Utilization of TEG to Monitor Rivaroxaban Activity

Anemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02651909
• Other study ID #: PRO15050224
• Status: Completed
• Start date: April 2016
• Est. completion date: November 4, 2019

Study information

• Verified date: November 2019
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: November 4, 2019
• Est. primary completion date: July 7, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Thrombosis
• Venous Thrombosis

Intervention

Other:
• blood sampling
blood sampling for TEG analysis, Thrombin time, thrombin generation, PT with neoplastine, ecarin chromogenic assay, anti-factor Xa (rivaroxaban assay

Locations

Country	Name	City	State
United States	University of Pittsburgh Medical Center, PUH, 200 Lothrop Street	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Matthew Neal MD	Janssen Scientific Affairs, LLC

Country where clinical trial is conducted

United States, 

References & Publications (6)

Beyer-Westendorf J, Lützner J, Donath L, Tittl L, Knoth H, Radke OC, Kuhlisch E, Stange T, Hartmann A, Günther KP, Weiss N, Werth S. Efficacy and safety of thromboprophylaxis with low-molecular-weight heparin or rivaroxaban in hip and knee replacement surgery: findings from the ORTHO-TEP registry. Thromb Haemost. 2013 Jan;109(1):154-63. doi: 10.1160/TH12-07-0510. Epub 2012 Nov 29. — View Citation

Bowry R, Fraser S, Archeval-Lao JM, Parker SA, Cai C, Rahbar MH, Grotta JC. Thrombelastography detects the anticoagulant effect of rivaroxaban in patients with stroke. Stroke. 2014 Mar;45(3):880-3. doi: 10.1161/STROKEAHA.113.004016. Epub 2014 Jan 14. — View Citation

Gordon JL, Fabian TC, Lee MD, Dugdale M. Anticoagulant and antiplatelet medications encountered in emergency surgery patients: a review of reversal strategies. J Trauma Acute Care Surg. 2013 Sep;75(3):475-86. doi: 10.1097/TA.0b013e3182a07391. Review. — View Citation

Holcomb JB, Minei KM, Scerbo ML, Radwan ZA, Wade CE, Kozar RA, Gill BS, Albarado R, McNutt MK, Khan S, Adams PR, McCarthy JJ, Cotton BA. Admission rapid thrombelastography can replace conventional coagulation tests in the emergency department: experience with 1974 consecutive trauma patients. Ann Surg. 2012 Sep;256(3):476-86. doi: 10.1097/SLA.0b013e3182658180. — View Citation

Müller MC, Meijers JC, Vroom MB, Juffermans NP. Utility of thromboelastography and/or thromboelastometry in adults with sepsis: a systematic review. Crit Care. 2014 Feb 10;18(1):R30. doi: 10.1186/cc13721. Review. — View Citation

Piccini JP, Hellkamp AS, Lokhnygina Y, Patel MR, Harrell FE, Singer DE, Becker RC, Breithardt G, Halperin JL, Hankey GJ, Berkowitz SD, Nessel CC, Mahaffey KW, Fox KA, Califf RM; ROCKET AF Investigators. Relationship between time in therapeutic range and comparative treatment effect of rivaroxaban and warfarin: results from the ROCKET AF trial. J Am Heart Assoc. 2014 Apr 22;3(2):e000521. doi: 10.1161/JAHA.113.000521. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Clinical Outcomes data to be collected from Subject's medical records	Bleeding complications; Transfusion requirements (red blood cells and blood components); Use, effects and costs of reversal agents; Use of tranexamic acid; Surgical or interventional procedures performed with outcome; Incidence of venous thromboembolism (VTE); Management and timing of VTE prophylaxis; Nosocomial infections; Mortality; ICU and hospital length of stay	During entire duration of hospital stay, an expected average of 30 days:
Primary	Change in thromboelastography (TEG) as a measure of anticoagulation following Rivaroxaban reversal in trauma and emergency general surgery patients	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	TEG as a point-of-care analysis following Rivaroxaban as compared to the standard of care measurement of coagulation.	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