Statin Use in Patients With Acute VTE

NCT02331095 | Terminated Early Phase 1 Results

• 1 other identifier: 2014H0262
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Venous Thromboembolism

Outcome Measures

Primary Outcomes (2)

• The Reduction of Endogenous Thrombin Potential

  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

  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 Outcomes (9)

• The Composite Rate of Recurrent Venous Thromboembolism (VTE) and VTE Related Mortality

  3 months and 9 months

• The Rate of Arterial Thrombotic Events

  3 months and 9 months

• The Rate of Residual (Chronic) Vein Obstruction by Doppler Ultrasound

  3 Months

• The Reduction of Clinical Post-thrombotic Syndrome (PTS), as Objectively Evaluated With Villalta Scoring System

  3 Months

• The Rate of Major, Non-major, and All Hemorrhages Defined by the International Society on Thrombosis and Haemostasis (ISTH) Criteria

  3 months and 9 months

Study Arms (2)

Anticoagulation

ACTIVE COMPARATOR

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)

Drug: Anticoagulation Therapy

Atorvastatin + anticoagulation

EXPERIMENTAL

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

Drug: Atorvastatin; Drug: Anticoagulation Therapy

Interventions

Atorvastatin DRUG

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).

Also known as: Lipitor

Atorvastatin + anticoagulation

Anticoagulation Therapy DRUG

Warfarin is a standard anticoagulation in the treatment for venous thromboembolism. The dose will be adjusted to goal INR of 2-3.

Also known as: warfarin or rivaroxaban

Anticoagulation; Atorvastatin + anticoagulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ohio State University: lead

Study Sites (1)

The Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Wang TF, Waller AP, Lin E, Wei L, Bartosic A, Riedl K, Kerlin BA. A pilot randomized trial of atorvastatin as adjunct therapy in patients with acute venous thromboembolism. Blood Coagul Fibrinolysis. 2021 Jan 1;32(1):16-22. doi: 10.1097/MBC.0000000000000968.

  PMID: 33196511 DERIVED

MeSH Terms

Conditions

Venous Thromboembolism

Interventions

Atorvastatin; Anticoagulation Bridge; Warfarin; Rivaroxaban

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Bridge Therapy; Therapeutics; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines

Limitations and Caveats

Our study was limited by the small sample size, early termination due to low recruitment rate and lack of funding. The protocol was amended to include patients on rivaroxaban (initially only warfarin). Lost to follow up is also significant.

Results Point of Contact

• Title: Dr. Tzu-Fei Wang
• Organization: The Ohio State University

tzufeiwang@gmail.com

614-366-8366

Study Officials

• Tzu-Fei Wang, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor of Internal Medicine

Study Record Dates

• First Submitted: December 22, 2014
• First Posted: January 6, 2015
• Study Start: January 1, 2015
• Primary Completion: October 27, 2017
• Study Completion: May 20, 2020
• Last Updated: October 19, 2020
• Results First Posted: October 19, 2020

Record last verified: 2020-09

Locations

US (1)