Venous ThromboembolismPhase 3EPCATIIINCT04075240
VTE Prevention Following Total Hip and Knee Arthroplasty
A Phase 3 study testing Rivaroxaban 10 MG and acetylsalicylic acid 81 mg and acetylsalicylic acid 81 mg in people with Venous Thromboembolism, run by Sudeep Shivakumar at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Venous Thromboembolism
- What is being tested?
- Rivaroxaban 10 MG and acetylsalicylic acid 81 mg and acetylsalicylic acid 81 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5,429 participants
- Where
- 1 siteCanada
- Study dates
- 4 Feb 2021to 10 Jun 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Venous Thromboembolism
- Being tested
- Rivaroxaban 10 MG and acetylsalicylic acid 81 mg, acetylsalicylic acid 81 mg
- Keywords
- total hip and knee arthroplasty
- Medical subject headings
- Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rivaroxaban 10 MG and acetylsalicylic acid 81 mgDrug
Also called Xarelto 10mg and aspirin 81mg
Starting post op, rivaroxaban (5 days) followed by aspirin (9 days for TKA; 30 days for THA)
acetylsalicylic acid 81 mgDrug
Also called aspirin 81mg
Starting post op, aspirin for 9 days for TKA and 30 days for THA
| Study group | Role | What they receive |
|---|---|---|
| THA-control arm | Active comparator | Total Hip Arthroplasty: 5 days of rivaroxaban, followed by 30 days of aspirin Receives: Drug: Rivaroxaban 10 MG and acetylsalicylic acid 81 mg |
| THA-study arm | Experimental | Total Hip Arthroplasty: 35 days of aspirin Receives: Drug: acetylsalicylic acid 81 mg |
| TKA-control arm | Active comparator | Total Knee Arthroplasty: 5 days of rivaroxaban, followed by 9 days of aspirin Receives: Drug: Rivaroxaban 10 MG and acetylsalicylic acid 81 mg |
| TKA-study arm | Experimental | Total Knee Arthroplasty: 14 days of aspirin Receives: Drug: acetylsalicylic acid 81 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Venous thromboembolism
symptomatic proximal deep vein thrombosis or pulmonary embolism
Measured: 90 days
Bleeding
major and clinically relevant, non-major bleeds
Measured: 90 days
Secondary outcomes (2)
Survival
all cause death
Measured: 90 days
Cost-effectiveness
quantitatively describe the costs of symptomatic thromboembolism events and major bleeding episodes
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2019
- Study start4 Feb 2021
- Primary completion16 Apr 2025
- Study completion10 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- randomized, controlled, double-blind
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5,429 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sudeep Shivakumar
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Nova Scotia Health Authority, Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
- Responsible party
- Sponsor-investigator, Sudeep Shivakumar, Nova Scotia Health Authority
- Investigators
- Sudeep P Shivakumar, MD, Principal investigator, Dalhousie University/Nova Scotia Health Authority
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04075240
- Sponsor's protocol ID
- EPCATIII.001
- Acronym
- EPCATIII
- Status last verified
- Jan 2026
- First submitted
- 29 Aug 2019
- Last updated
- 16 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shivakumar S, Matino D, Zukor D, Kahn SR, Vincent G, Mundi R, Vendittoli PA, Refaei M, Bohm E, Tanzer M, Pelet S, Richardson G, Powell J, Ikesaka R, Douketis J, Ward S, Kim P, Mann S, Pleasance S, Cormier J, Andreou P, Matheson K, Theriault C, West C, Anderson D, Gross PL; EPCAT III Trial Investigators. Rivaroxaban Then Aspirin vs. Aspirin Alone after Total Hip or Knee Arthroplasty. N Engl J Med. 2026 Jul 12. doi: 10.1056/NEJMoa2603649. Online ahead of print.
PubMed 42437501
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Extended Venous Thromboembolism Prophylaxis Comparing Rivaroxaban and Aspirin to Aspirin Alone Following Total Hip and Knee Arthroplasty (EPCATIII)
- ClinicalTrials.gov ID
- NCT04075240
- Acronym / sponsor ID
- EPCATIII / EPCATIII.001
- Conditions
- Venous Thromboembolism
- Keywords
- total hip and knee arthroplasty
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5,429 participants (actual)
- Lead sponsor
- Sudeep ShivakumarUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Nova Scotia Health Authority, Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
- Study start
- 4 Feb 2021 (actual)
- Primary completion
- 16 Apr 2025 (actual)
- Study completion
- 10 Jun 2026 (actual)
- First posted
- 30 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- randomized, controlled, double-blind
| Arm | Type | Receives |
|---|---|---|
| THA-control arm | Active comparator | Drug: Rivaroxaban 10 MG and acetylsalicylic acid 81 mgTotal Hip Arthroplasty: 5 days of rivaroxaban, followed by 30 days of aspirin |
| THA-study arm | Experimental | Drug: acetylsalicylic acid 81 mgTotal Hip Arthroplasty: 35 days of aspirin |
| TKA-control arm | Active comparator | Drug: Rivaroxaban 10 MG and acetylsalicylic acid 81 mgTotal Knee Arthroplasty: 5 days of rivaroxaban, followed by 9 days of aspirin |
| TKA-study arm | Experimental | Drug: acetylsalicylic acid 81 mgTotal Knee Arthroplasty: 14 days of aspirin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rivaroxaban 10 MG and acetylsalicylic acid 81 mgAlso: Xarelto 10mg and aspirin 81mgStarting post op, rivaroxaban (5 days) followed by aspirin (9 days for TKA; 30 days for THA) | Drug | THA-control arm, TKA-control arm |
| acetylsalicylic acid 81 mgAlso: aspirin 81mgStarting post op, aspirin for 9 days for TKA and 30 days for THA | Drug | THA-study arm, TKA-study arm |
Primary outcome
Venous thromboembolism
Time frame: 90 days
symptomatic proximal deep vein thrombosis or pulmonary embolism
Bleeding
Time frame: 90 days
major and clinically relevant, non-major bleeds
2 secondary outcomes
Survival
Time frame: 90 days
Cost-effectiveness
Time frame: 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2026.
- Derived from this study: PubMed 42437501Shivakumar S, Matino D, Zukor D, Kahn SR, Vincent G, Mundi R, Vendittoli PA, Refaei M, Bohm E, Tanzer M, Pelet S, Richardson G, Powell J, Ikesaka R, Douketis J, Ward S, Kim P, Mann S, Pleasance S, Cormier J, Andreou P, Matheson K, Theriault C, West C, Anderson D, Gross PL; EPCAT III Trial Investigators. Rivaroxaban Then Aspirin vs. Aspirin Alone after Total Hip or Knee Arthroplasty. N Engl J Med. 2026 Jul 12. doi: 10.1056/NEJMoa2603649. Online ahead of print.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sudeep P Shivakumar, MD principal investigator
Dalhousie University/Nova Scotia Health Authority
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rivaroxaban 10 MG and acetylsalicylic acid 81 mg and acetylsalicylic acid 81 mg in people with Venous Thromboembolism, run by Sudeep Shivakumar at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Venous thromboembolism (time frame: 90 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04075240, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2026.