Physical Activity in Children at Risk of Post-thrombotic Sequelae: A Pilot Randomized Controlled Trial
Phase: NA
Conditions: Post Thrombotic Syndrome, Deep Vein Thrombosis
Sponsor: University of Texas Southwestern Medical Center

OFFICIAL TITLE: PHYSICAL ACTIVITY IN CHILDREN AT RISK OF POST- THROMBOTIC 
SYNDROME: A PILOT RANDOMIZED CONTROLLED TRIAL 
NCT NUMBER:      NCT03075761 
IRB APPROVED DATE:   MARCH 02, 2021 – PROTOCOL VERSION: 5.1 
 

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TITLE: Physical Activity in Children at Risk of Post-thrombotic 
Syndrome: A Pilot Randomized Controlled Trial 
 
ClinicalTrials.gov ID: NCT03075761 
 
PROTOCOL VERSION: 5.1 
PROTOCOL VERSION DATE: February 25, 2021 
 
FUNDING: 
CCRAC 
 
ROLES AND RESPONSIBILITIES: 
Ayesha Zia, MD, Principal Investigator 
Janna Journeycake, MD, Faculty Mentor 
Ravi Sarode, MD, Faculty Mentor 
Shellie Josephs, MD, Co-Investigator 
Keshav Menon, MD, Co-Investigator 
An Pham, MD, Co-Investigator  
Michele Salinas, PNP 
Niavana Salas, Clinical Nurse 
Tatonisha Green-Henderson, Clincial Nurse 
Kendra Malone, MPH, Clinical Research Coordinator 
Anna Winborn, CCRC, Clinical Research Coordinator 
 
 
 
 
 
 
 

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Abbreviations Table: 
 
ACCP  
American College of Chest Physicians 
BMI 
Body mass index 
CBC 
Complete blood count 
CHST 
Children’s Health System of Texas 
CT 
Computed topography 
CTEPH  
Chronic thromboembolic pulmonary HTN 
DVT 
deep vein thrombosis 
eCRF 
Electronic Case Report Form 
ECS 
Elastic Compression Stocking 
ED 
Emergency Department 
FMH 
Family medical history 
HEENT 
Head, eyes, ear, nose, throat 
HTC 
Hemostasis Thrombosis Center 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
ISTH 
International Society of Thrombosis and 
Haemostasis 
MRI/MRA 
Magnetic resonance imaging/magnetic resonance 
angiography 
PE 
Pulmonary embolism 
PHI 
Protected Health Information 
PTS 
Post thrombotic syndrome 
QOL/Peds QL 
Quality of Life/Pediatric Quality of Life 
ROC 
 Receiver Operator Curve 
SOC 
Standard of Care 
TEG 
Thromboelastography 
TG 
Thrombin generation 
TGP 
thrombin generation potential 
VTE 
Venous thromboembolism 
 
 
 
 
 
 
 
 
 
 

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BACKGROUND AND RATIONALE 
Venous thromboembolism (VTE) is a major and growing problem in 
children. A 70% increase in the annual rate of VTE in hospitalized 
children has been documented in the past decade[1]. VTE often 
collectively referred to as deep venous thrombosis (DVT) and pulmonary 
embolism (PE), is now considered an important endemic complication of 
tertiary care settings. Although often perceived as an acute disorder, 
VTE entails a long-term risk of persistent or progressive thrombosis, 
post-thrombotic syndrome (PTS), recurrence and post-PE syndrome, 
also 
called 
chronic 
thromboembolic 
pulmonary 
hypertension 
(CTEPH)[2]. Of all the VTE outcomes, PTS is the most frequent, chronic 
and debilitating complication[3]. As such, current therapy is merely 
focused on treating the acute VTE, not attempting to prevent late 
sequelae like PTS. Despite appropriate anticoagulation, up to one half 
patients will develop these poor complications within 2 years of the acute 
event[4].   
 
VTE is not merely a ‘nuisance’ medical problem. Rather, VTE is costly 
and burdensome to patients and society, both in terms of dollars spent 
and effect on quality of life and productivity[5]. The estimated health care 
costs directly attributable to pediatric VTE for care of secondary VTE are 
five times higher than costs with an idiopathic VTE ($95,120 vs. 
$20,238)[5]. These costs are expected to be much higher in the 
presence of adverse outcomes of thrombosis[6]. 
  
Although PTS is a direct and most frequent DVT complication in 
children, effective treatments are lacking and new innovative 
approaches to manage PTS are sorely needed. The 9th edition of the 
American College of Chest Physicians (ACCP) guidelines on 
antithrombotic Therapy in Neonates and Children, widely considered to 
represent the standard of care for pediatric thrombosis do not currently 
have any recommendations for management of pediatric PTS[7]. 
Recently, the American Heart Association issued a scientific statement 
to provide an up-to-date overview of PTS and concluded, “as a result of 
the paucity of studies in this area, it is not possible to make specific 
recommendations on the prevention or treatment of pediatric PTS”, 
highlighting this as an area in pressing need of scientific 
investigation[8]. Despite receiving early detection and appropriate 
anticoagulation, up to a quarter to one half of DVT patients develop 
PTS[3]. Lack of effective and evidence-based treatment for PTS is a 

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source of difficulty and frustration for patients with PTS and clinicians 
alike. I propose that using technology to alter behavior and implement 
life style interventions may help curb the epidemic of DVT and its 
outcomes.  
 
Background  
PTS is the most frequent and debilitating complication after extremity 
DVT 
The annual rate of VTE- encompassing DVT and PE- has increased by 
70% in hospitalized children in the past decade, to approximately 1 in 
200[1, 6]. Accompanying this increase is the attendant increase in 
chronic sequelae of VTE, the most frequent of which is the PTS. PTS is 
the most burdensome complication of DVT. The lasting signs and 
symptoms of PTS include chronic pain, cramping, swelling, varicose 
collateral veins and in extreme cases, painful venous ulcers[9]. 
Children with PTS have an impaired QoL[10]. 
 
Children at risk of or with PTS do not have any effective, evidence-based 
treatments available  
In contrast to the gains achieved in treating acute DVT, there are very 
few treatment options for PTS in children. Clinicians often prescribe 
physical compression methods to counteract increased venous 
pressure. However, the SOX trial, the largest randomized trial so far of 
elastic compression stockings in adults did not prevent PTS with two 
years of use after a first proximal DVT[11]. Venoactive medications and 
surgical treatments for PTS such as venous valve repair or venous 
bypass have primarily been evaluated in small adult series only[12, 13]. 
Novel approaches to the treatment are sorely needed. 
 
