Residual Anti-Xa Activity After Last Treatment Dose of Enoxaparin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Residual Anti-Xa Activity After Last Treatment Dose of Enoxaparin (NCT03296033), a randomized phase 4 study. The primary outcome is Residual Anti-Xa Activity Levels Following Last Treatment Dose of Enoxaparin.

2. Clinical Question

The registry’s stated objective concerns a laboratory measure in patients arriving for elective surgery. Anti-Xa activity was measured using a chromogenic assay and a hybrid curve calibrated to both heparin and enoxaparin. The primary outcome timeframe was 24 hours or 36 hours after the last treatment dose, based on randomization. The record notes that actual laboratory draw timing would vary as planned according to surgical arrival time.

The central statistical distinction is between comparing average activity across assigned groups and determining whether activity is reliably below a threshold for individual patients. The posted results answer the first question by reporting a mean for each group and a mean difference. They do not report individual-level threshold counts or a distribution-based estimate of how many patients were below 0.2 IU/mL. That means the posted group averages should not be read as a direct answer about every patient’s level.

The registry also lists relationships between anti-Xa levels and age, and between anti-Xa levels and sex, as secondary outcomes. Results for those relationships are not reported in the registry record. The population definition, complete eligibility criteria, and participant characteristics beyond the posted outcome counts are not reported in the registry record.

3. Trial Design

This was a Phase 4 randomized, open-label, parallel-group study sponsored by Wake Forest University Health Sciences. The registry record lists enrollment of 122 and identifies the study status as terminated. The listed start date is 2017-10-24, and the primary completion date is 2022-01-14. A reason for termination is not reported in the registry record.

The two groups were named 24 Hours Group and 36 Hours Group. Their descriptions specify intended timing for the last enoxaparin dose in relation to a scheduled surgery time. For the 24 Hours group, the description gives a planned last dose at 07:00 on the day before surgery, with the example of a 07:00 surgery the following day. For the 36 Hours group, it gives a planned last dose at 19:00 two days before surgery, with the example of a 07:00 surgery two days later. The descriptions also indicate that surgery arrival time affects the interval and that the actual laboratory draw would vary according to arrival time.

Both listed interventions are enoxaparin. The comparison is therefore between timing groups, not between enoxaparin and an unrelated treatment or a placebo. The record identifies randomization but does not report the sequence-generation method, allocation concealment, or other implementation details. Masking is listed as none, so the study is described as unmasked; further details about who knew the assignment are not reported in the registry record.

The primary outcome is residual anti-Xa activity, recorded as a continuous measure in international units per milliliter. The posted group results include 51 participants in the 24 Hours group and 52 in the 36 Hours group. Those outcome counts are not the same as the registry’s overall enrollment figure, and the record does not explain the difference. The registry lists two secondary outcomes concerning age and sex, but does not report results for them. The reason the study was terminated and the original design assumptions are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The two groups/arms were compared here as this outcome was considered part of the demographic group comparison, much like age or sex.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Baseline characteristics only collected for subjects who completed

6. Primary Endpoint

The registry lists the primary outcome as Residual Anti-Xa Activity Levels Following Last Treatment Dose of Enoxaparin, measured over 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 primary endpoint is residual anti-Xa activity measured after the last treatment dose of enoxaparin. The registry describes a chromogenic assay using a hybrid curve calibrated to both heparin and enoxaparin. Activity is expressed in international units per milliliter, and the outcome is summarized as a mean with a standard deviation for each timing group.

Anti-Xa activity is used in the study as a laboratory measure relevant to its stated question: how much measurable activity remains after a specified interval following the last treatment dose. The registry’s objective focuses on identifying an interval at which the amount of activity is reliably less than 0.2 IU/mL in patients presenting for elective surgery. That threshold is part of the stated objective, while the posted primary outcome results are group-level means and standard deviations.

A group mean describes the average measured activity among participants with posted results in that group. It does not reveal the exact value for each participant, the range of values, or the proportion whose measurement fell below a threshold. A standard deviation describes the spread of measurements around the group mean, but does not by itself provide the individual measurements or a threshold count. The record does not report the proportion below 0.2 IU/mL, the distribution of individual results, or a separate threshold-based primary analysis.

The timeframe is described as 24 hours or 36 hours after the last treatment dose, based on randomization. The registry also notes that actual blood-draw timing would vary with surgical arrival time. Thus the endpoint is a laboratory measurement associated with assigned timing, not necessarily a measurement taken at an identical elapsed time for every participant.

