Rivaroxaban Anticoagulation for Superficial Vein Thrombosis

A Phase III, Multi-centre, Randomized Trial to Compare Rivaroxaban With Placebo for the Treatment of Symptomatic Leg Superficial Vein Thrombosis

This is a Phase III, randomized, placebo controlled, blinded, parallel two arm, multicentre trial that will compare rivaroxaban 10mg daily with placebo in patients with symptomatic leg Superficial Vein Thrombosis (> or = 5cm) that otherwise would not initially be treated with anticoagulant therapy.

Patients with symptomatic superficial leg thrombosis will be randomized into two arms, a) rivaroxaban 10mg 1 tablet daily for 45 days or b) placebo to determine if rivaroxaban (10 mg once daily) is an effective and safe treatment for superficial vein thrombosis.

Inclusion Criteria:

- Symptomatic Superficial Vein Thrombosis of the leg of ≥5 cm length (diagnosed clinically or with ultrasound)

Exclusion Criteria:

• Age <18 years

• Symptoms >42 days

• Receiving an anticoagulant for another indication (example: atrial fibrillation) when Superficial Vein Thrombosis started.

• Superficial Vein Thrombosis already treated with more than 3 days of anticoagulation (example. fondaparinux or Low Molecular Weight Heparin).

• Planned treatment of Superficial Vein Thrombosis with a course of anticoagulant therapy.

• Another indication for anticoagulant therapy (example. Deep Vein Thrombosis, Pulmonary Embolism, atrial fibrillation).

• Judged to require immediate ligation of the saphenofemoral junction or stripping of thrombosed varicose veins.

• proximal Deep Vein Thrombosis or Pulmonary Embolism within the past 12 months.

• Superficial Vein Thrombosis associated with sclerotherapy or an intravenous canula.

• A high risk of bleeding as evidenced by any of the following:

  1. Active bleeding
  2. Bleeding within the past 30 days due to a cause that has not fully resolved.
  3. Known or expected thrombocytopenia with a platelet count of less than 80,000 x 10 9/L.
  4. History of ever having had spontaneous intracranial bleeding, or any intracranial bleeding within the past 3 months.
  5. Receiving dual antiplatelet therapy (example. aspirin and clopidogrel).

• Elevated creatinine level is suspected and creatinine clearance has not been estimated, OR creatinine clearance (Cockcroft-Gault equation) of less than 30 ml/min.

• Clinically relevant hepatic disease (including Child-Pugh B and C) is known or suspected (example., associated with: International Normalized Ratio >1.7; total bilirubin >2 upper limit of normal; or Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) >3 times upper limit of normal).

• Ongoing requirement for systemic treatment with azole-antimycotics (except fluconazole), Human Immunodeficiency Virus (HIV) -protease inhibitors, or strong Cytochrome P450 3A4 (CYP3A4) inducers due to the potential interaction with rivaroxaban.

• Pregnant or lactating women, or at risk of becoming pregnant.

• Life expectancy less than 90 days

• Patient is unwilling or unable to comply with the protocol (example. unable to attend follow-up visits because of geographic inaccessibility).

• Participating in a competing clinical investigation and receiving any other investigational agent(s).