- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02331095
Statin Use in Patients With Acute VTE
A Pilot Study of Using Statins in Patients With Acute Venous Thromboembolism (VTE)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
VTE is a potentially life-threatening disease, with an estimated incidence of 1-2 per 1000. Despite anticoagulation as standard of care, many patients still suffer from its complications: 30% will have VTE recurrence after an unprovoked VTE, and 25-50% will develop post-thrombotic syndrome. Therefore, there is an urgent need for effective therapies to reduce long-term VTE morbidities. Limitations in our understanding of the underlying pathophysiology of VTE and the absence of accurate biomarkers are significant problems. Without this knowledge, improvement in treatment is unlikely. Therefore, the overall objective of the study is to determine important biomarker changes in acute VTE and the actions of innovative adjunct therapy on those biomarkers. The rationale of the study is that, once the biomarker changes following acute VTE and the actions of therapies are established, treatment for acute VTE could be improved.
Statins are effective in the prevention of arterial thrombosis. Recently, arterial and venous thromboses are shown to share common pathophysiological mechanisms, and effective therapies for arterial thrombosis could provide benefits in VTE. Several observational studies and the JUPITER trial, a large, randomized, placebo-controlled study, have demonstrated that statins significantly reduce the risk of first VTE by 40%. Additionally, as few as 3 days of atorvastatin increase plasma fibrin clot permeability and susceptibility to lysis. Statins have been commonly prescribed for many other medical conditions such as coronary artery diseases and hyperlipidemia, and have demonstrated good safety profiles. These promising results, as well as their safety profiles, make statins an attractive potential addition to the standard anticoagulation for treating acute VTE, in an effort to reduce long-term morbidity. The effects of statins on thrombin generation in patients with acute VTE have not been studied. A study in patients with atrial fibrillation on warfarin showed a 40% reduction in endogenous thrombin potential with only three months of intensive cholesterol-lowering treatment including statins. Similar effects could be seen in patients with acute VTE. In addition, previous studies evaluating the effects of statins on the reduction of D-dimer or inflammatory cytokines revealed promising results but were not focused on patients with acute VTE. Therefore, this study will generate important information for acute VTE patients. This is a pilot, randomized, open-labelled study. Eligible patients will be enrolled and randomized 1:1 into "anticoagulation" arm or "anticoagulation plus atorvastatin" arm, with atorvastatin given at 40 mg orally daily for 3 months. The targeted total accrual is 80 patients, with 40 in each arm. Patients will be recruited from the hospitals and clinics at The Ohio State University Wexner Medical Center. Follow up visits are planned at enrollment, 3 months, and 9 months after randomization. At each follow up, blood will be obtained and assessments will include structured interviews of signs and symptoms of recurrent venous thromboembolism (VTE), bleeding, post thrombotic syndrome, and adverse events from study drugs. The primary objective of the study is to determine the reduction of thrombin peak concentration and/or endogenous thrombin potential measured by Thrombin Generation Assay (TGA) at 3 months in the "anticoagulation +atorvastatin" arm as compared to the "anticoagulation" arm. The secondary objectives are to determine the chronological changes of hemostatic, inflammatory, and lipidomic biomarker profiles in patients with acute VTE receiving anticoagulation as standard of care, with and without statins. The biomarker profile of interest, in addition to thrombin generation, include: D-dimer, Interleukin- 6 (IL-6), Interleukin-8 (IL-8), tumor necrosis factor (TNF)-α, high sensitivity C-reactive protein, free fatty acids, lipoprotein-associated phospholipase A2 , pro- inflammatory eicosanoids. The ultimate goal is to study the mechanisms of VTE and use of statin in VTE patients. Other secondary objectives include determination of relevant clinical outcomes such as VTE recurrence, VTE related mortality, arterial thrombosis, hemorrhage, post thrombotic syndrome, and residual vein obstruction in patients receiving standard of care versus standard of care plus statins.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
Ohio
-
Columbus, Ohio, United States, 43210
- The Ohio State University Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- At least 18 years old
- A diagnosis of proximal DVT (proximal to and including popliteal vein), with or without PE, confirmed by objective imaging studies, such as Doppler ultrasound, venograms (for DVT) and/or computer tomography, angiograms, ventilation-perfusion scan (for PE)
- Treated with warfarin as anticoagulation (short-term bridging with heparin or lovenox is allowed)
Exclusion Criteria:
- Thrombolysis within 6 weeks prior to enrollment
- Patients with statin use within 6 weeks of enrollment
- Patients with known allergy or intolerance to statins or statins are contraindicated for any other reasons
- Patients with baseline aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin ≥2.0 x upper limit of normal (ULN)
- Pregnant or breastfeeding females are excluded
- Any malignancy diagnosed within the preceding 2 years, except for squamous cell carcinoma or basal cell carcinoma of skin treated with local resection only, or carcinoma in situ of the cervix
- Incarcerated patients are excluded from the study due to the inherent difficulties in maintaining close follow-up for study purposes in patients who are incarcerated.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Anticoagulation
Patients will be treated with warfarin with dose adjusted to goal International Normalized Ratio (INR) of 2-3 or rivaroxaban standard dose (15 mg twice daily for 3 weeks then 20 mg daily)
|
Warfarin is a standard anticoagulation in the treatment for venous thromboembolism.