 
Enhancing activity post DVT represents a new paradigm for pediatric 
PTS 
The pathophysiology of PTS involves: 1) damage to venous valves by 
thrombus or by associated inflammatory mediators[14], which causes 
valvular reflux; and 2) residual venous obstruction due to thrombus 
persistence leading to impaired venous return[15, 16]. Both processes 
result in venous hypertension. When DVT is diagnosed, standard 
anticoagulation treatment prevents clot extension and embolization, but 
does not lyse the acute clot. Follow-up studies of patients with DVT 
treated with anticoagulants have shown only partial clearance of 
thrombus and even in patients who do achieve clot lysis, permanent 

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damage to the valve occurs. This is thought to be via thrombus induced 
activation of inflammation or scarring associated with acute and 
resolving thrombosis, leading to valve incompetence as shown in studies 
of adults[14]. Aerobic activity increases oxygen delivery to muscle fibers, 
improves muscle metabolism and oxidative capacity[17]. It is plausible 
that this may counteract the hypoxic damage to muscle contractile fibers 
and decreased muscle perfusion caused by venous hypertension[18]. It 
may aid faster venous recanalization by improving blood flow. Indeed, 
adult data show a tendency for higher levels of self-reported physical 
activity in 300 patients one month after DVT to be associated with less 
severe PTS three months later, suggesting that increasing physical 
activity may reduce symptoms of PTS[19]. Similarly, in another 2-center 
Canadian pilot study, 42 adults with PTS were randomized to 6 months 
of exercise training or control. Supervised exercise training was 
associated with improvement in PTS severity, QoL, leg strength and leg 
flexibility[20]. The potential benefits of enhanced physical activity have 
not been previously studied in the pediatric setting.  
 
Activity trackers show promise in incentive based activity trials in children 
While previous efforts have relied on self-report measures to increase 
activity, more recently direct and objective fitness trackers have been 
used to track population levels of physical activity in children and 
adolescents[21, 22]. One such tracker, the Fitbit has shown high 
correlation with steps recorded by an accelerometer, accuracy when 
compared to a gold standard pedometer and has been validated[23]. 
Recent studies show that tailored intervention, such as responses and 
messaging created to address the needs of individuals on baseline 
steps/day maybe efficient and effective[24, 25]. Indeed, daily step target 
to measure physical activity in children has been shown to increase as a 
result of participating in activity tracker-based interventions in conjunction 
with daily step goals and incentives[26].  
 
Conceptual model of endothelial dysfunction and 
impaired 
fibrinolysis 
supports 
biomarker 
assessment in PTS 
The overall progression of the initial thrombotic 
event towards propagation or resolution depends 
on the balance between: 1) endothelial dysfunction 
and inflammation, and 2) residual venous 
obstruction from impaired fibrinolysis. Standard 
anticoagulation relies upon endogenous fibrinolytic 
 
Figure 1: Conceptual 
pathophysiological 
model underlying 
PTS. 

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mechanisms to remove thrombus, which are often impaired in children 
with DVT[27]. Even in those who achieve clot lysis, permanent damage 
to venous valves occurs frequently, likely via thrombus-induced activation 
of inflammation[14]. I propose that a bidirectional relationship between 
inflammation and abnormal fibrinolysis drives a feedback loop resulting 
in increased complications after DVT over time, including PTS (Figure 
1). Bringing together this insight and our current knowledge of 
coagulation assessment by global assays -focusing on PTS- may 
uncover new and better approaches to identify and treat at-risk 
individuals. Exercise has shown to decrease thrombin generation and 
fibrinolytic markers in children as well as adults. Alterations in the level of 
related biomarkers, reflecting coagulation activation, inflammation and 
markers of fibrinolysis, may be of interest when assessing a patient’s risk 
of developing PTS.  
 
Extrapolating from the above, I propose that an activity regimen for 
children after lower extremity DVT is unlikely to be harmful, maybe of 
benefit and needs further study. In the past, investigator initiated trials 
involving prevention or treatment of pediatric VTE have been terminated 
because of feasibility concerns[28]. Accordingly, a pilot study to establish 
feasibility of this approach is required before proceeding to a fully 
powered, definitive trial. 
 
INNOVATION 
This proposal is innovative because: (1) it will be the first trial to integrate 
modern technological tools, such as activity trackers to improve 
adherence to life style interventions aimed at preventing PTS. Although 
there are many ways to increase physical activity in children, my goal is 
to use a simple, user-friendly tool that will appeal to children across a 
broad age range; (2) activity/exercise as a therapeutic modality in 
children with DVT has not been previously studied; (3) there have been 
no previous randomized trials of PTS prevention or treatment in children; 
and (4) trial outcomes include patient reported outcomes (i.e. QoL) and 
laboratory based biomarkers. 
 
PRIMARY AIM: 
To demonstrate the feasibility and potential effectiveness of a personal 
“fitness tracker” to improve adherence to an activity regimen following an 
initial DVT in children.  
Hypothesis:  The intervention of using a fitness tracker to adhere to an 
activity regimen will be acceptable, and effective in improving adherence 

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to a post-DVT activity regimen in children. I propose a validated, fitness 
tracker, the Fitbit, to improve adherence to a 16-week activity regimen in 
a pilot randomized controlled trial (RCT), in which 44 subjects with DVT 
will be assigned to the intervention group or to a comparison group. The 
primary outcomes will consist of a) feasibility indicators determined a priori 
(eligibility, consent, adherence, retention) and b) estimates of effect size 
associated with the prescribed activity regimen, by describing within-
subject change in QoL and ‘potential’ biomarkers of PTS pre and post 
intervention in each group. 
 
STUDY DESIGN (Figure 2) 
The study design is that of a pilot RCT to test the feasibility of the 
proposed activity tracker to 
increase activity in children post 
DVT, against standard 
practice, which currently 
consists of providing education 
about PTS and instructions to 
‘be active’. I will use a validated 
activity tracker, the Fitbit and its 
data platform- the Fitabase. 
 
METHODS 
 
I. 
STUDY SETTING 
All newly diagnosed patients with first, lower extremity DVT diagnosed at 
Children’s Health System of Texas (CHST) or referred to the Hemostasis 
Thrombosis Center (HTC) at CHST who have completed 12 weeks (±2 
weeks) of anticoagulation therapy, will be approached for recruitment. 
 
II. 
ELIGIBILITY CRITERIA 
Parents must provide written, informed consent before any study 
procedures occur. 
 
INCLUSION CRITERIA 
RATIONALE 
1.  Age 7-21 years 
 
VTE is seen across all age groups 
2.  A radiologically confirmed, acute, 
proximal (iliofemoral and 
femoropopliteal) first lower 
extremity DVT and/or confirmed, 
Population with proximal DVT 
and/or PE deemed to be at highest 
risk of PTS 

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acute pulmonary embolism 
(unilateral or bilateral) 
3.  12 weeks (±2 weeks) after starting 
anticoagulation 
To mitigate the small theoretical 
risk of clot dislodgement with 
activity soon after DVT diagnosis 
4.  Out-patient ambulatory status 
Protocol involves increasing activity 
 
 
 
EXCLUSION CRITERIA 
 
1.  Contraindication to increasing 
activity such as patients with 
juvenile arthritis, poor balance, 
congestive heart failure etc. 
Protocol involves increasing activity 
 
III. STUDY PROTOCOL 
 
The study has 3-4 planned visits, which will coincide with the standard 
of care visits.  
 
