Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
1,424
Countries
1
Sites
35
Lower limb trauma requiring immobilisation
The main objective is to demonstrate the non-inferiority of Rivaroxaban versus LMWH in the primary prevention of symptomatic thromboembolic events in patients with orthopaedic immobilisation for lower limb trauma and considered as high-risk of VTE according to TRiP(cast) score (≥ 7)
Key facts
- Sponsor
- Centre Hospitalier Universitaire D'Angers
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 19 Jul 2024 → ongoing
- Decision date (initial)
- 2024-04-12
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- French Ministry of Health
External identifiers
- EU CT number
- 2023-509905-62-00
- ClinicalTrials.gov
- NCT06195540
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Prophylaxis
The main objective is to demonstrate the non-inferiority of Rivaroxaban versus LMWH in the primary prevention of symptomatic thromboembolic events in patients with orthopaedic immobilisation for lower limb trauma and considered as high-risk of VTE according to TRiP(cast) score (≥ 7)
Conditions and MedDRA coding
Lower limb trauma requiring immobilisation
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | SOC | 10042613 | Surgical and medical procedures | 25 |
| 21.1 | PT | 10060788 | Joint stabilisation | 100000004865 |
| 21.1 | LLT | 10062618 | Joint immobilization | 10042613 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- Age ≥ 18 years
- Consultation in one of the Emergency Departments of the participating centres
- Lower limb injury requiring rigid or semi-rigid orthopaedic immobilisation
- Intended duration of orthopaedic immobilisation of 2 weeks or more
- TRiP(cast) score ≥ 7
- Full insurance cover
- Signed and dated free informed consent
Exclusion criteria 7
- Active bleeding or high risk of bleeding
- Contra-indication to Rivaroxaban or LMWH
- Any anticoagulant or antiplatelet treatment prior to trauma (only antiaggregant treatment authorized: aspirin < 325mg/day)
- Pregnant or breastfeeding woman
- Factors rendering 3-month follow-up impossible
- Participation in any interventional study which modifies patient care or could influence study evaluation criteria
- Patient requiring hospitalization following emergency for a reason other than lower limb trauma
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint is the rate of symptomatic venous thromboembolic events (i.e., deep venous thrombosis and/or pulmonary embolism and/or death due to pulmonary embolism) within the 45 days after the inclusion
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Xarelto 10 mg film-coated tablets
PRD3003287 · Product
- Active substance
- Rivaroxaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 50 Day(s)
- Authorisation status
- Authorised
- ATC code
- B01AF01 — -
- Marketing authorisation
- EU/1/08/472/001
- MA holder
- BAYER AG
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- reconditionnement en étui de 50 comprimés (5 blisters de 10 comprimés commerciaux) ainsi que l’étiquetage des étuis et le contre-étiquetage des blisters de XARELTO® 10mg
Comparator 7
FRAGMINE 5 000 U.l. anti Xa/0,2 mL, solution injectable en seringue pré-remplie
PRD423117 · Product
- Active substance
- Dalteparin Sodium
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 5000 anti-Xa IU anti-Xa activity International Unit(s)
- Max total dose
- 250000 anti-Xa IU anti-Xa activity International Unit(s)
- Max treatment duration
- 50 Day(s)
- Authorisation status
- Authorised
- ATC code
- B01AB04 — DALTEPARIN
- Marketing authorisation
- 34009 556 085 0 9
- MA holder
- PFIZER HOLDING FRANCE
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
INNOHEP 4 500 UI anti-Xa/0,45 ml, solution injectable en seringue préremplie
PRD393914 · Product
- Active substance
- Tinzaparin Sodium
- Pharmaceutical form
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 4500 anti-Xa IU anti-Xa activity International Unit(s)
- Max total dose
- 225000 anti-Xa IU anti-Xa activity International Unit(s)
- Max treatment duration
- 50 Day(s)
- Authorisation status
- Authorised
- ATC code
- B01AB10 — TINZAPARIN
- Marketing authorisation
- 34009 342 171 3 5
- MA holder
- LABORATOIRES LEO
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Inhixa 4,000 IU (40 mg)/0.4 mL solution for injection in pre-filled syringe
PRD7926705 · Product
- Active substance
- Enoxaparin Sodium
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 4000 anti-Xa IU anti-Xa activity International Unit(s)
- Max total dose
