Residual Anti-Xa Activity After Last Treatment Dose of Enoxaparin

Wake Forest University (WFU)

Status and phase: Terminated; Phase 4

Conditions: Surgery; Regional Anesthesia Morbidity; Anticoagulants and Bleeding Disorders

Treatments: Drug: Enoxaparin

Study type: Interventional

Funder types: Other

Identifiers

NCT03296033

IRB00044503

Details and patient eligibility

About

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.

Full 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.

Enrollment: 122 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

122 participants in 2 patient groups

24 Hours group

Active Comparator group

Description:

Group one will be instructed to administer their last dose of enoxaparin at 07:00 in the morning on the day prior to their scheduled surgery date. This will mean that patients who have their surgery scheduled for 07:00 the following day will be 24-hours removed from their last dose. Patients presenting for surgery later in the day would be slightly farther removed from their last dose, however this is currently considered normal clinical practice.

Treatment:

Drug: Enoxaparin

Drug: Enoxaparin

36 Hours Group

Experimental group

Description:

Group 2 will be instructed to administer their last dose of enoxaparin at 19:00 in the evening two days prior to their scheduled surgery date. Patients presenting for surgery at 07:00 two days later will be 36-hours removed from their last dose. Patients presenting for surgery later in the day would be slightly farther removed from their last dose, but again this mimics normal clinical practice in which the timing of the last dose of self-administered enoxaparin is not routinely adjusted based on the scheduled surgical start time.

Treatment:

Drug: Enoxaparin

Drug: Enoxaparin