Deep Vein Thrombosis, Post Thrombotic Syndrome
Conditions
Keywords
Venous thromboembolism, Deep Vein Thrombosis, Lower Extremity, Blood clot, Anticoagulation, Physical Activity, Fitbit, Post-thrombotic syndrome, Post-phlebitic syndrome, Thrombosis
Brief summary
'The PACT trial' is randomized pilot trial to demonstrate the feasibility and potential effectiveness of a personal fitness tracker to improve adherence to an activity regimen following an initial acute DVT in children.
Detailed description
The feasibility of an innovative intervention of a validated fitness tracker, the Fitbit, to improve adherence to a 12-week activity regimen in a pilot randomized controlled trial (RCT) will be tested in 44 subjects with first, acute, proximal lower extremity deep vein thrombosis (DVT). 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 postthrombotic syndrome (PTS) pre and post intervention in each group.
Interventions
DEVICEFitbit
The Fitbit will be utilized in the intervention arm to improve adherence to a 12-week activity regimen.
BEHAVIORAL30-minute education session
Sponsors
Texas Scottish Rite Hospital for Children
National Heart, Lung, and Blood Institute (NHLBI)
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* A radiologically confirmed, acute, proximal first lower extremity DVT * 4 to 8 weeks after starting anticoagulation * Out-patient ambulatory status
Exclusion criteria
* Contraindication to increasing activity such as patients with juvenile arthritis, poor balance, congestive heart failure, etc.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Who Complete Post-randomization | Within 24 months of trial initiation | Feasibility criteria is met when assessed to be ≥ 80%. This includes the number of subjects who successfully completed the trial. |
| Feasibility as Measured by Number of Participants Who Meet Study Eligibility Criteria at Baseline | Baseline | Feasibility criteria for rate of study eligibility met when assessed to be ≥ 30% INCLUSION CRITERIA: 1.) Age 7-21 years 2.)2. A radiologically confirmed, acute, proximal (iliofemoral and femoropopliteal) first lower extremity DVT and/or confirmed, acute pulmonary embolism (unilateral or bilateral) 3.) 12 weeks (±2 weeks) after starting anticoagulation 4.) Out-patient ambulatory status |
| Number of Screened Subjects Who Provided Consent at Baseline | Baseline | Feasibility criteria for rate of consent was assessed to be ≥ 30% at baseline INCLUSION CRITERIA: 1.) Age 7-21 years 2.)2. A radiologically confirmed, acute, proximal (iliofemoral and femoropopliteal) first lower extremity DVT and/or confirmed, acute pulmonary embolism (unilateral or bilateral) 3.) 12 weeks (±2 weeks) after starting anticoagulation 4.) Out-patient ambulatory status |
| Mean Number of Participants Who Adhered to the Assigned Physical Activity During 8-week Period (Intervention Arm -FitBit Arm ) | 8 weeks | Adherence in the physical activity group is calculated based on the number of participants who complied with the target weekly goal or activity prescription during the active 8-week period. |
| Mean Physical Activity Questionnaire Score at 3 Months (Standard of Care Arm Only) | 3 months | The Godin-Shephard Leisure-Time Physical Activity Questionnaire was used to quantify physical activity levels. Individuals reporting moderate-to-strenuous activity levels ≥24 were classified as active (better outcome), whereas individuals reporting moderate-to-strenuous activity levels ≤23 were classified were insufficiently active (worse outcome). |
| Mean Physical Activity Questionnaire Score at 6 Months (Standard of Care Arm Only) | 6 months | The Godin-Shephard Leisure-Time Physical Activity Questionnaire was used to quantify physical activity levels. Individuals reporting moderate-to-strenuous activity levels ≥24 were classified as active (better outcome), whereas individuals reporting moderate-to-strenuous activity levels ≤23 were classified were insufficiently active (worse outcome). |
| Mean Physical Activity Questionnaire Score at 9 Months (Standard of Care Arm Only) | 9 months | The Godin-Shephard Leisure-Time Physical Activity Questionnaire was used to quantify physical activity levels. Individuals reporting moderate-to-strenuous activity levels ≥24 were classified as active (better outcome), whereas individuals reporting moderate-to-strenuous activity levels ≤23 were classified were insufficiently active (worse outcome). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in PTS Biomarkers (D-dimer) | From baseline to 6 months | Change in PTS biomarkers from baseline to post intervention of increased physical activity measured by coagulation activation marker D-dimer. |
| Percentage Change From Baseline in FVIII PTS Biomarker | From baseline to 6 month | Change in PTS biomarkers from baseline to post intervention of increased physical activity measured by the coagulation activation marker FVIII |
| Change in PTS Biomarkers (C-reactive Protein) | From baseline to 6 month | Change in PTS biomarkers from baseline to post intervention of increased physical activity measured by inflammation marker C-reactive protein (CRP) using a latex-enhanced immunoturbidimetric assay. |