- 50 anti-Xa IU anti-Xa activity International Unit(s)
- Max treatment duration
- 50 Day(s)
- Authorisation status
- Authorised
- ATC code
- B01AB05 — ENOXAPARIN
- Marketing authorisation
- EU/1/16/1132/036
- MA holder
- TECHDOW PHARMA NETHERLANDS B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
FRAXIPARINE 3 800 U.I. Axa/0,4 ml, solution injectable (S.C.) en seringue pré-remplie
PRD9342832 · Product
- Active substance
- Nadroparin Calcium
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 3800 anti-Xa IU anti-Xa activity International Unit(s)
- Max total dose
- 190000 anti-Xa IU anti-Xa activity International Unit(s)
- Max treatment duration
- 50 Day(s)
- Authorisation status
- Authorised
- ATC code
- B01AB06 — NADROPARIN
- Marketing authorisation
- NL 16495
- MA holder
- VIATRIS SANTE
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
LOVENOX 4 000 UI (40 mg)/0,4 ml, solution injectable en seringue préremplie
PRD432342 · Product
- Active substance
- Enoxaparin Sodium
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 4000 anti-Xa IU anti-Xa activity International Unit(s)
- Max total dose
- 200000 anti-Xa IU anti-Xa activity International Unit(s)
- Max treatment duration
- 50 Day(s)
- Authorisation status
- Authorised
- ATC code
- B01AB05 — ENOXAPARIN
- Marketing authorisation
- 34009 364 687 2 6
- MA holder
- SANOFI WINTHROP INDUSTRIE
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
FRAXIPARINE 5 700 U.I. Axa/0,6 ml, solution injectable (S.C.) en seringue pré-remplie
PRD9342833 · Product
- Active substance
- Nadroparin Calcium
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 5700 anti-Xa IU anti-Xa activity International Unit(s)
- Max total dose
- 285000 anti-Xa IU anti-Xa activity International Unit(s)
- Max treatment duration
- 50 Day(s)
- Authorisation status
- Authorised
- ATC code
- B01AB06 — NADROPARIN
- Marketing authorisation
- NL 13901
- MA holder
- VIATRIS SANTE
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
FRAGMINE 2 500 U.l. anti Xa/0,2 mL, solution injectable en seringue pré-remplie
PRD499512 · Product
- Active substance
- Dalteparin Sodium
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 2500 anti-Xa IU anti-Xa activity International Unit(s)
- Max total dose
- 125000 anti-Xa IU anti-Xa activity International Unit(s)
- Max treatment duration
- 50 Day(s)
- Authorisation status
- Authorised
- ATC code
- B01AB04 — DALTEPARIN
- Marketing authorisation
- 34009 556 084 4 8
- MA holder
- PFIZER HOLDING FRANCE
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Centre Hospitalier Universitaire D'Angers
- Sponsor organisation
- Centre Hospitalier Universitaire D'Angers
- Address
- 4 Rue Larrey
- City
- Angers
- Postcode
- 49100
- Country
- France
Scientific contact point
- Organisation
- Centre Hospitalier Universitaire D'Angers
- Contact name
- Coordinating investigator
Public contact point
- Organisation
- Centre Hospitalier Universitaire D'Angers
- Contact name
- Promotion interne CHU
Locations
1 EU/EEA country · 35 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 1,424 | 35 |
| Rest of world | — | 0 | — |
Investigational sites
GIE Groupe hospitalier Paris Saint-Joseph/Vinci
Service des urgences adultes, 185 Rue Raymond Losserand, 75674, Paris Cedex 14
Centre Hospitalier Universitaire De Toulouse
Pôle Médecine d’Urgence, 1 Place Du Docteur Joseph Baylac, 31300, Toulouse
Centre Hospitalier Et Universitaire De Limoges
Département d'urgences, 2 Avenue Martin Luther King, 87000, Limoges
Centre Hospitalier Universitaire De Montpellier
Département de Médecine d'urgence - SAMU34, 371 Avenue Du Doyen Gaston Giraud, 34090, Montpellier
Centre Hospitalier Universitaire De Poitiers
Urgences – SAMU – SMUR 86, 2 Rue De La Miletrie, 86000, Poitiers
Centre Hospitalier Universitaire De Rennes
Service des urgences, 2 Rue Henri Le Guilloux, 35000, Rennes
Centre Hospitalier Universitaire D'Angers
Département de Médecine d'Urgence, 4 Rue Larrey, 49100, Angers
Hospices Civils De Lyon
Service d'accueil des urgences, 165 Chemin Du Grand Revoyet, 69310, Pierre-Benite
Centre Hospitalier General D'Arpajon
Département de médecine d'urgence, 18 Avenue De Verdun, 91290, Arpajon
Centre Hospitalier De Cholet
Service d'Urgence, 1 Rue De Marengo, 49300, Cholet
Centre Hospitalier Universitaire Grenoble Alpes
Urgences adultes, Boulevard De La Chantourne, Cs 10217, Grenoble Cedex 9
Centre Hospitalier Agen-Nerac
Service des urgences, Route De Villeneuve, 47923, Agen Cedex 9
Centre Hospitalier Le Mans
Médecine d'Urgences, 194 Avenue Rubillard, 72037, Le Mans Cedex 9
CHU De Rouen
