Trial Outcomes & Findings for Role of a Novel Exercise Program to Prevent Post-thrombotic Syndrome (NCT NCT02148029)

Last Updated: 2024-10-23

Results Overview

The Villalta score quantifies severity of symptoms and can be used to diagnose Post-Thrombotic Syndrome (PTS). The Villalta score quantifies severity of symptoms and can be used to diagnose Post-Thrombotic Syndrome (PTS). Higher Villalta scores denote more severe symptoms and greater likelihood of PTS. The outcome measure is not the score itself, but change in scores over time, calculated by subtracting the baseline score from the score at the 2-year follow-up. The range of the Villalta score is 0-33, so the minimum possible change is -33 and the maximum possible change is 33, with 0 indicating no change in Villalta scores (same score at baseline and at 2-year follow-up). An increase (positive change) in Villalta score indicates worsening symptoms, while a decrease (negative change) indicates improving symptoms.

Recruitment status

COMPLETED

Study phase

Target enrollment

107 participants

Primary outcome timeframe

Change from baseline to 2-year follow-up

Results posted on

2024-10-23

Participant Flow

Adult (18+) patients who recently experienced acute lower extremity Deep Vein Thrombosis (DVT) were screened and enrolled within 28 days of the DVT diagnosis, received a 3-month treatment (either standard care alone or standard care + exercise program), followed for 2 years, and evaluated at 1 month, 3 months, 6 months, 1 year, and 2 years. Participants were recruited from a vascular imaging lab based on physician referral. Participants were enrolled September 2014 - June 2019.

Of 107 enrolled participants, 102 were randomized to one of the treatment groups.

Participant milestones

Participant milestones
Measure	Control Standard care (anticoagulation, compression, and ad-lib ambulation)	Exercise Standard care + 3-month exercise therapy Exercise: upper and lower extremity exercise Standard care: anticoagulation, compression, and ad-lib ambulation
Overall Study STARTED	48	54
Overall Study COMPLETED	36	31
Overall Study NOT COMPLETED	12	23

