Mesoglycan for long-term secondary prevention in patients with superficial vein thrombosis (METRO): a multicentre randomised clinical trial in Italy.

Background: Superficial vein thrombosis (SVT) of the legs is a common disease linked with venous thromboembolism (VTE), with an uncertain recurrence risk. Data on secondary prevention of recurrent or extending SVT and on its natural history are lacking. Mesoglycan (MGY) shows a mild antithrombotic effect and the capacity to repair the endothelial layer, by restoring the integrity of the glycocalyx. This study aimed to evaluate the efficacy and safety of MGY for secondary prevention of VTE after an episode of lower-limb SVT. Methods: This was a multicentre, randomised, double-blind, placebo-controlled, superiority, phase II study conducted at 16 sites in Italy. Patients (aged > 18 years) with lower-limb SVT, who completed a 45-day treatment course of fondaparinux were randomised (1:1) to receive either oral MGY 50 mg or matching placebo twice-daily for 12 months, and were subsequently followed-up for another 12 months. The efficacy outcome was a composite of symptomatic recurrence or extension of SVT; new symptomatic or asymptomatic proximal deep-vein thrombosis, or new symptomatic distal deep-vein thrombosis, or new symptomatic non-fatal pulmonary embolism, or fatal pulmonary embolism at 12 months (primary outcome) and 24 months (secondary outcome) post-enrolment. The primary safety outcome was the incidence of major bleeding and clinically relevant non-major bleeding at 12 months. This trial was registered with EudraCT (2016-005184-13) and ClinicalTrials.gov (NCT03428711). Findings: Between March 26, 2018, and Dec 31, 2024, 553 patients were randomly allocated to treatment (272 to MGY and 281 to placebo), below the planned sample size due to slow recruitment because of SARS-CoV2 pandemic. At 12 months, the cumulative rate of efficacy events was 21.8% (54 patients) in the MGY group and 24.5% (63 patients) in the placebo group, respectively, showing no difference between these two groups (HR 0.89, 95% C.I. 0.62-1.29; p = 0.56). At 24 months, the cumulative rate of efficacy events was 30.6% (74 patients) in the MGY group and 42.5% (105 patients) in the placebo group, respectively (p = 0.043). This difference was entirely accounted for by a lower rate of recurrent SVT in the MGY group. The 24-month recurrence rate of SVT was 39% in the placebo group. No bleeding events were observed in either group. Interpretation: No significant differences were observed between MGY and placebo in terms of recurrent or extending SVT, at the end of the 12-month treatment course. However, we recorded a significant difference in favour of MGY at 24 months. These findings should be interpreted cautiously, given that the incidence of recurrent or extending SVT in the placebo group was higher than previously reported and the planned sample size was not reached due to slow recruitment. Our findings need to be confirmed in future, larger studies. Funding: Neopharmed Gentili S.p.A.