvular incompetence than the EIV and CFV. All venous segments that were partially recanalized at 1 year 
were found to have significant reflux. The SFV had the highest incidence of total occlusion at the end of 1 year 
(36%).  Many of the occluded SFVs had established collateral pathways that displayed no evidence of reflux.  
Ramshorst et al.11 observed thrombosis resolution to occur in the first 1 to 3 weeks after acute DVT and 
appeared to occur at an almost exponential rate. They noted that recanalization occurred mainly in the first 6 
weeks after diagnosis, but clot resolution eventually occurred in 75% of the thrombosed segments within 6 
months. Caprini et al.12 reported that complete resolution had occurred in more than 40% of thrombosed venous 
segments within 3 months after the diagnosis of DVT, and lysis had occurred in more than 70% of segments 
within 6 months of treatment. 
To further reduce the VTE burden, better treatments are needed to resolve VTE other than 
anticoagulation alone. The largest randomized trial to date is the Pulmonary Embolism International 
Thrombolysis (PEITHO) trial,13 and resulted in 1,006 patients with acute sub-massive PE-defined as echo 
evidence of RV dysfunction or positive troponin-to receive anticoagulation with heparin plus tenecteplase or 
placebo. There was significantly (2.6% vs. 5.6%; P=0.015) lower death or hemodynamic collapse within 7 days 
and increased rates of intracranial hemorrhage (2.4% vs 0.2%; P=0.003) and major bleeding in the thrombolytic 
group.  The Seattle II study14 was a prospective, single-arm multicenter trial of ultrasound facilitated, low-dose 
fibrinolysis for acute massive and sub-massive PE. There was a 25% decrease in CT-measured RV/LV ratio 
over 48 hours, 0% intracranial bleeding, 2% in-hospital death, and 2.7% 30 day mortality due to catheter-
directed low-dose fibrinolysis.  The rational for the Seattle II study14 was to use catheter-directed-low dose 
fibrinolysis as a disruption device to help dissolve clot.  However, there is limited data on the use of vascular 
boot and warming plus standard anticoagulation in the long term management of patients with DVT and/or PE 
and its effect on the development of PTS. Warming of the lower extremity enhances blood flow in the treatment 
of superficial vein thrombosis. 
Currently the standard method for diagnosing and evaluating DVT is by 2-D ultrasound with 
compression and visualization of the vein. Due to the lack of accurate age determination method of DVT, about 
30% of DVTs are wrongly staged by using common diagnostic modalities and therefore this leads to therapeutic 
dilemmas.  As thrombus undergoes a stiffening process, the elasticity of the thrombus may serve as a predictor 

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for the staging of blood clots. Ultrasound elastography is a noninvasive technique to measure tissue stiffness 
and is a potential technique to determine the age of DVT. When DVT changes due to resolution the function 
and viscoelastic properties also change. We propose the use of a quantitative, noninvasive method call Shear 
wave Dispersion ultrasound vibrometry, to measure the viscoelastic properties of the vein.  
Instead of studying compressional waves propagation in the MHz range, other approaches to study the 
mechanical properties of soft tissues have used shear waves at low frequencies (typically ranging from 50 Hz to 
1000 Hz) (Muthupillai et al. 1995; Sarvazyan et al. 1998). Gennisson et al. in 2006 and Schmitt et al. in 2011 
used mechanical vibrators to generate shear waves in the blood samples, allowing the study of the dynamic 
process of blood coagulation (Gennisson et al. 2006) and the comparison of different rheological models 
(Schmitt et al. 2011). Another approach using radiation force was described by Viola et al. in 2010 in which 
they used the ultrasound push to move the blood clot and measured the displacement generated. This technique 
was used tomeasure the change in relative compliance of ex vivo clots as they were formed (Viola et al. 2010). 
Even though it has been shown that the composition of blood clots is not homogenous (Taber et al. 1996), to our 
knowledge there are no studies describing the elastic properties of blood clots.  
Therefore, there is a real interest in a noninvasive technique for the study of two-dimensional (2-D) 
elasticity properties of blood clots. This technique could be used to diagnose the age of thrombi, stratify the 
resolution of blood clots and help understand the coagulation process from a mechanical standpoint. It could 
also potentially be used to monitor the effect of therapies that are currently used on the clot elasticity.  
 
