Statins for Venous Event Reduction in Patients With Venous Thromboembolism

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Recurrent Major VTE [Срок оценки: Up to 60 months]

Вторичные конечные точки (4)

• Post Thrombotic Syndrome [Срок оценки: Up to 60 months]
• Number of participants diagnosed with non-major VTE during follow-up [Срок оценки: Up to 60 months]
• Number of participants diagnosed with an arterial vascular event during follow-up [Срок оценки: Up to 60 months]
• Number of deaths during study participation [Срок оценки: Up to 60 months]

Критерии участия

Критерии включения

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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Канада · 14 центров

• Foothills Medical Centre — Calgary
• Queen Elizabeth II Hospital — Halifax
• Hamilton General Hospital — Hamilton
• St. Joseph's Healthcare — Hamilton
• Juravinski Hospital — Hamilton
• The Ottawa Hospital — Ottawa
• Hôpital Montfort — Ottawa
• Niagara Health - St. Catharines Site — St. Catharines
• … и ещё 6 центров

Франция · 8 центров

• CHU d'Angers - Service d'accueil et traitement des Urgences — Angers
• Brest University Hospital Centre — Brest
• CHU de Clermont-Ferrand, Hôpital Gabriel Montpied — Clermont-Ferrand
• APHP Hôpital Louis Mourier — Colombes
• CHU de Dijon - Service d'imagerie diagnostique et thérapeutique — Dijon
• GH La Rochelle - Ré-Aunis - Service de Médecine vasculaire — La Rochelle
• Centre Hospitalier Universitaire De Saint Etienne — Saint-Etienne
• CHI Toulon - La Seyne sur Mer - Hôpital Sainte Musse — Toulon

Великобритания · 6 центров

• Aberdeen Royal Infirmary — Aberdeen
• Queen Elizabeth Hospital — Birmingham
• University Hospital of Wales — Cardiff
• Glasgow Royal Infirmary — Glasgow
• King's College Hospital NHS Foundation Trust — London
• Oxford University Hospitals NHS Foundation Trust — Oxford

Ирландия · 1 центр

• Mater Misericordiae University Hospital — Dublin

Италия · 1 центр

• University of Insubria — Varese

Норвегия · 1 центр

• Ostfold Hopsital — Sarpsborg

Идентификаторы

NCT: NCT04319627 · SAVER Trial

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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