A Study to Evaluate the Efficacy and Safety of Fondaparinux for the Prevention of Venous Blood Clots in Patients With a Plaster Cast or Other Type of Immobilization for a Below-knee Injury Not Needing Surgery
Condition: Thrombosis, Venous
MeSH terms: Thrombosis; Venous Thrombosis; Knee Injuries
Intervention: Fondaparinux sodium; Nadroparin
Intervention description: After randomization (Day 1), subjects will receive subcutaneously once daily fondaparinux 2.5 mg [0.5mL] (1.5 mg [0.3mL] in patients with creatinine clearance between 30 and 50 mL/min) for at least 21 Days, up to complete mobilization, corresponding to cast or brace removal. The maximal duration of treatment is 45 days.; After randomization (Day 1), subjects will receive subcutaneously once daily nadroparin 2850 anti-Xa IU (0.3 mL) for at least 21 Days, up to complete mobilization, corresponding to cast or brace removal. The maximal duration of treatment is 45 days.
Intervention MeSH terms: PENTA; Nadroparin; Fondaparinux
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1351.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: deep vein thrombosis; immobilization; nadroparin; isolated lower-extremity injuries distal to the knee; plaster cast; non-surgical leg injury; venous thromboembolism; bleeding events; fondaparinux

Summary:

      The purpose of this study is to evaluate the efficacy and safety of fondaparinux in
      comparison with a heparin (nadroparin) in preventing deep vein thrombosis (blood clots in the
      leg veins), whether symptomatic or detected by ultrasound, and pulmonary embolism (blood
      clots that migrate to the lungs) in patients with leg injuries below the knee that require a
      cast or other type of immobilization but not surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Requiring rigid or semi-rigid immobilization (e.g. with a plaster cast or brace) for
             at least 21 days and up to 45 days because of isolated non-surgical below-knee injury

          -  With a no weight-bearing recommendation at the time of inclusion (partial weight
             bearing is permitted e.g. crutches, walking cast, relief shoes),

          -  Presenting at least one of the following risk factors for venous thromboembolism:
             below-knee fracture or Achilles tendon rupture, age ≥40 years, body mass index > 30
             kg/m2, oestrogen-containing hormonal replacement therapy or oral contraception, active
             cancer (treatment ongoing or stopped for less than one year), history of VTE,
             congenital or acquired hypercoagulable state,

          -  Requiring thromboprophylaxis according to the Investigator's judgement up to complete
             mobilization (corresponding to cast or brace removal)

          -  Able and willing to provide written informed consent

        Exclusion Criteria:

          -  Delay between injury and randomization greater than two days,

          -  Treatment with antithrombotic or anticoagulant therapy, including low-dose
             anticoagulation, for more than 2 days prior to randomization,

          -  Anticoagulant therapy required or likely to be required during the study period for
             another reason (e.g. planned surgery justifying pharmacological thromboprophylaxis,
             curative dose for treatment of VTE, etc.)

          -  Known hypersensitivity to fondaparinux or nadroparin or their excipient,

          -  Known history of heparin-induced thrombocytopenia,

          -  Women of childbearing potential not using a reliable contraceptive method throughout
             the study period,

          -  Women pregnant or breast-feeding during the study period.

          -  Active, clinically significant bleeding,

          -  Clinically significant bleeding within the past six months,

          -  Major surgery within the previous three months,

          -  Intraocular (other than cataract), spinal, and/or brain surgery within the previous
             twelve months,

          -  Haemorrhagic stroke within the previous twelve months,

          -  Severe head injury within the previous three months,

          -  Documented congenital or acquired bleeding tendency/disorder(s),

          -  Previous (within 12 months) or active or currently treated peptic ulcer disease,

          -  Uncontrolled arterial hypertension (systolic blood pressure over 180 mm Hg or
             diastolic blood pressure over 110 mm Hg),

          -  Treatment with more than one antiplatelet agents (e.g. clopidogrel and aspirin) at any
             dose,

          -  Need for chronic aspirin at doses≥ 325 mg or chronic NSAIDs,

          -  Bacterial endocarditis,

          -  Severe hepatic impairment,

          -  Calculated creatinine clearance < 30 mL/min,

          -  Thrombocytopenia ( <100x10_9/L)

          -  Body weight < 50 kg.

          -  Any condition that could prevent the patient from providing written informed consent
             or from adhering to study treatment,

          -  Life expectancy under six months,

          -  Participation in any study using an investigational drug during the previous three
             months,

          -  Patient in whom V3 is unlikely to be feasible (e.g. patient moving house),

          -  In France, a subject will not be eligible for inclusion in this study if not either
             affiliated to or a beneficiary of a social security system. This is an additional
             exclusion criterion only applying to subjects enrolled in France.