Trial Outcomes & Findings for Residual Anti-Xa Activity After Last Treatment Dose of Enoxaparin (NCT NCT03296033)
NCT ID: NCT03296033
Last Updated: 2023-10-05
Results Overview
Anti-Xa level activity will be measured in both groups using a chromogenic assay and a hybrid curve calibrated to both heparin and enoxaparin.
TERMINATED
PHASE4
122 participants
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.
2023-10-05
Participant Flow
Participant milestones
| Measure |
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.
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)
|
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.
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.
|
|---|---|---|
|
Overall Study
STARTED
|
60
|
62
|
|
Overall Study
COMPLETED
|
51
|
52
|
|
Overall Study
NOT COMPLETED
|
9
|
10
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
24 Hours Group
n=51 Participants
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.
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)
|
36 Hours Group
n=52 Participants
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.
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.
|
Total
n=103 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.1 years
STANDARD_DEVIATION 12.1 • n=51 Participants
|
65.5 years
STANDARD_DEVIATION 13.5 • n=52 Participants
|
64.3 years
STANDARD_DEVIATION 12.8 • n=103 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=51 Participants
|
23 Participants
n=52 Participants
|
44 Participants
n=103 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=51 Participants
|
29 Participants
n=52 Participants
|
59 Participants
n=103 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United States
|
51 participants
n=51 Participants
|
52 participants
n=52 Participants
|
103 participants
n=103 Participants
|
PRIMARY outcome
Timeframe: 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.Population: The two groups/arms were compared here as this outcome was considered part of the demographic group comparison, much like age or sex.
Anti-Xa level activity will be measured in both groups using a chromogenic assay and a hybrid curve calibrated to both heparin and enoxaparin.
Outcome measures
| Measure |
24 Hours Group
n=51 Participants
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.
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)
|
36 Hours Group
n=52 Participants
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.
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.
|
|---|---|---|
|
Residual Anti-Xa Activity Levels Following Last Treatment Dose of Enoxaparin
|
.23 international units per mililiter IU/ mL
Standard Deviation .17
|
.11 international units per mililiter IU/ mL
Standard Deviation .06
|
PRIMARY outcome
Timeframe: 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.Population: On note: Arms/Groups were combined together for analysis purposes and results are reported in this same fashion. The approach was planned apriori. A comparison between the two groups in regard to this primary outcome was neither planned nor performed. Including both arms/groups in a single data set allowed for logistical regression, which was utilized to determine the overall estimate of time until residual anti-Xa level activity reliably fell below 0.2IU/mL).
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.
Outcome measures
| Measure |
24 Hours Group
n=103 Participants
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.
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)
|
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.
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.
|
|---|---|---|
|
Time Point at Which Anti-Xa Activity is Lower Than 0.2 International Unit Per Milliliter (IU/mL) Using Modeling
|
31.4 time in hours
Interval 25.0 to 31.5
|
—
|
SECONDARY outcome
Timeframe: Anti-Xa levels were measured at the time of presentation for surgery. Age was collected at the time of enrollment.Population: All patients were included in a single analysis (planned priori) to assess the association between age and residual anti-Xa level activity at the time of presentation, which reflects time from last dose. Data for the association between anti-Xa level activity and age is shown below. Note "number" represents Odds Ratio (OR) with corresponding 95% CI. This outcome was planned to be analyzed as one arm per protocol.
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).
Outcome measures
| Measure |
24 Hours Group
n=103 Participants
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.
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)
|
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.
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.
|
|---|---|---|
|
Relationship Between Anti-Xa Levels and Patient Age
|
0.99 Odds Ratio (Per 5-year change)
Interval 0.83 to 1.18
|
—
|
SECONDARY outcome
Timeframe: Anti-Xa levels were measured at the time of presentation for surgery. Gender was collected at the time of enrollment.Population: All patients were included in a single analysis (planned priori) to assess the association between gender (sex) and residual anti-Xa level activity at the time of presentation, which reflects time from last dose. Data for the association between anti-Xa level activity and gender (sex) is shown below. Note "number" represents Odds Ratio (OR) with corresponding 95% CI. This outcome was planned to be analyzed as one arm per protocol.
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).
Outcome measures
| Measure |
24 Hours Group
n=103 Participants
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.
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)
|
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.
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.
|
|---|---|---|
|
Relationship Between Anti-Xa Levels and Patients Gender (Sex)
|
0.91 Odds Ratio (OR) female vs male
Interval 0.38 to 2.2
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Anti-Xa levels were measured at the time of presentation for surgery as was glomerular filtration rates, which were used to calculate creatinine clearance.Population: All patients were included in a single analysis (planned priori) to assess the association between renal function and residual anti-Xa level activity at the time of presentation, which reflects time from last dose. Data for the association between anti-Xa level activity and renal function are shown below. Note "number" represents Odds Ratio (OR) with corresponding 95% CI. This outcome was planned to be analyzed as one arm per protocol.
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 renal function. 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).
Outcome measures
| Measure |
24 Hours Group
n=103 Participants
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.
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)
|
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.
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.
|
|---|---|---|
|
Relationship Between Anti-Xa Levels and Patient Renal Function
Using Cockcroft-Gault Forumula to estimate renal function
|
0.97 Odds Ratio Modified Cockcroft-Gault
Interval 0.89 to 1.06
|
—
|
|
Relationship Between Anti-Xa Levels and Patient Renal Function
Using modified Cockcroft-Gault formula to estimate renal function
|
0.98 Odds Ratio Modified Cockcroft-Gault
Interval 0.86 to 1.11
|
—
|
Adverse Events
24 Hours Group
36 Hours Group
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place