| Change in PTS Biomarkers (Fibrinolysis - Endogenous Thrombin Potential) | From baseline to 6 month | Change in PTS biomarkers from baseline to post intervention of increased physical activity measured by endogenous thrombin potential using calibrated automated thrombogram (CAT). CAT is a routine test that measures hyper- and hypocoagulability. |
| Change in PTS Biomarkers (Fibrinolysis - Thrombin Generation) | From baseline to 6 month | Change in PTS biomarkers from baseline to post intervention of increased physical activity measured by thrombin generation assay using calibrated automated thrombogram (CAT). CAT is a routine test that measures hyper- and hypocoagulability. |
| Percent Change in Fibrinolysis Biomarker | From baseline to 6 month | Percent Change in Fibrinolysis Biomarker from baseline to post intervention of increased physical activity is measured by thromboelastography (TEG). TEG is often used to predict bleeding and diagnose various bleeding disorders. Lysis 30% and Lysis 60% are measurements of percent amplitude reduction 30 and 60 minutes after maximum amplitude, respectively, on thromboelastography. Decreased clotting ability (negative value) = better outcome Increased clotting ability (positive value)= worse outcome |
| Change in Quality of Life | From baseline to 6 months | Change in Quality of Life from baseline to post intervention of increased physical activity assessed by PedsQL instrument. 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). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50,3=25,4=0, with higher scores indicating better health related QoL. The positive change from baseline to 6 months correspond to better quality of life. |
Countries
United States
Participant flow
Pre-assignment details
111 patients were screened, of whom 40 (36%) met study eligibility criteria. Of these, 23 (57.5%) consented to participate (11 randomized to physical activity arm and 12 to education or standard care arm)
Participants by arm
| Arm | Count |
|---|---|
| Intervention Participants randomized to the intervention arm will receive a Fitbit, formal 30-minute education session on post-thrombotic syndrome (PTS) and benefits of increased physical activity. An individualized activity prescription will be provided and participants will be asked to maintain the target level of activity for 12 weeks after determining their habitual activity in the first 4 weeks.
Fitbit: The Fitbit will be utilized in the intervention arm to improve adherence to a 12-week activity regimen.
30-minute education session | 11 |
| Control Participants randomized to the control arm will receive a formal 30-minute education session on post-thrombotic syndrome (PTS) and the benefits of increased physical activity. Their physical activity will be self-reported in an activity log and by the Gordin activity questionnaire over the 16-week intervention period.
30-minute education session | 12 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 6 |
Baseline characteristics
| Characteristic | Intervention | Control | Total |
|---|---|---|---|
| Age, Continuous | 15.18 years STANDARD_DEVIATION 2.04 | 14.25 years STANDARD_DEVIATION 2.56 | 14.70 years STANDARD_DEVIATION 2.32 |
| BMI | 29.83 kg/m^2 STANDARD_DEVIATION 12.34 | 26.86 kg/m^2 STANDARD_DEVIATION 5.58 | 28.28 kg/m^2 STANDARD_DEVIATION 9.69 |
| Clot burden at diagnosis occlusive | 7 Participants | 7 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 8 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| OW/obese | 6 Participants | 9 Participants | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 10 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 12 |
| other Total, other adverse events | 0 / 11 | 0 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 |
Outcome results
Primary
Feasibility as Measured by Number of Participants Who Meet Study Eligibility Criteria at Baseline
Feasibility criteria for rate of study eligibility met when assessed to be ≥ 30% INCLUSION CRITERIA: 1.) Age 7-21 years 2.)2. A radiologically confirmed, acute, proximal (iliofemoral and femoropopliteal) first lower extremity DVT and/or confirmed, acute pulmonary embolism (unilateral or bilateral) 3.) 12 weeks (±2 weeks) after starting anticoagulation 4.) Out-patient ambulatory status
Time frame: Baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inpatients and Outpatients With VTE | Feasibility as Measured by Number of Participants Who Meet Study Eligibility Criteria at Baseline | 40 Participants |
Primary
Mean Number of Participants Who Adhered to the Assigned Physical Activity During 8-week Period (Intervention Arm -FitBit Arm )
Adherence in the physical activity group is calculated based on the number of participants who complied with the target weekly goal or activity prescription during the active 8-week period.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inpatients and Outpatients With VTE | Mean Number of Participants Who Adhered to the Assigned Physical Activity During 8-week Period (Intervention Arm -FitBit Arm ) | 3 number of participants | Standard Deviation 1.2 |
Primary
Mean Physical Activity Questionnaire Score at 3 Months (Standard of Care Arm Only)
The Godin-Shephard Leisure-Time Physical Activity Questionnaire was used to quantify physical activity levels. Individuals reporting moderate-to-strenuous activity levels ≥24 were classified as active (better outcome), whereas individuals reporting moderate-to-strenuous activity levels ≤23 were classified were insufficiently active (worse outcome).
