RIVAroxaban Versus Low-molecular Weight Heparin in Patients With Lower Limb Trauma Requiring Brace or CASTing

• Rivaroxaban 10 MG (Drug): Administration of rivaroxaban 10 mg once daily to prevent venous thromboembolic events in patients with trauma to a lower limb. Consecutive patients with lower limb trauma and a TRiP(cast) score ≥ 7 are assessed for possible participation in the study. At the inclusion visit, if the patient meets the study's selection criteria, the investigator provides oral and written information (information letter written in a language the patient can understand) and answers any questions the patient may have. Depending on randomisation, the patient will receive either LMWH or rivaroxaban. The dose is rivaroxaban 10 mg orally once a day (no dosage adjustment). Treatment is started in the emergency department and continued at home for the duration of the immobilisation (i.e. until mobilisation with weight-bearing). The duration of treatment will be determined by the physician.
• Low Heparin Molecular Weight (Drug): Administration of standard prophylactic anticoagulant treatment with LMWH for the duration of immobilisation (i.e. until full mobilisation with weight-bearing). Consecutive patients with lower limb trauma and a TRiP(cast) score ≥ 7 are assessed for possible participation in the study. At the inclusion visit, if the patient meets the study's selection criteria, the investigator provides oral and written information (information letter written in a language the patient can understand) and answers any questions the patient may have. Depending on randomisation, the patient will receive either LMWH or rivaroxaban. The dose of LMWH is free, given according to local practices and national recommendations. Treatment is started in the emergency department and continued at home for the duration of the immobilisation (i.e. until mobilisation with weight-bearing). The duration of treatment will be determined by the physician.

Primary outcomes

• Rate of symptomatic venous thromboembolic events (45 days non-inferiority) [45 days]: The primary endpoint is the rate of symptomatic venous thromboembolic events (including deep vein thrombosis and/or pulmonary embolism and/or PE-related death) within 45 days (+/- 5 days) of inclusion. Symptomatic VTE is defined as follows: * Deep venous thrombosis (DVT) of the lower limbs: DVT confirmed by a non-compressible venous segment on compression ultrasound or by a filling defect on CT venography. Symptomatic proximal and distal DVTs will be taken into account. * Symptomatic pulmonary embolism documented by thoracic angioscan, high probability planar lung scan, SPECT scan, pulmonary angiography or by the combination of documented proximal deep vein thrombosis and thoracic symptomatology suggestive of pulmonary embolism. * PE-related deaths according to the ISTH (International Society of Thrombosis and Haemostasis) definition All events will need to be confirmed by the randomisation group's blinded clinical events adjudication committee.

Secondary outcomes

• Patient self reported treatment satisfaction [45 days]: The outcome is patient self-reported treatment satisfaction using the Anti-Clot Treatment Scales (ACTS) assessed at 45 days (+/- 5 days).
• Rate of symptomatic venous thromboembolic events (90 days superiority) [90 days]: This secondary outcome is the cumulative rate of symptomatic venous thromboembolism (i.e., deep venous thrombosis and/or pulmonary embolism) within the 90 days (± 7 days) after the inclusion. The definition of symptomatic VTE is the same as the primary outcome.
• Cumulative rates of major bleeding and of non-major clinically relevant bleeding (90 days) [90 days]: The cumulative rates of major bleeding and of non-major clinically relevant bleeding at 90 days (± 7 days). Major bleeding is defined according to the International Society of Thrombosis and Haemostasis (ISTH) criteria and includes: * Any bleeding resulting in death * Symptomatic bleeding in a critical organ including intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial bleeding and muscle bleeding resulting in compartment syndrome, * Symptomatic bleeding resulting in a decrease in the haemoglobin concentration of at least 2g/dL or resulting in the transfusion of at least two packs of blood red cells. Clinically Relevant Non-Major Bleeding is defined as: \- Any bleeding requiring hospitalisation or a medical intervention including temporary withholding of anticoagulant treatment to stop the bleeding.
• Incremental cost-utility ratio (rivaroxaban efficiency 45 days) [45 days]: The incremental cost-utility ratio (costs per quality-adjusted life year (QALY) gained) assessed at 45 days after inclusion. Health-related quality of life will be collected using EQ-5D-5L self-administered questionnaires at each scheduled follow-up at 45 days (±/- 5). Resources consumed will be taken from french national Health Data System.
• Incremental cost-utility ratio (rivaroxaban efficiency 90 days) [90 days]: The incremental cost-utility ratio (costs per quality-adjusted life year \[QALY\] gained) assessed at 90 days after inclusion. Health-related quality of life will be collected using EQ-5D-5L self-administered questionnaires at each scheduled follow-up at at 90 days (± 7). Resources consumed will be taken from french national Health Data System.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patient aged 18 or over ;
* Consultation in an emergency department of a participating centre;
* Trauma to the lower limb requiring rigid or semi-rigid orthopaedic immobilisation;
* Expected duration of orthopaedic immobilisation of at least 2 weeks;
* TRiP(cast) score ≥ 7 ;
* Patient affiliated to or benefiting from a social security scheme;
* Patient with prior informed consent.

Exclusion Criteria:

* Patient that have to be hospitalized after emergency department for other reason than lower limb trauma
* Active bleeding or high risk of bleeding,
* Known contraindication to rivaroxaban or LMWH;
* Taking any anticoagulant or antiplatelet agent before the trauma (only antithrombotic authorised: aspirin < 325mg/d);
* Pregnant or breastfeeding woman;
* Any factor making 3-month follow-up impossible; 6. Patient subject to a legal protection measure, Imprisonment 7. Participation in any interventional study which modifies patient care or could influence study evaluation criteria

• Delphine Douillet, Doctor, Study director, University Hospital, Angers

NIH grants: 2023