PROphylaxis in NOn Major Orthopaedic Surgery

NCT02401594 | Terminated Phase 3 DMC

• 2 other identifiers: 14081432015-000981-70
• Study Type: interventional
• Target: 3,608
• Locations: 1 country
• Sites: 38

Brief Summary

PRONOMOS is an international multicentre, interventional, parallel, randomised, double-blind non-inferiority study comparing rivaroxaban 10mg od to an active comparator, enoxaparin 4000 UI od in 4040 valid subjects requiring orthopaedic surgery (except low risk such material removal foot surgery or hallux valgus without patient risk factor \[6\], and major orthopaedic surgeries for femoral neck and trochanteric fractures, THR, TKR) Pre-randomization treatment with LMWH anticoagulant is allowed for a maximum duration of 24 hours. However, only a single pre-randomization dose of LMWH is allowed. After randomization, patients allocated to the rivaroxaban arm will receive rivaroxaban 10 mg once-daily started 6-10 hours provided haemostasis has been established after surgery or 24h hours after LMWH injection if needed for the intended treatment duration of 2 to 12 weeks based on medical judgment (according to immobilization). Patients allocated to the comparator arm will receive enoxaparin once daily for the same intended treatment duration. All patients will have a 30-day observational period after cessation of treatment.

Conditions

Non-major Orthopaedic Surgery

Keywords

Non-major orthopaedic surgery; deep vein thrombosis

Outcome Measures

Primary Outcomes (1)

• Major VTE

  composite of proximal DVT (asymptomatic and symptomatic) assessed by ultrasonography, symptomatic events (distal and proximal DVT, PE) and VTE related deaths. The treatment period ranges from 15 days to 3 months depending on the type of surgery

  From date of randomization until the date of the end of the treatment period (up to 3 months maximum).

Secondary Outcomes (4)

• Major bleeding

  From date of randomization until the date of the end of the treatment period (up to 3 months maximum).

• Clinically relevant non-major bleeding

  From date of randomization until the date of the end of the treatment period (up to 3 months maximum)..

• Overt thrombocytopenia

  From date of randomization until the date of the end of the treatment period (up to 3 months maximum)..

• Mortality

  From date of randomization until the date of the end of the treatment period (up to 3 months maximum)..

Study Arms (2)

Group 1: Rivaroxaban treatment

EXPERIMENTAL

Rivaroxaban active substance plus a placebo of enoxaparin

Drug: Rivaroxaban

Grouyp 2: Enoxaparine treatment

ACTIVE COMPARATOR

Enoxaparin active substance plus a placebo tablet of Rivaroxaban

Drug: Enoxaparin

Interventions

Rivaroxaban DRUG

10 mg once daily of Rivaroxaban active substance (10 mg tablet) plus a placebo syringe of enoxaparin 4000 UI once daily

Also known as: Group 1:

Group 1: Rivaroxaban treatment

Enoxaparin DRUG

A syringe of enoxaparin active substance 4000 UI once daily plus a placebo tablet of Rivaroxaban 10 mg.

Also known as: Group 2:

Grouyp 2: Enoxaparine treatment

Eligibility Criteria

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

You may qualify if:

• Signed and dated informed consent form,
• Age ≥ 18 years,
• Hospitalised for non-major orthopaedic surgery and requiring thromboprophylaxis according to the investigator's judgement on VTE risk such Achilles' repair, hip (except femoral neck and trochanteric fracture), knee, tibial plateau, femur (non femoral head), tibial and ankle fractures and tibial osteotomy, tibial transposition, arthrodesis of leg articulation, ligament repair of the knee or the ankle or any elective orthopaedic limb surgery requiring thromboprophylaxis).

You may not qualify if:

• Major orthopaedic surgery Hip and Knee replacement, femoral neck and trochanteric fractures, spine surgery,
• Low risk surgery without patient VTE risk: foot surgery (Hallux Valgus), material removal,
• Delay between hospitalisation and randomisation greater than two days,
• Women of childbearing potential not using a reliable contraceptive method throughout the study period (a list of reliable contraceptive methods is provided in the accompanying SPM),
• Women pregnant or breast-feeding during the study period,
• Body weight less than 50 kg (to avoid bleeding over risk) or over 120 kg,
• Long term treatment with VKA therapy or NOAC,
• Concomitant treatment with clopidogrel, prasugrel and ticagrelor,
• Platelet count \< 100 Giga/L,
• Documented history of acquired or inherited bleeding disorder (e.g., von Willebrand's disease),
• Severe renal failure with calculated creatinine clearance (Cockcroft Formula) \< 30 mL/min,
• Severe hepatic insufficiency with prothrombin time \< 60% or liver impairment associated with coagulation disorders,
• History of thrombocytopenia,
• Any other current significant medical condition that might interfere with treatment evaluation according to the investigator's judgement,
• Known hypersensitivity or other severe reaction to any component of the investigational medicinal product(s),

