Clinical trial NCT04319627: Statins for Venous Event Reduction in Patients With Venous Thromboembolism
Official title: Statins for Venous Event Reduction in Patients With Venous Thromboembolism
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Venous Thromboembolism
Blood Clot
Post Thrombotic Syndrome
Keywords: Rosuvastatin
Statin
PTS
VTE
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2020-03-24
Enrollment: 2700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

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.

Primary outcomes:
measure: Recurrent Major VTE
timeFrame: Up to 60 months
Secondary outcomes:
measure: Post Thrombotic Syndrome
timeFrame: Up to 60 months
measure: Number of participants diagnosed with non-major VTE during follow-up
timeFrame: Up to 60 months
measure: Number of participants diagnosed with an arterial vascular event during follow-up
timeFrame: Up to 60 months
measure: Number of deaths during study participation
timeFrame: Up to 60 months
Other outcomes:
measure: Number of participants who have a bleeding event during follow-up
timeFrame: Up to 60 months
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Halifax
country: Canada
facility: Queen Elizabeth II Hospital
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Hôpital Montfort
state: Ontario
city: St. Catharines
country: Canada
facility: Niagara Health - St. Catharines Site
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill Univeristy Health Centre
state: Quebec
city: Quebec City
country: Canada
facility: CHU de Quebec-Université Laval
state: Quebec
city: Brest
country: France
facility: Brest University Hospital Centre
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Varese
country: Italy
facility: University of Insubria
city: Amsterdam
country: Netherlands
facility: Amsterdam University
state: Holland
city: Sarpsborg
country: Norway
facility: Ostfold Hopsital
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Aurélien Delluc, MD
role: PRINCIPAL_INVESTIGATOR
References: