Utilization of TEG to Monitor Rivaroxaban Activity

November 6, 2019 updated by: Matthew Neal MD

Utilization of Thromboelastography to Monitor Rivaroxaban Activity in Trauma and Emergency Surgery Patients

The invesigators seek to devise a strategy for the assessment of Rivaroxaban activity in trauma and Emergency General Surgery (EGS) patients available as point-of-care testing.

Thromboelastography (TEG) is a point of care, viscoelastic measurement of coagulation that is widely used in trauma and is viewed by many as superior to standard coagulation studies for the assessment of coagulopathy following injury and may be useful in detecting rivaroxaban effect in trauma and EGS patients to assess the degree of functional factor Xa impairment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Rivaroxaban is a novel factor Xa inhibitor that is widely used for stroke prevention in nonvalvular atrial fibrillation, treatment of venous thromboembolism (VTE), and for VTE prophylaxis in patients undergoing knee or hip replacement surgery.

Current standard measurements of coagulation are relatively poor at reliably measuring detecting Rivaroxaban effects and more elaborate means of testing such as measurement of factor Xa activity are not immediately available so not useful in Urgent situations such as traumatic injury or emergent surgical indications. Due to the unmet need to devise a strategy for detecting Rivaroxaban activity in urgent situations, unnecessary reversal, which can lead to significant complications and cost, often results.

The investigators seek to devise a strategy for the assessment of Rivaroxaban activity in trauma and Emergency General Surgery (EGS) patient available as point-of-care testing.

Thromboelastography (TEG) is a point of care, viscoelastic measurement of coagulation that is widely used in trauma and is viewed by many as superior to standard coagulation studies for the assessment of coagulopathy following injury and may be useful in detecting Rivaroxaban effect in trauma and EGS patients to assess the degree of functional factor Xa impairment.

This proposed study is a observational, prospective, cross sectional, study evaluating the Pharmacokinetics of rivaroxaban utilization thromboelastography (TEG) in a population of 80 trauma and emergency EGS patients who were taking rivaroxaban prior to admission and 20 active control trauma and EGS patients who were not taking rivaroxaban prior to admission (matched by age gender injury mechanism or illness)

Study activities:

Prior to any resuscitation with blood, blood products, or reversal agents, the investigators will obtain a TEG as well as standard coagulation testing: prothrombin time, partial thromboplastin time,international normalized ratio (PT/PTT/INR). TEG and coagulation studies will be obtained as soon as possible on admission and again following reversal of rivaroxaban (if reversed as SOC) or at 24 hours post admission to assess for changes.

To assess the efficacy of TEG in monitoring Rivaroxaban activity, the investigators will also perform a battery of coagulation tests at the same timepoints described above in order to attempt to assess the degree of functional factor X inhibition. The coagulation battery will include: thrombin time, thrombin generation, PT with neoplastine, ecarin chromogenic assay, as well as the anti-factor Xa chromogenic assay (Rivaroxaban assay) run by our Institute for Transfusion Medicine.

TEG will be compared to these additional coagulation assays to determine whether prolongation of R time (the most sensitive measurement of coagulation factor activity) and other TEG parameters can be utilized as reliable measurements of Rivaroxaban activity. Each of these tests will be performed at the two aforementioned timepoints: admission and post reversal or 24 hours post admission if clinical team does not opt to reverse patent.

Study Type

Observational

Enrollment (Actual)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center, PUH, 200 Lothrop Street

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients that have taken the drug Rivaroxaban with-in the past 48hours that arrive in the ED with traumatic injury or with illness requiring emergent surgery

Description

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Evidence of Rivaroxaban use with-in the last 48hours per medical records or report by patient, family, or other healthcare member familiar with patients drug medical history
  3. Willingness of subject or legally authorized representative to provide written consent for study procedures.

Exclusion Criteria:

  1. Known to be pregnant
  2. Known to be a prisoner
  3. Known Chronic liver disease
  4. Documented hypo coagulation condition (hemophilia, Von Willebrands, any congenital factor deficiency (V,X,XII) leukemia)
  5. Use of any anticoagulant medication other than Rivaroxaban (examples: Warfarin, lovenox, arixtra, fragmin, eliquis)
  6. Prehospital blood product administration (FFP, platelets, Prothrombin Complex Concentrate (PCC), tranexamic acid (TXA)
  7. Non-survivable traumatic brain Injury
  8. Comfort Measure Only (CMO) status

