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

Pulmonary Embolism Clinical Trial

— RIVACAST  

Official title:

RIVACAST : RIVAroxaban Versus Low-molecular Weight Heparinin Patients With Lower Limb Trauma Requiring Brace or CASTing

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06195540
• Other study ID #: 49RC21_0376
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 31, 2024
• Est. completion date: August 31, 2026

Study information

• Verified date: January 2024
• Source: University Hospital, Angers
• Contact: Delphine Douillet, Doctor
• Phone: 0241353637
• Email: Delphine.Douillet[@]chu-angers.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1424
• Est. completion date: August 31, 2026
• Est. primary completion date: August 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

• Expected hospital stay of less than or equal to 72 hours;

• TRiP(cast) score = 7 ;

• Patient affiliated to or benefiting from a social security scheme;

• Patient with prior informed consent.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Deep Vein Thrombosis
• Embolism
• Lower Limb Trauma
• Pulmonary Embolism
• Thromboembolism
• Thromboprophylaxis
• Thrombosis
• Venous Thromboembolism
• Venous Thrombosis
• Wounds and Injuries

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
France	Angers University Hospital, Emergency department	Angers
France	Argenteuil hospital, Emergency department	Argenteuil
France	Caen University hospital, Emergency department	Caen
France	Tours University Hospital, Emergency department	Chambray-lès-Tours
France	Cholet Hospital, Emergency department	Cholet
France	Clermont-Ferrand University Hospital, Emergency department	Clermont-Ferrand
France	Grenoble University Hospital, Emergency Department	Grenoble
France	Le Mans Hospital, Emergency department	Le Mans
France	Limoges University hospital, Emergency department	Limoges
France	Edouard Herriot University Hospital, Emergency Department	Lyon
France	Montpellier University Hospital, emergency department	Montpellier
France	Nantes University Hospital, Emergency department	Nantes
France	Nice University Hospital, Emergency department	Nice
France	Niort Hospital, Emergency Department	Niort
France	Cochin Hospital, Emergency department	Paris
France	HEGP, Emergency Department	Paris
France	La Pitié-Salpétrière Hospital, Emergency Department	Paris
France	Lariboisière hospital, emergency department	Paris
France	Saint-Antoine Hospital, Emergency department	Paris
France	South Lyon University Hospital, Emergency department	Pierre-Bénite
France	Poitiers University Hospital, Emergency department	Poitiers
France	Rennes University Hospital, Emergency department	Rennes
France	Rouen University Hospital	Rouen
France	Strasbourg University Hospital, Emergency Department	Strasbourg
France	Toulouse University Hospital, Emergency Department	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Angers

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of symptomatic venous thromboembolic events (45 days non-inferiority)	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.	45 days
Secondary	Patient self reported treatment satisfaction	The outcome is patient self-reported treatment satisfaction using the Anti-Clot Treatment Scales (ACTS) assessed at 45 days (+/- 5 days).	45 days
Secondary	Rate of symptomatic venous thromboembolic events (90 days superiority)	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.	90 days
Secondary	Cumulative rates of major bleeding and of non-major clinically relevant bleeding (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.	90 days
Secondary	Incremental cost-utility ratio (rivaroxaban efficiency 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.	45 days
Secondary	Incremental cost-utility ratio (rivaroxaban efficiency 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.	90 days