Venous ThromboembolismPhase 2NCT03251963
Fixed Versus Weight-Based Enoxaparin Dosing in Thoracic Surgery Patients
A Phase 2 study testing Fixed Dose Enoxaparin and Variable Dose Enoxaparin in people with Venous Thromboembolism and Deep Venous Thrombosis, run by University of Utah at 1 site in United States.
Trial summary
The aim of this research is to better understand how patient-level factors can be used to predict the appropriate enoxaparin dose to maximize venous thromboembolism (VTE) risk reduction and minimize bleeding. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Venous Thromboembolism, Deep Venous Thrombosis, Surgery
- What is being tested?
- Fixed Dose Enoxaparin and Variable Dose Enoxaparin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 131 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Sep 2017to 27 Jul 2019
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- receiving Video-Assisted Thoracoscopic Surgery
- able to have Enoxaparin initiated within 8 hours after procedure
Who cannot join
- Contraindication to use of enoxaparin
- Intracranial bleeding/stroke
- Hematoma or bleeding disorder
- Heparin-induced thrombocytopenia positive
- Creatinine clearance less than or equal to 30 mL/min
- Serum creatinine greater than 1.6 mg/dL
- Epidural catheter
Trial locations and contacts
1 site in 1 country.
About this study
The aim of this research is to better understand how patient-level factors can be used to predict the appropriate enoxaparin dose to maximize venous thromboembolism (VTE) risk reduction and minimize bleeding.
Read the detailed description
VTE encompasses deep venous thrombosis and pulmonary embolus and is the proximate cause of death in over 100,000 hospitalized patients per year 4,5. To put this in better context, VTE kills more people each year than the annual morbidity from motor vehicle crashes and breast cancer combined-and one third of these deaths are known to occur after surgical procedures 34. "Breakthrough" VTE events occur in patients despite the receipt of guideline-compliant chemical prophylaxis. These events can be frustrating for surgeons, can represent a resource and financial burden for hospital systems, and most importantly, can be life or limb threatening for patients.
Existing data from our group and others suggests that inadequate enoxaparin dosing, quantified by aFXa levels, represents a plausible explanatory mechanism for "breakthrough" VTE events that occur among thoracic surgery patients. This project will examine the pharmacodynamics of fixed dose enoxaparin (40mg/day) after VATS-this dose and frequency were the most commonly prescribed VTE chemical prophylaxis strategy in a recent survey of thoracic surgeons 35. If inadequate aFXa levels are observed with fixed enoxaparin dosing, the study will design, implement and test a weight-based dosing approach to optimize aFXa levels. The study will also examine how alteration of enoxaparin dose magnitude affects peak aFXa levels and risk for VTE and major bleeding events.
Aim 1: To evaluate peak steady-state aFXa levels in response to a fixed dose of enoxaparin prophylaxis (40mg once daily) in VATS patients.
Rationale: Over 12% of thoracic surgery patients have "breakthrough" VTE events despite receipt of fixed dose chemical prophylaxis 29. Fixed dose enoxaparin prophylaxis has been shown to be inadequate for the majority of patients in other surgical subspecialties.
Hypothesis: Peak steady state aFXa levels will be within the accepted range (0.3-0.5 IU/mL) in 40% of patients after VATS.
Aim 2: To compare the effect of fixed (40mg once daily) and weight-based (0.5mg/kg once daily) enoxaparin prophylaxis on peak steady state aFXa levels after VATS.
Rationale: Our preliminary data shows a potential association between body weight and aFXa levels in response to fixed dosing; this will be confirmed using a multi-center approach in Aim #1. Body weight may be an important predictor of appropriate enoxaparin dose.
Hypothesis: Weight-based enoxaparin prophylaxis, when compared to fixed dose prophylaxis, will increase the proportion of patients with in-range peak aFXa levels from 40% to 80%.
Aim 3: To examine rates of 90-day VTE and clinically relevant bleeding events in VATS patients who receive fixed dose vs. weight-based enoxaparin prophylaxis.
Rationale: This observational Aim will allow us to better understand VTE and bleeding rates after VATS. Since these are rare events it is impossible to power the study to detect increases or decreases in risk between the dose groups. This study does provide a way to demonstrate an unexpected, very large difference in risk.
Hypothesis: Rates of post-operative VTE and clinically relevant bleeding will be less than 2% in each group.
- Conditions
- Venous Thromboembolism, Deep Venous Thrombosis, Surgery
- Being tested
- Fixed Dose Enoxaparin, Variable Dose Enoxaparin
- Medical subject headings
- Venous Thromboembolism, Venous Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fixed Dose EnoxaparinDrug
Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.