Study Rationale Innovation and significance:   
Warming of the lower extremity enhances blood flow in the treatment of superficial vein thrombosis and 
has been well established.16 However, the effect of vascular boot warming plus standard anticoagulation on 
deep venous disease progression is unknown and may prove to reduce DVT with standard anticoagulation more 
effectively and quicker with reduced risk for PTS.  To date, there is no randomized control study evaluating the 
effect of vascular boot warming plus standard anticoagulation in venous insufficiency. We hypothesize that the 
combination of vascular boot warming and standard anticoagulation will result in improvement in calf muscle 
pump function, thus improvement in venous physiology and quicker resolution of DVT and associated clinical 
symptomatology of post thrombotic syndrome. Ultrasonography with shear wave elastography imaging  is a 
novel ultrasound technology that potentially can quantify and assess thrombosis age, evolution of thrombosis, 
and risk of detachment. These evaluations can be readily performed in the patient’s examination room on a 
single ultrasound system. The overall anticipated results of our research proposal are to demonstrate that: 1) 
DVT may resolve more effectively with a vascular boot through warming evaluated by standard 2-D 
ultrasonography with compression (standard therapy); 2) shear wave elastography  is a feasible diagnostic tool 
in those with lower extremity thrombosis; 3) shear wave elastography can provide a more accurate and reliable 
method to assess the age of thrombosis and better quantification of thrombosis resolution while assessing the 
natural history, progression, and risk of detachment; 4) this technology can readily be incorporated into the 
daily workflow to improve diagnostic and prognostic value for detection of DVT and resolution [It has been 
estimated that the average image acquisition time to be added to a standard ultrasound study is minimal (7-10 
minutes for shear wave elastography imaging) 5) these techniques can improve prediction of complications 
among those with DVT and; 6) these techniques can help decrease the number of age indeterminate thrombus 
that may result in unnecessary treatment with anticoagulation and its associated risks.   
 

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Subject Information – charts, records, images, or specimens are considered ‘subjects’ 
 
Target accrual is the proposed number of subjects to be included in your study at your site. “Subjects” may 
include Mayo Clinic charts, records, or specimens, and/or charts, records, or specimens received at Mayo 
Clinic from external sources for collaborating analysis by the investigator under this IRB application:    
 
Target accrual: 30 patients (15 patients with vascular boot vs 15 patients without vascular boot) 
 
Subject population:   
All patients diagnosed with acute lower extremity DVT per ultrasound ± pulmonary embolism (PE) per 
computed tomography scan seen in the Thrombophilia clinic or Mayo Hospital for start of anticoagulation will 
be approached for participation in the study. 
 
Inclusion Criteria 
1. Age ≥18 
2. Able to tolerate wearing a vascular boot, if randomized to this group. 
3. Diagnosis of acute DVT±PE (within 24 - 48 hours) and received approximately 24 hours of 
anticoagulation prior to starting the study.  
Exclusion Criteria 
1. Unable to tolerate wearing a vascular boot 
2. Unable to comply with keeping log of activity/ of wearing a vascular boot. 
3. Weight > 300 pounds. (weight limit for the venous plethysmography chair) 
4. Previous history of DVT or PE. 
5. On anticoagulation for another purpose (example stroke prevention with atrial fibrillation). 
6. Patients who do not accept to participate in research studies.  
7. Pregnant women will not be allowed to participate 
8. Patients less than 18 yrs 
 Yes  
  No   Will a Certificate of Confidentiality (COC) be obtained from NIH?   
 
 

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Study Design  
 
Methods 
  
Patients with diagnosis of acute lower extremity DVT (proximal and distal) and/or pulmonary embolism will be 
identified and approached for participation, when they are seen in the Thrombophilia Clinic or Mayo Hospital 
for management of the acute VTE.  If they match the preset inclusion and exclusion criteria, they would then be 
consented during this visit and scheduled for baseline studies at a later date.  
 
