Role of a Novel Exercise Program to Prevent Post-thrombotic Syndrome (EFFORT2)

Despite standard care, 25%-50% of patients with clots in the deep veins of the arms and legs progress to chronic post-clot problems resulting in significant disability, loss of productivity, and healthcare costs. Reverse flow in the veins from an organizing clot is the primary cause of post-clot problems. Veins with early clot breakdown have a lower incidence of reverse flow. The investigators have observed that clot breakdown is enhanced by increased blood flow and that moderate arm and leg exercise result in increased venous blood flow. Hence, the investigators predict that a supervised exercise program in patients with deep vein clots could increase leg vein blood flow, accelerate clot breakdown, and decrease the risk of post clot problems. The primary hypothesis is that increased blood flow across the clot (induced by supervised exercise) will increase clot breakdown and decrease severity of post clot problems. The investigators are conducting a randomized clinical trial of standard therapy compared to progressive exercise training in patients with leg deep vein clots.

Study Overview

• Status: Completed
• Conditions: Acute Deep Vein Thrombosis
• Intervention / Treatment: Other: Exercise; Other: Standard Care

Detailed Description

Standard anticoagulation therapy for acute deep vein thrombosis (DVT) reflects the current short term focus on preventing pulmonary embolism (PE) and recurrent DVT. Despite standard care, 25% to 50% of patients with DVT progress to the chronic post-thrombotic syndrome (PTS) resulting in significant disability, loss of productivity, and healthcare costs. The investigators postulate that a supervised exercise program in patients with acute DVT could increase lower extremity venous flow, accelerate thrombus resolution, and thereby decrease the risk of PTS. If the patient is unable to perform exercises, neuromuscular electrical stimulation (NMES) will be used to induce contraction of the muscles of the lower extremities.

Aim 1 will test whether a 3-month exercise program has long-term clinical benefits in acute DVT. The primary outcome measures will be the 2-year change in Villalta score for PTS and VEINES-QOL score (Venous Insufficiency Epidemiological and Economic Study-QOL).

Aim 2 will evaluate whether exercise therapy in patients with acute DVT enhances thrombus resolution. The outcome measure will be 3-month change in thrombus volume.

Aim 3 will assess the relationship between PTS, venous hemodynamics and exercise capacity. The outcome measures will be Villalta score, common femoral reflux, and 400-meter walk time.

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Acute Lower Extremity DVT
• DVT documented by ultrasound, CT/Magnetic Resonance imaging (MR) venogram, or conventional venogram
• Enrolled within 4 weeks of onset of symptoms
• Age 18 years or older

Exclusion Criteria:

• Peripheral arterial disease (disabling claudication, rest pain, tissue loss) with ankle brachial index (ABI)<0.5
• Immediate need for thrombolysis/thrombectomy
• DVT involving the inferior vena cava (IVC)
• Contraindication to anticoagulation
• Contraindications to exercise training
• Medical illness interfering with evaluation/follow-up
• Life expectancy <2 years
• Pregnancy
• Inability to walk
• Hemodynamically significant PE

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; Standard care: anticoagulation, compression, and ad-lib ambulation	Other: Standard Care; anticoagulation, compression, and ad-lib ambulation
Experimental: Exercise; Standard care + Interventional Exercise therapy	Other: Exercise; Upper and Lower extremity exercise; Other: Standard Care; anticoagulation, compression, and ad-lib ambulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year Change in Villalta Score	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.	Change from baseline to 2-year follow-up
2-year Change in VEINES-QOL Summary Score	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.	Change from baseline to 2-year follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year Change in SF-36 Domain Scores	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.	Change from baseline to 2-year follow-up
3-month Percent-change in Thrombus Volume	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.	Change from baseline to 3-month follow-up

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: University of Maryland
• Investigators: Principal Investigator: Brajesh K Lal, MD, Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2014
• Primary Completion (Actual): August 31, 2021
• Study Completion (Actual): August 31, 2021

Study Registration Dates

• First Submitted: May 21, 2014
• First Submitted That Met QC Criteria: May 21, 2014
• First Posted (Estimated): May 28, 2014

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: October 21, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Post thrombotic syndrome; Deep vein thrombosis; Thrombus resolution
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis; Peripheral Vascular Diseases; Venous Insufficiency; Phlebitis; Thrombosis; Venous Thrombosis; Postthrombotic Syndrome; Postphlebitic Syndrome
• Other Study ID Numbers: F0995-R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No