Clinical trial NCT03296033: Residual Anti-Xa Activity After Last Treatment Dose of Enoxaparin
Official title: Evaluation of Residual Anti-Xa Activity As A Function Of Time Following The Last Treatment Dose of Enoxaparin In Patients Presenting For Elective Surgery
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Anticoagulants and Bleeding Disorders
Surgery
Regional Anesthesia Morbidity
Keywords: enoxaparin
thromboembolism
coagulation
factor Xa
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2017-09-28
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: After consenting to the study, patients will be randomized to one of two groups.
Primary purpose: BASIC_SCIENCE

Brief summary: The main objective of this study is to determine the time interval following the last treatment dose of enoxaparin at which the amount of anti-Xa level activity is reliably less than 0.2 international unit per milliliter (IU/mL) in patients presenting for elective surgery.

Detailed description: Enoxaparin is a factor Xa inhibitor commonly used for both prophylaxis against and treatment of thromboembolism. It is also frequently used off-label as a perioperative bridge for patients that are chronically anticoagulated prior to surgery, such as those taking Warfarin. It is an attractive option for perioperative use secondary to its predictable pharmacologic profile and the lack of recommended routine blood monitoring. Therefore, it is common to encounter a patient who has recently received a treatment dose of Enoxaparin prior to presenting for surgery. For these patients, and those on other anticoagulant medications, published guidelines have been developed to help guide clinical decision-making when the anesthetic/analgesic plan includes regional anesthesia.1 Currently, these guidelines recommend that a minimum of 24-hours should elapse following the last treatment dose of Enoxaparin before a neuraxial procedure is performed. However, a recently completed quality improvement project conducted at Wake Forest Baptist Medical Center found that almost 60% of patients presenting for surgery while on treatment dose enoxaparin still had significant anticoagulant activity 24-hours following their last dose, as demonstrated by anti-Xa level assay testing. Given that the risk of epidural hematoma formation is increased in the setting of abnormal coagulation parameters, the significance of this finding is that the risk of bleeding complications following a neuraxial procedure may still be increased 24-hours after the last treatment dose of enoxaparin.

While the routine use of anti-Xa level testing may be a viable option to determine when residual enoxaparin activity is present before proceeding with a neuraxial procedure on a patient-by-patient basis, it is not universally available at all hospitals. Therefore, it is important to determine the time interval following the last enoxaparin dose at which the likelihood that a clinically relevant amount of residual anti-Xa level activity no longer persists, so that providers can confidently proceed with a neuraxial procedure when anti-Xa level testing is not available.

Eligibility criteria: Inclusion Criteria:

Eligible patients need:

* to be on treatment dose (1mg/kg twice daily or 1.5mg/kg daily) enoxaparin at the time of presentation for elective surgery
* and must be able to accurately report the timing of their last dose and the administered dosage.
* Patients must also be between the ages of 18-100 years of age
* and must be able to give written consent to participate.

Exclusion Criteria:

* Patients with severe renal insufficiency (creatinine clearance \<30ml/min) will be excluded from the study, as the elimination of enoxaparin is known to be affected in this patient population.
* Pregnant patients will also be excluded, as the elimination and metabolism of enoxaparin is known to be altered in this patient population, and dose adjustments are recommended if treatment dose enoxaparin is used during pregnancy.
* Patients who are receiving enoxaparin as a bridge from another anti-Xa inhibiting medication will be excluded as this could unpredictably affect the results of anti-Xa testing. These medications include: Apixaban, Edoxaban, Fondaparinux, and Xarelto.

Primary outcomes:
measure: Residual Anti-Xa Activity Levels Following Last Treatment Dose of Enoxaparin
timeFrame: Time Frame: 24 hours or 36 hours (based on randomization) after the last treatment dose of enoxaparin. Actual lab draw will vary, as planned, given surgical arrival time.
measure: Time Point at Which Anti-Xa Activity is Lower Than 0.2 International Unit Per Milliliter (IU/mL) Using Modeling
timeFrame: Time Frame: 24 hours or 36 hours (based on randomization) after the last treatment dose of enoxaparin. Actual lab draw will vary, as planned, given surgical arrival time.
Secondary outcomes:
measure: Relationship Between Anti-Xa Levels and Patient Age
timeFrame: Anti-Xa levels were measured at the time of presentation for surgery. Age was collected at the time of enrollment.
measure: Relationship Between Anti-Xa Levels and Patients Gender (Sex)
timeFrame: Anti-Xa levels were measured at the time of presentation for surgery. Gender was collected at the time of enrollment.
Other outcomes:
measure: Relationship Between Anti-Xa Levels and Patient Renal Function
timeFrame: Anti-Xa levels were measured at the time of presentation for surgery as was glomerular filtration rates, which were used to calculate creatinine clearance.
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Daryl S Henshaw, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Horlocker TT, Wedel DJ, Rowlingson JC, Enneking FK, Kopp SL, Benzon HT, Brown DL, Heit JA, Mulroy MF, Rosenquist RW, Tryba M, Yuan CS. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Third Edition). Reg Anesth Pain Med. 2010 Jan-Feb;35(1):64-101. doi: 10.1097/aap.0b013e3181c15c70.
citation: Henshaw DS, Turner JD, Forest DJ, Thompson GR, Weller RS. Residual Enoxaparin Activity, Anti-Xa Levels, and Concerns About the American Society of Regional Anesthesia and Pain Medicine Anticoagulation Guidelines. Reg Anesth Pain Med. 2017 Jul/Aug;42(4):432-436. doi: 10.1097/AAP.0000000000000617.