Efficacy of RIvaroxaban for Prevention of Venous Thromboembolism After Knee Arthroscopy

Efficacy of RIvaroxaban for Prevention of Venous Thromboembolism After Knee Arthroscopy: a Randomized Double-blind Trial (ERIKA Study)

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

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%).

Inclusion Criteria:

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

Exclusion Criteria:

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