Clinical trial NCT02651909: Utilization of TEG to Monitor Rivaroxaban Activity
Official title: Utilization of Thromboelastography to Monitor Rivaroxaban Activity in Trauma and Emergency Surgery Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Anemia
Venous Thrombosis
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Janssen Scientific Affairs, LLC
First posted: 2016-01-11
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in thromboelastography (TEG) as a measure of anticoagulation following Rivaroxaban reversal in trauma and emergency general surgery patients
timeFrame: 2 time-points: First TEG immediately upon presentation to the emergency department - 2nd timepoint is within 1 hour of Rivaroxaban reversal
Secondary outcomes:
measure: TEG as a point-of-care analysis following Rivaroxaban as compared to the standard of care measurement of coagulation.
timeFrame: 2 time-points: First TEG immediately upon presentation to the emergency department - 2nd timepoint is within 1 hour of Rivaroxaban reversal
Other outcomes:
measure: Clinical Outcomes data to be collected from Subject's medical records
timeFrame: During entire duration of hospital stay, an expected average of 30 days:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center, PUH, 200 Lothrop Street
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh, Division of Trauma and Acute Care Surgery Department of Surgery
name: Matthew D Neal, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Beyer-Westendorf J, Lutzner J, Donath L, Tittl L, Knoth H, Radke OC, Kuhlisch E, Stange T, Hartmann A, Gunther 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.
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. No abstract available.
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.
citation: Muller 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.
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.