Baseline studies will include: 
(1) Venous plethysmography: (ejection fraction, VFR, PDR T90, EDV T90, MV, F1.0). 
(2) Lower Extremity Ultrasound: DVT (thrombus) evaluation with 2-D ultrasonography (standard) and shear 
wave  elastography (done within 1 day of baseline clinical ultrasonography).   
(3) Other relevant clinical information (such as height, weight, BMI, bilateral calf circumference, edema, leg 
pain, ulcerations, previous LE surgery, use of compression stockings, and any current set exercise program).  
Demographical data, common vascular risk factors (including tobacco use, coronary and peripheral arterial 
occlusive disease, diabetes, hypercholesterolemia, and hypertension) and the treatment information, will be 
obtained from chart review via ACE database and Synthesis. All data will be entered and stored in RedCap 
research tool.  
(4) Anatomic distribution of thrombi at initial examination will be documented as single segment and/or multi-
segment(s) involved.  The segments will be label as: external iliac vein (EIV), only if clot extends above the 
common femoral vein; common femoral vein (CFV); femoral vein (FV) (upper, middle, lower); deep femoral 
vein (DFV); popliteal vein (PV); posterior tibial vein (PTV); gastrocnemius (G-calf); peroneal vein-calf (PV-
calf); soleal vein-calf (SV-calf) (see Table 1).  
 
Table 1.0 
Site 
Anatomic Distribution of Thrombi  
Initial 
3 days 
10 days 
3 months 
 
Single Segments 
 
 
 
 
External Iliac (EIV); if evaluated 
 
 
 
 
Common femoral (CFV) 
 
 
 
 
Femoral- Upper (FV) 
 
 
 
 
Femoral - Middle 
 
 
 
 

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Femoral - Lower 
 
 
 
 
Deep Femoral (DFV) 
 
 
 
 
Popliteal (PV) 
 
 
 
 
Posterior Tibial (PT-calf) 
 
 
 
 
Gastrocnemius  (G-calf) 
 
 
 
 
Peroneal  (P-calf) 
 
 
 
 
Soleal (S-calf) 
 
 
 
 
Total 
 
 
 
 
 
Multisegment 
 
 
 
 
EIV- CFV 
 
 
 
 
EIV- CFV-FV 
 
 
 
 
EIV- CFV-FV-PV 
 
 
 
 
EIV- CFV-FV-PV-calf 
 
 
 
 
CFV-FV 
 
 
 
 
CFV-FV-PV 
 
 
 
 
CFV-FV-PV-calf 
 
 
 
 
FV-PV 
 
 
 
 
FV-PV-calf 
 
 
 
 
Total 
 
 
 
 
 
Patient will then be randomized to vascular boot plus standard anticoagulation program or standard 
anticoagulation using the randomizer built into RedCap. 

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Standard of Care (SOC) Group (no vascular boot utilized): Patients will receive standard anticoagulation 
(determined at discretion of the treating provider), baseline studies, and follow up at the end of treatment 
(3months).  
 
Vascular Boot (VB) Group (includes vascular boot in addition to SOC): Patients will receive standard 
anticoagulation (determined at discretion of the treating provider), baseline studies and standardized vascular 
boot warming (see below). All patients randomized to this group will wear the vascular boot for a minimum of 
30 minutes per day for the first 10 days of participation. Patients in this group may initially be enrolled at either 
the thrombophilia clinic or the hospital.  
 
Standardization of the vascular boot warming: 
The vascular boot is designed to completely surround the foot, heel and calf, insulating the limb.  For each 
vascular boot session, the following data will be recorded: 
(1) Total duration of wearing vascular boot during first 10 days of study participation 
(2) Affected leg pain measured on a 0-10 scale at initial vascular boot warming (baseline) and every day during 
the calf warming while participating in the study. 
 
Follow up data (SOC and VB Groups) include: 
(1) Ultrasound of the leg with DVT and leg circumference measurement at 3 days, 10 days, and 3 months. 
Ultrasound data will include data on thrombus resolution, such as size and recanalization present. 
(2) Venous plethysmography at 3 months. 
(3) Study Questionnaires:  
a. Godin questionnaire (validated questionnaires to measure physical activity) 
b. VEINES-QOL  (generic physical quality of life questionnaire) 
c. Villalta Score (to assess Post-Thrombotic Syndrome) 
 
Ultrasound Measurements and Criteria: 
The criteria for complete occlusion (occlusive) were absence of flow with distal augmentation and 
incompressibility of the vein. Minimal clot will be defined by wall thickening, webbing, etc. Partial 
recanalization will be defined by >50% or <50% normal or diminished flow with distal augmentation and 
partial incompressibility of the vein. Complete recanalization (resolved or no clot) will be defined by 
spontaneous phasic flow and a completely compressible vein and no residual clot (see Table 2). 
Table 2.0 
Site 
No 
Residual 
Clot 
Minimal 
Clot 
(wall 
thickening, 
webbing, 
etc) 
Recanalized 
>50% 
Recanalized 
<50% 
Near 
Occlusive 
No 
Change 
Worse 
Or  
Extension 
External Iliac (EIV); 
if evaluated 
 
 
 
 
 
 
 

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Common femoral 
(CFV) 
 
 
 
 
 
 
 
Femoral- Upper (FV) 
 
 
 
 
 
 
 
Femoral - Middle 
 
 
 
 
 
 
 
Femoral - Lower 
 
 
 
 
 
 
 
Deep femoral (DFV) 
 
 
 
 
 
 
 
Popliteal (PV) 
 
 
 
 
 
 
 
Posterior tibial (PT-
calf) 
 
 
 
 
 
 
 
Gastrocnemius  (G-
calf) 
 
 
 
 
 
 
 
Peroneal  (P-calf) 
 
 
 
 
 
 
 
Soleal (S-calf) 
 
 
 
 
 
 
 
Total 
 
 
 
 
 
 
 
 
Study Procedure 
 
All subjects included in this study will have a diagnosis of deep vein thrombosis that will undergo standard 
anticoagulation with or without wearing a vascular boot. Medical charts will be abstracted for clinical, 
laboratory, medications, imaging and pathologic findings. Subjects will undergo their initial (baseline) clinically 
indicated DVT ultrasound for diagnosis of lower extremity DVT. The second clinically indicated limited 
venous ultrasound will be completed on post-DVT day 90 (14±days) to evaluate resolution. Research 
ultrasound intervals will then occur on days 0 (+1 days), 3 (-2/+5 days), 10 (±5 days), and 90 (14±days). Shear 
wave elastography will be conducted at all post-treatment ultrasound intervals. We will compare the shear wave 
elastography to the opposite lower extremity veins on the same individual for a control if DVT is not present in 
that extremity at that time or previously.  
 

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Commercially available ultrasound systems (Logiq E9, GE Medical Systems, Milwaukee, WI, USA) equipped 
with phased-array and linear transducers will be utilized. Longitudinal and short axis images of each clot will be 
acquired and digitally stored for offline analysis. The short axis images will be acquired. 2-D images, 2D shear 
wave and elastography images will be acquired and digitally stored for off-line analysis. All measurements will 
be made in a blinded fashion by a single observer. 
 
Shear Wave Elastography: The subject will be asked to lay on a hospital bed for ultrasound imaging. The 
veins of the lower extremity will be visualized using ultrasound imaging, and the depth of the venous wall will 
be noted. The focal depth on the device will be set to measure shear wave propagation in the walls of the vein 
and in the thrombus. Measurements will be made at multiple locations along the veins length. 
 
 
Human Subjects 
Recruitment of Subjects: Informed written consent will be obtained prior to the participation in the study and 
recorded in clinical documents as per Institutional stipulations. Each patient will be contacted by the principal 
investigator or IRB approved designees.  The potential risks to participants will be minimal. The ultrasound 
output level used in this study is well under the current FDA safety limits for diagnostic ultrasound. No 
additional drugs or invasive procedures will be used in their study. The decision to participate in this study or 
not will not affect the treatment of patient subjects. This study involves minimal risk to the patients. All 
participants included in this study must have given authorization for use of their medical records in research. All 
subject data will be collected, reviewed, and protected according to current HIPAA regulations and as stipulated 
by the IRB. The data will be analyzed anonymously and all results will only be published in aggregate.   
 
