Evaluation of Sulodexide for the Prevention of Recurrent Venous Thromboembolism in Elderly Patients Post-First Episode of Deep Vein Thrombosis or Pulmonary Embolism

The primary objective of the study is to evaluate the **efficacy** of two different doses of **Sulodexide** (Vessel®) compared to a placebo in reducing the incidence of recurrent **venous thromboembolism** (VTE) in elderly patients aged 75 years or older who have experienced a recent episode of deep vein thrombosis (DVT) in the proximal lower extremity and/or pulmonary embolism (PE). The study aims to achieve a 35% reduction in VTE relapses compared to placebo. Additionally, the study seeks to verify the **safety** of Sulodexide therapy by demonstrating non-inferiority to placebo, with an incidence of major bleeding around 1%, ensuring the upper confidence limit does not exceed 3%.

The clinical trial focuses on the **prevention of recurrence** after a first episode of **Venous Thromboembolism (VTE)**, specifically targeting elderly patients aged 75 years and older. The study population includes both male and female participants who have experienced a recent episode of deep vein thrombosis (DVT) in the proximal lower extremity and/or pulmonary embolism (PE). Participants are required to have undergone at least three months of anticoagulant therapy prior to enrollment, with no other indications for anticoagulant therapy. The trial does not involve a vulnerable population. Key lifestyle considerations include the presence of risk factors for bleeding, such as hypertension, renal failure, and ongoing ASA therapy, among others. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the efficacy and safety of **sulodexide** in preventing recurrent venous thromboembolism (VTE) in elderly patients who have experienced a first episode of deep vein thrombosis (DVT) or pulmonary embolism (PE). This study is a randomized, double-blind, controlled trial comparing two different doses of sulodexide (treatment A and treatment B) with a placebo (treatment C). The trial is expected to run from December 21, 2020, to January 30, 2027, with a maximum treatment period of 12 months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥75 years), history of a first VTE event, and completion of at least three months of prior anticoagulant therapy. Follow-up visits will be scheduled at regular intervals to monitor the incidence of new VTE episodes, overall mortality due to VTE, and the occurrence of major bleeding events, as defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria. The end-of-study visit will assess the cumulative incidence of major and non-major but clinically relevant hemorrhages.

The expected length of participant involvement is up to 12 months, with conditions for early termination including withdrawal of consent, adverse events, or non-compliance with study procedures. The primary efficacy endpoint is the cumulative result of new VTE episodes and overall mortality due to VTE, while the primary safety endpoint focuses on the incidence of major bleeding. Secondary endpoints include the incidence of superficial vein thrombosis, isolated distal DVT, cardiovascular events requiring hospitalization, and death from cardiovascular events. The trial aims to demonstrate a 35% reduction in VTE relapses with sulodexide compared to placebo, while maintaining a safety profile with major bleeding incidence around 1%.

The clinical trial involves the administration of **Sulodexide**, marketed under the name VESSEL® 250 ULS, which is an antithrombotic agent. The pharmaceutical form of this experimental medication is a soft capsule, known as "capsule molli." Each capsule contains 250 ULS of Sulodexide. The route of administration is oral, and the maximum daily dose is 1000 ULS. The treatment period extends up to 12 months. Sulodexide is a mixture, and its primary objective in this study is to evaluate its efficacy in reducing the incidence of recurrent venous thromboembolism (VTE) in elderly patients who have experienced a recent episode of deep vein thrombosis (DVT) or pulmonary embolism (PE). The study aims to verify the safety of Sulodexide, ensuring non-inferiority compared to placebo, with an incidence of major bleeding around 1%.

The placebo used in this trial is a soft capsule designed to be indistinguishable from the active Sulodexide capsules. The placebo capsules are administered orally, following the same dosing schedule as the active treatment, to maintain blinding and ensure the integrity of the study. The placebo serves as a comparator to evaluate the efficacy and safety of Sulodexide in preventing VTE relapses. Compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol.

Efficacy in the clinical trial will be assessed using both primary and secondary endpoints. The primary efficacy endpoint is the cumulative result of new episodes of **venous thromboembolism** (VTE), including proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE), as well as overall mortality due to VTE. Secondary efficacy endpoints include the occurrence of superficial vein thrombosis, isolated distal deep vein thrombosis, cardiovascular events that necessitate hospitalization, and death from cardiovascular events such as myocardial infarction and ischemic stroke.

The trial aims to verify the efficacy of two different doses of Sulodexide (Vessel®) compared to a placebo in reducing the incidence of VTE relapses in elderly patients who have experienced a recent episode of DVT or PE. The efficacy will be measured by a 35% reduction in VTE relapses compared to the placebo group. The trial will also assess the safety of the treatment, with a focus on the incidence of major bleeding, adhering to the International Society on Thrombosis and Haemostasis (ISTH) criteria.