7. Results Posted in the Registry

• 36 Hours Group: mean 0.11 versus 0.23 on control; difference -0.12 (95% CI -0.17 to -0.07), standardized effect d = -0.95; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

A continuous outcome can take many values across participants, rather than being limited to categories such as yes or no. Anti-Xa activity is reported as a continuous measure. For each timing group, the registry gives a mean and a standard deviation. The mean is the arithmetic average of the recorded measurements. The standard deviation describes how dispersed the measurements are around that average. A smaller standard deviation generally indicates measurements clustered more closely around the group mean, while a larger one indicates more spread. Neither summary shows the full shape of the data or the value for any particular participant.

The posted group means are 0.23 IU/mL for the 24 Hours group and 0.11 IU/mL for the 36 Hours group. Their standard deviations are 0.17 and 0.06, respectively. These are descriptive summaries. The reported mean difference is -0.12 for the 36 Hours group relative to the 24 Hours group. The negative sign reflects the stated comparison direction: the 36 Hours group’s mean is lower than the 24 Hours group’s mean. The comparison also reports a standardized effect size of -0.945. A standardized effect expresses a difference in relation to variability, rather than in the original IU/mL units; it does not replace the original-unit mean difference or convey the individual measurements.

A confidence interval gives a range of estimates compatible with the observed data and the method used to calculate the interval. It conveys precision as well as direction: a narrower interval indicates less statistical uncertainty about the estimated quantity, while a wider interval indicates more. The registry’s interval for the mean difference excludes zero. In conventional interpretation, zero is the value representing no difference between group means. The interval therefore aligns with the reported unadjusted p-value of <0.001. The exact statistical procedure used to calculate the interval and p-value is not reported in the registry record, so the interval should be described as reported rather than attributed to a specific test or model.

A p-value describes how compatible the observed data are with a specified null hypothesis under the assumptions of the statistical procedure. It is not the probability that the null hypothesis is true, and it does not measure the probability that the finding will replicate. The posted value is unadjusted. That qualifier matters because the registry lists multiple outcomes, while the record does not report a multiplicity plan or adjustments. The p-value also does not express the size of the difference; the mean difference and its interval address effect size and precision more directly.

Randomization is intended to create groups whose baseline characteristics are comparable on average, but the registry record does not give details about how the random sequence was generated or concealed. The record identifies a randomized, parallel-group design and no masking. It does not report whether the primary comparison was adjusted for any participant characteristics. The primary outcome description says the groups were compared as part of a demographic group comparison, but that wording does not specify an analysis model.

General statistical context: when a continuous measure is skewed or has unusually extreme values, the mean and standard deviation may not fully represent its distribution. The registry does not report distributional diagnostics or individual values, so the shape of anti-Xa measurements cannot be assessed from these summaries alone. Over-dispersion is a concern when observed variability is greater than a model assumes; if present and not accounted for, uncertainty estimates can be too small. The record does not state whether over-dispersion was assessed, and the posted summaries do not establish whether it occurred.

General statistical context: a confidence interval and a p-value depend on assumptions about sampling and the analysis. For a comparison of means, those assumptions can relate to the distribution of measurements, the independence of observations, and the method used to estimate uncertainty. The registry does not describe the inferential procedure or diagnostic checks. Consequently, the posted interval and p-value can be reported as registry results, but their exact model-based interpretation cannot be reconstructed from the record.

The endpoint has an additional timing consideration. Assignment was to a 24-hour or 36-hour interval, but the registry states that actual laboratory draw timing would vary as planned with surgical arrival time. If measurements are collected at varying elapsed times, the assigned group label and the exact time since last dose are related but not identical descriptions of exposure timing. The record does not report each participant’s actual elapsed time or an analysis accounting for variation in draw timing.

General statistical context: planning calculations use assumptions about the effect to detect, the significance criterion, allocation, and statistical method. Those calculations estimate how many participants would be needed under the specified assumptions; they do not describe how many participants were actually analyzed. The planning illustration associated with this study uses the observed effect and specified planning assumptions. The original trial design assumptions and sample-size justification are not reported in the registry record.

The registry’s outcome results give group-level summaries and one reported between-group comparison. They do not report individual participant data, adjusted estimates, subgroup analyses, missing-data methods, or model diagnostics. Those features should not be inferred from the existence of a mean difference, confidence interval, and p-value.

10. Confidence Intervals and Precision

The reported mean difference is -0.12, with the comparison defined as the 36 Hours group relative to the 24 Hours group. Its confidence interval excludes zero, indicating that the reported interval does not include no difference in group means. The unadjusted p-value is <0.001. Together, the interval and p-value indicate that the posted estimate is not centered on equality of the group means under the reported analysis.

Precision is not the same as importance, reliability for an individual patient, or certainty about a clinical outcome. The interval concerns the estimated difference in group means. It does not give an interval for an individual participant’s anti-Xa activity, and it does not quantify the proportion of participants below 0.2 IU/mL. The registry does not report such a proportion or a confidence interval for threshold attainment.

