VTE Prevention Following Total Hip and Knee Arthroplasty (EPCATIII)

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

Consented patients undergoing elective total hip and total knee arthroplasty will be randomized to receive either aspirin alone or aspirin and rivaroxaban for prevention of venous thromboembolism.

Study Overview

• Status: Recruiting
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: Rivaroxaban 10 MG and acetylsalicylic acid 81 mg; Drug: acetylsalicylic acid 81 mg

Detailed Description

Aspirin and rivaroxaban prevent venous thromboembolism (VTE) via different mechanisms. Aspirin is significantly cheaper than rivaroxaban. Aspirin in combination with rivaroxaban was shown to be safe and efficacious in a non-inferiority trial (EPCATII) when compared to rivaroxaban alone.

This study will assess if aspirin alone is non-inferior to rivaroxaban and aspirin in the prevention of venous thromboembolism.

• Study Type: Interventional
• Enrollment (Estimated): 5400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Susan L Pleasance, BScN; Phone Number: 902-719-5203; Email: susan.pleasance@nshealth.ca

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • Recruiting
      • Queen Elizabeth II HSC
      • Contact: Joanne Douglas, BSc; Phone Number: 902-473-7339; Email: JoAnneE.Douglas@nshealth.ca
      • Principal Investigator: Glen Richardson, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients undergoing elective THA/TKA at the participating institutions will be potentially eligible for this study
2. Written informed consent in accordance with federal, local and institutional guidelines

Exclusion Criteria:

1. Previous documented VTE (proximal DVT or any PE)
2. Hip or lower limb fracture in the previous three months, not related to present surgery
3. Metastatic cancer
4. Life expectancy less than 6 months
5. History of major bleeding that in the judgment of the investigator precludes use of anticoagulant prophylaxis
6. History of aspirin allergy, active peptic ulcer disease or gastritis that in the judgment of investigator precludes use of aspirin
7. History of significant hepatic disease or any other condition that in the judgment of the investigator precludes the use of rivaroxaban
8. Creatinine clearance less than 15 ml per minute
9. Pre-operative platelet count less than 100 x 109 /L
10. Need for long-term anticoagulation due to a pre-existing co-morbid condition or due to the development of VTE following surgery but prior to randomization
11. Received anticoagulation post operatively
12. Bilateral THA/TKA or simultaneous hip and knee arthroplasty
13. Major surgical procedure within the previous 3 months
14. Requirement for major surgery post arthroplasty within a 90 day period
15. Chronic daily aspirin use with dose greater than 100 mg a day
16. Women of childbearing potential who are not abstinent or do not use effective contraception or are breast-feeding throughout the study drug period
17. Unwilling or unable to give consent
18. Previous participation in the EPCAT III study
19. Under 18 years of age
20. Concomitant use of drugs that are strong inhibitors of P-gp AND CYP3A4 (e.g., systemic treatment with ketoconazole, itraconazole, or ritonavir) or strong inducers of P-gp AND CYP3A4 (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's Wort)
21. Known allergy to food dye

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: THA-control arm; Total Hip Arthroplasty: 5 days of rivaroxaban, followed by 30 days of aspirin	Drug: Rivaroxaban 10 MG and acetylsalicylic acid 81 mg; Starting post op, rivaroxaban (5 days) followed by aspirin (9 days for TKA; 30 days for THA); Other Names: Xarelto 10mg and aspirin 81mg
Experimental: THA-study arm; Total Hip Arthroplasty: 35 days of aspirin	Drug: acetylsalicylic acid 81 mg; Starting post op, aspirin for 9 days for TKA and 30 days for THA; Other Names: aspirin 81mg
Active Comparator: TKA-control arm; Total Knee Arthroplasty: 5 days of rivaroxaban, followed by 9 days of aspirin	Drug: Rivaroxaban 10 MG and acetylsalicylic acid 81 mg; Starting post op, rivaroxaban (5 days) followed by aspirin (9 days for TKA; 30 days for THA); Other Names: Xarelto 10mg and aspirin 81mg
Experimental: TKA-study arm; Total Knee Arthroplasty: 14 days of aspirin	Drug: acetylsalicylic acid 81 mg; Starting post op, aspirin for 9 days for TKA and 30 days for THA; Other Names: aspirin 81mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Venous thromboembolism	symptomatic proximal deep vein thrombosis or pulmonary embolism	90 days
Bleeding	major and clinically relevant, non-major bleeds	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	all cause death	90 days
Cost-effectiveness	quantitatively describe the costs of symptomatic thromboembolism events and major bleeding episodes	90 days

Collaborators and Investigators

• Sponsor: Sudeep Shivakumar
• Collaborators: Canadian Institutes of Health Research (CIHR); Nova Scotia Health Authority; Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
• Investigators: Principal Investigator: Sudeep P Shivakumar, MD, Dalhousie University/Nova Scotia Health Authority

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: August 29, 2019
• First Submitted That Met QC Criteria: August 29, 2019
• First Posted (Actual): August 30, 2019

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: total hip and knee arthroplasty
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Aspirin; Rivaroxaban
• Other Study ID Numbers: EPCATIII.001

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No