Screening  
The parents/legal guardians will be given an explanation about the 
study and informed consent and/or assent will be obtained. This may 
occur in the inpatient or the outpatient setting. Demographic 
information and relevant medical history, including results of scans and 
thrombophilia testing will be collected. All medications, including 
anticoagulant medication received for the thrombotic event will be 
recorded.   
a. Baseline Assessments (collected as SOC (standard of care)):   
i. History and Physical Examination: 
1. Detailed history regarding medical disorders 
predisposing to thrombosis and potential triggers 
(birth control pills, recent travel or surgery or 
immobility) and predispositions (thrombophilia, 
obesity etc.) will be collected. 
2. Review of existing medical records recorded on 
Children’s Medical Center electronic medical 
record to review past medical, family and social 
history will be performed.   
3. Comprehensive physical exam (PE) consisting 
of vital signs, general appearance, head, eyes, 

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ears, nose, throat (HEENT), cardio-respiratory, 
abdominal, extremities and skin will be 
performed at each visit as per standard of care. 
ii. 
Laboratory: 
1. Complete blood count (CBC), reticulocyte count, 
baseline coagulation studies, and a 
comprehensive thrombophilia panel performed 
as SOC will be recorded. 
 
 
 
iii. 
Treatment: 
1. Information on anticoagulant therapy 
(medication of choice, intensity of 
anticoagulation, planned duration of therapy) 
prescribed as per the treating physician will be 
collected for subjects who meet eligibility criteria 
and whose parents provide written informed 
consent  
iv. 
Radiological: 
1. All information related to site, extent and venous 
segments involved of the thrombotic venous 
segment at the time of diagnosis, and at 
completion of therapy will be collected. 
Information on reflux assessment at the time of 
end of therapy ultrasound will also be collected. 
v. 
Assessment of Post-thrombotic syndrome (PTS): 
All subjects with will be assessed with standardized, 
validated outcome assessment tools: the Manco-
Johnson Instrument and the modified Villalta scale 
starting at 6 months post diagnosis of DVT as per 
standard of care. See appendix 1 for these scales. 
 
b. Study Interventions: 
i. 
Study procedures/Randomization: 
Eligible, consenting subjects will be individually 
randomized via a web-based program to the Fitbit arm 
or the control arm (1:1 allocation ratio).  
1. Intervention (Fitbit) arm. The intervention arm will 
wear a Fitbit for a 16-week period (Figure 2). 
General Principles of an aerobic activity regimen: 

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As the principal muscles affected by PTS are the 
lower limb muscles, we have opted to use a 
walking-jogging program to capture steps/day by 
the Fitbit. This will target all potentially affected 
muscles 
(quadriceps, 
hamstrings 
ad 
gastrocnemius/soleus). If preferred by the subject, 
other weight bearing exercises could replace the 
walk/jog, for example, dancing or team sports such 
as basketball or volleyball. Because of the 
unfamiliarity with activity trackers, subjects will be 
provided with hands-on training to promote 
successful use of the Fitbit and Fitabase.  
a. Schedule and procedures (Table 1): After 
consent (baseline visit), subjects in this arm will 
receive a standardized 15-20 minute education 
session  on PTS (what constitutes PTS, why 
patients get it, how to manage it) and enhanced 
activity after DVT. Subjects will be asked to wear 
the Fitbit for a period of four weeks to establish 
baseline or ‘habitual’ activity. Using steps/day 
data received at the end of four weeks, we will 
determine an individualized activity prescription 
of ‘target  
steps/day’, corresponding to a 25% increase 
above the baseline.  
 
Table 1 
Visit 1 
Visit 2 
Visit 3 
  
12 wks post DVT 
Dx (±2 weeks) 
16 wks after 
Visit 1 (±4 
weeks) 
8 wks after Visit 2 
(±4 weeks) 
  
SOC Visit  
SOC Visit 
SOC Visit (Exit 
Visit) 
ALL SUBJECTS 
  
  
  
Informed Consent 
X* 
  
  
Full Medical History 
and Exam 
X 
X 
  
Biomarker Testing^ 
X$ 
X 
X 
FVIII, D-dimer, CRP 
X 
X 
X^^ 
QOL forms 
X 
X 
X 
PTS Assessment 
  
X 
 X 
ECS and Log 
X 
X~ 
X~ 
Activity Logs/ 
Questionnaire 
X 
X 
X 
Medication Log*** 
X 
X 
X 

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Phone Calls (monthly) 
X 
X 
  
Formal Education 
Session 
X 
  
  
Honoraria** 
X 
X 
X 
SUBJECTS IN FITBIT 
ARM 
  
  
  
Hands on Fitbit 
Training 
X 
  
  
Steps/Day Data 
(weekly) 
X 
X 
X 
Phone Calls (weekly) 
X 
X 
  
Return Fitbit 
  
X  
 
 
 
 
 
 
 
 
Subjects will be asked to maintain the 
target steps/day for a period of 8 weeks. At 
the end of this period, subjects will either 
maintain the increased activity or resume 
habitual activity for another 4 weeks, per 
patient preference. A phone call will be 
made periodically for encouragement and 
to ensure adherence to the activity regimen 
throughout the initial 16-week period. 
Subjects will have another visit 8 weeks 
(±4 weeks) after the end of the 16-week 
period corresponding to the ~ 9 month 
post-diagnosis SOC visit. For subjects 
having 
difficulty 
with 
the 
activity 
prescription or use of the Fitbit, a phone 
call or face-to-face session will be 
arranged 
with 
the 
study 
research 
coordinator and physical therapist. Such 
changes will be carefully documented. 
2. Control arm. The control intervention will consist of: 
1) a standardized 15-20 minute education session  
on PTS (what constitutes PTS, why patients get it, 
how to manage it) and benefits of enhanced activity 
*Informed consent can occur any time after DVT diagnosis until Visit 1; ^Biomarker 
testing includes: D-Dimer, FVIII, Thrombin generation, markers of fibrinolysis; 
$Biomarker testing at Visit 1 may be combined with other SOC labs for those still on 
anticoagulation at this time; ~ only ECS logs; ** $25 at Visit 1 and 2, and $50 at Visit 3; 
***Medication logs only for participants on Rivaroxaban or Xarelto; ^^Factor VIII, D-
dimer, and CRP can be completed as research procedures at Visit 3 for participant’s 
whose values were within normal range at Visit 2. 

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(activity will not be specifically addressed and will 
be up to the choice of the subject) after DVT; 2) 
monthly phone contacts will be made to check in 
with patients/families and remind them about 
completion of activity logs and follow-up visits.  
 