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Rivaroxaban Cohort
Evidence of Rivaroxaban use with-in the last 48hours Participating subjects will not undergo any procedures associated with this study except data collection and minimal blood sampling of which results will not be become part of the medical record and no clinical decisions will be made using the results of research lab results. Blood samples are for TEG analysis and for Thrombin time, thrombin generation, PT with neoplastine, ecarin chromogenic assay, anti-factor Xa (rivaroxaban assay
Other: blood sampling
blood sampling for TEG analysis, Thrombin time, thrombin generation, PT with neoplastine, ecarin chromogenic assay, anti-factor Xa (rivaroxaban assay
Control cohort not taking Rivaroxaban
Not taking Rivaroxaban - matched to Rivaroxaban group by age gender, type of injury or illness requiring urgent surgery Participating subjects will not undergo any procedures associated with this study except data collection and minimal blood sampling of which results will not be become part of the medical record and no clinical decisions will be made using the results of research lab results. Blood samples are for TEG analysis and for Thrombin time, thrombin generation, PT with neoplastine, ecarin chromogenic assay, anti-factor Xa (rivaroxaban assay
Other: blood sampling
blood sampling for TEG analysis, Thrombin time, thrombin generation, PT with neoplastine, ecarin chromogenic assay, anti-factor Xa (rivaroxaban assay

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in thromboelastography (TEG) as a measure of anticoagulation following Rivaroxaban reversal in trauma and emergency general surgery patients
Time Frame: 2 time-points: First TEG immediately upon presentation to the emergency department - 2nd timepoint is within 1 hour of Rivaroxaban reversal
To best observe inhibition of factor Xa, the investigators will perform kaolin TEGs as opposed to alternative forms of activated TEG (rapid-TEG) which may artificially induce coagulation and miss an effect on factor Xa activity. Additional TEG formats that may better target factor Xa inhibition will be investigated in parallel. As a control group, a second cohort of trauma and EGS patients (matched by demographics, injury mechanism, and illness) who are not taking Rivaroxaban will be identified. TEG and coagulation studies will be obtained on admission as described above. Following reversal of Rivaroxaban for subjects that a clinical decision is made to give reversal agents, or at 24 hours post admission for all other subjects, the TEG and PT/PTT/INR will be repeated to assess for changes in both groups.
2 time-points: First TEG immediately upon presentation to the emergency department - 2nd timepoint is within 1 hour of Rivaroxaban reversal

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
TEG as a point-of-care analysis following Rivaroxaban as compared to the standard of care measurement of coagulation.
Time Frame: 2 time-points: First TEG immediately upon presentation to the emergency department - 2nd timepoint is within 1 hour of Rivaroxaban reversal
To assess the efficacy of TEG in monitoring Rivaroxaban activity, the investigators will perform a battery of coagulation tests in order to attempt to assess the degree of functional factor X inhibition. The coagulation battery will include: thrombin time, thrombin generation, PT with neoplastine, INR, PTT, ecarin chromogenic assay, as well as the anti-factor Xa chromogenic assay (Rivaroxaban assay) run by the Institute for Transfusion Medicine at the University of Pittsburgh. TEG will be compared to these additional coagulation assays to determine whether prolongation of R time (the most sensitive measurement of coagulation factor activity) and other TEG parameters can be utilized as reliable measurements of Rivaroxaban activity. Each of these tests will be performed at the two aforementioned time points: admission and post-reversal/24 hours post admission
2 time-points: First TEG immediately upon presentation to the emergency department - 2nd timepoint is within 1 hour of Rivaroxaban reversal

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Outcomes data to be collected from Subject's medical records
Time Frame: During entire duration of hospital stay, an expected average of 30 days:
  1. Bleeding complications
  2. Transfusion requirements (red blood cells and blood components)
  3. Use, effects and costs of reversal agents
  4. Use of tranexamic acid
  5. Surgical or interventional procedures performed with outcome
  6. Incidence of venous thromboembolism (VTE)
  7. Management and timing of VTE prophylaxis
  8. Nosocomial infections
  9. Mortality
  10. ICU and hospital length of stay
During entire duration of hospital stay, an expected average of 30 days:

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Matthew Neal MD

Collaborators

Janssen Scientific Affairs, LLC

Investigators

  • Principal Investigator: Matthew D Neal, MD, University of Pittsburgh, Division of Trauma and Acute Care Surgery Department of Surgery

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2016

Primary Completion (Actual)

July 7, 2018

Study Completion (Actual)

November 4, 2019

Study Registration Dates

First Submitted

June 15, 2015

First Submitted That Met QC Criteria

January 8, 2016

First Posted (Estimate)

January 11, 2016

Study Record Updates

Last Update Posted (Actual)

November 8, 2019

Last Update Submitted That Met QC Criteria

November 6, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRO15050224

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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