VTE Prevention Following Total Hip and Knee Arthroplasty

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Venous Thromboembolism

Intervention / Treatment
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* Drug: Rivaroxaban 10 MG and acetylsalicylic acid 81 mg
* Drug: acetylsalicylic acid 81 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing elective THA/TKA at the participating institutions will be potentially eligible for this study Written informed consent in accordance with federal, local and institutional guidelines Exclusion Criteria: Previous documented VTE (proximal DVT or any PE) Hip or lower limb fracture in the previous three months, not related to present surgery Metastatic cancer Life expectancy less than 6 months History of major bleeding that in the judgment of the investigator precludes use of anticoagulant prophylaxis History of aspirin allergy, active peptic ulcer disease or gastritis that in the judgment of investigator precludes use of aspirin History of significant hepatic disease or any other condition that in the judgment of the investigator precludes the use of rivaroxaban Creatinine clearance less than 15 ml per minute Pre-operative platelet count less than 100 x 109 /L 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 Received anticoagulation post operatively Bilateral THA/TKA or simultaneous hip and knee arthroplasty Major surgical procedure within the previous 3 months Requirement for major surgery post arthroplasty within a 90 day period Chronic daily aspirin use with dose greater than 100 mg a day Women of childbearing potential who are not abstinent or do not use effective contraception or are breast-feeding throughout the study drug period Unwilling or unable to give consent Previous participation in the EPCAT III study Under 18 years of age 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) Known allergy to food dye Diagnosis of COVID-19 in previous 3 months

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: randomized, controlled, double-blind
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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total hip and knee arthroplasty