Residual Anti-Xa Activity After Last Treatment Dose of Enoxaparin

NCT03296033 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: IRB00044503
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

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.

Conditions

Anticoagulants and Bleeding Disorders; Surgery; Regional Anesthesia Morbidity

Keywords

enoxaparin; thromboembolism; coagulation; factor Xa

Outcome Measures

Primary Outcomes (2)

• Residual Anti-Xa Activity Levels Following 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.

  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.

• Time Point at Which Anti-Xa Activity is Lower Than 0.2 International Unit Per Milliliter (IU/mL) Using Modeling

  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 0.2 IU/mL.

  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 (2)

• Relationship Between Anti-Xa Levels and Patient Age

  Anti-Xa levels were measured at the time of presentation for surgery. Age was collected at the time of enrollment.

• Relationship Between Anti-Xa Levels and Patients Gender (Sex)

  Anti-Xa levels were measured at the time of presentation for surgery. Gender was collected at the time of enrollment.

Other Outcomes (1)

• Relationship Between Anti-Xa Levels and Patient Renal Function

  Anti-Xa levels were measured at the time of presentation for surgery as was glomerular filtration rates, which were used to calculate creatinine clearance.

Study Arms (2)

24 Hours group

ACTIVE COMPARATOR

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

36 Hours Group

EXPERIMENTAL

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

Interventions

Enoxaparin DRUG

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.

Also known as: Lovenox

36 Hours Group

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead

Study Sites (1)

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (3)

• 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.

  PMID: 20052816 BACKGROUND

• 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.

  PMID: 28492441 RESULT

• Henshaw DS, Edwards CJ, Dobson SW, Jaffe D, Turner JD, Reynolds JW, Thompson GR, Russell G, Weller R. Evaluating residual anti-Xa levels following discontinuation of treatment-dose enoxaparin in patients presenting for elective surgery: a prospective observational trial. Reg Anesth Pain Med. 2024 Feb 5;49(2):94-101. doi: 10.1136/rapm-2023-104571.

  PMID: 37280083 DERIVED

MeSH Terms

Conditions

Hemostatic Disorders; Thromboembolism; Thrombosis

Interventions

Enoxaparin

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Embolism and Thrombosis

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Daryl Henshaw, MD
• Organization: Wake Forest School of Medicine

dhenshaw@wakehealth.edu

336-716-6344

Study Officials

• Daryl S Henshaw, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: After consenting to the study, patients will be randomized to one of two groups.

Study Record Dates

• First Submitted: July 6, 2017
• First Posted: September 28, 2017
• Study Start: October 24, 2017
• Primary Completion: January 14, 2022
• Study Completion: January 14, 2022
• Last Updated: October 5, 2023
• Results First Posted: October 5, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)