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Bayer: collaborator

Study Sites (38)

CHU AMIENS Picardie

Amiens, 80054, France

Location

CHU Angers

Angers, 49933, France

Location

Clinique Générale d'ANNECY

Annecy, 74000, France

Location

CHU BESANCON- Hôpital Jean Minjoz

Besançon, 25030, France

Location

Hopital Ambroise Pare

Boulogne-Billancourt, 92100, France

Location

Médipôle de Savoie

Challes-les-Eaux, 73190, France

Location

Clinique Léonard de Vinci

Chambray-lès-Tours, 37170, France

Location

CHU de Dijon- Bocage

Dijon, 21079, France

Location

Hôpitaux Universitaires de Strasbourg C.C.O.M

Illkirch-Graffenstaden, 67403, France

Location

CHU de Grenoble 6 Hôpital Michallon

La Tronche, 38700, France

Location

Chu Kremlin Bicetre

Le Kremlin-Bicêtre, 94275, France

Location

CHRU Lille -Hôpital Roger Sallengro

Lille, France

Location

CHU Dupuytren

Limoges, 87042, France

Location

Ch Lyon Sud Pierre Benite

Lyon, France

Location

Chu Marseille La Timone

Marseille, 13385, France

Location

Ch Les Chanaux

Mâcon, 71000, France

Location

CHU de MONTPELLIER - Lapeyronnie

Montpellier, 34000, France

Location

CHRU NANTES - Hôtel Dieu

Nantes, 44093, France

Location

CHU Carémeau

Nîmes, 30000, France

Location

Clinique ARAGO

Paris, 75014, France

Location

GH Paris Saint-Joseph

Paris, 75014, France

Location

Hopital Cochin

Paris, 75014, France

Location

Hopital Europeen Georges POMPIDOU

Paris, 75015, France

Location

Ch Paris Pitie Salpetriere

Paris, France

Location

Ch Saint Louis-Lariboisiere

Paris, France

Location

CHU Bordeaux

Pessac, 33604, France

Location

Polyclynique de Poitiers

Poitiers, 86000, France

Location

CHU de Reims - Hôpital MAsion Blanche

Reims, 51000, France

Location

Hôpital Robert Debré

Reims, 51092, France

Location

CHU de Rennes - Hôpital Pontchaillou

Rennes, France

Location

CHU de Rouen

Rouen, 76000, France

Location

CHU de SAINT-ETIENNE

Saint-Etienne, 42000, France

Location

Clinique de la Mutualiste

Saint-Etienne, 42013, France

Location

Chp Saint Gregoire

Saint-Grégoire, 35760, France

Location

Polyclinique Du Parc

Saint-Saulve, 59880, France

Location

CHRU de Strasbourg- Hôpital Hautepierre

Strasbourg, France

Location

Clinique Médipôle

Toulouse, 31036, France

Location

CHU Toulouse - Hôpital Pierre-Paul Riquet

Toulouse, 31059, France

Location

Related Publications (1)

• Samama CM, Laporte S, Rosencher N, Girard P, Llau J, Mouret P, Fisher W, Martinez-Martin J, Duverger D, Deygas B, Presles E, Cucherat M, Mismetti P; PRONOMOS Investigators. Rivaroxaban or Enoxaparin in Nonmajor Orthopedic Surgery. N Engl J Med. 2020 May 14;382(20):1916-1925. doi: 10.1056/NEJMoa1913808. Epub 2020 Mar 29.

  PMID: 32223113 DERIVED

MeSH Terms

Conditions

Venous Thrombosis

Interventions

Rivaroxaban; Enoxaparin

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

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

• Marc SAMAMA, PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

• Nadia ROSENCHER, MD

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

• Patrick MISMETTI, PhD

  Centre Hospitalier Universitaire de Saint Etienne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2015
• First Posted: March 30, 2015
• Study Start: December 8, 2015
• Primary Completion: April 11, 2018
• Study Completion: April 16, 2018
• Last Updated: December 7, 2018

Record last verified: 2018-12

Locations

FR (38)