Mechanisms of Deep Vein Thrombosis (DVT) and Vein Wall Fibrosis

The goal of this study is to determine the safety and tolerability or efficacy of adjunctive treatments (including rosuvastatin 20 mg daily) in combination with standard anticoagulation therapy (Factor Xa inhibitors) in patients with lower extremity deep vein thrombosis (DVT). The efficacy of adjunctive treatments to prevent the development of post thrombotic syndrome (PTS) after DVT will be evaluated.

Study Overview

• Status: Recruiting
• Conditions: Deep Vein Thrombosis Leg; Post-thrombotic Syndrome
• Intervention / Treatment: Drug: Rosuvastatin

Detailed Description

Post-thrombotic syndrome (PTS) is a significant complication that occurs up to 75% of patients after DVT. Rosuvastatin is a HMGCoA reductase inhibitor that has anti-inflammatory effects. In this study, the investigators will evaluate the safety and tolerability of combination standard anticoagulation therapy (e.g. Factor Xa inhibitor, rivaroxaban, apixaban) and three months of 20 mg dose of rivaroxaban and its efficacy as prophylaxis against PTS after lower extremity DVT. After the diagnosis of lower extremity DVT with either duplex venous ultrasound or other imaging, study participants will initiate standard rivaroxaban therapy as per standard medical care. All consented participants in this trial will receive three months of rosuvastatin (20 mg daily dose). Assessment of post thrombotic syndrome follow up will continue for 365 days from the time of DVT diagnosis or until resolution or stabilization of any clinically significant drug related adverse event, after which they will be considered off-study.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Khanh P Nguyen, MD; Phone Number: 5034947145; Email: nguykha@ohsu.edu
• Study Contact Backup: Name: Tahnee Groat, MPH; Phone Number: 56888 503-220-8262; Email: groat@ohsu.edu

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • VA Portland Health Care System (VAPORHCS)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women
• Diagnosis of a first episode of acute proximal leg DVT within 4 weeks of initial DVT diagnosis and without symptomatic pulmonary embolism (PE)
• Must have ECOG performance status ≤ 2
• Expected life expectancy of >2 years
• Before initiation of anticoagulation, must have adequate platelet count: Platelet count > 100 x 10^9/L,
• Before initiation of anticoagulation, must have adequate hemoglobin (Hgb) count: Hgb > 9 mg/DL
• Before initiation of anticoagulation, must have normal INR and PTT: INR ≤ 1.5 and aPTT≤40

Exclusion Criteria:

• Concurrent participation in another therapeutic clinical trial
• History of prior DVT in the previous 2 years
• Recurrent deep vein thrombosis (DVT)
• Established post thrombotic syndrome (PTS)
• Limb-threatening circulatory compromise
• Pulmonary embolism with hemodynamic compromise
• Deranged baseline coagulation profile before initiation of anticoagulation: INR > 1.5 or aPTT prolonged >40
• Active bleeding within last 3 months
• Anemia with Hemoglobin<9 mg/dL
• Thrombocytopenia with platelets < 100,000/ml
• Previously documented hypersensitivity to either the drug or excipients
• Any contraindication to anticoagulation or allergy to factor V inhibitors or ferumoxytol
• Any contraindication to magnetic resonance imaging (MRI) including metal implants or claustrophobia
• Severe hepatic impairment as defined by Childs-Pugh Class B or C
• Severe renal impairment with CrCl<30 ml/min,
• Taking any P-GP or strong CYP3A4 inhibitors or inducers
• History of major bleeding including history of gastrointestinal bleeding or intracranial bleeding
• Known history of bleeding diathesis
• History of chronic atrial fibrillation or stroke
• History of active cancer or malignancy within 1 year,
• Life expectancy <2 years.
• Patients requiring emergent or urgent surgery or procedures within the first 3 months of the study that cannot be postponed will be excluded.
• Patients who are breastfeeding or anticipate pregnancy
• Participant is pregnant or breastfeeding
• Participant is a prisoner (protected population)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rosuvastatin; Subjects will receive 20 mg daily dose of rosuvastatin for at least 3 months	Drug: Rosuvastatin; Oral administration of 20 mg rosuvastatin for at least 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-thrombotic syndrome	Incidence of post-thrombotic syndrome as measured by the Villalta Scale (score = or > 4). Minimum score=0, Maximum score=33, and a higher score indicates worse outcome.	365 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of post-thrombotic syndrome (PTS)	Villalta score severity of post-thrombotic syndrome	365 day

Collaborators and Investigators

• Sponsor: Khanh Nguyen
• Investigators: Principal Investigator: Khanh P Nguyen, MD, Portland VA Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Anticipated): June 1, 2025
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: April 2, 2021
• First Submitted That Met QC Criteria: April 2, 2021
• First Posted (Actual): April 6, 2021

Study Record Updates

• Last Update Posted (Actual): October 15, 2021
• Last Update Submitted That Met QC Criteria: October 14, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Venous thrombosis; Deep vein thrombosis; Anticoagulant; Contact pathway inhibition; Coagulation factor XI inhibition
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Peripheral Vascular Diseases; Venous Insufficiency; Phlebitis; Thrombosis; Venous Thrombosis; Postthrombotic Syndrome; Postphlebitic Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: eIRB19051/M4069

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: Yes
• Studies a U.S. FDA-regulated device product: No