Trial Outcomes & Findings for Physical Activity in Children at Risk of Post-thrombotic Sequelae (PACT) (NCT NCT03075761)

NCT ID: NCT03075761

Last Updated: 2021-05-18

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 111 participants
• Primary outcome timeframe: Baseline
• Results posted on: 2021-05-18

Participant Flow

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)

Participant milestones

Measure	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	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
Overall Study STARTED	11	12
Overall Study COMPLETED	10	6
Overall Study NOT COMPLETED	1	6

Reasons for withdrawal

Measure	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	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
Overall Study Lost to Follow-up	1	6

Baseline Characteristics

Physical Activity in Children at Risk of Post-thrombotic Sequelae (PACT)

Baseline characteristics by cohort

Measure	Intervention n=11 Participants 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	Control n=12 Participants 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	Total n=23 Participants Total of all reporting groups
Age, Continuous	15.18 years STANDARD_DEVIATION 2.04 • n=5 Participants	14.25 years STANDARD_DEVIATION 2.56 • n=7 Participants	14.70 years STANDARD_DEVIATION 2.32 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
BMI	29.83 kg/m^2 STANDARD_DEVIATION 12.34 • n=5 Participants	26.86 kg/m^2 STANDARD_DEVIATION 5.58 • n=7 Participants	28.28 kg/m^2 STANDARD_DEVIATION 9.69 • n=5 Participants
OW/obese	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Clot burden at diagnosis occlusive	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	Inpatients and Outpatients With VTE n=111 Participants All Inpatients and outpatients with VTE from following 3 sources: (1) new patient referrals to the Bleeding Disorders and Thrombosis outpatient clinic, (2) inpatient admissions to the hematology service, and (3) inpatient consultations for VTE that were not on primary hematology service.	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
Feasibility as Measured by Number of Participants Who Meet Study Eligibility Criteria at Baseline	40 Participants	—

PRIMARY outcome

Timeframe: Baseline

Population: For this specific outcome, we only assess the screened subjects who met the eligibility criteria are included in this cohort.

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

Outcome measures

Measure	Inpatients and Outpatients With VTE n=40 Participants All Inpatients and outpatients with VTE from following 3 sources: (1) new patient referrals to the Bleeding Disorders and Thrombosis outpatient clinic, (2) inpatient admissions to the hematology service, and (3) inpatient consultations for VTE that were not on primary hematology service.	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
Number of Screened Subjects Who Provided Consent at Baseline	23 Participants	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Inpatients and Outpatients With VTE n=11 Participants All Inpatients and outpatients with VTE from following 3 sources: (1) new patient referrals to the Bleeding Disorders and Thrombosis outpatient clinic, (2) inpatient admissions to the hematology service, and (3) inpatient consultations for VTE that were not on primary hematology service.	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
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 outcome

Timeframe: 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).

Outcome measures

Measure	Inpatients and Outpatients With VTE n=11 Participants All Inpatients and outpatients with VTE from following 3 sources: (1) new patient referrals to the Bleeding Disorders and Thrombosis outpatient clinic, (2) inpatient admissions to the hematology service, and (3) inpatient consultations for VTE that were not on primary hematology service.	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
Mean Physical Activity Questionnaire Score at 3 Months (Standard of Care Arm Only)	56 score on a scale Standard Deviation 29	—

PRIMARY outcome

Timeframe: 6 months

Population: Participants who submitted the questionnaire were included.

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).

Outcome measures

Measure	Inpatients and Outpatients With VTE n=10 Participants All Inpatients and outpatients with VTE from following 3 sources: (1) new patient referrals to the Bleeding Disorders and Thrombosis outpatient clinic, (2) inpatient admissions to the hematology service, and (3) inpatient consultations for VTE that were not on primary hematology service.	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
Mean Physical Activity Questionnaire Score at 6 Months (Standard of Care Arm Only)	52 score on a scale Standard Deviation 32	—

PRIMARY outcome

Timeframe: 9 months

Population: Participants who submitted the questionnaire were included.

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).

Outcome measures

Measure	Inpatients and Outpatients With VTE n=9 Participants All Inpatients and outpatients with VTE from following 3 sources: (1) new patient referrals to the Bleeding Disorders and Thrombosis outpatient clinic, (2) inpatient admissions to the hematology service, and (3) inpatient consultations for VTE that were not on primary hematology service.	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
Mean Physical Activity Questionnaire Score at 9 Months (Standard of Care Arm Only)	38 score on a scale Standard Deviation 36	—

PRIMARY outcome

Timeframe: 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.

Feasibility criteria is met when assessed to be ≥ 80%. This includes the number of subjects who successfully completed the trial.