Variable Dose EnoxaparinDrug
Eligible patients will be administered 0.5 mg/kg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.
| Study group | Role | What they receive |
|---|---|---|
| Fixed Dose Enoxaparin | Experimental | Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. Receives: Drug: Fixed Dose Enoxaparin |
| Variable Dose Enoxaparin | Experimental | Eligible patients will be administered 0.5 mg/kg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. Receives: Drug: Variable Dose Enoxaparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With in Range Initial Peak Xa Level
Number of patients with in range initial peak Xa level
Measured: 36 hours
Secondary outcomes (2)
Number of Participants With Venous Thromboembolism Events or Death
Any symptomatic venous thromboembolism events, including deep venous thrombosis or pulmonary embolus occurring within 90 days of surgery
Measured: 90 days
Number of Participants With Bleeding Events
Bleeding events requiring alteration in the course of care within 90 days of surgery
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2017
- Study start15 Sep 2017
- Primary completion27 Mar 2019
- Study completion27 Jul 2019
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 (2)Papers the sponsor has linked to this study.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- More trials run by University of UtahThe 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 2
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Participants enrolled in months 1-6 of the study will all receive a fixed dose of enoxaparin. Patients enrolled in months 7-12 of the study will all receive a variable dose of enoxaparin.
- Masking
- None (open label)
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- University of Michigan
- Responsible party
- Principal investigator, Christopher Pannucci, University of Utah
- Investigators
- Christopher Puccini, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03251963
- Sponsor's protocol ID
- 100484
- Status last verified
- Jul 2020
- First submitted
- 14 Aug 2017
- Last updated
- 8 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Pannucci CJ, Fleming KI, Varghese TK Jr, Stringham J, Huang LC, Pickron TB, Prazak AM, Bertolaccini C, Momeni A. Low Anti-Factor Xa Level Predicts 90-Day Symptomatic Venous Thromboembolism in Surgical Patients Receiving Enoxaparin Prophylaxis: A Pooled Analysis of Eight Clinical Trials. Ann Surg. 2022 Dec 1;276(6):e682-e690. doi: 10.1097/SLA.0000000000004589. Epub 2020 Oct 19.
PubMed 33086312Pannucci CJ, Fleming KI, Bertolaccini C, Moulton L, Stringham J, Barnett S, Lin J, Varghese TK Jr. Fixed or Weight-Tiered Enoxaparin After Thoracic Surgery for Venous Thromboembolism Prevention. Ann Thorac Surg. 2020 Jun;109(6):1713-1721. doi: 10.1016/j.athoracsur.2019.12.058. Epub 2020 Feb 8.
PubMed 32045583
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fixed Versus Weight-Based Enoxaparin Dosing in Thoracic Surgery Patients
- ClinicalTrials.gov ID
- NCT03251963
- Acronym / sponsor ID
- 100484
- Conditions
- Venous Thromboembolism, Deep Venous Thrombosis, Surgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 131 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- University of Michigan
- Study start
- 15 Sep 2017 (actual)
- Primary completion
- 27 Mar 2019 (actual)
- Study completion
- 27 Jul 2019 (actual)
- First posted
- 16 Aug 2017 (actual)
- Results
- Posted 8 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this research is to better understand how patient-level factors can be used to predict the appropriate enoxaparin dose to maximize venous thromboembolism (VTE) risk reduction and minimize bleeding.
Detailed description
VTE encompasses deep venous thrombosis and pulmonary embolus and is the proximate cause of death in over 100,000 hospitalized patients per year 4,5. To put this in better context, VTE kills more people each year than the annual morbidity from motor vehicle crashes and breast cancer combined-and one third of these deaths are known to occur after surgical procedures 34. "Breakthrough" VTE events occur in patients despite the receipt of guideline-compliant chemical prophylaxis. These events can be frustrating for surgeons, can represent a resource and financial burden for hospital systems, and most importantly, can be life or limb threatening for patients.
Existing data from our group and others suggests that inadequate enoxaparin dosing, quantified by aFXa levels, represents a plausible explanatory mechanism for "breakthrough" VTE events that occur among thoracic surgery patients. This project will examine the pharmacodynamics of fixed dose enoxaparin (40mg/day) after VATS-this dose and frequency were the most commonly prescribed VTE chemical prophylaxis strategy in a recent survey of thoracic surgeons 35. If inadequate aFXa levels are observed with fixed enoxaparin dosing, the study will design, implement and test a weight-based dosing approach to optimize aFXa levels. The study will also examine how alteration of enoxaparin dose magnitude affects peak aFXa levels and risk for VTE and major bleeding events.
