Efficacy of RIvaroxaban for Prevention of Venous Thromboembolism After Knee Arthroscopy

Phase 2

Completed

Brief Summary: Study Objective: To assess the value of Rivaroxaban for the prevention of venous thromboembolism (VTE) after knee arthroscopy (KA) taking the placebo as standard of reference.

Study Population: Patients undergoing therapeutic KA at the study Centers, irrespective of the type and duration of the procedure, will be eligible for the study.

Study Design: Multicenter, randomized, double blind superiority, phase II trial comparing two arms:

* (R-7d) Rivaroxaban (10 mg od os) for 7 days

* (PL-7d) Placebo for 7 days.

Follow-up: 3-month period after the randomization

Standard of Reference:Placebo will be the standard of reference in accordance to international guidelines

Study length May 2012-December 2012

Total patients number: 500 patients

Primary Efficacy End-Point: Occurrence in the 3-month period after the randomization of at least one of the following events, objectively proven (by means of CCDU; multi-slice chest TC-angio; autopsy, if necessary, or clinical ground):

* All-cause mortality

* Symptomatic VTE

* Asymptomatic proximal DVT

Secondary Efficacy End-point:

• Combined incidence of all DVT plus symptomatic PE

Primary Safety End-point: Incidence of major bleedings.

Secondary Safety End-point: Overall incidence of bleeding

Detailed Description: The treatments will be administered postoperatively (1st dose 8-10 hours after procedure), for prevention of venous thromboembolism after KA.

A bilateral whole-leg colour-coded Doppler ultrasonography (CCDU) is scheduled for all patients at 7 (+1) days of follow-up; additionally, CCDU was due if the patients developed symptoms or signs suggestive of venous thromboembolism earlier.

Statistical \& Analytical Plan and Methodology: In the absence of prophylaxis the incidence of venous thromboembolism (primary efficacy end-point) after KA, as assessed by CCDU, is about 8.0% (combining weighted results of various paper). Prophylaxis with low-molecular weight heparins assures approximately a 60-70% relative risk reduction in this setting. Based on the findings of published trials investigating the efficacy of Rivaroxaban for prevention of venous thromboembolism after elective hip and knee surgery, when using a low-molecular-weight heparin as comparator, investigators can speculate that Rivaroxaban will further reduce this incidence (at least 1.2%).

Recruitment & Eligibility

Inclusion Criteria

Adult patient (18 years and older)
Knee arthroscopy not combined with open surgery.
Patients eligible for surgical treatment.
Patients are willing and able to continue study participation to ensure completion of all procedures and observations required by the study.
Written informed consent

Exclusion Criteria

Diagnostic arthroscopy
Patients concomitantly treated systemically with strong concurrent CYP3A4 and P-gp-inhibitors, i.e. azole-antimycotics or HIV protease inhibitors.
Hypersensitivity to the active substance or to any of the excipients of study drug
Pregnant women or breast-feeding.
Hepatic disease associated with coagulopathy and clinically relevant bleeding risk
Known thrombophilia (hereditary or acquired)
Mandatory anticoagulation.
Known severe bleeding tendency
Clinically significant active bleeding.
Severe renal failure (GFR<30mL/min/1.73m2)
Patients participating in another clinical trial.
Recent mayor surgery (6 to 12 weeks)

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	oral placebo od for 7 days
Rivaroxaban	Rivaroxaban	Oral Rivaroxaban 10 mg od for 7 days

Primary Outcome Measures

Name	Time	Method
Incidence of Symptomatic Venous Thromboembolism Plus Asymptomatic Proximal Vein Thrombosis and All-cause Mortality	3-month period	During the scheduled visit in case of suspected DVT a bilateral whole-leg colour-coded Doppler ultrasonography (CCDU) is scheduled for all patients at 7 (+1) days of follow-up; additionally, CCDU will be performed if the patients develop symptoms or signs suggestive of venous thromboembolism earlier; in case of suspected PE a multi-slice chest TC-angio is arranged; in case of death for all cause autoptic findings are requested or, if necessary, clinical ground is considered. A follow-up visit is planned 3-month period after the randomization.
Major Bleedings	3 months	Major bleeding include: clinically overt haemorrhage associated with haemoglobin drop of at least 2 g/L or requiring the transfusion of two or more units of packed red-blood cells; retroperitoneal or intracranial events; bleeding requiring re-intervention; and hemarthrosis with a joint drainage of more than 450 millilitres of blood.

Secondary Outcome Measures

Name	Time	Method
Combined Incidence of All DVT Plus Symptomatic PE	3 months	As described for the assessment of the primary efficacy outcomes
Overall Incidence of Bleeding	3 months	As described for the primary safety outcome

Locations (9): Department of Internal Medicine, Hospital of Piacenza
🇮🇹
Piacenza, Italy
Thrombosis Center & Knee Arthroscopy and Sports Medicine Center, Humanitas Clinical Insitute
🇮🇹
Rozzano, Milano, Italy
Department of Orthopaedics and Traumatology, University Hospital "Galliera" of Genova
🇮🇹
Genova, Italy
Unit of Angiology, Hospital of Venice
🇮🇹
Venice, Italy
Department of Internal Medicine, University Hospital of Napoli
🇮🇹
Napoli, Italy
Section of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia
🇮🇹
Perugia, Italy
Department of Orthopaedics and Traumatology, University Hospital of Pavia
🇮🇹
Pavia, Italy
Unit of Angiology, Department of Internal Medicine, Azienda Ospedaliera - IRCCS
🇮🇹
Reggio Emilia, Italy
Department of Orthopedics and Surgery of the Hand, Catholic University "Sacro Cuore"
🇮🇹
Rome, Italy