Urgences adultes, 1 Rue De Germont, Bp 96031, Rouen Cedex
Assistance Publique Hopitaux De Paris
Service d'accueil des urgences, Num Voie 47 A 83, 47 Boulevard De L Hopital, Paris
Les Hopitaux Universitaires De Strasbourg
Urgences adultes, 1 Avenue Moliere, Bp 49, Strasbourg Cedex 2
University Hospital Of Clermont-Ferrand
Service d'accueil des urgences, 58 Rue Montalembert, 63003, Clermont Ferrand Cedex 1
Groupement Hospitalier Eaubonne Montmorency Simone Veil
Service Urgences Adultes, 14 Rue De Saint Prix, 95600, Eaubonne
Assistance Publique Hopitaux De Paris
Service d'accueil des urgences, 27 Rue Du Faubourg Saint Jacques, 75014, Paris
Hospices Civils De Lyon
Service d'accueil des urgences, 5 Place D Arsonval, 69437, Lyon Cedex 03
Assistance Publique Hopitaux De Paris
Service d'accueil des urgences, 20 Rue Leblanc, 75015, Paris
Centre Hospitalier Bretagne Atlantique
Service SAMU 56 et Urgences, 20 Boulevard General Maurice Guillaudot, 56000, Vannes
Centre Hospitalier Universitaire De Nantes
Service d'urgences, 7 Quai Moncousu, 44000, Nantes
Assistance Publique Hopitaux De Paris
Service d'accueil des urgences, 2 Rue Ambroise Pare, 75010, Paris
Assistance Publique Hopitaux De Paris
Service d'accueil des urgences, 184 Rue Du Faubourg Saint Antoine, 75012, Paris
Groupe Hospitalier Du Sud Ile De France
Urgences, 270 Avenue Marc Jacquet, 77000, Melun
Centre Hospitalier De Niort
Service des urgences SAMU SMUR, 40 Avenue Charles De Gaulle, 79000, Niort
Assistance Publique Hopitaux De Paris
Service des Urgences Adultes, 46 Rue Henri Huchard, 75877, Paris Cedex 18
Centre Hospitalier Universitaire De Nice
Département de médecine d'Urgences, 30 Voie Romaine, 06000, Nice
Centre Hospitalier Groupe Hospitalier De La Rochelle Re Aunis
Urgences Générales Adultes, 1 Rue Du Docteur Schweitzer, 17000, La Rochelle
Centre Hospitalier Regional Universitaire De Tours
Urgences adultes, Avenue De La Republique, 37170, Chambray Les Tours
Centre Hospitalier Eure-Seine
Service des Urgences - Unité Urgences Adultes, Sis Boulevard Schwartzenberg, 27015, Evreux
Centre Hospitalier Universitaire De Caen Normandie
Service de Médecine d'Urgence, Avenue De La Cote De Nacre, Cs 30001, Caen Cedex 9
Centre Hospitalier Regional De Marseille
Service d'Urgences, 264 Rue Saint Pierre, 13005, Marseille
Centre Hospitalier Victor Dupouy
Service d'Urgence, 69 Rue Du Lieutenant Colonel Prudhon, 95107, Argenteuil Cedex
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2024-07-19 | 2024-07-19 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 19 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2023-509905-62-00 | 6 |
| Protocol (for publication) | D4_Patient-facing-documents_Carte-patients | 1 |
| Protocol (for publication) | D4_Patient-facing-documents_Echelle-ACTS | 1 |
| Protocol (for publication) | D4_Patient-facing-documents_Echelle-ACTS | 1 |
| Protocol (for publication) | D4_Patient-facing-documents_Questionnaire-EQ-5D-5L | 1 |
| Protocol (for publication) | D4_Patient-facing-documents_Questionnaire-EQ-5D-5L | 1 |
| Recruitment arrangements (for publication) | K-Recruitment and Informed consent procedure template | 1 |
| Subject information and informed consent form (for publication) | L1_SIS-and-ICF_adults | 6 |
| Subject information and informed consent form (for publication) | L1_SIS-reinfo-SNDS_adults | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC-Fragmine2500 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC-Fragmine5000 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC-Fraxiparine3800 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC-Fraxiparine5700 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC-Innohep4500 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC-Lovenox4000 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC-RCP-Inhixa4000 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC-Xarelto | 1 |
| Synopsis of the protocol (for publication) | D1-Protocol-synopsis_2023-509905-62-00 | 5 |
| Synopsis of the protocol (for publication) | D1-Protocol-synopsis_2023-509905-62-00 | 5 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-12-22 | France | Acceptable 2024-04-10
|
2024-04-12 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-06-12 | France | Acceptable 2024-07-23
|
2024-07-25 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-01-22 | France | Acceptable 2025-03-07
|
2025-03-12 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-09-04 | France | Acceptable | 2025-10-06 |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2026-02-13 | France | Acceptable 2026-03-04
|
2026-04-07 |