Statins for Venous Event Reduction in Patients With Venous Thromboembolism

Venous Thromboembolism Clinical Trial

— SAVER  

Official title:

Statins for Venous Event Reduction in Patients With Venous Thromboembolism

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04319627
• Other study ID #: SAVER Trial
• Status: Recruiting
• Phase: Phase 3
• Start date: February 10, 2021
• Est. completion date: January 2027

Study information

• Verified date: May 2023
• Source: Ottawa Hospital Research Institute
• Contact: Jennifer Brinkhurst
• Phone: +16137378899
• Email: jbrinkhurst[@]ohri.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The standard or usual treatment for patients diagnosed with deep vein thrombosis or pulmonary embolism is treatment with blood thinners (called anticoagulants).

While treatment of blood clots with blood thinners is effective, some research has shown that adding a statin (medication used to lower cholesterol) may give extra protection. It is thought that statins can improve how cells along the walls of the vein control inflammation, which can prevent new blood clots from forming.

The medication in this study, rosuvastatin, is approved in Canada for use as a cholesterol-lowering medication. The use of rosuvastatin in this study is considered investigational. This means that Health Canada has not approved the use of rosuvastatin as a treatment for blood clots. However, it has been approved for use in this research study.

The purpose of this study is to examine if adding a statin (rosuvastatin) to the usual blood thinner treatment will decrease the risk of another blood clot forming. The investigators also hope to discover if taking a statin reduces damage to your veins. To do this, some of the participants in this study will get rosuvastatin and others will receive a placebo (a substance that looks like the study rosuvastatin but does not have any active or medicinal ingredients). The placebo in this study is not intended to have any effect on your blood clot. A placebo is used to make the results of the study more reliable.

Description:

Recent research has demonstrated that it is plausible that statins have additive, and potentially even synergistic effects, in reducing recurrent VTE in patients managed with anticoagulant-based strategies. Furthermore, it is plausible that statins may reduce the risk of recurrent VTE in those not on anticoagulants and therefore offer an alternative in patients with contraindications to anticoagulants (e.g. after major intracranial bleed), who refuse to take anticoagulants long-term (e.g. due to lifestyle modifications or fear of bleeding) or who cannot afford anticoagulants (e.g. vulnerable or impoverished populations). Finally, statins may also provide protection from recurrent VTE in patients who are not fully compliant with anticoagulant therapy. However, no known RCTs have been done to explore these possibilities.

This study aims to determine if generic rosuvastatin reduces the risk of recurrent VTE compared to placebo in patients with symptomatic major VTE.

Primary Objectives

• To determine the primary outcome event rate (i.e. symptomatic recurrent major VTE [proximal DVT or segmental or larger PE]) in patients taking generic rosuvastatin compared to placebo.

Secondary Objectives

• To determine the major bleeding event rate in patients taking generic rosuvastatin compared to placebo.

• To explore if rosuvastatin reduces the incidence of PTS, as measured by the Villalta scale at end of study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2700
• Est. completion date: January 2027
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Symptomatic objectively confirmed proximal leg DVT (above the trifurcation of the popliteal vein) and/or PE (segmental or greater) diagnosed in the last 30 days.

Exclusion criteria

1. Unable or unwilling to provide written informed consent;

2. = 18 years of age;

3. Women of childbearing potential unwilling to use appropriate contraception;

4. Currently prescribed a statin;

5. A known medical history or current diagnosis of any of the following for which statins are indicated in secondary prevention:

1. Diabetes;

2. Abdominal aortic aneurysm;

3. Peripheral arterial disease;

4. Stroke;

5. Transient ischemic attack (TIA);

6. Myocardial infarction (MI);

7. Acute coronary syndromes;

8. Stable/unstable angina;

9. Coronary or other arterial revascularization;

6. Known diagnosis of hypercholesterolemia or dyslipidemia;

7. Contraindication to rosuvastatin;

1. Known hypersensitivity or intolerance to statins;

2. History of muscle disorders or statin-related muscle pain;

3. Known liver disease (active liver disease, e.g. Hepatitis A, B, C, non-alcoholic fatty liver);

4. Chronic kidney disease (creatinine clearance < 30ml/min);

5. Currently pregnant or breast feeding;

6. Taking cyclosporine;

7. Taking atazanavir/ritonavir;

8. Taking darolutamide;

9. Taking regorafenib;

8. Unstable medical or psychological condition that would interfere with trial participation.

Related Conditions & MeSH terms

• Blood Clot
• Post Thrombotic Syndrome
• Postphlebitic Syndrome
• Postthrombotic Syndrome
• Thromboembolism
• Thrombosis
• Venous Thromboembolism