Aim 1: To evaluate peak steady-state aFXa levels in response to a fixed dose of enoxaparin prophylaxis (40mg once daily) in VATS patients.
Rationale: Over 12% of thoracic surgery patients have "breakthrough" VTE events despite receipt of fixed dose chemical prophylaxis 29. Fixed dose enoxaparin prophylaxis has been shown to be inadequate for the majority of patients in other surgical subspecialties.
Hypothesis: Peak steady state aFXa levels will be within the accepted range (0.3-0.5 IU/mL) in 40% of patients after VATS.
Aim 2: To compare the effect of fixed (40mg once daily) and weight-based (0.5mg/kg once daily) enoxaparin prophylaxis on peak steady state aFXa levels after VATS.
Rationale: Our preliminary data shows a potential association between body weight and aFXa levels in response to fixed dosing; this will be confirmed using a multi-center approach in Aim #1. Body weight may be an important predictor of appropriate enoxaparin dose.
Hypothesis: Weight-based enoxaparin prophylaxis, when compared to fixed dose prophylaxis, will increase the proportion of patients with in-range peak aFXa levels from 40% to 80%.
Aim 3: To examine rates of 90-day VTE and clinically relevant bleeding events in VATS patients who receive fixed dose vs. weight-based enoxaparin prophylaxis.
Rationale: This observational Aim will allow us to better understand VTE and bleeding rates after VATS. Since these are rare events it is impossible to power the study to detect increases or decreases in risk between the dose groups. This study does provide a way to demonstrate an unexpected, very large difference in risk.
Hypothesis: Rates of post-operative VTE and clinically relevant bleeding will be less than 2% in each group.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants enrolled in months 1-6 of the study will all receive a fixed dose of enoxaparin. Patients enrolled in months 7-12 of the study will all receive a variable dose of enoxaparin.
| Arm | Type | Receives |
|---|---|---|
| Fixed Dose Enoxaparin | Experimental | Drug: Fixed Dose EnoxaparinEligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. |
| Variable Dose Enoxaparin | Experimental | Drug: Variable Dose EnoxaparinEligible patients will be administered 0.5 mg/kg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- receiving Video-Assisted Thoracoscopic Surgery
- able to have Enoxaparin initiated within 8 hours after procedure
Key exclusion criteria (7 listed)
- Contraindication to use of enoxaparin
- Intracranial bleeding/stroke
- Hematoma or bleeding disorder
- Heparin-induced thrombocytopenia positive
- Creatinine clearance less than or equal to 30 mL/min
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 |
|---|---|---|
| Fixed Dose EnoxaparinEligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose. | Drug | Fixed Dose Enoxaparin |
| Variable Dose EnoxaparinEligible patients will be administered 0.5 mg/kg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose. | Drug | Variable Dose Enoxaparin |
Primary outcome
Number of Patients With in Range Initial Peak Xa Level
Time frame: 36 hours
Number of patients with in range initial peak Xa level
2 secondary outcomes
Number of Participants With Venous Thromboembolism Events or Death
Time frame: 90 days
Number of Participants With Bleeding Events
Time frame: 90 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33086312Pannucci CJ, Fleming KI, Varghese TK Jr, Stringham J, Huang LC, Pickron TB, Prazak AM, Bertolaccini C, Momeni A. Low Anti-Factor Xa Level Predicts 90-Day Symptomatic Venous Thromboembolism in Surgical Patients Receiving Enoxaparin Prophylaxis: A Pooled Analysis of Eight Clinical Trials. Ann Surg. 2022 Dec 1;276(6):e682-e690. doi: 10.1097/SLA.0000000000004589. Epub 2020 Oct 19.
- Derived from this study: PubMed 32045583Pannucci CJ, Fleming KI, Bertolaccini C, Moulton L, Stringham J, Barnett S, Lin J, Varghese TK Jr. Fixed or Weight-Tiered Enoxaparin After Thoracic Surgery for Venous Thromboembolism Prevention. Ann Thorac Surg. 2020 Jun;109(6):1713-1721. doi: 10.1016/j.athoracsur.2019.12.058. Epub 2020 Feb 8.
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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.
Christopher Puccini, MD principal investigator
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fixed Dose Enoxaparin and Variable Dose Enoxaparin in people with Venous Thromboembolism and Deep Venous Thrombosis, run by University of Utah 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 2 inclusion and 7 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: finished, as of the sponsor's last update on 8 Jul 2020. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 8 Jul 2020). 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?
Number of Patients With in Range Initial Peak Xa Level (time frame: 36 hours). 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 NCT03251963, which also lists 2 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 8 Jul 2020.