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

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

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.

Study Overview

• Status: Completed
• Conditions: Hemorrhage
• Intervention / Treatment: Biological: Plasma; Biological: Kcentra®

• Study Type: Observational
• Enrollment (Actual): 2238

Contacts and Locations

Study Locations

• United States
  • California
    • Oakland, California, United States, 94612
      • Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult members of the Kaiser Permanente Northern and Southern California health care delivery systems, receiving chronic warfarin therapy and meeting study eligibility criteria.

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Retrospective; 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
Prospective; 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: Plasma; Biological: Kcentra®; 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.; Other Names: Prothrombin Complex Concentrate (Human); Beriplex

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CSL Behring
• Collaborators: Kaiser Permanente
• Investigators: Principal Investigator: Alan S. Go, MD, Kaiser Permanente; Study Director: Clinical Epidemiologist, CSL Behring; Principal Investigator: Kristi Reynolds, PhD, MPH, Kaiser Permanente

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2014
• Primary Completion (Actual): June 30, 2020
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: December 15, 2014
• First Submitted That Met QC Criteria: December 17, 2014
• First Posted (Estimate): December 18, 2014

Study Record Updates

• Last Update Posted (Actual): May 26, 2021
• Last Update Submitted That Met QC Criteria: May 24, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Vitamin K Reversal Antagonist Therapy of Acute Major Bleeding; Warfarin Reversal
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Hemorrhage; Thromboembolism; Hemostatics; Coagulants; Thrombin
• Other Study ID Numbers: BE1116_4001