Sulodexide, VESSEL®, for the Prevention of Recurrent Venous Thromboembolism (The Jason Study)

Official title

Sulodexide (VESSEL®) for the Prevention of Recurrent Venous Thromboembolism in Elderly Patients After a First Episode of Venous Thrombembolism

Overview

The study aims at optimizing extended management of elderly patients (\> 75 years) with at least one of the known bleeding risk factor, who suffered from first episode of venous thromboembolism of the lower extremity (proximal deep vein thrombosis with or without pulmonary embolism) (VTE). Patients were randomized to receive three different treatment: Sulodexide 250 mg BIS in die; Sulodexide 500 BID in die or indistinguishable placebo to verify the efficacy and safety of extended treatment for 12 months with Sulodexide (Vessel®) in the secondary prevention of Deep Vein Thrombosis / Pulmonary Embolism (DVT/PE) recurrence.

Detailed description

This prospective cohort study aims to assess the efficacy and safety of the extended treatment with Sulodexide (Vessel®) in the secondary prevention of DVT / PE recurrence in elderly outpatients (≥ 75 years old at the time of inclusion) ), with at least one of the known bleeding risk factor, who had a first episode of lower extremity proximal DVT and / or PE, idiopathic or associated with weak or removed risk factors, and who have received standard treatment with any oral anticoagulant drug lasting at least 3 months. The study seeks to verify the safety of the Sulodexide therapy, demonstrating non-inferiority compared to placebo, with an incidence of major bleeding around 1% (upper confidence limit not \> 3%).

Interventions

• Drug Sulodexide
  2 soft capsules of Vessel® 250 LSU BID for 12 months
• Drug Sulodexide and placebo
  1 soft capsule of Vessel® 250 LSU and 1 soft capsule of placebo BID for 12 months
• Drug Placebo
  Sugar pill manufactured to mimic sulodexide 250 LSU

Primary outcome measures

• Number and rate of patients with confirmed recurrent VTE and VTE-related death (efficacy). [Time frame: From date of enrollment until the date of first documented event assessed up to 12 months]
• Number and rate of major Bleeding events (defined according to International Society on Thrombosis and Haemostasis guidelines (safety) [Time frame: From date of enrollment until the date of first documented event assessed up to 12 months]

Secondary outcome measures (4)

• Number of and rate of thromboembolic events [Time frame: From date of enrollment until the date of first documented event assessed up to 12 months]
• Presence of severe post-thrombotic syndrome according to Villalta Score [Time frame: 12 months]
• Number and rate of non major bleeding complications [Time frame: From date of enrollment until the date of first documented event assessed up to 12 months]
• Number and rate of dead patients (overall mortality) [Time frame: From date of enrollment until the date of first documented event assessed up to 12 months]

Eligibility criteria

Inclusion criteria

• Patients with a first event of proximal lower extremity DVT and / or PE, idiopathic or associated with weak or removed risk factors.
• Patients aged ≥75 years at the time of enrolment
• Patients with at least one of the known risk factors of bleeding (APPENDIX 1):

• Hypertension
• Renal failure
• Thrombocytopenia
• Diabetes
• Antiplatelet therapy (ASA maximum 140 mg/die)
• Frequent falls (>2 /years)
• Nonsteroidal anti-inflammatory drug
• Liver failure
• Previous Stroke
• Anemia
• Poor anticoagulant control
• Alcohol abuse
• Patients of both sexes.
• Patients who at the time of enrolment have already undergone a period of anticoagulant therapy (AT, with any medication) of at least 3 months and the therapy has not been suspended for more than 30 days.
• Patients with no other AT indications.
• Patients capable and able to provide informed consent

Exclusion criteria

• Patients aged <75 years at the time of the recruitment visit.
• "Provoked" index event, which occurred:

• Within 3 months of surgery or major trauma,
• Bed Rest > 4 days,
• Cast / immobility within 3 months.
• Index event represented by severe PE, with life threatening risk or treated with thrombolytic therapy.
• Index event represented by isolated distal DVT or superficial venous thrombosis.
• Thrombotic event in sites other than the deep proximal veins of the lower limbs.
• Anticoagulant therapy for less than 3 months at the time of enrolment.
• Discontinuation of anticoagulant therapy for over thirty days at the time of enrolment
• Recurrent episodes of DVT ± PE

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

Italy · 1 center

• Corrado Lodigiani — Rozzano

Publications

• Palareti G, Legnani C, Antonucci E, Zorzi S, Bignamini AA, Lodigiani C, Tosetto A, Bertu L, Pengo V, Testa S, Ageno W, Prisco D, Prandoni P, Poli D. Design and rationale of a randomized, placebo-controlled trial on the efficacy and safety of sulodexide for extended treatment in elderly patients after a first venous thromboembolism. Intern Emerg Med. 2021 Mar;16(2):359-368. doi: 10.1007/s11739-020- PMID 32451933

Identifiers

NCT: NCT04257487 · FAAI2.10.2018 · 2019-000570-33

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