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Patients who underwent physical examination at baseline (some patients could not tolerate the physical examination necessary to ascertain Villalta score).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Control n=48 Participants Standard care (anticoagulation, compression, and ad-lib ambulation)	Exercise n=54 Participants Standard care + 3-month exercise therapy Exercise: upper and lower extremity exercise Standard care: anticoagulation, compression, and ad-lib ambulation	Total n=102 Participants Total of all reporting groups
Age, Continuous	55 years STANDARD_DEVIATION 15 • n=48 Participants	52 years STANDARD_DEVIATION 12 • n=54 Participants	53 years STANDARD_DEVIATION 14 • n=102 Participants
Sex: Female, Male Female	21 Participants n=48 Participants	18 Participants n=54 Participants	39 Participants n=102 Participants
Sex: Female, Male Male	27 Participants n=48 Participants	36 Participants n=54 Participants	63 Participants n=102 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=48 Participants	2 Participants n=54 Participants	2 Participants n=102 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	47 Participants n=48 Participants	50 Participants n=54 Participants	97 Participants n=102 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=48 Participants	2 Participants n=54 Participants	3 Participants n=102 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=48 Participants	0 Participants n=54 Participants	0 Participants n=102 Participants
Race (NIH/OMB) Asian	1 Participants n=48 Participants	0 Participants n=54 Participants	1 Participants n=102 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=48 Participants	0 Participants n=54 Participants	0 Participants n=102 Participants
Race (NIH/OMB) Black or African American	27 Participants n=48 Participants	26 Participants n=54 Participants	53 Participants n=102 Participants
Race (NIH/OMB) White	19 Participants n=48 Participants	24 Participants n=54 Participants	43 Participants n=102 Participants
Race (NIH/OMB) More than one race	0 Participants n=48 Participants	2 Participants n=54 Participants	2 Participants n=102 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=48 Participants	2 Participants n=54 Participants	3 Participants n=102 Participants
Villalta score	5.4 units on a scale STANDARD_DEVIATION 4.5 • n=46 Participants • Patients who underwent physical examination at baseline (some patients could not tolerate the physical examination necessary to ascertain Villalta score).	4.2 units on a scale STANDARD_DEVIATION 3.8 • n=49 Participants • Patients who underwent physical examination at baseline (some patients could not tolerate the physical examination necessary to ascertain Villalta score).	4.8 units on a scale STANDARD_DEVIATION 4.1 • n=95 Participants • Patients who underwent physical examination at baseline (some patients could not tolerate the physical examination necessary to ascertain Villalta score).
VEINES-QOL summary score	84.2 units on a scale STANDARD_DEVIATION 15.0 • n=42 Participants • Patients who completed the VEINES-QOL questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	85.4 units on a scale STANDARD_DEVIATION 16.8 • n=49 Participants • Patients who completed the VEINES-QOL questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	84.8 units on a scale STANDARD_DEVIATION 15.9 • n=91 Participants • Patients who completed the VEINES-QOL questionnaire at baseline (some patients refused or were unable to complete the questionnaire).
SF-36 domain scores PF domain score	44.9 units on a scale STANDARD_DEVIATION 32.5 • n=43 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	66.7 units on a scale STANDARD_DEVIATION 29.7 • n=49 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	56.5 units on a scale STANDARD_DEVIATION 32.7 • n=92 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).
SF-36 domain scores RP domain score	7.4 units on a scale STANDARD_DEVIATION 10.2 • n=43 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	9.8 units on a scale STANDARD_DEVIATION 10.4 • n=49 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	8.7 units on a scale STANDARD_DEVIATION 10.3 • n=92 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).
SF-36 domain scores RE domain score	15.1 units on a scale STANDARD_DEVIATION 11.3 • n=43 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	15.6 units on a scale STANDARD_DEVIATION 10.7 • n=49 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	15.6 units on a scale STANDARD_DEVIATION 10.9 • n=92 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).
SF-36 domain scores VT domain score	54.2 units on a scale STANDARD_DEVIATION 27.9 • n=43 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	59.9 units on a scale STANDARD_DEVIATION 25.2 • n=49 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	57.2 units on a scale STANDARD_DEVIATION 26.5 • n=92 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).
SF-36 domain scores MH domain score	68.4 units on a scale STANDARD_DEVIATION 25.0 • n=43 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	72.3 units on a scale STANDARD_DEVIATION 20.3 • n=49 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	70.5 units on a scale STANDARD_DEVIATION 22.6 • n=92 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).
SF-36 domain scores SF domain score	58.1 units on a scale STANDARD_DEVIATION 35.7 • n=43 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	65.6 units on a scale STANDARD_DEVIATION 31.2 • n=49 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	62.1 units on a scale STANDARD_DEVIATION 33.4 • n=92 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).
SF-36 domain scores BP domain score	47.9 units on a scale STANDARD_DEVIATION 36.3 • n=43 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	52.2 units on a scale STANDARD_DEVIATION 29.4 • n=49 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	50.2 units on a scale STANDARD_DEVIATION 32.7 • n=92 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).
SF-36 domain scores GH domain score	55.2 units on a scale STANDARD_DEVIATION 25.3 • n=43 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	62.5 units on a scale STANDARD_DEVIATION 22.0 • n=49 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).	59.1 units on a scale STANDARD_DEVIATION 23.8 • n=92 Participants • Patients who completed the SF-36 questionnaire at baseline (some patients refused or were unable to complete the questionnaire).
Thrombus volume	3.0 mL STANDARD_DEVIATION 6.7 • n=42 Participants • Patients for whom thrombus volume could be determined through imaging (thrombus volume could not be determined for some patients).	2.4 mL STANDARD_DEVIATION 4.4 • n=47 Participants • Patients for whom thrombus volume could be determined through imaging (thrombus volume could not be determined for some patients).	2.7 mL STANDARD_DEVIATION 5.6 • n=89 Participants • Patients for whom thrombus volume could be determined through imaging (thrombus volume could not be determined for some patients).

