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

Primary Purpose

Venous Thromboembolism, Blood Clot, Post Thrombotic Syndrome

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Rosuvastatin Calcium
Placebo Oral Tablet
Sponsored by
Ottawa Hospital Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Venous Thromboembolism focused on measuring Rosuvastatin, Statin, PTS, VTE

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Foothills Medical CentreRecruiting
  • Queen Elizabeth II HospitalRecruiting
  • Hamilton General HospitalRecruiting
  • St. Joseph's Healthcare
  • Juravinski HospitalRecruiting
  • The Ottawa HospitalRecruiting
  • Hôpital MontfortRecruiting
  • Niagara Health - St. Catharines SiteRecruiting
  • Sunnybrook Hospital
  • University Health Network
  • Jewish General HospitalRecruiting
  • McGill Univeristy Health CentreRecruiting
  • CHU de Quebec-Université LavalRecruiting
  • Brest University Hospital Centre
  • Mater Misericordiae University Hospital
  • University of Insubria
  • Amsterdam University
  • Ostfold Hopsital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Rosuvastatin

Placebo

Arm 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.

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
March 20, 2020
Last Updated
May 30, 2023
Sponsor
Ottawa Hospital Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT04319627
Brief Title
Statins for Venous Event Reduction in Patients With Venous Thromboembolism
Acronym
SAVER
Official Title
Statins for Venous Event Reduction in Patients With Venous Thromboembolism
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 10, 2021 (Actual)
Primary Completion Date
January 2026 (Anticipated)
Study Completion Date
January 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thromboembolism, Blood Clot, Post Thrombotic Syndrome
Keywords
Rosuvastatin, Statin, PTS, VTE

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
2700 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Rosuvastatin
Arm Type
Experimental
Arm 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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Rosuvastatin Calcium
Other Intervention Name(s)
Rosuvastatin
Intervention Description
Each participant will receive the usual treatment for their newly diagnosed blood clot in addition to the intervention they are randomized to.
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Other Intervention Name(s)
Placebo
Intervention Description
Each participant will receive the usual treatment for their newly diagnosed blood clot in addition to the intervention they are randomized to.
Primary Outcome Measure Information:
Title
Recurrent Major VTE
Description
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.
Time Frame
Up to 60 months
Secondary Outcome Measure Information:
Title
Post Thrombotic Syndrome
Description
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.
Time Frame
Up to 60 months
Title
Number of participants diagnosed with non-major VTE during follow-up
Description
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.
Time Frame
Up to 60 months
Title
Number of participants diagnosed with an arterial vascular event during follow-up
Description
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.
Time Frame
Up to 60 months
Title
Number of deaths during study participation
Description
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.
Time Frame
Up to 60 months
Other Pre-specified Outcome Measures:
Title
Number of participants who have a bleeding event during follow-up
Description
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.
Time Frame
Up to 60 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 Unable or unwilling to provide written informed consent; ≤ 18 years of age; Women of childbearing potential unwilling to use appropriate contraception; Currently prescribed a statin; A known medical history or current diagnosis of any of the following for which statins are indicated in secondary prevention: Diabetes; Abdominal aortic aneurysm; Peripheral arterial disease; Stroke; Transient ischemic attack (TIA); Myocardial infarction (MI); Acute coronary syndromes; Stable/unstable angina; Coronary or other arterial revascularization; Known diagnosis of hypercholesterolemia or dyslipidemia; Contraindication to rosuvastatin; Known hypersensitivity or intolerance to statins; History of muscle disorders or statin-related muscle pain; Known liver disease (active liver disease, e.g. Hepatitis A, B, C, non-alcoholic fatty liver); Chronic kidney disease (creatinine clearance < 30ml/min); Currently pregnant or breast feeding; Taking cyclosporine; Taking atazanavir/ritonavir; Taking darolutamide; Taking regorafenib; Unstable medical or psychological condition that would interfere with trial participation.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jennifer Brinkhurst
Phone
+16137378899
Ext
71068
Email
jbrinkhurst@ohri.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aurélien Delluc, MD
Organizational Affiliation
Ottawa Hospital Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Foothills Medical Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 2T9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jill Baxter
First Name & Middle Initial & Last Name & Degree
Leslie Skeith, MD
Facility Name
Queen Elizabeth II Hospital
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 2Y9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sudeep Shivakumar, MD
Facility Name
Hamilton General Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8L 2X2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sam Schulman, MD
Facility Name
St. Joseph's Healthcare
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 4A6
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jim Douketis, MD
Facility Name
Juravinski Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 1C3
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Gross, MD
Facility Name
The Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Brinkhurst
Phone
6137378899
Ext
71068
Email
jbrinkhurst@ohri.ca
First Name & Middle Initial & Last Name & Degree
Aurélien Delluc, MD
Facility Name
Hôpital Montfort
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1K 0T2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Melanie Potvin
First Name & Middle Initial & Last Name & Degree
Miriam Kimpton, MD
Facility Name
Niagara Health - St. Catharines Site
City
St. Catharines
State/Province
Ontario
ZIP/Postal Code
L2S 0A9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kailee Morrison
First Name & Middle Initial & Last Name & Degree
Blair Leonard, MD
Facility Name
Sunnybrook Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Philippe Galanaud, MD
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Erik Yeo, MD
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susan Kahn, MD
Facility Name
McGill Univeristy Health Centre
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Véronique Naessens, MD
Facility Name
CHU de Quebec-Université Laval
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1V 4G2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guillaume Roberge, MD
Facility Name
Brest University Hospital Centre
City
Brest
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Raphael Le Mao, MD
Facility Name
Mater Misericordiae University Hospital
City
Dublin
Country
Ireland
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fionnuala Ní Áinle, MD
Facility Name
University of Insubria
City
Varese
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Walter Ageno, MD
Facility Name
Amsterdam University
City
Amsterdam
State/Province
Holland
ZIP/Postal Code
1098XH
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michiel Coppens, MD
Facility Name
Ostfold Hopsital
City
Sarpsborg
Country
Norway
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sven Arne Sogn
First Name & Middle Initial & Last Name & Degree
Waleed Ghanima, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Statins for Venous Event Reduction in Patients With Venous Thromboembolism

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