An Observational Cohort Study to Investigate the Risk of Thromboembolic Events in Patients Receiving Kcentra® or Plasma to Reverse Vitamin K Antagonist (VKA) Therapy in the Setting of Acute Major Bleeding

Study Overview
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Brief Summary
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This observational cohort study is designed to obtain product safety information from the routine clinical setting within large, diverse, community-based populations. In the setting of acute major bleeding in which patients are treated for Vitamin K antagonist reversal, the risk of thromboembolic events (TEE) in patients treated with Kcentra® and in patients treated with plasma will be assessed.

Official Title
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An Observational Cohort Study of the Risk of Thromboembolic Events Among Adult Patients Treated With KCENTRA® Compared With Plasma for Urgent Reversal of Vitamin K Antagonist Therapy in the Setting of Acute Major Bleeding

Conditions
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Hemorrhage

Intervention / Treatment
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* Biological: Kcentra®
* Biological: Plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years and older at admission for VKA-associated major bleeding A minimum of 365 days of continuous health plan enrollment before the index hospitalization involving acute VKA reversal treatment A minimum of 365 days of continuous pharmacy benefit before the index hospitalization involving acute VKA reversal treatment Exclusion Criteria: Patients will be excluded from the primary analyses if they: Require urgent reversal of VKA therapy in the setting of bleeding due to major trauma (eg, motor vehicle accident) Requiring urgent reversal of VKA therapy for a surgical procedure unrelated to major bleeding (eg, appendicitis)

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Retrospective<br>Retrospective cohort of adults hospitalized for major bleeding during 2008 to 2013 who receive plasma for urgent reversal of acquired coagulation factor deficiency induced by oral VKA therapy | Biological: Plasma<br> <br> |
| Prospective<br>Prospective parallel cohort of adults hospitalized for major bleeding during 2014 to 2020 who either receive Kcentra® or plasma for urgent reversal of acquired coagulation factor deficiency induced by oral VKA therapy | Biological: Kcentra®<br>* Kcentra®, Prothrombin Complex Concentrate (Human), is a blood coagulation factor replacement product that contains coagulation Factors II, VII, IX and X, and antithrombotic Proteins C and S as a lyophilized concentrate.<br>* Other names: Beriplex;Biological: Plasma<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk of thromboembolic events (TEE) for patients without a recent history of TEE | The risk of confirmed thromboembolic events (TEE) will be estimated for patients without a recent history of TEE treated with Kcentra® compared to patients treated with plasma. The index date is the date of acute VKA reversal for major bleeding event. | Within 45 days after the index date | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk of thromboembolic events | The risk of confirmed TEE and confirmed fatal TEE will be each estimated for patients treated with Kcentra® compared to patients treated with plasma, overall and for patients in the following subgroups: Recent history of TEE No recent history of TEE Any history of TEE The index date is the date of acute VKA reversal for major bleeding event. | Within 45 days after the index date | 
| Risk of death from any cause | The risk of death from any cause will be estimated for patients treated with Kcentra® compared to patients treated with plasma, overall and for patients in the following subgroups: Recent history of TEE No recent history of TEE Any history of TEE The index date is the date of acute VKA reversal for major bleeding event. | Within 45 days after the index date | 
| Rates of use of VKA therapy after the index date | The rates of use of VKA therapy or other antithrombotic agents will be assessed among patients with and without any history of TEE. The index date is the date of acute VKA reversal for major bleeding event. | Within 90 days after the index date | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin K Reversal Antagonist Therapy of Acute Major Bleeding, Warfarin Reversal