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Residual Anti-Xa Activity After Last Treatment Dose of Enoxaparin

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ClinicalTrials.gov Identifier: NCT03296033
Recruitment Status : Recruiting
First Posted : September 28, 2017
Last Update Posted : June 11, 2019
Sponsor:
Information provided by (Responsible Party):
Wake Forest University Health Sciences

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 0.2IU/mL in patients presenting for elective surgery.

Condition or disease Intervention/treatment Phase
Anticoagulants and Bleeding Disorders Surgery Regional Anesthesia Morbidity Drug: Enoxaparin Phase 4

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 parameters2, 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: After consenting to the study, patients will be randomized to one of two groups.
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Actual Study Start Date : October 24, 2017
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : September 2020

Arm Intervention/treatment
Active Comparator: 24 Hours group
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.
Drug: Enoxaparin
This is the historical control arm. 24 hours removed from their last dose (time period from the last dose of treatment dose Enoxaparin to the blood sampling for anti-Xa testing)
Other Name: Lovenox

Experimental: 36 Hours Group
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.
Drug: Enoxaparin
The intervention is the implementation of a 36-hour time period from the last dose of treatment dose Enoxaparin to the blood sampling for anti-Xa testing.
Other Name: Lovenox




Primary Outcome Measures :
  1. Anti-Xa activity levels following last treatment dose of enoxaparin [ Time Frame: 24 hours or 36 hours (based on randomization) after the last treatment dose of enoxaparin. ]
    Anti-Xa level activity will be measured in both groups using a chromogenic assay and a hybrid curve calibrated to both heparin and enoxaparin.

  2. Time point at which anti-Xa activity is lower than 0.2IU/mL using modeling [ Time Frame: 24 hours or 36 hours after last treatment dose of enoxaparin. ]
    The randomization of patients to either the 24-hour group or the 36-hour group will allow for modeling, which will generate a prediction of the time point at which the level of anti-Xa activity can reliably be assumed to be lower than 0.2IU/mL.


Secondary Outcome Measures :
  1. Anti-Xa activity over time [ Time Frame: 24 hours or 36 hours after last treatment dose of enoxaparin. ]
    Determining the relationship of anti-Xa level activity over time, 24 and 36 hours, by using curve fitting or best-fit function.

  2. Relationship between anti-Xa levels and patients age [ Time Frame: 24 hours or 36 hours after last treatment dose of enoxaparin. ]
    Explore clinical predictor (age) for any anti-Xa activity levels > 1 standard deviation over the mean from the above function.

  3. Relationship between anti-Xa levels and patients weight [ Time Frame: 24 hours or 36 hours after last treatment dose of enoxaparin. ]
    Explore clinical predictor (weight) for any anti-Xa activity levels > 1 standard deviation over the mean from the above function.

  4. Relationship between anti-Xa levels and patients gender [ Time Frame: 24 hours or 36 hours after last treatment dose of enoxaparin. ]
    Explore clinical predictor (gender= male or female) for any anti-Xa activity levels > 1 standard deviation over the mean from the above function.



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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03296033


Contacts
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Contact: Daryl S Henshaw, MD 336-716-4498 dhenshaw@wakehealth.edu

Locations
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United States, North Carolina
Wake Forest University Baptist Medical Center Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Daryl S Henshaw, MC    336-716-4498    dhenshaw@wakehealth.edu   
Principal Investigator: Daryl S Henshaw, MD         
Sub-Investigator: Robert Weller, MD         
Sub-Investigator: James Turner, MD         
Sub-Investigator: Daniel J Forest, MD         
Sponsors and Collaborators
Wake Forest University Health Sciences
Investigators
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Principal Investigator: Daryl S Henshaw, MD Wake Forest University Health Sciences

Publications of Results:
Other Publications:
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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03296033     History of Changes
Other Study ID Numbers: IRB00044503
First Posted: September 28, 2017    Key Record Dates
Last Update Posted: June 11, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Wake Forest University Health Sciences:
enoxaparin
thromboembolism
coagulation
factor Xa

Additional relevant MeSH terms:
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Blood Coagulation Disorders
Hemostatic Disorders
Hematologic Diseases
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Heparin, Low-Molecular-Weight
Dalteparin
Enoxaparin
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action