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

Sponsor

Khanh Nguyen (U.S. Fed)

Overall Status

Recruiting

CT.gov ID

NCT04833764

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Post-thrombotic Syndrome Deep Vein Thrombosis Leg	Drug: Rosuvastatin	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is a prospective, single arm Phase 1/Phase 2 study of patients with lower extremity DVT. Phase 1 will assess safety and tolerability of xisomab 3G3 in patients with lower extremity DVT on standard rivaroxaban therapy in 12-18 subjects. Three doses of xisomab 3G3 (42, 126, or 252 mg IV) will be tested to determine the maximum tolerated dose (MTD) with the dose limiting toxicity as any major bleeding or serious adverse event. Phase 2 will assess the efficacy of xisomab 3G3 for the prevention of PTS and compare the 1 year incidence of PTS as determined by the Villalta score in patients with lower extremity DVT on standard rivaroxaban therapy in 30 study participants.This is a prospective, single arm Phase 1/Phase 2 study of patients with lower extremity DVT. Phase 1 will assess safety and tolerability of xisomab 3G3 in patients with lower extremity DVT on standard rivaroxaban therapy in 12-18 subjects. Three doses of xisomab 3G3 (42, 126, or 252 mg IV) will be tested to determine the maximum tolerated dose (MTD) with the dose limiting toxicity as any major bleeding or serious adverse event. Phase 2 will assess the efficacy of xisomab 3G3 for the prevention of PTS and compare the 1 year incidence of PTS as determined by the Villalta score in patients with lower extremity DVT on standard rivaroxaban therapy in 30 study participants.

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jun 1, 2021

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Jun 1, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Post-thrombotic syndrome [365 day]
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.

Secondary Outcome Measures

Severity of post-thrombotic syndrome (PTS) [365 day]
Villalta score severity of post-thrombotic syndrome

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)