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

Condition(s) studied

Investigational drug(s) / intervention(s)

Rivaroxaban 10 MG: 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: 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.

Study summary

Lower limb trauma requiring immobilization is a very frequent condition that is associated with an increased risk of developing venous thromboembolism (VTE). The TRiP(cast) score has been developed to provide individual VTE risk stratification and help in thromboprophylactic anticoagulation decision. The recent CASTING study had confirmed that patients with a TRiP(cast) score \<7 have a very low risk of VTE and could be safely manage without prophylactic treatment. Conversely, patients with a score ≥ 7 have a high-risk of VTE and require a prophylactic anticoagulant treatment. Low molecular weight heparins (LMWH) have been shown to be effective in this indication. However, in the CASTING study, the 3-month symptomatic VTE rate was 2.6% in this subgroup despite LMWH prophylactic treatment. This result suggests that LMWH are not sufficiently effective in this particular subgroup of high-risk patients. Direct oral anticoagulants, and in particular rivaroxaban, may be an effective and safe alternative to LMWH. In the PRONOMOS study, comparing LMWH with rivaroxaban in patients who had undergone non-major lower limb surgery, the relative risk of symptomatic VTE was 0.25 (95% CI = 0.09 - 0.75) in favor of rivaroxaban 10mg. No significant increase in bleeding was found. In addition, as LMWH treatment requires subcutaneous daily injections, the use of rivaroxaban may positively impact patients' quality of life as well as being effective in medico-economic terms.

The aims of this study are to demonstrate that rivaroxaban is at least as effective, easier to use and more efficient than LMWH in patients with trauma to the lower limb requiring immobilisation and deemed to be at risk of venous thromboembolism (TRiP(cast) score ≥ 7). High-risk patients are randomized to receive either rivaroxaban or LMWH. They are followed up at 45 days and 90 days to assess the occurrence of thrombotic events or bleeding, as well as their satisfaction with the treatment received.

Eligibility

Primary outcome measure(s)

• 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.

Trial sites (37)

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