The two groups have different reported standard deviations: 0.17 in the 24 Hours group and 0.06 in the 36 Hours group. These summaries describe the observed spread within each group, while the confidence interval describes uncertainty around the between-group mean difference. A confidence interval is affected by sample size and variability as well as the analysis method. The record does not report the method used for the interval, so its specific assumptions cannot be independently evaluated from the registry entry.

Although the interval excludes zero, uncertainty remains about the exact size of the mean difference and about how the finding applies beyond the posted outcome measurements. The trial’s registry status is terminated, and the reason is not reported. The record also does not describe missing-data handling, participant-level timing variation, or the analysis population. Those reporting gaps constrain a fuller assessment of precision and generalizability.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total event counts. This is a continuous-outcome comparison, and the planning assumptions specify equal allocation between the two arms. The calculations use a two-sided significance level of 0.05 and a normal approximation. They are planning illustrations based on the observed effect, with alternative calculations using 100%, 75%, and 50% of that observed effect.

The 80% power column gives the number of participants per arm estimated to be needed, under those assumptions, for an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column gives the corresponding planning estimate for a 90% chance. For 100% of the observed effect, the figures are 18 participants per arm for 80% power and 24 for 90% power. For 75% of the observed effect, they are 32 and 42. For 50% of the observed effect, they are 71 and 95.

Smaller effects are harder to distinguish from random variation, so the planning figures rise as the assumed effect becomes smaller. These values are not the trial’s reported enrollment or outcome counts, and they do not establish that the original study was designed using these assumptions. The original sample-size justification and design assumptions are not reported in the registry record. This is not observed power; it is a planning illustration under stated assumptions.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.120; pooled standard deviation σ = 0.127.
2. n = 2 × (1.96 + 0.842)² × 0.127² / -0.120² = 17.6, rounded up to 18 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.12                      # observed difference in means
sigma <- 0.126983276360502                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3296033)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 18 (80% power), 24 (90% power)
 75% of observed effect: n per arm = 32 (80% power), 42 (90% power)
 50% of observed effect: n per arm = 71 (80% power), 95 (90% power)
power.t.test: 18.6 
Simulated power at n = 18 per arm: 0.783 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary outcome of residual anti-Xa activity and two secondary outcomes: the relationship between anti-Xa levels and age, and the relationship between anti-Xa levels and sex. Results for the secondary outcomes are not reported in the registry record. The registry also lists no analysis entries. It is not clear from that listing whether additional analyses were conducted outside the registry record.

The primary comparison reports an unadjusted p-value of <0.001. An unadjusted p-value does not account for testing multiple outcomes or multiple comparisons. The registry does not report a multiplicity adjustment, a hierarchy among outcomes, or a strategy for controlling the overall chance of false-positive findings. It also does not report whether the primary result was selected from a broader set of analyses. The reported result can therefore be described as an unadjusted comparison, but the record does not support a claim that multiplicity was addressed.

Missing-data handling is not reported in the registry record. The primary outcome results list 51 participants in the 24 Hours group and 52 in the 36 Hours group, while overall enrollment is listed as 122. The record does not explain the relationship between those figures, state how many randomized participants contributed data, or say whether any measurements were unavailable. It does not describe imputation, complete-case analysis, or sensitivity analyses.

The analysis population is also not reported in the registry record. There is no statement specifying whether the comparison followed assigned groups, included only participants who completed the planned timing, or used another population definition. The registry identifies randomization but does not provide a detailed analysis plan, interim-analysis information, or rules for handling protocol deviations. These omissions limit evaluation of selective reporting and the impact of missing data; they do not justify assuming that a particular method was used.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry reports serious adverse events for both groups. In the 24 Hours group, 51 participants were listed as at risk and zero serious adverse events were posted. In the 36 Hours group, 52 participants were listed as at risk and zero serious adverse events were posted. The registry also reports zero other adverse events in each group and zero deaths in each group.

These figures are counts in the registry record, not proof that no adverse event could occur. The record does not describe the adverse-event collection period, definitions, completeness of surveillance, or whether all randomized participants were included in safety follow-up. The number listed as at risk is a denominator for the posted count, not an assessment of the certainty of safety.

No serious adverse event terms are listed. The absence of posted event counts should be read narrowly: the registry reports zero in the displayed categories for the groups and counts at risk. It should not be extended into a broader conclusion about risk, nor interpreted as evidence about outcomes that were not reported.

15. What the Result Does, and Does Not, Mean

The registry’s stated goal was to examine when residual anti-Xa activity after a last treatment dose is reliably less than 0.2 IU/mL. The posted group mean was 0.23 IU/mL for the 24 Hours group and 0.11 IU/mL for the 36 Hours group. The reported comparison estimated a mean difference of -0.12 for the 36 Hours group relative to the 24 Hours group, with an interval excluding zero and an unadjusted p-value of <0.001. These results describe a difference in average laboratory measurements between the timing groups.

