Efficacy of RIvaroxaban for Prevention of Venous Thromboembolism After Knee Arthroscopy (ERIKA)

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

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism; Haemorrhage
• Intervention / Treatment: Drug: Rivaroxaban; Drug: placebo

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%).

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Genova, Italy
    • Department of Orthopaedics and Traumatology, University Hospital "Galliera" of Genova
  • Napoli, Italy
    • Department of Internal Medicine, University Hospital of Napoli
  • Pavia, Italy
    • Department of Orthopaedics and Traumatology, University Hospital of Pavia
  • Perugia, Italy, 06123
    • Section of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia
  • Piacenza, Italy
    • Department of Internal Medicine, Hospital of Piacenza
  • Reggio Emilia, Italy, 42100
    • Unit of Angiology, Department of Internal Medicine, Azienda Ospedaliera - IRCCS
  • Rome, Italy
    • Department of Orthopedics and Surgery of the Hand, Catholic University "Sacro Cuore"
  • Venice, Italy
    • Unit of Angiology, Hospital of Venice
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Thrombosis Center & Knee Arthroscopy and Sports Medicine Center, Humanitas Clinical Insitute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rivaroxaban; Oral Rivaroxaban 10 mg od for 7 days	Drug: Rivaroxaban; 10 mg os once daily for 1 week; Other Names: Xarelto
Placebo Comparator: Placebo; oral placebo od for 7 days	Drug: placebo; 10 mg os once daily for 1 week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Symptomatic Venous Thromboembolism Plus Asymptomatic Proximal Vein Thrombosis and All-cause Mortality	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.	3-month period
Major Bleedings	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.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Combined Incidence of All DVT Plus Symptomatic PE	As described for the assessment of the primary efficacy outcomes	3 months
Overall Incidence of Bleeding	As described for the primary safety outcome	3 months

Collaborators and Investigators

• Sponsor: University of Padova
• Investigators: Study Chair: Giuseppe Camporese, MD, Unit of Angiology, University Hospital of Padua, Italy

Publications and helpful links

General Publications

• Camporese G, Bernardi E, Noventa F, Bosco M, Monteleone G, Santoro L, Bortoluzzi C, Freguja S, Nardin M, Marullo M, Zanon G, Mazzola C, Damiani G, Maniscalco P, Imberti D, Lodigiani C, Becattini C, Tonello C, Agnelli G; ERIKA Study Group. Efficacy of Rivaroxaban for thromboprophylaxis after Knee Arthroscopy (ERIKA). A phase II, multicentre, double-blind, placebo-controlled randomised study. Thromb Haemost. 2016 Aug 1;116(2):349-55. doi: 10.1160/TH16-02-0118. Epub 2016 Apr 14.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: May 9, 2011
• First Submitted That Met QC Criteria: June 25, 2012
• First Posted (Estimate): June 27, 2012

Study Record Updates

• Last Update Posted (Actual): May 21, 2021
• Last Update Submitted That Met QC Criteria: April 29, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: prevention; venous thromboembolism; knee arthroscopy
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Hemorrhage; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: 2010-024338-43

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No