Evaluation of Rosuvastatin Calcium for Reducing Recurrent Venous Thromboembolism in Patients with Pulmonary Embolism or Deep Vein Thrombosis

The primary objective of the SAVER Trial is to determine the primary outcome event rate, specifically the incidence of symptomatic recurrent major **venous thromboembolism** (VTE), which includes proximal deep vein thrombosis (DVT) or segmental or larger pulmonary embolism (PE), in patients administered generic **rosuvastatin** compared to a placebo. This is clinically relevant as it evaluates the efficacy of rosuvastatin in reducing the recurrence of major VTE events, which are significant contributors to morbidity and mortality in affected patients.

Secondary objectives include:

• Determining the major bleeding event rate in patients taking generic rosuvastatin compared to placebo.
• Exploring if rosuvastatin reduces the incidence of post-thrombotic syndrome (PTS), as measured by the Villalta scale at the end of the study.
• Determining if rosuvastatin reduces the incidence of arterial vascular events.
• Determining if rosuvastatin reduces the incidence of recurrent non-major VTE.
• Assessing the safety of rosuvastatin.

The clinical trial involves a total of **1750 participants** diagnosed with conditions such as **Pulmonary Embolism**, **Venous Thromboembolism**, and **Deep Vein Thrombosis**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on the presence of symptomatic, objectively confirmed proximal leg **Deep Vein Thrombosis** or **Pulmonary Embolism** diagnosed within the last 30 days. The trial does not include vulnerable populations. Lifestyle factors such as diet, physical activity, or habits were not specified by the sponsor. The selection criteria ensure that the study population is representative of individuals who have experienced recent thromboembolic events, allowing for the assessment of the primary outcome event rate in patients taking generic rosuvastatin compared to placebo.

The clinical trial is designed to evaluate the efficacy of **rosuvastatin calcium** in reducing venous thromboembolism (VTE) events in patients with a history of **pulmonary embolism** or **deep vein thrombosis**. This is a randomized, double-blind, placebo-controlled trial, which will compare the outcomes of patients receiving rosuvastatin calcium tablets to those receiving placebo tablets. The trial is expected to run until December 31, 2027, with recruitment starting on November 1, 2023.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on the principal inclusion criterion of symptomatic, objectively confirmed proximal leg DVT or PE diagnosed within the last 30 days. Following randomization, participants will attend regular follow-up visits to monitor for the primary endpoint, which is the occurrence of symptomatic recurrent major VTE. Secondary endpoints include the development of post-thrombotic syndrome, non-major VTE events, arterial vascular events, and all-cause mortality.

The expected duration of participant involvement is up to 60 months, depending on the timing of recruitment and the occurrence of endpoints. Participants may be withdrawn from the study early if they experience significant adverse events, withdraw consent, or if the investigator deems it necessary for their safety. The end-of-study visit will occur at the completion of the trial, where final assessments will be conducted to evaluate the long-term effects of the treatment.

The clinical trial involves the administration of **Rosuvastatin Calcium**, an experimental medication, in the form of a tablet. The active substance, **rosuvastatin calcium**, is a chemical compound classified under statins, specifically HMG-CoA reductase inhibitors. The dosage for this trial is set at 20 mg per tablet, with a maximum daily dose of 20 mg. The total maximum dose over the treatment period is 36,000 mg. The medication is administered orally, and the treatment period extends up to 60 days. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

The study also includes a **placebo** group, which receives Placebo Rosuvastatin Calcium 20 mg tablets. These tablets are identical in appearance to the active medication but do not contain the active substance. The placebo is administered orally at the same frequency and dosage as the experimental medication, serving as a comparator to evaluate the efficacy of rosuvastatin calcium in reducing venous thromboembolism events. The use of a placebo control is essential for maintaining the study's integrity and ensuring unbiased results.

Efficacy in the clinical trial titled "StAtins for Venous Event Reduction in Patients with Venous Thromboembolism: The SAVER Trial" will be assessed using specific primary and secondary endpoints. The primary endpoint is the rate of symptomatic recurrent major **Venous Thromboembolism (VTE)**, which includes proximal Deep Vein Thrombosis (DVT) or segmental or larger Pulmonary Embolism (PE), occurring between randomization and the end of follow-up in patients taking generic rosuvastatin compared to placebo. Secondary endpoints include the incidence of post-thrombotic syndrome as measured by the Villalta score, non-major VTE events such as distal DVT, isolated sub-segmental PE, upper extremity DVT, unusual site DVT, and superficial vein thrombosis. Additionally, arterial vascular events, including fatal and non-fatal myocardial infarction, hospitalization for unstable angina, coronary artery revascularization, sudden cardiac death, and ischemic stroke, will be evaluated. All-cause mortality will also be assessed without the need for adjudication.