PRIMARY outcome

Timeframe: Change from baseline to 2-year follow-up

Population: Patients who underwent physical examination at baseline and at the 2-year visit (some patients could not tolerate the physical examination necessary to ascertain Villalta score, and some patients did not complete a 2-year follow-up visit).

Outcome measures

Outcome measures
Measure	Control n=30 Participants Standard care (anticoagulation, compression, and ad-lib ambulation)	Exercise n=30 Participants Standard care + 3-month exercise therapy Exercise: upper and lower extremity exercise Standard care: anticoagulation, compression, and ad-lib ambulation
2-year Change in Villalta Score	-1.5 units on a scale Standard Deviation 4.3	-0.5 units on a scale Standard Deviation 3.7

PRIMARY outcome

Timeframe: Change from baseline to 2-year follow-up

Population: Patients who completed the VEINES-QOL questionnaire at baseline and at the 2-year visit (some patients refused or were unable to complete the questionnaire, and some patients did not complete a 2-year follow-up visit).

The VEINES-QOL summary score is calculated from the Venous Insufficiency Epidemiological and Economic Study (VEINES) Quality of Life (QOL) questionnaire, and it provides an estimate of the overall impact of deep venous thrombosis (DVT) on the patient's quality of life. A higher VEINES-QOL score indicates better quality of life. The outcome measure is not the score itself, but change in scores over time, calculated by subtracting the baseline score from the score at the 2-year visit. The range of the VEINES-QOL summary score is 25-117, so the minimum possible change is -92 and the maximum possible change is 92, with 0 indicating no change in VEINES-QOL scores (same score at baseline and at 2-year follow-up). An increase (positive change) in VEINES-QOL score indicates an improvement in quality of life, and a decrease (negative change) indicates worsening quality of life.

Outcome measures

Outcome measures
Measure	Control n=23 Participants Standard care (anticoagulation, compression, and ad-lib ambulation)	Exercise n=30 Participants Standard care + 3-month exercise therapy Exercise: upper and lower extremity exercise Standard care: anticoagulation, compression, and ad-lib ambulation
2-year Change in VEINES-QOL Summary Score	6.4 units on a scale Standard Deviation 8.2	6.9 units on a scale Standard Deviation 16.5

SECONDARY outcome

Timeframe: Change from baseline to 2-year follow-up

Population: Patients who completed the SF-36 questionnaire at baseline and at the 2-year visit (some patients refused or were unable to complete the questionnaire, and some patients did not complete a 2-year follow-up visit).

The 36-Item Short Form survey (SF-36) produces 8 domain scores, each quantifying a different aspect of quality of life: * PF = Physical Functioning * RP = Role limitations due to Physical health problems * RE = Role limitations due to mental health or Emotional problems * VT = energy/fatigue/Vitality * MH = Mental Health/emotional well-being * SF = Social Functioning * BP = Bodily Pain * GH = General Health The outcome measure is not the score itself, but change in scores over time, calculated by subtracting the baseline score from the score at the 2-year visit. The range for each domain score is 0-100, so the minimum possible change is -100 and the maximum possible change is +100, with 0 indicating no change in domain scores (same score at baseline and at 2-year follow-up). An increase (positive change) in a domain score indicates improvement in that specific aspect of quality of life, and a decrease (negative change) indicates worsening quality of life in that domain.

