Extended Venous Thromboembolism Prophylaxis Comparing Rivaroxaban to Aspirin Following Total Hip and Knee Arthroplasty (EPCAT II)

In this study the investigators want to look at whether using aspirin instead of rivaroxaban (after initial treatment with rivaroxaban) works as well at preventing blood clots while also reducing risk of bleeding and is more cost effective in patients who have either a total hip replacement or total knee replacement.

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: rivaroxaban and ASA

• Study Type: Interventional
• Enrollment (Actual): 3426
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • Capital Health

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. All patients undergoing elective total hip or knee arthroplasty at the participating institutions will be potentially eligible for this study

Exclusion Criteria:

1. Hip or lower limb fracture in the previous three months
2. Metastatic cancer
3. Life expectancy less than 6 months
4. History of major bleeding that in the judgment of the investigator precludes use of anticoagulant prophylaxis
5. History of aspirin allergy, active peptic ulcer disease or gastritis that in judgment of investigator precludes use of aspirin
6. History of significant hepatic disease or any other condition that in the judgement of the investigator precludes the use of rivaroxaban
7. Creatinine clearance less than 30 ml per minute
8. Platelet count less than 100 x 109 /L
9. Need for long-term anticoagulation due to a preexisting co-morbid condition or due to the development of venous thromboembolism following surgery but prior to randomization
10. Did not or will not receive rivaroxaban post-operatively for VTE prophylaxis
11. Bilateral total hip arthroplasty or simultaneous hip and knee arthroplasty
12. Major surgical procedure within the previous three months
13. Requirement for major surgery post arthroplasty within 90 day period
14. Chronic daily aspirin use with dose greater than 100 mg a day
15. Women of child bearing potential who are not abstinent or do not use appropriate contraception throughout the study drug period
16. Geographical inaccessibility for follow-up
17. Unwilling or unable to give consent
18. Previous participation in the study
19. Concomitant use with drugs that are strong inhibitors or inducers of both P-gp and CYP3A4

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: rivaroxaban; rivaroxaban 10mg x 9 days for total knee arthroplasty patients; x 30 days for total hip athroplasty patients	Drug: rivaroxaban and ASA
Experimental: ASA; ASA 81mg x 9 days for total knee arthroplasty patients; x 30 days for total hip athroplasty patients	Drug: rivaroxaban and ASA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
symptomatic venous thromboembolism	up to 4 years
major or clinically relevant non-major bleeding	up to 4 years

Secondary Outcome Measures

Outcome Measure	Time Frame
survival	up to 4 years
myocardial infarction	up to 4 years
stroke	up to 4 years
wound infection	up to 4 years
cost-effectiveness	up to 4 years

Collaborators and Investigators

• Sponsor: David Anderson
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: David R Anderson, MD, Nova Scotia Health Authority

Publications and helpful links

General Publications

• Anderson DR, Dunbar M, Murnaghan J, Kahn SR, Gross P, Forsythe M, Pelet S, Fisher W, Belzile E, Dolan S, Crowther M, Bohm E, MacDonald SJ, Gofton W, Kim P, Zukor D, Pleasance S, Andreou P, Doucette S, Theriault C, Abianui A, Carrier M, Kovacs MJ, Rodger MA, Coyle D, Wells PS, Vendittoli PA. Aspirin or Rivaroxaban for VTE Prophylaxis after Hip or Knee Arthroplasty. N Engl J Med. 2018 Feb 22;378(8):699-707. doi: 10.1056/NEJMoa1712746.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2013
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: October 30, 2012
• First Submitted That Met QC Criteria: October 31, 2012
• First Posted (Estimate): November 2, 2012

Study Record Updates

• Last Update Posted (Actual): January 25, 2018
• Last Update Submitted That Met QC Criteria: January 23, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; 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: EPCATII.001

Plan for Individual participant data (IPD)

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