Rosuvastatin Use to Improve the Coagulation Profile in Patients With Venous Thrombosis (START)

Prospective Randomized Controlled, Open Label, Clinical Trial to Study if Rosuvastatin Use Improves the Coagulation Profile in Patients With Venous Thrombosis

Epidemiological studies have shown a 2-3 fold increased long-term risk of arterial cardiovascular disease after venous thrombosis, most predominant in the first year following initial venous thrombosis. The results of recent observational studies that showed 40-50% risk reductions for first venous thrombosis occurrence when using a statin are in this aspect promising. The results are also somewhat surprising, because the mechanism behind this effect is unclear. Dyslipidemia may be the most plausible explanation to be considered. However, as dyslipidemia is not related to an increased risk of venous thrombosis, it is unlikely that statins decrease venous thrombosis risk by lipid lowering activities. Recent observations indicate that coagulation can activate the initial formation of atherosclerosis. Our hypothesis is therefore that the coagulation profile in persons with venous thrombosis is improved when using a statin, ultimately leading to less atherosclerosis: another well known property of statin use.

Study Overview

• Status: Completed
• Conditions: Deep Vein Thrombosis; Pulmonary Embolism
• Intervention / Treatment: Drug: Rosuvastatin

• Study Type: Interventional
• Enrollment (Actual): 255
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Rotterdam, Netherlands
    • Erasmus Medical Center
  • Zuid Holland
    • Hoofddorp, Zuid Holland, Netherlands, 2134TM
      • Trombosedienst Medial
    • Leiden, Zuid Holland, Netherlands, 2300RC
      • Leiden anticoagulation clinic

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Provision of informed consent prior to any study specific procedures
• Persons with (initial or recurrent) confirmed symptomatic proximal deep vein thrombosis or pulmonary embolism who after a time period of at least 3 to 12 months are allowed to stop, - or stopped using < 1 month anticoagulant treatment as indicated by their treating physician
• Persons aged 18 years or above

Exclusion Criteria:

• Persons already using statins or lipid lowering drugs, or any other disallowed concomitant medications (erythromycin, HIV protease inhibitors, or cyclosporine)
• History of statin-induced myopathy, or serious hypersensitivity reaction to other HMG-CoA reductase inhibitors (statins), including rosuvastatin
• Life expectancy less than 6 months
• Pregnant woman or woman with childbearing potential who are not willing to use contraception
• Active liver or kidney disease or dysfunction or muscle disorders
• Unstable medical or psychological condition that interferes with study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No intervention
Experimental: Rosuvastatin	Drug: Rosuvastatin; 20 mg od; Other Names: crestor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coagulation factor VIII	Change in factor VIII level from baseline to 28 days of intervention	28 days

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: Netherlands Heart Foundation

Publications and helpful links

General Publications

• Lijfering WM, Flinterman LE, Vandenbroucke JP, Rosendaal FR, Cannegieter SC. Relationship between venous and arterial thrombosis: a review of the literature from a causal perspective. Semin Thromb Hemost. 2011 Nov;37(8):885-96. doi: 10.1055/s-0031-1297367. Epub 2011 Dec 23.
• Ramberg C, Hindberg K, Biedermann JS, Cannegieter SC, van der Meer FJ, Snir O, Leebeek FWG, Kruip MJHA, Hansen JB, Lijfering WM. Rosuvastatin treatment decreases plasma procoagulant phospholipid activity after a VTE: A randomized controlled trial. J Thromb Haemost. 2022 Apr;20(4):877-887. doi: 10.1111/jth.15626. Epub 2022 Jan 8.
• Biedermann JS, Cannegieter SC, Roest M, van der Meer FJ, Reitsma PH, Kruip MJ, Lijfering WM. Platelet reactivity in patients with venous thrombosis who use rosuvastatin: a randomized controlled clinical trial. J Thromb Haemost. 2016 Jul;14(7):1404-9. doi: 10.1111/jth.13343. Epub 2016 Jun 10.
• Lippi G, Favaloro EJ, Sanchis-Gomar F. Venous thrombosis associated with HMG-CoA reductase inhibitors. Semin Thromb Hemost. 2013 Jul;39(5):515-32. doi: 10.1055/s-0033-1343892. Epub 2013 Apr 29.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: May 31, 2012
• First Submitted That Met QC Criteria: June 6, 2012
• First Posted (Estimate): June 7, 2012

Study Record Updates

• Last Update Posted (Estimate): January 16, 2017
• Last Update Submitted That Met QC Criteria: January 13, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Deep vein thrombosis; Pulmonary embolism; Pharmacologic actions; Rosuvastatin treatment
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thrombosis; Venous Thrombosis; Pulmonary Embolism; 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: 2011T012; 2012-000223-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED