PB1490 - Mesoglycan versus Placebo in secondary prevention of superficial vein thrombosis. Rationale and protocol

Background: About 10-15% of patients with superficial vein thrombosis (SVT) develop venous thromboembolic (VTE) complications at 3-6 months, despite an adequate treatment of the acute phase. No data is available about pharmacological secondary prevention of SVT.

Aims: To verify efficacy and safety of mesoglycan vs placebo in reducing the incidence of SVT recurrence and VTE complications after the acute phase of an initial SVT adequately treated.

Methods: Phase III multicentric, double-blind, randomized, superiority clinical trial comparing mesoglycan 50 mg bid vs placebo. Consecutive patients > 18 y, with a SVT extended at least 5 cm, after a 45 days fondaparinux 2.5 mg once-daily treatment course and giving their informed consent are included.
Primary efficacy outcome (PEO): SVT recurrence/extension, symptomatic VTE, asymptomatic proximal deep-vein thrombosis, death
Primary safety outcome (PSO): major bleeding
We hypotesized a 15% risk for the PEO in placebo group at 12 months and a 50% risk reduction in mesoglycan group. A bilateral log-rank test with a sample of 650 patients (randomization 1:1) reach a 90% power, with an α-error of 0.025, of detecting a 7.0% difference (HR=0.51) after 12 months of treatment, considering a 10% patients drop-out.
The study was approved by a recognized medical ethics committee. ClinicalTrials.gov: NCT 03428711

Results: At deadline (December 31, 2022) 570 patients have been randomized (10% drop rate). Mean age was 63.9 years, 58.8% were women. SVT involved great saphenous vein in 69.3% of patients, small saphenous vein in 13.1%, and collaterals in 17.6%. SVT was the first episode in 61.7% and a recurrence in 38.3%, provoked in 50.2% and unprovoked in 49.8%. Graduated compression stockings were used by 74.7% of patients
.

Conclusion(s): Patients not experiencing a PEO/PSO or not retiring their consent will be followed up to December 31, 2024 when the study will be concluded and the final data analysis will be done.