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

• ClinicalTrials.gov Identifier: NCT04319627
• Recruitment Status: Recruiting
• First Posted: March 24, 2020
• Last Update Posted: February 24, 2021
• Sponsor: Ottawa Hospital Research Institute
• Information provided by (Responsible Party): Ottawa Hospital Research Institute

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Venous Thromboembolism; Blood Clot; Post Thrombotic Syndrome	Drug: Rosuvastatin Calcium; Drug: Placebo Oral Tablet	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 2700 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Statins for Venous Event Reduction in Patients With Venous Thromboembolism
• Actual Study Start Date: February 10, 2021
• Estimated Primary Completion Date: January 2026
• Estimated Study Completion Date: January 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Rosuvastatin; 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.	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.; Other Name: Rosuvastatin
Placebo Comparator: Placebo; Participants randomized to the control arm will take one placebo tablet by mouth every day for the duration of their participation in the study.	Drug: 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.; Other Name: Placebo

Outcome Measures

Primary Outcome Measures :

1. Recurrent Major VTE [ Time Frame: Up to 60 months ]
   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.

Secondary Outcome Measures :

1. Post Thrombotic Syndrome [ Time Frame: Up to 60 months ]

   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.

2. Number of participants diagnosed with non-major VTE during follow-up [ Time Frame: Up to 60 months ]

   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.
3. Number of participants diagnosed with an arterial vascular event during follow-up [ Time Frame: Up to 60 months ]

   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.
4. Number of deaths during study participation [ Time Frame: Up to 60 months ]
   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.

Other Outcome Measures:

1. Number of participants who have a bleeding event during follow-up [ Time Frame: Up to 60 months ]
   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.

Eligibility Criteria

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

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. Currently prescribed a statin;

4. A known medical history or current diagnosis of any of the following:

   • Diabetes,
   • Abdominal aortic aneurysm,
   • Peripheral arterial disease presumed to be of atherosclerotic origin,
   • Stroke,
   • Transient ischemic attack (TIA),
   • Myocardial infarction (MI),
   • Acute coronary syndromes,
   • Stable/unstable angina,
   • Coronary or other arterial revascularization;
5. Known diagnosis of hypercholesterolemia or dyslipidemia;

6. Contraindication to rosuvastatin:

   • Known hypersensitivity or intolerance to statins,
   • History of muscle disorders or statin-related muscle pain,
   • Known liver disease (active liver disease or unexplained elevations of serum transaminases exceeding 3 times the upper limit of normal),
   • Chronic kidney disease (Creatinine clearance < 30ml/min within previous 3 months),
   • Currently pregnant or breast-feeding,
   • Taking cyclosporine;
7. Unstable medical or psychological condition that would interfere with trial participation.

Contacts and Locations

Contacts

Contact: Lesley Yeung; +16137378899 ext 71068; lyeung@ohri.ca

Contact: Penny Phillips; +16137378899 ext 73440; pphillips@ohri.ca

Locations

Canada, Ontario

Hamilton General Hospital; Not yet recruiting

Hamilton, Ontario, Canada, L8L 2X2

Principal Investigator: Sam Schulman, MD

St. Joseph's Healthcare; Not yet recruiting

Hamilton, Ontario, Canada, L8N 4A6

Principal Investigator: Jim Douketis, MD

Juravinski Hospital; Not yet recruiting

Hamilton, Ontario, Canada, L8V 1C3

Principal Investigator: Peter Gross, MD

The Ottawa Hospital; Recruiting

Ottawa, Ontario, Canada, K1H 8L6

Contact: Lesley Yeung 6137378899 ext 71068 lyeung@ohri.ca

Principal Investigator: Aurélien Delluc, MD

Canada, Quebec

Jewish General Hospital; Not yet recruiting

Montreal, Quebec, Canada, H3T 1E2

Principal Investigator: Susan Kahn, MD

McGill Univeristy Health Centre; Not yet recruiting

Montreal, Quebec, Canada, H4A 3J1

Principal Investigator: Véronique Naessens, MD

CHU de Quebec-Université Laval; Not yet recruiting

Quebec City, Quebec, Canada, G1V 4G2

Principal Investigator: Guillaume Roberge, MD

France

Brest University Hospital Centre; Not yet recruiting

Brest, France

Principal Investigator: Karine Lacut, MD

Ireland

Mater Misericordiae University Hospital; Not yet recruiting

Dublin, Ireland

Principal Investigator: Fionnuala Ní Áinle, MD

Italy

University of Insubria; Not yet recruiting

Varese, Italy

Principal Investigator: Walter Ageno, MD

Netherlands

Amsterdam University; Not yet recruiting

Amsterdam, Holland, Netherlands, 1098XH

Principal Investigator: Nick Van Es, MD

Norway

Ostfold Hopsital; Not yet recruiting

Sarpsborg, Norway

Contact: Christina Roaldsnes Christina.Roaldsnes@so-hf.no

Principal Investigator: Waleed Ghanima, MD

Sponsors and Collaborators

Ottawa Hospital Research Institute

Investigators

• Principal Investigator: Aurélien Delluc, MD; Ottawa Hospital Research Institute

More Information

• Responsible Party: Ottawa Hospital Research Institute
• ClinicalTrials.gov Identifier: NCT04319627
• Other Study ID Numbers: SAVER Trial
• First Posted: March 24, 2020
• Last Update Posted: February 24, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Ottawa Hospital Research Institute:

Rosuvastatin; Statin; PTS; VTE

Additional relevant MeSH terms:

Thromboembolism; Venous Thromboembolism; Thrombosis; Postthrombotic Syndrome; Postphlebitic Syndrome; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Venous Thrombosis; Venous Insufficiency; Phlebitis; Peripheral Vascular Diseases; Rosuvastatin Calcium; Calcium; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors