Non-major Orthopaedic Surgery Clinical Trial
Official title:
A Multicentre, Randomised, Double-blind, Controlled, Phase IIIb Study to Assess the Efficacy and Safety of Rivaroxaban 10mg od Versus Enoxaparin 4000 UI for VTE PROphylaxis in NOn Major Orthopaedic Surgery
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.
Major orthopedic surgery (hip, knee replacements and hip fracture) represents only a small
part of all orthopaedic surgery procedures. Procedures for trauma patients and orthopaedic
lower limb surgery without trauma are much more frequent (tibia osteotomy, arthrodesis,
ligament repair….).
The incidence of trauma patients requiring surgery and prolonged immobilisation is rising,
mainly because of the increasing popularity of recreational sports. However, the epidemiology
and prevention of VTE after such injuries have been poorly studied. The combination of limb
surgery with or without trauma in orthopaedic surgery is responsible for an increase in
venous thromboembolism (VTE). Usually, surgery of lower limb is considered as moderate or
high risk for DVT with different duration related to immobilisation. For instance tibia
osteotomy is at very high risk during at least 6 weeks and knee arthroscopy for ligament
repair is at moderate risk during 10 days. However LMWH is recommended in both surgeries.
Non-major orthopaedic surgery represents a major additional risk factor by itself; therefore
such patients undergoing surgery deserve to receive VTE prophylaxis.
Rivaroxaban is a new oral anticoagulant developing a potent anti-Xa activity. In major
orthopaedic surgery, it has shown to be more effective and as safe as LMWH (Enoxaparin 4000
IU once daily) in THR and TKR patients (RECORD program). Up to now, pending the limited
number of surgical settings in which it has been developed in orthopaedic surgery, it is only
approved for the prevention of venous thromboembolism (VTE) in THR and TKR procedures, which
represent only 20% of all orthopaedic interventions. Non-major elective lower limb surgery
and traumatology population is younger as compared to prosthetic orthopaedic surgery
patients. Fewer VTE and cardiovascular events are to be feared. These patients receive quite
often injectable thromboprophylaxis for a total duration lying between approximately 6 weeks
to 3 months. In the one hand, the risk of major bleeding is low in this younger population.
On the other hand, compliance and cost should be in favour of Rivaroxaban, because no
injection and no platelets counts are needed.
The results of Xamos descriptive sub-analysis in non-elective (fracture related) orthopaedic
surgery are consistent with the overall results of Xamos and are in favour of further
investigations in this area. In this small subset of patients (n=790), the incidence of
symptomatic thromboembolic events observed was low in patients treated with Xarelto and the
overall frequency of treatment emergent major bleedings was low in both groups and serious
adverse events occurred less frequently in patients treated with Xarelto. Therefore,
collection of clinical data in this population is needed and awaited by many orthopaedic
surgeons and anaesthetists in charge of VTE prophylaxis.
The population with femoral neck and trochanteric fracture is a specific one with different
characteristics, elderly, frail and with a higher bleeding risk. This population will be
excluded.
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