FactOr XIa inhibiTion for the pRevention of venOus Thromboembolism in Patients Undergoing Total Knee Arthroplasty

Study Overview
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Brief Summary
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This study was to compare the study drug BAY1213790 to existing therapies, i.e. enoxaparin or apixaban, for the prevention of blood clotting and safety in patients undergoing total knee arthroplasty (TKA). The study was open-label, but observer-blinded for the different doses of BAY1213790. This means that it was known which treatment was given, but it was not known which dose of BAY1213790 was administered.

Official Title
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A Randomized, Active-comparator-controlled, Multicenter Study to Assess the Safety and Efficacy of Different Doses of BAY1213790 for the Prevention of Venous Thromboembolism in Patients Undergoing Elective Primary Total Knee Arthroplasty, Open-label to Treatment and Observer-blinded to BAY1213790 Doses

Conditions
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Knee Arthroplasty, Total

Intervention / Treatment
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* Drug: Enoxaparin
* Drug: Apixaban
* Drug: BAY1213790


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥18 years and undergoing elective primary, unilateral Total Knee Arthroplasty (TKA) Women of non-childbearing potential Exclusion Criteria: High risk for clinically significant bleeding Prior deep vein thrombosis Body weight above 135 kg Creatinine clearance below 60 ml/min Recent (<6 months) myocardial infarction or ischemic stroke Contraindication listed in the local label of the comparator treatments Requirement for full dose anticoagulation or dual antiplatelet therapy

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Enoxaparin<br>Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received enoxaparin for at least 10 days until venography was performed. | Drug: Enoxaparin<br>* 40 mg enoxaparin administered as subcutaneous injection once daily<br>|
| Active Comparator: Apixaban<br>Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received apixaban for at least 10 days until venography was performed. | Drug: Apixaban<br>* 2.5 mg apixaban administered as tablet orally twice daily<br>|
| Experimental: BAY1213790 0.3 mg/kg (post-surgery)<br>Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received 0.3 mg BAY1213790 once post-surgery. | Drug: BAY1213790<br>* Single dose of BAY1213790 administered as intravenous infusion<br>* Other names: Osocimab;|
| Experimental: BAY1213790 0.6 mg/kg (post-surgery)<br>Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received 0.6 mg BAY1213790 once post-surgery. | Drug: BAY1213790<br>* Single dose of BAY1213790 administered as intravenous infusion<br>* Other names: Osocimab;|
| Experimental: BAY1213790 1.2 mg/kg (post-surgery)<br>Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received 1.2 mg BAY1213790 once post-surgery. | Drug: BAY1213790<br>* Single dose of BAY1213790 administered as intravenous infusion<br>* Other names: Osocimab;|
| Experimental: BAY1213790 1.8 mg/kg (post-surgery)<br>Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received 1.8 mg BAY1213790 once post-surgery. | Drug: BAY1213790<br>* Single dose of BAY1213790 administered as intravenous infusion<br>* Other names: Osocimab;|
| Experimental: BAY1213790 0.3 mg/kg (pre-surgery)<br>Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received 0.3 mg BAY1213790 once pre-surgery. | Drug: BAY1213790<br>* Single dose of BAY1213790 administered as intravenous infusion<br>* Other names: Osocimab;|
| Experimental: BAY1213790 1.8 mg/kg (pre-surgery)<br>Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received 1.8 mg BAY1213790 once pre-surgery. | Drug: BAY1213790<br>* Single dose of BAY1213790 administered as intravenous infusion<br>* Other names: Osocimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of composite endpoint consisting of asymptomatic DVT as detected by mandatory bilateral venography, objectively confirmed symptomatic DVT, non-fatal PE, fatal PE, unexplained death for which PE cannot be excluded | DVT - Deep vein thrombosis / PE - Pulmonary embolism All suspected events were reviewed and classified by the Central Independent Adjudication Committee. | Up to 15 days | 
| Incidence of composite endpoint of major and clinically relevant non-major bleeding | All suspected events were reviewed and classified by the Central Independent Adjudication Committee. | Up to 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of composite endpoint of symptomatic DVT, non-fatal PE, fatal PE, unexplained death for which PE cannot be excluded up to Day 157 or objectively confirmed asymptomatic DVT up to Day 15 | All suspected events were reviewed and classified by the Central Independent Adjudication Committee. | Up to 157 days | 
| Incidence of composite endpoint of major and clinically relevant non-major bleeding | All suspected events were reviewed and classified by the Central Independent Adjudication Committee. | Up to 157 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Orthopedic surgery, Venous thromboembolism, Deep vein thrombosis (DVT), Anticoagulation