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inpatients and Outpatients With VTE | Mean Physical Activity Questionnaire Score at 3 Months (Standard of Care Arm Only) | 56 score on a scale | Standard Deviation 29 |
Primary
Mean Physical Activity Questionnaire Score at 6 Months (Standard of Care Arm Only)
The Godin-Shephard Leisure-Time Physical Activity Questionnaire was used to quantify physical activity levels. Individuals reporting moderate-to-strenuous activity levels ≥24 were classified as active (better outcome), whereas individuals reporting moderate-to-strenuous activity levels ≤23 were classified were insufficiently active (worse outcome).
Time frame: 6 months
Population: Participants who submitted the questionnaire were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inpatients and Outpatients With VTE | Mean Physical Activity Questionnaire Score at 6 Months (Standard of Care Arm Only) | 52 score on a scale | Standard Deviation 32 |
Primary
Mean Physical Activity Questionnaire Score at 9 Months (Standard of Care Arm Only)
The Godin-Shephard Leisure-Time Physical Activity Questionnaire was used to quantify physical activity levels. Individuals reporting moderate-to-strenuous activity levels ≥24 were classified as active (better outcome), whereas individuals reporting moderate-to-strenuous activity levels ≤23 were classified were insufficiently active (worse outcome).
Time frame: 9 months
Population: Participants who submitted the questionnaire were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inpatients and Outpatients With VTE | Mean Physical Activity Questionnaire Score at 9 Months (Standard of Care Arm Only) | 38 score on a scale | Standard Deviation 36 |
Primary
Number of Screened Subjects Who Provided Consent at Baseline
Feasibility criteria for rate of consent was assessed to be ≥ 30% at baseline INCLUSION CRITERIA: 1.) Age 7-21 years 2.)2. A radiologically confirmed, acute, proximal (iliofemoral and femoropopliteal) first lower extremity DVT and/or confirmed, acute pulmonary embolism (unilateral or bilateral) 3.) 12 weeks (±2 weeks) after starting anticoagulation 4.) Out-patient ambulatory status
Time frame: Baseline
Population: For this specific outcome, we only assess the screened subjects who met the eligibility criteria are included in this cohort.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inpatients and Outpatients With VTE | Number of Screened Subjects Who Provided Consent at Baseline | 23 Participants |
Primary
Proportion of Subjects Who Complete Post-randomization
Feasibility criteria is met when assessed to be ≥ 80%. This includes the number of subjects who successfully completed the trial.
Time frame: Within 24 months of trial initiation
Population: For this specific outcome, we only assess the 11 subjects in the intervention arm and 12 subjects in the control arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inpatients and Outpatients With VTE | Proportion of Subjects Who Complete Post-randomization | 10 Participants |
| Control | Proportion of Subjects Who Complete Post-randomization | 6 Participants |
Secondary
Change in PTS Biomarkers (C-reactive Protein)
Change in PTS biomarkers from baseline to post intervention of increased physical activity measured by inflammation marker C-reactive protein (CRP) using a latex-enhanced immunoturbidimetric assay.
Time frame: From baseline to 6 month
Population: For this specific outcome, we only assess the 11 subjects in the intervention arm and 12 subjects in the control arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inpatients and Outpatients With VTE | Change in PTS Biomarkers (C-reactive Protein) | -0.4 mg/dL | Standard Deviation 1.6 |
| Control | Change in PTS Biomarkers (C-reactive Protein) | -0.6 mg/dL | Standard Deviation 1.6 |
Secondary
Change in PTS Biomarkers (D-dimer)
Change in PTS biomarkers from baseline to post intervention of increased physical activity measured by coagulation activation marker D-dimer.