Outcome measures

Measure	Inpatients and Outpatients With VTE n=11 Participants All Inpatients and outpatients with VTE from following 3 sources: (1) new patient referrals to the Bleeding Disorders and Thrombosis outpatient clinic, (2) inpatient admissions to the hematology service, and (3) inpatient consultations for VTE that were not on primary hematology service.	Control n=12 Participants 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
Proportion of Subjects Who Complete Post-randomization	10 Participants	6 Participants

SECONDARY outcome

Timeframe: 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.

Change in PTS biomarkers from baseline to post intervention of increased physical activity measured by coagulation activation marker D-dimer.

Outcome measures

Measure	Inpatients and Outpatients With VTE n=11 Participants All Inpatients and outpatients with VTE from following 3 sources: (1) new patient referrals to the Bleeding Disorders and Thrombosis outpatient clinic, (2) inpatient admissions to the hematology service, and (3) inpatient consultations for VTE that were not on primary hematology service.	Control n=12 Participants 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
Change in PTS Biomarkers (D-dimer)	-4675 µg/mL Standard Deviation 5633	-6241 µg/mL Standard Deviation 6780

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Inpatients and Outpatients With VTE n=11 Participants All Inpatients and outpatients with VTE from following 3 sources: (1) new patient referrals to the Bleeding Disorders and Thrombosis outpatient clinic, (2) inpatient admissions to the hematology service, and (3) inpatient consultations for VTE that were not on primary hematology service.	Control n=12 Participants 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
Percentage Change From Baseline in FVIII PTS Biomarker	-39.6 percent change Standard Deviation 92	-50.4 percent change Standard Deviation 82.5

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Inpatients and Outpatients With VTE n=11 Participants All Inpatients and outpatients with VTE from following 3 sources: (1) new patient referrals to the Bleeding Disorders and Thrombosis outpatient clinic, (2) inpatient admissions to the hematology service, and (3) inpatient consultations for VTE that were not on primary hematology service.	Control n=12 Participants 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
Change in PTS Biomarkers (C-reactive Protein)	-0.4 mg/dL Standard Deviation 1.6	-0.6 mg/dL Standard Deviation 1.6

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Inpatients and Outpatients With VTE n=11 Participants All Inpatients and outpatients with VTE from following 3 sources: (1) new patient referrals to the Bleeding Disorders and Thrombosis outpatient clinic, (2) inpatient admissions to the hematology service, and (3) inpatient consultations for VTE that were not on primary hematology service.	Control n=12 Participants 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
Change in PTS Biomarkers (Fibrinolysis - Endogenous Thrombin Potential)	41.0 nM*min Standard Deviation 223	-60.1 nM*min Standard Deviation 148

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Inpatients and Outpatients With VTE n=11 Participants All Inpatients and outpatients with VTE from following 3 sources: (1) new patient referrals to the Bleeding Disorders and Thrombosis outpatient clinic, (2) inpatient admissions to the hematology service, and (3) inpatient consultations for VTE that were not on primary hematology service.	Control n=12 Participants 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
Change in PTS Biomarkers (Fibrinolysis - Thrombin Generation)	60.5 nmol/L Standard Deviation 164	0.2 nmol/L Standard Deviation 28.4

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Inpatients and Outpatients With VTE n=11 Participants All Inpatients and outpatients with VTE from following 3 sources: (1) new patient referrals to the Bleeding Disorders and Thrombosis outpatient clinic, (2) inpatient admissions to the hematology service, and (3) inpatient consultations for VTE that were not on primary hematology service.	Control n=12 Participants 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
Percent Change in Fibrinolysis Biomarker Lysis 30, % (percent amplitude change 30 minutes after maximum amplitude)	-0.05 percent amplitude change Standard Deviation 3.3	2.1 percent amplitude change Standard Deviation 3.1
Percent Change in Fibrinolysis Biomarker Lysis 60, % (percent amplitude change 60 minutes after maximum amplitude)	-0.04 percent amplitude change Standard Deviation 11.6	6.2 percent amplitude change Standard Deviation 6.5

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Inpatients and Outpatients With VTE n=11 Participants All Inpatients and outpatients with VTE from following 3 sources: (1) new patient referrals to the Bleeding Disorders and Thrombosis outpatient clinic, (2) inpatient admissions to the hematology service, and (3) inpatient consultations for VTE that were not on primary hematology service.	Control n=12 Participants 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
Change in Quality of Life	5.4 score on a scale Standard Deviation 14.3	24.5 score on a scale Standard Deviation 14.2

Adverse Events

Intervention

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Control

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Ayesha Zia, MD

The University of Texas Southwestern Medical Center

Phone: 214-456-7000

Email: Ayesha.Zia@UTSouthwestern.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place