The dose will be adjusted to goal INR of 2-3.
Other Names:
|
Experimental: Atorvastatin + anticoagulation
In addition to standard anticoagulation, patients will be given concurrent atorvastatin 40 mg daily for the study period of 9 months, starting from the time of enrollment
|
Warfarin is a standard anticoagulation in the treatment for venous thromboembolism.
The dose will be adjusted to goal INR of 2-3.
Other Names:
Atorvastatin belongs to the "statin" class of drugs, and is routinely used for prevention of cardiovascular diseases and/or reduction of cholesterol levels.
It has been shown to decrease the risk of first venous thromboembolism in an otherwise healthy population with elevated high-sensitivity C-reactive protein (hs-CRP).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Reduction of Endogenous Thrombin Potential
Time Frame: 3 Months
|
Determine the reduction of endogenous thrombin potential measured by Thrombin Generation Assay (TGA) at 3 months in the "anticoagulation +atorvastatin" arm as compared to the "anticoagulation" arm.
|
3 Months
|
The Reduction of Peak Thrombin Concentration
Time Frame: 3 Months
|
Determine the reduction of thrombin peak concentration measured by Thrombin Generation Assay (TGA) at 3 months in the "anticoagulation +atorvastatin" arm as compared to the "anticoagulation" arm.
|
3 Months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Composite Rate of Recurrent Venous Thromboembolism (VTE) and VTE Related Mortality
Time Frame: 3 months and 9 months
|
Recurrent PE was defined as new filling defect(s) seen on CT angiogram or a new high-probability ventilation-perfusion lung scan (22, 23).
Recurrent DVT was defined as new uncompressible segments seen on vascular Doppler ultrasonography in a previously uninvolved limb, clearly extending from the prior thrombosis, or a new venous segment in a previously involved limb.
|
3 months and 9 months
|
The Rate of Arterial Thrombotic Events
Time Frame: 3 months and 9 months
|
Arterial thromboembolism was defined a new myocardial infarction (based on typical electrocardiographic findings and/or elevation of cardiac enzymes) or cerebral vascular accident (based on clinical syndrome of development of focal or global loss of brain function thought to be vascular in origin, confirmed by appropriate standard imaging studies).
|
3 months and 9 months
|
The Rate of Residual (Chronic) Vein Obstruction by Doppler Ultrasound
Time Frame: 3 Months
|
Residual venous obstruction was assed by Doppler Ultrasonography.
Residual chronic DVT (to any degree) was reported.
|
3 Months
|
The Reduction of Clinical Post-thrombotic Syndrome (PTS), as Objectively Evaluated With Villalta Scoring System
Time Frame: 3 Months
|
The Villata score for Post-Thrombotic Syndrome (PTS) stratifies the severity of post-thrombotic syndrome in lower extremity DVT.
The score contains a combination of 5 subjective symptoms as reported by the patient (cramps, itching, pins and needles, heaviness, and pain) and 6 objective signs measured by a provider (edema, skin induration, hyperpigmentation, prominent veins on legs, redness, and tenderness on calf compression).
Each sign is scaled from 0 (no or minimal) to 3 (severe) with a total score ranged from 0 to 33.