Resources:  
 Funding for the vascular boot and vascular studies (ultrasound, venous plethysmography) will be 
through the Vascular Center research fund.  
 
 
Check all that apply. If none apply, leave blank: 
 
  This is a multisite study involving Mayo Clinic and non-Mayo Clinic sites.  
When checked, describe the research procedures/activities being conducted only at Mayo Clinic: 
 
  Mayo Clinic staff will be engaged in research activity at a non-Mayo Clinic site.  When checked, provide 
the location and a detailed description of the Mayo Clinic research staff involvement. 
 
 
  This study is to establish and/or maintain an ongoing database or registry for research purposes only. 
 
  The research involves contact or interaction with subjects, for example, surveys, questionnaires, 
observation, blood draw. 
 

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  The study involves photographing, audiotaping or videotaping subjects (and guests).  
 
Blood Collection 
 
If this study involves prospective blood collection by finger, heel, ear stick or venipuncture, complete the 
following:  
 
 
  From healthy, non pregnant, adult subjects who weigh at least 110 pounds. For a minimal risk 
application, the amount of blood drawn from these subjects may not exceed 550ml in an 8 week period 
and collection may not occur more frequently than 2 times per week. 
Volume per blood draw: _____ml   
Frequency of blood draw (e.g. single draw, time(s) per week, per year, etc.) _______ 
 
 
  From other adults and children considering age, weight, and health of subject. For a minimal 
risk application, the amount of blood drawn from these subjects may not exceed the lesser of 50 ml or 3 
ml per kg in an 8 week period, and collection may not occur more frequently than 2 times per week. 
Volume per blood draw: _____ml 
Frequency of blood draw (e.g. single draw, time(s) per week, per year, etc.)_______  
 
 
Review of Chart, Images, Specimens 
Provide the date range for collection of data and/or specimens that will be included in your research dataset.  
Example: 01/01/2000 to 12/31/2013 or all records through mm/dd/yyyy.  
For a retrospective chart review, enter the date range:   
 
Check all that apply: 
 
  This study involves only data and/or specimens that exist at the time this application is submitted to the IRB 
(IRB submission date). No data or specimens will be collected beyond this date.  
 
 
  This study involves only data and/or specimens that will be collected after submission to the IRB. 
 
  The study involves data and/or specimens that exist at the time of submission to the IRB and data and/or 
specimens that will be collected after submission to the IRB, for example a study that includes collection of 
existing data and prospective collection of specimens. 
 

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  Data and/or specimens used in this study are collected under another IRB protocol. When checked, provide 
the IRB number(s) from which the research material will be obtained. When appropriate, check the box below 
to attest that subjects have provided consent for future use of their data and/or specimens, as described in this 
protocol.  
 
 
IRB Number/s - Data Only:  _____________________________________________ 
 
IRB Number/s - Specimens Only: _________________________________________ 
 
IRB Number/s - Data and Specimens:  _____________________________________ 
 
Note:  When subjects provided consent for use of their data and/or specimens, as described in this protocol. 
 
  Other data sources will be utilized in this study, e.g. receiving data/specimens from an external party. When 
checked, provide all data sources: 
Data Confidentiality, HIPAA Subject Identifiers 
 
Review the list of subject identifiers below and, if applicable, check the box next to each subject identifier being 
recorded at the time you are collecting/abstracting data/specimens for use in this study. 
 
Subject Identifiers:  Individually identifiable information, including demographic data, that identifies the 
individual or for which there is reasonable basis to believe it can be used to identify the individual.  NOTE: 
Identifiers apply to subjects enrolled in your study and to the subject’s relatives, household members, 
employers, etc. 
 
Internal refers to subject identifiers that will be included in the dataset maintained by the study team. 
 
External refers to subject identifiers that will be shared with persons outside of the immediate study team, for 
example, sent to an external collaborator or shared with a national registry.  
 
