Statins for Venous Event Reduction in Patients With Venous Thromboembolism (SAVER)

Ottawa Hospital Research Institute

Status and phase: Enrolling; Phase 3

Conditions: Venous Thromboembolism; Blood Clot; Post Thrombotic Syndrome

Treatments: Drug: Rosuvastatin Calcium; Drug: Placebo Oral Tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT04319627

SAVER Trial

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2,700 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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2,700 participants in 2 patient groups, including a placebo group

Rosuvastatin

Experimental group

Description:

Participants randomized to the experimental arm will take one rosuvastatin 20 mg tablet by mouth every day for the duration of their participation in the study.

Treatment:

Drug: Rosuvastatin Calcium

Placebo

Placebo Comparator group

Description:

Participants randomized to the control arm will take one placebo tablet by mouth every day for the duration of their participation in the study.

Treatment:

Drug: Placebo Oral Tablet