Higher scores represent more severe disease.
|
3 Months
|
The Rate of Major, Non-major, and All Hemorrhages Defined by the International Society on Thrombosis and Haemostasis (ISTH) Criteria
Time Frame: 3 months and 9 months
|
Major bleeding events were defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria, with overt bleeding in critical organs (e.g.
central nervous system, retroperitoneum), a >2 gram/dL drop in hemoglobin from baseline, or requiring at least two units of packed red blood cell transfusion meeting the criteria for major bleeding.
Clinically relevant, non-major bleeding (CRNMB) events were defined as any other bleeding events reported by patients but not otherwise meeting the above listed criteria for major bleeding.
|
3 months and 9 months
|
Change in the Levels of D-Dimer at 3 Months
Time Frame: 3 Months
|
3 Months
|
|
Change in the Levels of C-Reactive Protein at 3 Months
Time Frame: 3 Months
|
C-Reactive (CRP) was measured using high sensitivity.
|
3 Months
|
Change in Low-Density Lipoproteins (LDL) at 3 Months
Time Frame: 3 Months
|
3 Months
|
|
Change in Triglyceride Levels at 3 Months
Time Frame: 3 Months
|
3 Months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Tzu-Fei Wang, MD, The Ohio State University Wexner Medical Center
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Embolism and Thrombosis
- Thromboembolism
- Venous Thromboembolism
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Protease Inhibitors
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Factor Xa Inhibitors
- Antithrombins
- Serine Proteinase Inhibitors
- Anticoagulants
- Atorvastatin
- Rivaroxaban
- Warfarin
Other Study ID Numbers
- 2014H0262
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Venous Thromboembolism
-
BayerWithdrawnTotal Hip Replacement | Total Knee Replacement | Prophylaxis, Thromboembolism, Venous
-
University Hospital, BrestRecruitingVenous Thromboembolism (VTE)France
-
University of ArizonaRecruitingPediatric Venous ThromboembolismUnited States
-
National Taiwan University HospitalUnknownDeep Venous ThromboembolismTaiwan
-
BayerCompletedTreatment of Venous ThromboembolismJapan
-
Azidus BrasilUnknownPrevention of Venous ThromboembolismBrazil
-
Ya-Wei XuFirst Affiliated Hospital, Sun Yat-Sen University; Nanfang Hospital of Southern...RecruitingVenous Thromboembolism (VTE)China
-
Bristol-Myers SquibbCompletedVenous Thromboembolism (VTE)United States
-
Fadoi Foundation, ItalyCompletedPrevention of Venous ThromboembolismItaly
-
Fadoi Foundation, ItalyUniversity Of PerugiaCompletedPrevention of Venous ThromboembolismItaly
Clinical Trials on Anticoagulation Therapy
-
University of ArizonaInari MedicalRecruitingPulmonary Hypertension | Pulmonary Embolism | Chronic Thromboembolic Pulmonary HypertensionUnited States
-
University of California, San FranciscoWithdrawnStroke | Atrial Fibrillation | Deep Vein Thrombosis | Anticoagulation | Atrial Flutter | Pulmonary Embolus/Emboli | Hypercoagulability
-
Johns Hopkins UniversityNational Heart, Lung, and Blood Institute (NHLBI)RecruitingAtrial FibrillationUnited States
-
National Institute of Cardiology, Warsaw, PolandMedical Research Agency, Poland; Soft Communication, PolandEnrolling by invitationAtrial Fibrillation | Mitral Regurgitation | AnticoagulationPoland
-
University of TurkuActive, not recruitingAtrial Fibrillation | Stroke, IschemicFinland
-
Medical University InnsbruckNot yet recruitingDelirium | Heart Surgery | Vascular Surgery | Hyperinflammatory SyndromeAustria
-
University of Sao Paulo General HospitalUniversity of Sao Paulo; InCor Heart Institute; Farmoquimica S.A.UnknownAtrial FibrillationBrazil
-
Vanderbilt University Medical CenterRecruitingThromboembolism | Acute Hypoxemic Respiratory Failure | Anticoagulant-induced BleedingUnited States
-
University of Massachusetts, WorcesterBristol-Myers SquibbCompletedAtrial Fibrillation | Anticoagulants | Prescribing PracticesUnited States
-
University of Toledo Health Science CampusWithdrawnPost Thrombotic Syndrome | Deep Venous ThrombosisUnited States