Study assessments for both arms 
1. Biomarker testing: Blood for biomarker  of 
coagulation activation  (D-dimer, FVIII, thrombin 
generation), markers of inflammation (CRP), and 
markers of fibrinolysis {modified 
thromboelastogram (TEG) with fibrinolysis, PAI-1, 
will be obtained at each visit One and a half extra 
teaspoons will be collected at each visit for a total 
of 4.5 teaspoons collected during the subject’s 
time in the study. 
2. Elastic compression stockings (ECS) 
i. Subjects in both arms will be provided with 
custom fitted compression stockings and their 
use will be tracked using ECS logs throughout 
study 
period. 
In 
general, 
SOC 
recommendations are to wear ECS starting 
after the diagnosis of DVT and to continue as 
long as they provide benefit in regards to pain 
and swelling, up to a period of two years post 
DVT diagnosis. For the sake of the study, their 
use will be documented strictly during the 
study period. 
3. Activity log completion during the intervention period 
will be used to record physical activities. These logs 
will capture information on the type of activity, and 
the frequency and duration of activity 
4. Quality of life (all visits): QoL will be measured using 
the PedsQL TM which is a modular approach to 
measure generic health related quality of life in both 
healthy children and adolescents, as well as those 
with acute and chronic health conditions. It consists 
of structured interview with the parents and the child 
with 23 items divided among 4 sub-scales to assess 
function in 4 domains: Physical; Emotional; social; 
and School. The instrument is brief, takes 15 

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minutes to administer, and is developmentally 
adjusted for a broad age range. 
5. PTS : Modified Villalta’s scale and Marilyn-Manco 
Johnson Instruments, the two validated PTS scales, 
will be used to diagnose and grade severity of PTS 
at the 6 month mark corresponding to Visit 2 and the 
9 month mark (corresponding to Visit 3). The 
principal and co-investigators will complete PTS 
evaluations as is standard of care at Visit 2 and Visit 
3. In addition, a blinded PTS assessment will also be 
completed by the physical therapist (currently 
routinely assigned to the Thrombosis and Bleeding 
Disorders Program) at both visits. 
6. Medication adherence: Anti-Xa and INR will be 
collected for participants on lovenox and warfarin, 
respectively. 
Families 
with 
participants 
on 
Rivaroxaban will be asked to complete a medication 
log because no assay will be used to measure 
adherence for Rivaroxaban. The medication log will 
measure compliance with anticoagulation during 
active treatment period and will include the subject’s 
specific anticoagulant, dose, and date and time 
medication was taken. 
 
See 
appendix 
for 
copies 
of 
above 
questionnaires, 
administration 
and 
scoring 
procedures. 
 
IV. PARTICIPANT TIMELINE  
All study visits will coincide with standard-of-care visits for patients with 
VTE at our center. All visits will be allowed a time window to 
accommodate preferences of subjects and families  ± 2 weeks for visit 1 
and ±4 weeks for visit 2 and 3. 
 
Study assessments: (Table 1 for schedule of events).  
 
V.MODIFICATIONS 
a. RISKS  
i. 
Blood Draws: Risks associated with drawing blood 
include minimal discomfort and/or bruising, infection, 

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excess bleeding, clotting, and/or fainting are 
possible. 
ii. 
Doppler Ultrasound: There are no risks from the 
sound waves used for ultrasound.  The test is not 
painful and does not have any radiation. This will be 
done as per standard of care. 
iii. 
Skin irritation or allergies with wearing the activity 
tracker 
iv. 
Injuries or falls related to increased physical activity 
v. 
As we plan to use an online data format to gather 
subject information, security of information may be a 
concern. Fitabase code and databases reside on 
the Microsoft Windows Azure Platform and rely on 
the robust security, both physical on-premise 
guarding, and over network, provided as part of that 
platform. Windows Azure runs in data centers that 
comply with key industry standards for security and 
reliability. 
vi. 
Loss of confidentiality related to use of protected 
health information (PHI). 
 
b. BENEFITS 
Study subjects may discontinue their participation at any 
time. However, information regarding the potential benefits 
to continue on the study will be made explicitly clear prior to 
their discontinuation.  
i. 
Whether or not the subject or their family consents, 
the schedule of the clinic visits will remain the same 
as proposed in the study. All patients with 
thrombosis are followed until they become adults 
with more frequent visits in the first 24 months after 
the acute event and then yearly afterwards. 
ii. 
Subjects will also derive benefit from the careful 
monitoring of activity after thrombosis as well as 
interval telephone calls to promote compliance and 
answer questions.  
iii. 
Successful monitoring after the acute thrombotic 
event is expected to improve their overall well-being 
and possibly prevent any physical, cardiac, cognitive 
and behavioral abnormalities resulting from 
thrombosis.  

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iv. 
Subjects will be provided with custom fitted 
compression stockings as part of the study.  
Compression stockings help to relieve swelling and 
pain and reduce the risk of developing post-
thrombotic syndrome after a DVT. Although 
prescribed for all post DVT patients, many do not 
use them due to the expense of the stockings and 
lack of availability. 
c. Every effort will be made to retain study subjects in the trial 
for the entire ~9 months to enable complete follow-up and 
data collection. 
 
V. 
WITHDRAWAL/TERMINATION 
a. Subjects that ‘No Show’ for Visit 2, are unable to provide 
>80% of the ‘steps/day’ data and are unable to be 
contacted/rescheduled. Data already collected will be used 
in the analysis. 
b. Subjects for whom an alternative diagnosis discovered. 
c. In the investigator’s medical opinion, it is best to withdraw 
the subject from the protocol 
 
VI. 
CONCOMITANT CARE 
a. Patients who initially receive thrombosis care elsewhere 
prior to enrollment may participate in the study if all 
eligibility criteria are met. 
b. Subjects who need to continue long term prophylactic 
anticoagulation will still be eligible and will be included at 
discretion of their attending hematologist. 
c. The activity tracker, the Fitbit, is made up of a flexible 
durable material used in many sports watches (and one 
that does not contain latex) with a surgical grade stainless 
steel clasp and contains traces of nickel. It is meant to be 
worn day and night on the wrist. Because there’s a 
possibility of skin irritation and allergies with any type of 
jewelry, all participants in this study will be warned and care 
and wearing tips will be provided. They will be monitored for 
any skin problems during the clinic visits and a treatment 
plan will be made in collaboration with their primary 
pediatrician should any skin irritation develop. I will ask to 
be notified immediately of any such occurrence at home 
and will then contact the participant or the family to assess 

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their clinical condition and make a treatment plan based on 
the severity of the skin condition. 
 
VII. OUTCOMES AND POWER CALCULATIONS 
Primary Outcomes will be 1) feasibility indicators (Table 2) 
measured throughout trial. The level of adherence in the 
intervention group will be calculated as the proportion meeting the 
weekly steps/day goal during the 
‘active’ 8-week period of the total 16 
weeks of intervention as determined 
by the Fitabase data platform output, 
and 2) change in clinical outcomes 
such as PTS biomarkers at baseline and Visit 2, and QoL (at all 
visits).  Secondary outcome: I will assess for PTS with validated 
scales at the 6 and 9 month follow-up visit as is standard of care.  
Analyses: The objectives of this trial are to assess the feasibility of 
the design and to measure the effect size of the intervention. All 
analyses will therefore be descriptive and will be performed once, 
at the end of the trial. Means and standard deviations, or when 
appropriate, medians and semi-inter-quartile ranges will be used 
to describe demographic and clinical characteristics. Reasons for 
non-eligibility, lack of consent, dropout and lack of compliance will 
be documented. For feasibility indicators, we (study investigators 
and Song Zhang-biostatistician) will describe rate of eligibility 
(proportion of subjects screened who fully meet trial eligibility 
criteria to participate in the trial), rate of consent (the proportion of 
eligible subjects who consent to participate) and rate of loss to 
follow-up (proportion of randomized subjects who drop out of the 
trial, in total, and by allocated intervention). We will also describe 
the level of compliance in the intervention group, calculated as the 
ratio of who complied with the activity prescription to the number 
given the prescription. We will consider the trial successful if the 
following criteria are met: rate of eligibility ≥ 30%, rate of consent 
≥ 30%, rate of loss of follow-up <20%, level of compliance ≥ 60% 
and proportion of subjects who complete the trial ≥ 80%. For the 
clinical outcomes (including the secondary outcomes), we will 
describe change (means and standard deviations) in the 
intervention and control groups, from baseline to 6 month, in the 
QoL scores and PTS biomarkers. Each change score will be 
interpreted for clinical significance and common responses 
counted for frequency of occurrence. The impact of the activity 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
 
tracker to promote continued physical activity in the last 2 weeks 
of the 12-week period would be explored.  We will also assess the 
impact of covariates such as age, sex, BMI, baseline activity, 
intensity of activity over and above the activity prescription, on 
change scores.  
Sample size calculation: For reasons of practicality and cost, we 
have decided to limit the size of this pilot RCT to 44 subjects (20 
in each arm; 22 after considering a 20% drop out rate). We 
anticipate that the probable primary outcome for the larger trial 
will be change in rate of PTS development and/or progression. 
This trial may also provide compelling preliminary data for future 
studies. For example, if this intervention reduces the risk of PTS 
from 26% (known probability of PTS) to 10%, this pilot study has 
71% chance of showing a promising trend (p-value<0.2) that the 
intervention reduces the risk of PTS. We acknowledge that the 
small size of this pilot study limits the validity of the findings; 
therefore, we will be cautious with such analyses. 
 
 
I. 
RECRUITMENT 
a. Information about the clinical study will be provided via 
direct communication by study investigators and physicians 
at Children’s Medical Center including ED physicians, 
hospitalists, and general pediatricians attending on the 
inpatient medicine services and outpatient continuity clinic 
as well as house officers.  
b. Information regarding the study will be available on the 
University of Texas Southwestern clinical trials website and 
at clinicaltrials.gov. 
c. Potential subjects will be identified through review of new 
patient referrals to Children’s Medical Center, inpatient 
admissions and/or consultations for thrombosis.  
d. Each subject will receive financial compensation for 
participation. Payment will be made at completion of the 
study visits at Visits 1 and 2 ($25 each) and at the end of 
Visit 3 ($50) based on attendance and return of the tracking 
logs. 
e. Expected recruitment rate will be 2-3 participants per 
month. 
f. Duration of recruitment period is expected to be 
approximately 24 months. 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
 
g. Assessment of study recruitment and retention will be 
performed when 20 participants have been enrolled on the 
study, or at approximately 9 -12 months. 
 
II. 
DATA COLLECTION, MANAGEMENT AND ANALYSIS 
a. DATA COLLECTION METHODS  
Clinical information will be collected from each patient’s 
electronic medical record at all visits while on study.  This 
information will include the following: name, gender, race, 
ethnicity, date of birth, current medications, social history, 
patient medical and hospitalization history; family history, 
physical exam and laboratory results. Additional information 
to be collected from self reported diaries include adherence 
data and adverse reaction data. Returned diaries will be 
maintained in a research binder, while medical history, lab 
results, and medications will be recorded in the electronic 
medical record and then on electronic Case Report Forms 
(eCRF). Contact phone numbers for parents and relatives 
will be collected for the interim visit phone calls. 
 
b. DATA MANAGEMENT  
The eCRF will be housed in UT Southwestern REDCap. 
REDCap is a self-managed, secure, web-based data 
support system.  The data is backed up offsite nightly and 
hosted in a secure environment maintained by Information 
Resources. This password protected study database will 
include a subject’s personal identifiers and all Protected 
Health Information (PHI) such as medical history. All 
personnel who will be accessing the data will be trained in 
REDCap and have individual user ID and passwords. 
Subjects will have a study ID number that will be utilized in 
lieu of personally identifiable information for all research 
data provided to statisticians.  
 
c. STATISTICAL ANALYSES  
The following will be calculated: the proportion of screened patients 
who fully met trial eligibility criteria, the proportion of eligible patients 
who consented to participate, the proportion in the physical activity/ 
Fitbit group who adhered to prescribed activity, and the proportion of 
randomized patients who completed the trial (in total, and by allocated 
intervention). The feasibility outcomes will be reported descriptively 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
 
using mean (standard deviations [SD]) for continuous outcomes, and 
raw counts (%) for categorical outcomes are reported. For the clinical 
end points, using an intent-to-treat analysis that includes all participants 
with data at baseline and 6 months (end of the intervention period), 
within-patient change from baseline (diagnosis or pre-VTE levels) to 6 
months (mean, SD) in the physical activity will be compared to 
standard care in the following measures: D-dimer, FVIII, CRP, thrombin 
generation assay parameters of endogenous thrombin potential and 
peak thrombin, fibrinolysis on thromboelastography, QoL (total and 
physical), selfreported physical activity levels, and PTS (change from 6 
to 9 months). This will be averaged for each group, and within-group 
differences will be compared between the standard care and physical 
activity groups using a t test. ECS use will be descriptively described 
but not included in a formal analysis. 
ETHICS AND DISSEMINATION 
 
I. 
RESEARCH ETHICS APPROVAL 
This protocol and template informed consent forms will be 
reviewed and approved UT Southwestern IRB with respect to 
scientific content and compliance with applicable research and 
human subjects regulations. Subsequent to initial review and 
approval, the investigators will submit progress reports to the 
IRB at least annually and at study closure. 
 
II. 
PROTOCOL AMMENDMENTS 
Any modifications to the protocol, which impact the conduct of 
the study, or potential risk/benefit of the participants, will 
require a formal amendment to the protocol with IRB approval. 
 
III. 
CONSENT OR ASSENT 
Informed consent will be obtained after information has been 
provided to patients’ families along with a discussion of the 
risks and benefits along with opportunity for questions. 
Consent forms will be provided for all parents involved in the 
trial. 
 
IV. 
CONFIDENTIALITY 
Records of each patient’s participation in this study, including 
the original informed consent document, will be kept in a 
locked file cabinet in the Center for Cancer and Blood 
Disorders at Children’s Medical Center. Access to local 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
 
research files is limited to treating physicians and nurses, data 
management personnel and the Institutional Review Board. 
These entities may need to view data for quality assurance 
and data management purposes. Confidentiality of all medical 
records would be maintained by correct identification of the 
appropriate person before viewing the medical record and 
ascertaining the reason for the viewing of the medical records.  
 
V. 
DECLARATION OF INTERESTS 
Ayesha Zia, MD, No financial or other competing interests. 
 
VI. 
ACCESS TO DATA 
All trial investigators will be given direct access to the data 
sets.  
 
VII. ANCILLARY AND POST TRIAL CARE 
Participants who develop adverse outcomes of thrombosis 
upon study completion will receive treatment at discretion of 
their provider.  
 
VIII. DISSEMINATION POLICY 
Every attempt will be made to reduce the interval between 
completion of data collection and the release of the study 
results. We expect to take about 3 to 4 months to compile the 
final results and submit them for presentation at a prominent 
society meeting and publication in a high profile peer reviewed 
journal. The study results will also be released to the 
participating physicians, referring physicians, subjects and the 
general medical community. 
 
 
APPENDICES 
 
Appendix 1 - Components of the standardized outcome measures for 
post thrombotic syndrome (PTS) employed in pediatric studies, 
including the Manco-Johnson Instrument (A) and the modified Villalta 
scoring system (B). 
 
Appendix 2 - Health-Related Quality of Life (QoL) Instruments 
 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
 
Appendix 3 – Medication Administration Log (For participants on 
Rivaroxaban) 
 
Appendix 4 – Electronic Compression Stocking Log 
 
Appendix 5 – Activity Log/questionnaire (Initial and Follow Up), Godin 
questionnaire 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix 1 
 
 
A- Manco-Johnson Instrument (MJI) 
 
 
PHYSICAL FINDINGS 
Please measure to nearest tenth of one centimeter 
Limb Circumference 
Measurements 
Right 
Left 
Mid-proximal limb 
________._____ 
cm 
________._____ 
cm 
Mid-distal limb 
________._____ 
cm 
________._____ 
cm 
 
Basic CEAP Mark an “X” where applicable/present. 
Physical Findings 
Right 
Left 
0. No visible or palpable signs of 
venous disease 
 
 
1. Swelling, with or without pitting 
edema 
 
 
2. Dilated collateral circulation of 
extremity only 
 
 
3. Skin changes ascribed to venous 
disease (i.e., pigmentation, venous 
eczema) 
 
 
4. Skin changes as in 3 with 
ulceration or superior vena cava 
syndrome 
 
 
 
 
 

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FUNCTIONAL FINDINGS (Pain Symptoms) 
Wong-Baker Faces Pain Rating (Oucher Scale: Score 0-5 for each) 
Pain Outcome: Wong-Baker 
(Oucher) Scale 
Right 
Left 
With aerobic exercise only 
 
 
With activities of daily living 
 
 
At rest 
 
 
If pain is present (i.e., score 1-5): Does the pain interfere with activities?     
   YES         NO 
Comments: 
_______________________________________________________________
________________________ 
 
Aerobic exercise only: Implies that symptoms are present only when child 
engages in vigorous age-appropriate sport such as running, lap swimming, 
soccer, basketball or volleyball. 
 
Activities of daily living: Implies that a child is symptomatic when engaging 
in ordinary age-appropriate activities in the home, school and community short 
of organized sports and vigorous aerobic activities. These symptoms limit and 
alter a child’s ordinary day-to-day activities such as walking at school, 
shopping with the family or participation in a birthday party. 
 
At rest: Implies a constant presence of symptoms that is independent of 
activity. The child’s daily life is severely limited by symptoms. 
 
Signs 
Edema 
Dilated superficial collateral veins 
Venous stasis dermatitis 
Venous stasis ulcers 
 
1 
1 
1 
1 

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Symptoms 
Chronic lower-extremity pain 
 Limiting aerobic activities 
 Limiting activities of daily 
living 
 At rest 
 
 
0-5 
0-5 
0-5 
Post Thrombotic Syndrome absent 
Any Post-Thrombotic Syndrome 
present 
0 
≥ 1 
Physically and functionally 
significant PTS 
Signs ≥ 1 and Symptoms ≥ 
1 
 
 
B- Modified Villalta Score 
 
Symptoms 
Pain or abnormal use 
Swelling 
 
1 
1 
Signs 
Increased limb circumference 
Change in skin color 
Pitting edema 
Venous Collaterals on skin 
Pigmentation of skin 
Tenderness on palpations of deep veins 
Varicosities 
Head Swelling 
Ulceration 
 
1 
1 
1 
1 
1 
1 
1 moderate; 2 severe 
1 moderate; 2 severe 
9 
Mild Post-Thrombotic Syndrome 
1-3 
Moderate Post-Thrombotic Syndrome 
4-8 
Severe 
≥ 9 
 
Components of the standardized outcome measures for post thrombotic 
syndrome (PTS) employed in pediatric studies, including the Manco-
Johnson Instrument (A) and the modified Villalta scoring system (B). 
 
 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
 
 
 
Appendix 2 
 
Health-Related Quality of Life (QoL) Instruments 
 
General QoL: 
The PedsQL TM is a modular approach to measure generic health 
related quality of life in both healthy children and adolescents, as well 
as those with acute and chronic health conditions. It consists of 
structured interview with the parents and the child with 23 items divided 
among 4 sub-scales to assess function in 4 domains: Physical; 
Emotional; social; and School. Each item is a statement of a problem, 
which the subject rates in severity from 0-4, indicating a problem never 
occurs (score of 0) to almost always occurs (score of 4). The 
instrument is brief, takes 15 minutes to administer, and is 
developmentally adjusted for a broad age range. 
 
Venous Disease-Specific QoL 
The VEINS-QoL is a venous disease specific QoL tool that has been 
validated in adults with DVT and PTS. This is a 26-item questionnaire 
that measures the impact of DVT and PTS on symptoms and quality of 
life from the patient’s perspective.  The item covers symptoms (10 
items), limitations on daily activities (9 items), time of day of greatest 
intensity (1 item), change over the past year (1 item), and psychological 
impact (5 items). 
 
Scoring of QoL Instruments 
Scoring of PedsQL TM 
 
Description of the questionnaire 
Dimensions 
Number of 
Items 
Cluster of 
Items 
Reversed 
Scoring 
Direction of 
Dimensions 
Physical 
Functioning 
8 
1-8 
1-8 
 
Higher 
scores 
indicate 
better health 
related QoL 
Emotional 
Functioning 
5 
1-5 
1-5 
Social 
Functioning 
5 
1-5 
1-5 
School 
Functioning 
5 
1-5 
1-5 

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Scoring of Dimensions 
Item Scaling 
5-point Likert scale from 0 
(Never) to 4(Almost always) 
Weighting of items 
No 
Extension of the scoring scale 
Scores are transformed on a 
scale from 0-100 
Scoring Procedure 
Step 1: Transform Score 
Items are reversed scored and 
linearly transformed to a 0-100 
scale as follows: 
0=100, 1=75, 2=50,3=25,4=0 
 
Step 2: Calculate Scores 
Score by Dimensions 
 If more than 50% of the 
items in the scale are 
missing, the scale scores 
should not be computed 
 Mean Score= Sum of the 
items over the number of 
items answered 
 
Psychological Health Summary 
Score= sum of the items over the 
number of items answered in the 
Emotional, Social, and School 
Functioning Scales. 
 
