Fondaparinux 2.5mg for the Treatment of Symptomatic, Isolated Superficial Vein Thrombosis (SVT): Preliminary Data From the Randomized Placebo-Controlled CALISTO Trial (on Behalf of the CALISTO Investigators).

SVT is a common disease, associated with risks of clinically relevant venous thromboembolic complications. Currently, treatment of isolated SVT (i.e. without concomitant deep-vein thrombosis, DVT, or pulmonary embolism, PE) is based on analgesic agents, topical or oral nonsteroidal anti-inflammatory drugs, elastic stockings and occasionally surgery. Previous clinical trials have suggested the benefit of an extended antithrombotic therapy. Yet the optimal antithrombotic treatment remains unknown. Fondaparinux (Arixtra®) is a synthetic selective inhibitor of factor Xa with a favorable benefit-risk profile in the prevention and treatment of venous and arterial thrombosis in various medical and surgical settings. The large-scale, double-blind, randomized, placebo-controlled, CALISTO trial was designed to evaluate the benefit-risk ratio of fondaparinux 2.5 mg subcutaneously once daily during 45 days in 3000 patients with symptomatic, isolated SVT of the lower limbs documented by compression ultrasound (CUS).

The study concerned male or female patients 18 years of age or greater with acute symptomatic isolated SVT of the lower limbs at least 5 cm long documented by standard CUS. After randomization (Day 1), subjects received fondaparinux 2.5 mg or placebo subcutaneously once daily up to Day 45. Study treatments were administered on an outpatient basis. Follow-up continued up to Day 75. Permitted medications included analgesic agents, topical non-steroidal anti-inflammatory drugs, graduated compression (elastic) stockings, aspirin at low dose (up to 325 mg per day) and other oral antiplatelet agents if the subject was receiving these drugs at the time of screening for a chronic medical condition. The primary efficacy outcome was confirmed symptomatic thromboembolic complications (a composite of PE, DVT, extension of SVT with thrombus head ≤3 cm from the saphenofemoral junction or recurrence of SVT) or all-cause death up to Day 45. Safety outcomes included major bleeding, clinically relevant non-major bleeding and death. All efficacy and safety outcomes were adjudicated by a central adjudication committee, unaware of treatment assignment.

The study started in March 2007 and inclusions were completed on May 15^th 2009, with the recruitment of 3002 patients. The follow-up of the last patient was completed on July 31^st 2009. Overall, on blinded preliminary data available on June 23^rd 2009 (n=2994), the median age of patients was 58 [range: 19-92] years; 63.9% were women; 37.0% were obese (BMI ≥30 kg/m²). The main predisposing risk factors for SVT were varicose veins (88.6%) and a history of SVT (11.9%). More than one SVT was observed on baseline CUS in 19.2% of patients. The qualifying SVT predominantly involved the great saphenous vein alone (64.6% of patients). At Day 45, the overall incidence of adjudicated and adjudicated-pending symptomatic thromboembolic complications or death was 4.4% (Table). There was one adjudicated major bleeding. The final results according to treatment groups will be presented during the congress.

There is an unmet medical need for an evidence-based anticoagulant treatment for isolated SVT. CALISTO is the first large randomized, controlled trial designed to establish standard anticoagulant therapy in patients with isolated SVT. It also provides a large database on the clinical characteristics of this disease.

Décousus:GSK: Consultancy, Research Funding. Leizorovicz:GSK: Consultancy.