Intervention

Drug:
• Rosuvastatin Calcium
Each participant will receive the usual treatment for their newly diagnosed blood clot in addition to the intervention they are randomized to.
• Placebo Oral Tablet
Each participant will receive the usual treatment for their newly diagnosed blood clot in addition to the intervention they are randomized to.

Locations

Country	Name	City	State
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	Queen Elizabeth II Hospital	Halifax	Nova Scotia
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	Juravinski Hospital	Hamilton	Ontario
Canada	St. Joseph's Healthcare	Hamilton	Ontario
Canada	Jewish General Hospital	Montreal	Quebec
Canada	McGill Univeristy Health Centre	Montreal	Quebec
Canada	Hôpital Montfort	Ottawa	Ontario
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	CHU de Quebec-Université Laval	Quebec City	Quebec
Canada	Niagara Health - St. Catharines Site	St. Catharines	Ontario
Canada	Sunnybrook Hospital	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
France	Brest University Hospital Centre	Brest
Ireland	Mater Misericordiae University Hospital	Dublin
Italy	University of Insubria	Varese
Netherlands	Amsterdam University	Amsterdam	Holland
Norway	Ostfold Hopsital	Sarpsborg

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute

Countries where clinical trial is conducted

Canada,  France,  Ireland,  Italy,  Netherlands,  Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of participants who have a bleeding event during follow-up	Bleeding event (major, clinically relevant non-major, minor) occurring between randomization and the end of follow-up (i.e. completion of the trial) in patients taking generic rosuvastatin as compared with placebo.	Up to 60 months
Primary	Recurrent Major VTE	Symptomatic recurrent major VTE (proximal DVT or segmental or larger PE) occurring between randomization and the end of follow-up (i.e. completion of the trial) in patients taking generic rosuvastatin as compared with placebo.	Up to 60 months
Secondary	Post Thrombotic Syndrome	Post-thrombotic syndrome as measured by the Villalta scale throughout the follow-up period in patients taking generic rosuvastatin as compared with placebo. The Villalta PTS scale has been adopted by the International Society on Thrombosis and Haemostasis (ISTH) as a standard to diagnose and grade the severity of PTS in clinical studies.; Points are summed to yield total score: 0-4: No PTS; 5-9: Mild PTS; 10-14: Moderate PTS; 15 or more, or presence of ulcer: Severe PTS.	Up to 60 months
Secondary	Number of participants diagnosed with non-major VTE during follow-up	Symptomatic non-major VTE (see below) occurring between randomization and the end of follow-up (i.e. completion of the trial) in patients taking generic rosuvastatin as compared with placebo.; Non-major VTE: Distal DVT (distal to the trifurcation of the popliteal vein); Isolated sub-segmental PE; Upper extremity DVT; Superficial phlebitis > 5 cm; Superficial phlebitis = 5 cm.	Up to 60 months
Secondary	Number of participants diagnosed with an arterial vascular event during follow-up	Components of composite arterial vascular events (see below) occurring between randomization and the end of follow-up (i.e. completion of the trial) in patients taking generic rosuvastatin as compared with placebo.; Components of composite arterial vascular events: Fatal myocardial infarction; Non-fatal myocardial infarction; Hospitalization for unstable angina; Coronary artery revascularization; Sudden cardiac death; Ischemic stroke.	Up to 60 months
Secondary	Number of deaths during study participation	All-cause mortality occurring between randomization and the end of follow-up (i.e. completion of the trial) in patients taking generic rosuvastatin as compared with placebo.	Up to 60 months