Physical Health Summary Score= 
Physical Functioning Scale Score 
 
Total Score: Sum of all the items 
over the number of items 
answered on all the scales. 
Interpretation and Analysis of 
missing Data 
If more than 50% of the items in 
the sacle are missing, the Scale 
Scores should not be computed 
If 50% or more items are 
completed: impute the mean of 
the completed items in a scale 
 
 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
 
Appendix 3 
 
DAILY MEDICATION ADMINISTRATION LOG 
 
Name:                                                                     Medication:                                                          
.          
 
Date 
Given 
Dose 
Times per 
day 
Reactions and Side 
effects* 
 
Reason 
For 
not 
taking 
med 
Other 
Notes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*nose bleeds, mouth bleeding, GI bleeding, heavy periods, bruising, 
burning and pain with shots, hair loss 
 
 

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Appendix 4 
 
COMPRESSION STOCKINGS LOG 
 
Name:    
                                                                  
Compression Stocking type:  ☐ Knee-high     ☐ Thigh-high       ☐ Arm 
sleeve 
 
Compression level: ☐ 15-20 mm Hg    ☐ 20-30 mm Hg    ☐ 30-40 mm Hg                             
 
Date 
Worn 
Times  
per 
day 
worn    
No of hours 
worn 
Reactions and Side effects* 
Other 
Notes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Discomfort, worsening of pain, color changes, ulcers, difficulty wearing 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
 
Appendix 5 
 
Physical Activity Questionnaire (Initial) 
                                                                        
 
                                     Start time:                                                   End 
time: 
 
This is short survey to find out about your level of physical activity 
before and after you developed a blood clot. These includes sports or 
dance that make you sweat or make your legs feel tired, or games that 
make you breathe hard, like tag, skipping, running, climbing, and 
others.  
 
Your answers will help us understand how a blood clot affects your 
ability to be active.  We believe your answers will help us treat you and 
other children with blood clots better.                                     
 
Remember:  
1. There are no right or wrong answers- this is not a test. 
2. Please answer all questions as honestly and accurately as you 
can- this is very important. 
 
ID :_________________________                                                
Age:___________                      
  
 
Sex:     M_______ F_______                                                         
Grade:__________ 
                        
BEFORE the diagnosis of a blood clot: 
Answer the following questions for the time before you had a blood clot. 
 
1. Were you involved in any physical activity? 
                         Yes 
                                 No 
                  
 
2. If yes, was this physical activity part of: 
 Recreation/leisure (sports/game/exercise) 
 Work/School 
 Transportation 
 

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3. Were these activities organized competitive activities or sports? (Check one only.) 
No (or gym class only)……………………………………...
 
 
Yes, but WITHOUT an official or judge (such as a club or pickup games)...
 
 
Yes, with an official or judge……………………….............
 
 
Yes, at a national or professional level…………………… 
 
 
Not sure……………………………………………………… 
 
 
AFTER the diagnosis of blood clot: 
 
1. Describe your current activity level. 
                  
               
 Unchanged 
                  
               
 Decreased 
 
               
 Increased 
 
2. If your overall activity is increased after the blood clot, what is 
the reason? If it is not increased, move to the next question. 
   
 Reason: 
 
3. If your overall activity is decreased after the blood clot, what is 
the reason? Check all that apply. If it is not decreased, move to 
the next question. 
 
               
 Leg pain 
 
               
Leg discomfort or heaviness 
 
               
Leg swelling 
 
   
Chest pain 
 
   
Trouble breathing 
 
   
No desire to be active 
 
   
Fear that the clot may move in my body 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
 
 
   
Other 
 
4. If your overall activity is decreased after the blood clot, check 
one of the boxes below. If it is not decreased, move to the next 
question. 
 
 Wholly inactive, dependent on others, and cannot leave residence 
 
 Mostly inactive or restricted to minimum activities of daily living 
 
Sometimes participates in mild activities, such as walking, limited 
housework and limited shopping 
 
Regularly participates in mild activities 
 
Sometimes participates in moderate activities such as swimming, or 
could do unlimited housework or shopping 
 
Regularly participates in moderate activity as before 
 
Regularly participates in active events, such as bicycling, bowling of 
golf 
 
 Sometimes participates in impact sports such as jogging, tennis, 
football or heavy labor 
 
 Regularly participates in impact sports 
 
5. Were you sick in the past week (s), or did anything prevent you from doing your 
normal physical activities? (Check one.)  
 
                          Yes 
                                 No 
                  
 
If yes, what prevented you? __________________________________ 
 
Thank you for your time and participation. Please contact Dr. Zia or Dr. 
Journeycake at 214-648-3896 for any questions and concerns that you may have 
related to this questionnaire. 
 
 
 
 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
 
References:  
Godin,G,. Shephard,R.J..(1997) Godin Leisure-Time Exercise 
Questionnaire. Medicine and Science in Sports and Exercise. 29 June 
Supplement: S36-S38 
Kowalski, K.C., Validation of the physical activity questionnaire for older 
children. Pediatric Exercise Science, 9, 342-352 
 
 
Godin Leisure-Time Exercise Questionnaire 
 
1. During a typical 7-Day period (a week), how many times on the average do you do the 
following kinds of exercise for more than 15 minutes during your free time (write on each line 
the appropriate number). 
 
 
 
 
 
a) STRENUOUS EXERCISE 
(HEART BEATS RAPIDLY) 
(e.g., running, jogging, hockey, football, soccer, 
squash, basketball, cross country skiing, judo, 
roller skating, vigorous swimming, 
vigorous long distance bicycling) 
 
 
 
 
b) MODERATE EXERCISE 
(NOT EXHAUSTING) 
(e.g., fast walking, baseball, tennis, easy bicycling, 
volleyball, badminton, easy swimming, alpine skiing, 
popular and folk dancing) 
 
 
c) MILD EXERCISE 
(MINIMAL EFFORT) 
(e.g., yoga, archery, fishing from river bank, bowling, 
horseshoes, golf, snow-mobiling, easy walking) 
Times Per 
Week 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
 
 
 
 
2. During a typical 7-Day period (a week), in your leisure time, how often do you engage in any 
regular activity long enough to work up a sweat (heart beats rapidly)? 
 
OFTEN 
SOMETIMES 
NEVER/RARELY 
1. 
2. 
3. 
 
