Mechanisms of Deep Vein Thrombosis (DVT) and Vein Wall Fibrosis
Primary Purpose
Post-thrombotic Syndrome, Deep Vein Thrombosis Leg
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Rosuvastatin
Sponsored by
About this trial
This is an interventional prevention trial for Post-thrombotic Syndrome focused on measuring Contact pathway inhibition, Coagulation factor XI inhibition, Anticoagulant, Deep vein thrombosis, Venous thrombosis
Eligibility Criteria
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)
Sites / Locations
- VA Portland Health Care System (VAPORHCS)Recruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rosuvastatin
Arm Description
Subjects will receive 20 mg daily dose of rosuvastatin for at least 3 months
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Severity of post-thrombotic syndrome (PTS)
Villalta score severity of post-thrombotic syndrome
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04833764
Brief Title
Mechanisms of Deep Vein Thrombosis (DVT) and Vein Wall Fibrosis
Official Title
Mechanisms of Deep Vein Thrombosis (DVT) and Vein Wall Fibrosis
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2021 (Actual)
Primary Completion Date
June 1, 2025 (Anticipated)
Study Completion Date
June 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Khanh Nguyen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-thrombotic Syndrome, Deep Vein Thrombosis Leg
Keywords
Contact pathway inhibition, Coagulation factor XI inhibition, Anticoagulant, Deep vein thrombosis, Venous thrombosis
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Rosuvastatin
Arm Type
Experimental
Arm Description
Subjects will receive 20 mg daily dose of rosuvastatin for at least 3 months
Intervention Type
Drug
Intervention Name(s)
Rosuvastatin
Intervention Description
Oral administration of 20 mg rosuvastatin for at least 3 months
Primary Outcome Measure Information:
Title
Post-thrombotic syndrome
Description
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.
Time Frame
365 day
Secondary Outcome Measure Information:
Title
Severity of post-thrombotic syndrome (PTS)
Description
Villalta score severity of post-thrombotic syndrome
Time Frame
365 day
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Khanh P Nguyen, MD
Phone
5034947145
Email
nguykha@ohsu.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Tahnee Groat, MPH
Phone
503-220-8262
Ext
56888
Email
groat@ohsu.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Khanh P Nguyen, MD
Organizational Affiliation
Portland VA Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Portland Health Care System (VAPORHCS)
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
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Mechanisms of Deep Vein Thrombosis (DVT) and Vein Wall Fibrosis
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