Clinical trial NCT01629381: Efficacy of RIvaroxaban for Prevention of Venous Thromboembolism After Knee Arthroscopy
Official title: Efficacy of RIvaroxaban for Prevention of Venous Thromboembolism After Knee Arthroscopy: a Randomized Double-blind Trial (ERIKA Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Venous Thromboembolism
Haemorrhage
Keywords: knee arthroscopy
venous thromboembolism
prevention
Lead sponsor: University of Padova
Sponsor class: OTHER
First posted: 2012-06-27
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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%).

Eligibility criteria: 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)

Primary outcomes:
measure: Incidence of Symptomatic Venous Thromboembolism Plus Asymptomatic Proximal Vein Thrombosis and All-cause Mortality
timeFrame: 3-month period
measure: Major Bleedings
timeFrame: 3 months
Secondary outcomes:
measure: Combined Incidence of All DVT Plus Symptomatic PE
timeFrame: 3 months
measure: Overall Incidence of Bleeding
timeFrame: 3 months
Other outcomes:
Locations:
city: Rozzano
country: Italy
facility: Thrombosis Center & Knee Arthroscopy and Sports Medicine Center, Humanitas Clinical Insitute
state: Milano
city: Genova
country: Italy
facility: Department of Orthopaedics and Traumatology, University Hospital "Galliera" of Genova
city: Napoli
country: Italy
facility: Department of Internal Medicine, University Hospital of Napoli
city: Pavia
country: Italy
facility: Department of Orthopaedics and Traumatology, University Hospital of Pavia
city: Perugia
country: Italy
facility: Section of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia
city: Piacenza
country: Italy
facility: Department of Internal Medicine, Hospital of Piacenza
city: Reggio Emilia
country: Italy
facility: Unit of Angiology, Department of Internal Medicine, Azienda Ospedaliera - IRCCS
city: Rome
country: Italy
facility: Department of Orthopedics and Surgery of the Hand, Catholic University "Sacro Cuore"
city: Venice
country: Italy
facility: Unit of Angiology, Hospital of Venice
Study officials:
affiliation: Unit of Angiology, University Hospital of Padua, Italy
name: Giuseppe Camporese, MD
role: STUDY_CHAIR
References:
citation: 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.