Outcome measures

Outcome measures
Measure	Control n=24 Participants Standard care (anticoagulation, compression, and ad-lib ambulation)	Exercise n=30 Participants Standard care + 3-month exercise therapy Exercise: upper and lower extremity exercise Standard care: anticoagulation, compression, and ad-lib ambulation
2-year Change in SF-36 Domain Scores Change in PF domain score	20.2 units on a scale Standard Deviation 30.9	14.4 units on a scale Standard Deviation 22.2
2-year Change in SF-36 Domain Scores Change in RP domain score	5.2 units on a scale Standard Deviation 13.8	10.2 units on a scale Standard Deviation 10.4
2-year Change in SF-36 Domain Scores Change in RE domain score	3.1 units on a scale Standard Deviation 11.5	5.8 units on a scale Standard Deviation 8.8
2-year Change in SF-36 Domain Scores Change in VT domain score	3.1 units on a scale Standard Deviation 26.9	8.7 units on a scale Standard Deviation 25.4
2-year Change in SF-36 Domain Scores Change in MH domain score	1.9 units on a scale Standard Deviation 22.4	-0.7 units on a scale Standard Deviation 18.6
2-year Change in SF-36 Domain Scores Change in SF domain score	21.4 units on a scale Standard Deviation 28.4	17.5 units on a scale Standard Deviation 31.8
2-year Change in SF-36 Domain Scores Change in BP domain score	12.5 units on a scale Standard Deviation 34.8	22.0 units on a scale Standard Deviation 38.4
2-year Change in SF-36 Domain Scores Change in GH domain score	1.1 units on a scale Standard Deviation 22.0	-2.4 units on a scale Standard Deviation 16.6

SECONDARY outcome

Timeframe: Change from baseline to 3-month follow-up

Population: Patients for whom thrombus volume could be determined through imaging at baseline and at the 3-month visit (thrombus volume could not be determined for some patients, and some patients did not complete a 3-month follow-up visit).

Percent-change in thrombus volume (mL) is calculated by subtracting the baseline volume from the volume at the 3-month visit then dividing the result by the baseline volume and multiplying by 100. A negative change indicates a decrease in thrombus volume; i.e. the thrombus shrank in size and is therefore closer to complete resolution. A percent-change of -100% indicates complete thrombus resolution.

Outcome measures

Outcome measures
Measure	Control n=24 Participants Standard care (anticoagulation, compression, and ad-lib ambulation)	Exercise n=35 Participants Standard care + 3-month exercise therapy Exercise: upper and lower extremity exercise Standard care: anticoagulation, compression, and ad-lib ambulation
3-month Percent-change in Thrombus Volume	-35.9 Percent of baseline thrombus size Standard Deviation 138.1	-69.8 Percent of baseline thrombus size Standard Deviation 63.2

POST_HOC outcome

Timeframe: Baseline

Population: Patients who underwent physical examination (to ascertain Villalta score) as well as lower extremity Ultrasonography (to assess hemodynamics of the common femoral vein) at baseline.

Common femoral reflux (yes/no) is used as a measure of hemodynamics; determined through lower extremity Ultrasonography. The Villalta score quantifies severity of symptoms and can be used to diagnose Post-Thrombotic Syndrome (PTS). Higher Villalta scores denote more severe symptoms and greater likelihood of PTS. The minimum possible score is 0, and the maximum possible score is 33.

Outcome measures

Outcome measures
Measure	Control n=52 Participants Standard care (anticoagulation, compression, and ad-lib ambulation)	Exercise n=42 Participants Standard care + 3-month exercise therapy Exercise: upper and lower extremity exercise Standard care: anticoagulation, compression, and ad-lib ambulation
Villalta Score in People With vs Without Common Femoral Reflux Exercise	3.9 units on a scale Standard Deviation 3.8	4.4 units on a scale Standard Deviation 3.9
Villalta Score in People With vs Without Common Femoral Reflux Control	4.1 units on a scale Standard Deviation 3.0	6.9 units on a scale Standard Deviation 5.5

POST_HOC outcome

Timeframe: Baseline

Population: Patients who underwent physical examination to ascertain Villalta score and completed 400-meter walk at baseline (some patients could not tolerate physical examination and some patients were unable to complete walk).

The 400-meter walk tests exercise capacity. Post-thrombotic syndrome (PTS) is defined as a Villalta score of 5 or higher.