 
 
 
 
 
 
 
Thank you for your patience. You are almost done.                                       
--------------------------------------------------------------------------------------------------------------
----------For Research Use: 
 
1. Time taken to complete survey (minutes): 
 
2. Subject’s Habitual Physical Activity (i.e before the diagnosis of DVT): 
 
 Mild (gardening, yoga, archery, fishing, bowling, golf, walking, swimming, 
snow mobiling) 
 
 Moderate (dancing, baseball, bicycling, volleyball, badminton, cross-country 
skiing, skating) 
 
 Strenuous (tennis, running, jogging, hockey, football, soccer, squash, 
basketball, alpine skiing, judo) 
 
 Mostly Inactive 
 
 
*If a subject has participated in activities qualifying for more than 1 intensity 
category, classify in the highest category 
 
3. Godin Score before the diagnosis of VTE: 
 
 
4. PAQ-C/ PAQ-A Score before the diagnosis of VTE: 
 
 
5. Subject’s Physical Activity as assessed at the current visit: 
 None 
 
 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
 
 Mild (gardening, yoga, archery, fishing, bowling, golf, walking, swimming, snow 
mobiling) 
 
 Moderate (dancing, baseball, bicycling, volleyball, badminton, cross-country 
skiing, skating) 
 
 Strenuous (tennis, running, jogging, hockey, football, soccer, squash, 
basketball, alpine skiing, judo) 
 
           
 Mostly Inactive 
 
 
 
6. Godin Score after the diagnosis of VTE: 
 
 
7. PAQ-C/ PAQ-A Score before the diagnosis of VTE: 
 
 
8. Other comments: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
 
Godin Leisure-Time Exercise Questionnaire 
 
3. During a typical 7-Day period (a week), how many times on the average do you do the 
following kinds of exercise for more than 15 minutes during your free time (write on each line 
the appropriate number). 
 
 
 
 
 
d) STRENUOUS EXERCISE 
(HEART BEATS RAPIDLY) 
(e.g., running, jogging, hockey, football, soccer, 
squash, basketball, cross country skiing, judo, 
roller skating, vigorous swimming, 
vigorous long distance bicycling) 
 
 
 
 
e) MODERATE EXERCISE 
(NOT EXHAUSTING) 
(e.g., fast walking, baseball, tennis, easy bicycling, 
volleyball, badminton, easy swimming, alpine skiing, 
popular and folk dancing) 
 
 
f) 
MILD EXERCISE 
(MINIMAL EFFORT) 
(e.g., yoga, archery, fishing from river bank, bowling, 
horseshoes, golf, snow-mobiling, easy walking) 
Times 
Per 
Week 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
36 
4. During a typical 7-Day period (a week), in your leisure time, how often do you engage in any regular 
activity long enough to work up a sweat (heart beats rapidly)? 
 
OFTEN 
SOMETIMES 
NEVER/RARELY 
1. 
2. 
3. 
 
 
 
 
 
 
 
 
 
Thank you for your patience. You are almost done.                                       
 
 
1. Describe your current activity level. 
                  
               
 Unchanged 
                  
               
 Decreased 
 
               
 Increased 
 
2. If you overall activity is increased since the last visit, what is the reason? If it is not increased, 
move to the next question. 
   
              Reason:                
 
3. If you overall activity is decreased since the last visit, what is the reason? Check all that apply. 
If it is not decreased, move to the next question. 
 
               
 Leg pain 
 
               
Leg discomfort or heaviness 
 
               
Leg swelling 
 
   
Chest pain 
 
   
Trouble breathing 
 
   
No desire to be active 
 
   
Fear that the clot may move in my body 
 
   
Other 
 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
37 
4. If your overall activity is decreased since the last visit, check one of the boxes below. If it is 
not decreased, move to the next question. 
 
 Wholly inactive, dependent on others, and cannot leave residence 
 
            
 Mostly inactive or restricted to minimum activities of daily living 
 
Sometimes participates in mild activities, such as walking, limited housework and 
limited shopping 
 
Regularly participates in mild activities 
 
Sometimes participates in moderate activities such as swimming, or could do 
unlimited housework or shopping 
 
Regularly participates in moderate activity as before 
 
Regularly participates in active events, such as bicycling, bowling of golf 
 
 Sometimes participates in impact sports such as jogging, tennis, football or heavy 
labor 
 
 Regularly participates in impact sports 
 
 
5. Were you sick in the past week (s), or did anything prevent you from doing your normal 
physical activities? (Check one.)  
 
                          Yes 
                                 No 
                  
 
If yes, what prevented you? __________________________________ 
 
Thank you for your time and participation. Please contact Dr. Zia or Dr. Journeycake at 214-
648-3896 for any questions and concerns that you may have related to this questionnaire. 
 
 
For Research Use: 
 
1. Time taken to complete survey (minutes) 
 
 
2. Subject’s Physical Activity as assessed at the current visit: 
 None 
 
 Mild (gardening, yoga, archery, fishing, bowling, golf, walking, swimming, snow mobiling) 
 
 Moderate (dancing, baseball, bicycling, volleyball, badminton, cross-country skiing, skating) 
 
 Strenuous (tennis, running, jogging, hockey, football, soccer, squash, basketball, alpine 
skiing, judo) 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
38 
 
           
 Mostly Inactive 
 
 
 
3. Godin Score: 
 
 
4. PAQ-C/ PAQ-A Score: 
 
 
5. Other comments: 
 
 
For Research Use: 
 
6. Time taken to complete survey (minutes): 
 
7. Subject’s Habitual Physical Activity (i.e before the diagnosis of DVT): 
 
 Mild (gardening, yoga, archery, fishing, bowling, golf, walking, swimming, snow mobiling) 
 
 Moderate (dancing, baseball, bicycling, volleyball, badminton, cross-country skiing, 
skating) 
 
 Strenuous (tennis, running, jogging, hockey, football, soccer, squash, basketball, alpine 
skiing, judo) 
 
*If a subject has participated in activities qualifying for more than 1 intensity category, classify 
in the highest category 
 
8. Godin Score before the diagnosis of VTE: 
 
 
9. PAQ-C/ PAQ-A Score before the diagnosis of VTE: 
 
 
10. Subject’s Physical Activity after the diagnosis of DVT: 
 Mild (gardening, yoga, archery, fishing, bowling, golf, walking, swimming, snow mobiling) 
 
 Moderate (dancing, baseball, bicycling, volleyball, badminton, cross-country skiing, 
skating) 
 
 Strenuous (tennis, running, jogging, hockey, football, soccer, squash, basketball, alpine 
skiing, judo) 
 
 
11. Godin Score after the diagnosis of VTE: 
 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
39 
 
12. PAQ-C/ PAQ-A Score before the diagnosis of VTE: 
 
13. Other comments: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
References: 
 

STU022016-057, Zia, FormA-ResearchProtocol, Mod_18, 03-02-21 
40 
1. 
Raffini L, Huang YS, Witmer C, et al. Dramatic increase in venous 
thromboembolism in children's hospitals in the United States from 2001 to 2007. 
Pediatrics 2009;124:1001-1008. 
2. 
Goldenberg NA. Long-term outcomes of venous thrombosis in children. Current 
opinion in hematology 2005;12:370-376. 
3. 
Goldenberg NA, Donadini MP, Kahn SR, et al. Post-thrombotic syndrome in 
children: a systematic review of frequency of occurrence, validity of outcome measures, 
and prognostic factors. Haematologica 2010;95:1952-1959. 
4. 
Monagle P, Adams M, Mahoney M, et al. Outcome of pediatric thromboembolic 
disease: a report from the Canadian Childhood Thrombophilia Registry. Pediatric 
research 2000;47:763-766. 
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