RIVACAST : RIVAroxaban Versus Low-molecular Weight Heparinin Patients With Lower Limb Trauma Requiring Brace or CASTing
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Enrollment
- 1,424
- Locations
- 72
- Primary Endpoint
- Rate of symptomatic venous thromboembolic events (45 days non-inferiority)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Single (Outcomes Assessor)
Masking Description
Open label with blind assessment of study's outcomes
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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;
- •Patient subject to a legal protection measure, Imprisonment
- •Participation in any interventional study which modifies patient care or could influence study evaluation criteria
Arms & Interventions
Rivaroxaban arm
Intervention: Rivaroxaban 10 MG (Drug)
Low-molecular-weight heparin arm
Treatment with LMWH is the standard-of-care in this population of lower limb trauma patients at risk of thrombosis.
The control group is therefore the group of patients who receive prophylactic anticoagulant treatment with LMWH for the duration of immobilization (i.e. until full mobilization with weight-bearing).
Intervention: Low Heparin Molecular Weight (Drug)
Outcomes
Primary Outcomes
Rate of symptomatic venous thromboembolic events (45 days non-inferiority)
Time Frame: 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)
- Rate of symptomatic venous thromboembolic events (90 days superiority)(90 days)
- Cumulative rates of major bleeding and of non-major clinically relevant bleeding (90 days)(90 days)
- Incremental cost-utility ratio (rivaroxaban efficiency 45 days)(45 days)
- Incremental cost-utility ratio (rivaroxaban efficiency 90 days)(90 days)
- Patient self reported treatment satisfaction(45 days)
- Rate of symptomatic venous thromboembolic events (90 days superiority)(90 days)
- Cumulative rates of major bleeding and of non-major clinically relevant bleeding (90 days)(90 days)
- Incremental cost-utility ratio (rivaroxaban efficiency 45 days)(45 days)
- Incremental cost-utility ratio (rivaroxaban efficiency 90 days)(90 days)