Time frame: From baseline to 6 months
Population: For this specific outcome, we only assess the 11 subjects in the intervention arm and 12 subjects in the control arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inpatients and Outpatients With VTE | Change in PTS Biomarkers (D-dimer) | -4675 µg/mL | Standard Deviation 5633 |
| Control | Change in PTS Biomarkers (D-dimer) | -6241 µg/mL | Standard Deviation 6780 |
Secondary
Change in PTS Biomarkers (Fibrinolysis - Endogenous Thrombin Potential)
Change in PTS biomarkers from baseline to post intervention of increased physical activity measured by endogenous thrombin potential using calibrated automated thrombogram (CAT). CAT is a routine test that measures hyper- and hypocoagulability.
Time frame: From baseline to 6 month
Population: For this specific outcome, we only assess the 11 subjects in the intervention arm and 12 subjects in the control arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inpatients and Outpatients With VTE | Change in PTS Biomarkers (Fibrinolysis - Endogenous Thrombin Potential) | 41.0 nM*min | Standard Deviation 223 |
| Control | Change in PTS Biomarkers (Fibrinolysis - Endogenous Thrombin Potential) | -60.1 nM*min | Standard Deviation 148 |
Secondary
Change in PTS Biomarkers (Fibrinolysis - Thrombin Generation)
Change in PTS biomarkers from baseline to post intervention of increased physical activity measured by thrombin generation assay using calibrated automated thrombogram (CAT). CAT is a routine test that measures hyper- and hypocoagulability.
Time frame: From baseline to 6 month
Population: For this specific outcome, we only assess the 11 subjects in the intervention arm and 12 subjects in the control arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inpatients and Outpatients With VTE | Change in PTS Biomarkers (Fibrinolysis - Thrombin Generation) | 60.5 nmol/L | Standard Deviation 164 |
| Control | Change in PTS Biomarkers (Fibrinolysis - Thrombin Generation) | 0.2 nmol/L | Standard Deviation 28.4 |
Secondary
Change in Quality of Life
Change in Quality of Life from baseline to post intervention of increased physical activity assessed by PedsQL instrument. 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). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50,3=25,4=0, with higher scores indicating better health related QoL. The positive change from baseline to 6 months correspond to better quality of life.
Time frame: From baseline to 6 months
Population: For this specific outcome, we only assess the 11 subjects in the intervention arm and 12 subjects in the control arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inpatients and Outpatients With VTE | Change in Quality of Life | 5.4 score on a scale | Standard Deviation 14.3 |
| Control | Change in Quality of Life | 24.5 score on a scale | Standard Deviation 14.2 |
Secondary
Percentage Change From Baseline in FVIII PTS Biomarker
Change in PTS biomarkers from baseline to post intervention of increased physical activity measured by the coagulation activation marker FVIII
Time frame: From baseline to 6 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inpatients and Outpatients With VTE | Percentage Change From Baseline in FVIII PTS Biomarker | -39.6 percent change | Standard Deviation 92 |
| Control | Percentage Change From Baseline in FVIII PTS Biomarker | -50.4 percent change | Standard Deviation 82.5 |
Secondary
Percent Change in Fibrinolysis Biomarker
Percent Change in Fibrinolysis Biomarker from baseline to post intervention of increased physical activity is measured by thromboelastography (TEG). TEG is often used to predict bleeding and diagnose various bleeding disorders. Lysis 30% and Lysis 60% are measurements of percent amplitude reduction 30 and 60 minutes after maximum amplitude, respectively, on thromboelastography. Decreased clotting ability (negative value) = better outcome Increased clotting ability (positive value)= worse outcome
Time frame: From baseline to 6 month
Population: For this specific outcome, we only assess the 11 subjects in the intervention arm and 12 subjects in the control arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inpatients and Outpatients With VTE | Percent Change in Fibrinolysis Biomarker | Lysis 30, % (percent amplitude change 30 minutes after maximum amplitude) | -0.05 percent amplitude change | Standard Deviation 3.3 |
| Inpatients and Outpatients With VTE | Percent Change in Fibrinolysis Biomarker | Lysis 60, % (percent amplitude change 60 minutes after maximum amplitude) | -0.04 percent amplitude change | Standard Deviation 11.6 |
| Control | Percent Change in Fibrinolysis Biomarker | Lysis 30, % (percent amplitude change 30 minutes after maximum amplitude) | 2.1 percent amplitude change | Standard Deviation 3.1 |
| Control | Percent Change in Fibrinolysis Biomarker | Lysis 60, % (percent amplitude change 60 minutes after maximum amplitude) | 6.2 percent amplitude change | Standard Deviation 6.5 |