Outcome measures

Outcome measures
Measure	Control n=23 Participants Standard care (anticoagulation, compression, and ad-lib ambulation)	Exercise n=36 Participants Standard care + 3-month exercise therapy Exercise: upper and lower extremity exercise Standard care: anticoagulation, compression, and ad-lib ambulation
Time Required to Walk 400 Meters in Patients With vs Without PTS Exercise	5.9 minutes Standard Deviation 2.0	5.4 minutes Standard Deviation 1.1
Time Required to Walk 400 Meters in Patients With vs Without PTS Control	4.9 minutes Standard Deviation 1.3	5.6 minutes Standard Deviation 1.4

Adverse Events

Control

Serious events: 14 serious events

Other events: 0 other events

Deaths: 6 deaths

Exercise

Serious events: 9 serious events

Other events: 0 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Dr. Brajesh K. Lal

Veterans Administration of Baltimore Maryland

Phone: 410-328-5840

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Control n=48 participants at risk Standard care: anticoagulation, compression \& ad-lib ambulation Control: Standard care: anticoagulation, compression \& ad-lib ambulation	Exercise n=54 participants at risk Standard care + Interventional Exercise therapy Exercise: Upper and Lower extremity exercise Standard care: anticoagulation, compression \& ad-lib ambulation
Renal and urinary disorders Renal Failure	2.1% 1/48 • Number of events 1 • Adverse events were collected for 2 years	1.9% 1/54 • Number of events 1 • Adverse events were collected for 2 years
Surgical and medical procedures Hernia repair	0.00% 0/48 • Adverse events were collected for 2 years	1.9% 1/54 • Number of events 1 • Adverse events were collected for 2 years
Gastrointestinal disorders Bowel Obstruction	2.1% 1/48 • Number of events 1 • Adverse events were collected for 2 years	1.9% 1/54 • Number of events 1 • Adverse events were collected for 2 years
Gastrointestinal disorders Colon Cancer	0.00% 0/48 • Adverse events were collected for 2 years	1.9% 1/54 • Number of events 1 • Adverse events were collected for 2 years
Renal and urinary disorders Prostate Cancer	2.1% 1/48 • Number of events 1 • Adverse events were collected for 2 years	1.9% 1/54 • Number of events 1 • Adverse events were collected for 2 years
Musculoskeletal and connective tissue disorders Chronic Pain After Fracture	0.00% 0/48 • Adverse events were collected for 2 years	3.7% 2/54 • Number of events 2 • Adverse events were collected for 2 years
Gastrointestinal disorders Cholecystectomy	0.00% 0/48 • Adverse events were collected for 2 years	1.9% 1/54 • Number of events 1 • Adverse events were collected for 2 years
Endocrine disorders Neuroendocrine tumor	0.00% 0/48 • Adverse events were collected for 2 years	1.9% 1/54 • Number of events 1 • Adverse events were collected for 2 years
Infections and infestations Disseminated infection	2.1% 1/48 • Number of events 1 • Adverse events were collected for 2 years	0.00% 0/54 • Adverse events were collected for 2 years
Respiratory, thoracic and mediastinal disorders Tumor	4.2% 2/48 • Number of events 2 • Adverse events were collected for 2 years	0.00% 0/54 • Adverse events were collected for 2 years
Musculoskeletal and connective tissue disorders Gun Shot Wound	2.1% 1/48 • Number of events 1 • Adverse events were collected for 2 years	0.00% 0/54 • Adverse events were collected for 2 years
Respiratory, thoracic and mediastinal disorders Respirtory failure	6.2% 3/48 • Number of events 3 • Adverse events were collected for 2 years	0.00% 0/54 • Adverse events were collected for 2 years
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	2.1% 1/48 • Number of events 1 • Adverse events were collected for 2 years	0.00% 0/54 • Adverse events were collected for 2 years
Gastrointestinal disorders Gastrointestinal Bleed	2.1% 1/48 • Number of events 1 • Adverse events were collected for 2 years	0.00% 0/54 • Adverse events were collected for 2 years
Vascular disorders Intracranial bleeding	2.1% 1/48 • Number of events 1 • Adverse events were collected for 2 years	0.00% 0/54 • Adverse events were collected for 2 years
Psychiatric disorders Homicidal ideation	2.1% 1/48 • Number of events 1 • Adverse events were collected for 2 years	0.00% 0/54 • Adverse events were collected for 2 years