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

NCT06195540 | Recruiting Phase 3 DMC

• 2 other identifiers: 49RC21_03762023-509905-62-00
• Study Type: interventional
• Target: 1,424
• Locations: 1 country
• Sites: 35

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.

Conditions

Venous Thromboembolism; Deep Vein Thrombosis; Pulmonary Embolism; Lower Limb Trauma; Thromboprophylaxis; Immobilisation

Keywords

Emergency department; direct oral anticoagulant; rivaroxaban; Low-Molecular-weight heparin; randomized control trial; Prevent VTE

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

Study Arms (2)

Rivaroxaban arm

EXPERIMENTAL

Drug: Rivaroxaban 10 MG

Low-molecular-weight heparin arm

ACTIVE COMPARATOR

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).

Drug: Low Heparin Molecular Weight

Interventions

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.

Low-molecular-weight heparin arm

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.

Rivaroxaban arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Angers: lead

Study Sites (35)

Agen-Nerac Hospital, Emergency Department

Agen, 47923, France

NOT YET RECRUITING

Angers University Hospital, Emergency department

Angers, 49000, France

RECRUITING

Argenteuil hospital, Emergency department

Argenteuil, 95100, France

RECRUITING

Arpajon Hospital, Emergency Department

Arpajon, 91294, France

NOT YET RECRUITING

Caen University hospital, Emergency department

Caen, 14000, France

WITHDRAWN

Tours University Hospital, Emergency department

Chambray-lès-Tours, 37170, France

WITHDRAWN

Cholet Hospital, Emergency department

Cholet, 49300, France

RECRUITING

Clermont-Ferrand University Hospital, Emergency department

Clermont-Ferrand, 63000, France

RECRUITING

Simone Veil Hospital, Emergency Department

Eaubonne, 95600, France

RECRUITING

Eure-Seine Hospital, Emergency Departement

Évreux, 27015, France

RECRUITING

Grenoble University Hospital, Emergency Department

Grenoble, 38000, France

RECRUITING

La Rochelle Hospital, Adult emergency departement

La Rochelle, 17000, France

RECRUITING

Le Mans Hospital, Emergency department

Le Mans, 72000, France

RECRUITING

Limoges University hospital, Emergency department

Limoges, 87000, France

RECRUITING

Edouard Herriot University Hospital, Emergency Department

Lyon, 69000, France

RECRUITING

Marseille University Hospital, Emergency department

Marseille, 13005, France

RECRUITING

Melun Hospital, Emergency Department

Melun, 77000, France

NOT YET RECRUITING

Montpellier University Hospital, emergency department

Montpellier, 34000, France

RECRUITING

Nantes University Hospital, Emergency department

Nantes, 44000, France

RECRUITING

Nice University Hospital, Emergency department

Nice, 06000, France

WITHDRAWN

Niort Hospital, Emergency Department

Niort, 79000, France

RECRUITING

Lariboisière hospital, emergency department

Paris, 75010, France

NOT YET RECRUITING

Saint-Antoine Hospital, Emergency department

Paris, 75012, France

RECRUITING

La Pitié-Salpétrière Hospital, Emergency Department

Paris, 75013, France

NOT YET RECRUITING

Cochin Hospital, Emergency department

Paris, 75014, France

RECRUITING

St-Joseph Hospital, Emergency Department

Paris, 75014, France

RECRUITING

HEGP, Emergency Department

Paris, 75015, France

RECRUITING

Bichat Hospital, Adult Emergency department

Paris, 75018, France

RECRUITING

South Lyon University Hospital, Emergency department

Pierre-Bénite, 69495, France

RECRUITING

Poitiers University Hospital, Emergency department

Poitiers, 86000, France

RECRUITING

Rennes University Hospital, Emergency department

Rennes, 35000, France

RECRUITING

Rouen University Hospital, Emergency Department

Rouen, 76000, France

NOT YET RECRUITING

Strasbourg University Hospital, Emergency Department

Strasbourg, 67000, France

RECRUITING

Toulouse University Hospital, Emergency Department

Toulouse, 31000, France

RECRUITING

Vannes Hospital, Emergency Department

Vannes, 56000, France

NOT YET RECRUITING

MeSH Terms

Conditions

Venous Thromboembolism; Venous Thrombosis; Pulmonary Embolism; Emergencies

Interventions

Rivaroxaban; Dalteparin

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thrombosis; Lung Diseases; Respiratory Tract Diseases; Embolism; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Delphine Douillet, Doctor

  Angers University Hospital

  STUDY DIRECTOR

Central Study Contacts

Delphine Douillet, Doctor

CONTACT

0241353637; Delphine.Douillet@chu-angers.fr

Cindy Augereau, Mrs

CONTACT

0241354143; Cindy.Augereau@chu-angers.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Open label with blind assessment of study's outcomes
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2023
• First Posted: January 8, 2024
• Study Start: July 19, 2024
• Primary Completion (Estimated): November 19, 2026
• Study Completion (Estimated): November 19, 2026
• Last Updated: December 8, 2025

Record last verified: 2025-12

Locations

FR (35)