 
SUBJECT IDENTIFIERS 
Check all that apply 
INTERNAL 
IDENTIFIER 
EXTERNAL 
IDENTIFIER 
Name 
X 
 
Social Security number 
 
 
Medical record/patient registration number, lab accession, specimen or 
radiologic image number 
X 
 
Study number, subject ID, or any other unique identifying number, 
characteristic or code that can be used to link the identity of the subject to the 
data 
 
X 
 
Dates: All elements of dates [month, day, and year] directly related to an 
individual. Their birth date, date of death, date of diagnosis, etc.   
X 
 

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Note: Recording a year only is not a unique identifier.  
Medical device identifiers and serial numbers 
 
 
Biometric identifiers, including finger and voice prints, full face photographic 
images and any comparable images 
 
 
Web Universal Resource Locators (URLs), Internet Protocol (IP) address 
numbers, email address 
 
 
Street address, city, county, precinct, zip code, and their equivalent geocodes 
X 
 
Phone or fax numbers 
X 
 
Account, member, certificate or professional license numbers, health 
beneficiary numbers 
 
 
Vehicle identifiers and serial numbers, including license plate numbers 
 
 
If None of the above identifiers will be recorded or maintained in the 
dataset and/or sent outside of the study team, please check “None”. 
 None 
 None 
 
 
Statistical Information 
 
Note: Power analyses and study endpoints are not needed for a pilot or feasibility studies.  
 
 
 No statistical information.  
 
Statistical Considerations 
 
Data Analysis Plan:  
This is a pilot study including 30 volunteers.  Sample size cannot be calculated statistically due to lack of prior 
studies in the literature for those with DVT and use of warming boot. We will recruit up to 30 subjects who 
have valid measurements as described in the Data Analysis plan.  
 
The ultrasound measurements (elastography) will be assessed for validity using data analysis techniques and to 
examine the visualization of the venous wall to see if we can quantify the thrombosis.   
 
All statistical tests will be 2-tailed at a significance level of P<0.05. Demographic and physical characteristics 
laboratory values and comorbid conditions will be presented as mean ± standard deviation for continuous 
variables and as frequencies and percentages for categorical variables. Counts and percentages will be presented 
for categorical variables, while means ±standard deviations and 95% confidence intervals will describe 
continuous variables for which normality assumptions are met. If the distribution of a continuous parameter is 
skewed, transformations will be considered, or medians and interquartile ranges (IQR) will be presented. 
Continuous variables will be compared between 2 groups using unpaired t-tests. For comparison of continuous 
variables in ≥3 groups, one-way analysis of variance (ANOVA) followed by a Scheffé test may be performed. 
Frequencies will be compared using Chi square analysis. The correlation between 2 continuous variables will be 
determined using a linear regression analysis. Cox proportional hazards regression will be used to estimate the 

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association between thrombosis and short-term and long-term outcomes. Logistic regression will be used to 
estimate the association between thrombosis and binary outcomes. Adjustment for potential confounders will be 
accomplished through, either, covariance regression modeling, propensity score stratification, or propensity 
matching, according to the discretion of the statistical analyst. Statistical analyses will be performed using SAS 
and/or R software. 
    
 
Endpoints 
    
 
Primary:  
Early resolution of the DVT±PE as measured by the ultrasound. Partial recanalization will be defined by normal 
or diminished flow with distal augmentation and partial incompressibility of the vein (>50% or <50%). 
Complete recanalization will be defined by spontaneous phasic flow and a completely compressible vein. 
 
Secondary:  
i. Improvements in calf muscle function as measured by venous plethysmograthy (ejection fraction, VFR, 
PDR T90, EDV T90). 
ii. Improved quality of function : Godin questionnaire (validated questionnaires to measure physical 
activity), VEINES-QOL  (generic physical quality of life questionnaire) and Villalta Score (to assess 
Post-Thrombotic Syndrome) 
iii. Analyze whether shear wave elastrography will provide a more accurate and reliable method to assess 
the age of thrombosis and better quantification of thrombosis resolution. 
 
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