Venous Thromboembolism, Deep Vein Thrombosis, Pulmonary Embolism, Lower Limb Trauma, Thromboprophylaxis, Immobilisation
Conditions
Keywords
Emergency department, direct oral anticoagulant, rivaroxaban, Low-Molecular-weight heparin, randomized control trial, Prevent VTE
Brief 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.
Interventions
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.
DRUGLow 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.
Sponsors
University Hospital, Angers
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Masking description
Open label with blind assessment of study's outcomes
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
France
Contacts
Primary ContactDelphine Douillet, Doctor
Backup ContactCindy Augereau, Mrs
Outcome results
None listed