Anticoagulants and Bleeding DisordersPhase 4NCT03296033
Residual Anti-Xa Activity After Last Treatment Dose of Enoxaparin
A Phase 4 study testing Enoxaparin in people with Anticoagulants and Bleeding Disorders and Surgery, run by Wake Forest University Health Sciences at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Anticoagulants and Bleeding Disorders, Surgery, Regional Anesthesia Morbidity
- What is being tested?
- Enoxaparin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 122 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Oct 2017to 14 Jan 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
United States1 site
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, 27157
About this study
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
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.
Read the 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.
- Being tested
- Enoxaparin
- Keywords
- enoxaparin, thromboembolism, coagulation, factor Xa
- Medical subject headings
- Hemostatic Disorders, Thromboembolism, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnoxaparinDrug
Also called Lovenox
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.
EnoxaparinDrug
Also called Lovenox
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)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Enoxaparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Analyze and determine the best-fit function (beta and standard error) for anti-Xa activity level activity (IU/mL) to determine if there is a significant association between anti-Xa activity at the time of presentation and patient age (years).
Individual patient characteristics were assessed to determine their impact on the odds of success, defined as an anti-Xa level of <0.2IU/mL. Patient characteristics assessed included age, sex, renal function (calculated by Cockcroft-Gault and modified Cockcroft-Gault formulae), and body mass index (BMI), the latter of which was assessed post-hoc.
Odds ratios were calculated with both groups combined, as time from last dose varied and even overlapped between groups, which was expected/anticipated as part of the study design. All patient characteristics were analyzed using three separate time intervals from last dose (<24-hours, 24-hours through 35.9-hours, and >36-hours).
Measured: 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)
Analyze and determine the best-fit function (beta and standard error) for anti-Xa activity level activity (IU/mL) to determine if there is a significant association between anti-Xa activity at the time of presentation and (gender= male or female).
Individual patient characteristics were assessed to determine their impact on the odds of success, defined as an anti-Xa level of <0.2IU/mL. Patient characteristics assessed included age, sex, renal function (calculated by Cockcroft-Gault and modified Cockcroft-Gault formulae), and body mass index (BMI), the latter of which was assessed post-hoc.
Odds ratios were calculated with both groups combined, as time from last dose varied and even overlapped between groups, which was expected/anticipated as part of the study design. All patient characteristics were analyzed using three separate time intervals from last dose (<24-hours, 24-hours through 35.9-hours, and >36-hours).
Measured: Anti-Xa levels were measured at the time of presentation for surgery. Gender was collected at the time of enrollment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2017
- Study start24 Oct 2017
- Primary completion14 Jan 2022
- Study completion14 Jan 2022
Why it stopped: enrollment proved to be a challenge due to the changing of the guidelines for bridging off the new anticoagulants that are being prescribed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Anticoagulants and Bleeding DisordersStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- After consenting to the study, patients will be randomized to one of two groups.
- Masking
- None (open label)
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Daryl S Henshaw, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03296033
- Sponsor's protocol ID
- IRB00044503
- Status last verified
- Sep 2023
- First submitted
- 6 Jul 2017
- Last updated
- 5 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 20052816Henshaw 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.
PubMed 28492441Henshaw 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.
PubMed 37280083
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03296033
- Acronym / sponsor ID
- IRB00044503
- Keywords
- enoxaparin, thromboembolism, coagulation, factor Xa
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: enrollment proved to be a challenge due to the changing of the guidelines for bridging off the new anticoagulants that are being prescribed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- 24 Oct 2017 (actual)
- Primary completion
- 14 Jan 2022 (actual)
- Study completion
- 14 Jan 2022 (actual)
- First posted
- 28 Sep 2017 (actual)
- Results
- Posted 5 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- After consenting to the study, patients will be randomized to one of two groups.
| Arm | Type | Receives |
|---|---|---|
| 24 Hours group | Active comparator | Drug: EnoxaparinGroup 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. |
| 36 Hours Group | Experimental | Drug: EnoxaparinGroup 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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EnoxaparinAlso: LovenoxThe 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. | Drug | 36 Hours Group |
| EnoxaparinAlso: LovenoxThis 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) | Drug | 24 Hours group |
Primary outcome
Residual Anti-Xa Activity Levels Following Last Treatment Dose of Enoxaparin
Time frame: 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.
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 Point at Which Anti-Xa Activity is Lower Than 0.2 International Unit Per Milliliter (IU/mL) Using Modeling
Time frame: 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.
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.
2 secondary outcomes
Relationship Between Anti-Xa Levels and Patient Age
Time frame: 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)
Time frame: Anti-Xa levels were measured at the time of presentation for surgery. Gender was collected at the time of enrollment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20052816Horlocker 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.
- Results publication: PubMed 28492441Henshaw 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.
- Derived from this study: PubMed 37280083Henshaw 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daryl S Henshaw, MD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Enoxaparin in people with Anticoagulants and Bleeding Disorders and Surgery, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Residual Anti-Xa Activity Levels Following Last Treatment Dose of Enoxaparin (time frame: 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03296033, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2023.