They do not show that each participant in the 36 Hours group had a value below 0.2 IU/mL. A group mean below a threshold is not equivalent to every individual measurement being below it, and a group mean above a threshold does not show that every measurement exceeded it. The registry does not report the number or proportion of participants below 0.2 IU/mL, or an analysis of reliability at the individual level. The stated threshold question therefore cannot be fully answered from the posted group means alone.

The registry describes randomized assignment to timing groups, but actual laboratory draw timing was expected to vary according to surgical arrival time. Participant-level elapsed time since the last dose is not reported. The outcome comparison also does not establish effects on bleeding, surgical outcomes, anesthesia outcomes, or any other clinical endpoint; those results are not reported in the registry record.

The results are limited to the posted laboratory outcome summaries and the reported statistical comparison. The record does not report the analysis population, missing-data methods, or the study’s reason for termination. No medical recommendation follows from these registry data alone. The clinical question, individual threshold status, and broader implications require evidence beyond the group averages.

16. Why This Trial Matters Statistically

This trial highlights a common distinction in clinical biostatistics: a comparison of group averages is not the same as estimating the proportion of individuals who meet a clinically defined threshold. The stated objective concerns whether anti-Xa activity is reliably less than 0.2 IU/mL after a specified interval, while the posted primary outcome is summarized using means and standard deviations. The group-level summaries describe average activity but do not directly quantify threshold attainment.

It also illustrates why outcome timing matters. The study assigns participants to timing groups, but the registry notes that actual laboratory draw time would vary with surgical arrival. When the time between a last dose and measurement varies, interpretation depends on how assigned interval relates to actual measurement time. The registry does not report participant-level elapsed times or how that variation was handled analytically.

Another statistical point is the difference between an effect estimate and its uncertainty. The mean difference of -0.12 communicates the estimated contrast in original units, while its confidence interval and unadjusted p-value address uncertainty under the reported analysis. Neither establishes a threshold result for every participant or a clinical outcome. The registry does not report enough detail to assess the exact inferential method or any multiplicity plan.

Finally, the posted planning illustration demonstrates how power assumptions depend on the effect size selected for planning. Smaller assumed effects require more participants per arm under the stated assumptions. Those planning numbers are distinct from the study’s enrollment and analyzed outcome counts, and the original study design assumptions are not reported. Keeping those quantities separate is essential when reading registry results.

17. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record lists the study as terminated but does not state why. It therefore does not establish whether termination was related to recruitment, operational issues, interim results, or another reason. The overall enrollment is 122, while the primary outcome results list 51 participants in the 24 Hours group and 52 in the 36 Hours group. The record does not reconcile these numbers or identify the analysis population.

The primary outcome is reported as a group mean and standard deviation. The registry does not report participant-level values, the proportion below 0.2 IU/mL, distributional summaries beyond standard deviation, or a direct analysis of whether activity was reliably below that threshold. As a result, the objective’s individual-threshold language cannot be evaluated from the group summaries alone.

The registry notes that the actual laboratory draw would vary with surgical arrival time, but does not report actual elapsed time for each participant or analyses addressing that variation. The arm descriptions give intended dose timing in relation to example surgery times; adherence to those schedules is not reported. The record also does not give the detailed eligibility criteria, baseline participant characteristics, or the reason for any difference between enrollment and outcome counts.

The statistical analysis plan, exact method for the confidence interval and p-value, handling of missing measurements, multiplicity strategy, and analysis population are not reported in the registry record. The secondary outcomes concerning age and sex are listed without results. Safety counts are posted, but the event collection period and completeness of safety follow-up are not described. These limitations constrain interpretation and do not establish that any particular analysis or study procedure was used.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Residual Anti-Xa Activity After Last Treatment Dose of Enoxaparin — NCT03296033.
• Registry record last updated 2023-10-05; status last verified 2023-09.
• Results first posted 2023-10-05.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

21. Record Summary

The registry record is for NCT03296033, titled Residual Anti-Xa Activity After Last Treatment Dose of Enoxaparin. Its official title describes evaluation of residual anti-Xa activity over time following the last treatment dose in patients presenting for elective surgery. Wake Forest University Health Sciences is listed as sponsor.

The study is listed as Phase 4, randomized, unmasked, and parallel-group, with enrollment of 122 and status terminated. Its listed start date is 2017-10-24, and its primary completion date is 2022-01-14. The primary outcome is residual anti-Xa activity measured at 24 hours or 36 hours based on randomization. The posted group means are 0.23 IU/mL and 0.11 IU/mL, and the reported mean difference for the 36 Hours group relative to the 24 Hours group is -0.12, with p < 0.001. The reason for termination and the original design assumptions are not reported in the registry record.