IO Vancomycin in TSA: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for IO Vancomycin in TSA (NCT05831774), a randomized phase 4 study. The primary outcome is Systemic Levels of Vancomycin.

2. Clinical Question

The study is titled “IO Vancomycin in TSA.” Its brief summary describes a broader objective: comparing vancomycin levels in bone, soft tissue, and systemic samples between the groups. The posted primary outcome, however, is specifically systemic levels at 24 hours. The reported comparison therefore addresses that measurement only; it does not by itself answer whether bone or soft-tissue levels were comparable.

The registry also describes a secondary objective of comparing post-operative infection complications at 30 days and 90 days. The stated hypothesis is that complication rates would not differ between groups. The record lists post-operative complication rates as a secondary outcome, but results for those infection rates are not reported in the registry record. The questions about systemic drug levels and post-operative infection are distinct, and the systemic-level result should not be treated as an infection result.

This page describes the posted information and the comparison calculated from the reported summary statistics. It does not determine whether either administration approach is preferable. The registry record does not report further detail on the target population, eligibility criteria, or the planned interpretation of a particular difference in systemic levels.

3. Trial Design

This is a Phase 4 study listed as randomized, double masked, and parallel in design. It compares two groups: standard IV vancomycin administration and intraosseous vancomycin administration. The registry lists an enrollment of 33 and identifies The Methodist Hospital Research Institute as sponsor. The listed condition is Shoulder Injuries.

The record gives a study start date of 2023-06-01 and a primary completion date of 2024-07-15. Its current status is active, not recruiting. These entries describe the registry status and dates; they do not establish that all outcomes or follow-up have been reported. The registry record does not report which people were masked, how masking was maintained, or the method used to generate and conceal the random allocation.

In the control description, patients receive the hospital orthopedic surgeon's standard pre-operative antibiotic regimen for primary total shoulder arthroplasty. It typically includes IV ancef or cefepime and vancomycin, with antibiotics started in the pre-operative period; the description is truncated after “approximately 1”. The intervention description says IV antibiotics are given according to physician standard of care, typically ancef or cefepime within 1 hour of incision, and IO vancomycin is administered after sterile preparation and draping. It specifies injection into the proximal humerus.

For the primary systemic-level outcome, the posted group summaries include 17 control participants and 15 intervention participants. The registry's outcome description notes that one sample from one participant was unusable because of a laboratory processing error, so values were not obtained for that sample. The safety figures use different at-risk counts, which are described separately below. The record does not report why those counts differ from the endpoint counts.

The brief summary names bone, soft-tissue, and systemic drug levels as areas of interest, and describes infection complications at 30 days and 90 days as secondary objectives. The posted primary result concerns systemic levels at 24 hours. The registry record does not report further details of the study's original sample-size justification, detailed analysis plan, or the methods used for the other listed outcome measures.

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: Please note that these numbers will differ from the participant flow module because one sample from one of the participants was not usable. There was a processing error with the sample in the lab, so values were not obtained.

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.

6. Primary Endpoint

The registry lists the primary outcome as Systemic Levels of Vancomycin, measured over 24 hours.

The primary endpoint is titled “Systemic Levels of Vancomycin.” It is a continuous measure reported in ug/mL, summarized as a mean with standard error, at a timeframe of 24 hours. In practical terms, this endpoint describes the average measured systemic vancomycin level in each group at that timepoint. It is not a direct measure of vancomycin levels in bone or soft tissue, nor is it an infection outcome.

The study summary says its primary objective is to find comparable vancomycin levels in bone, soft tissue, and systemic samples. The posted primary endpoint captures only the systemic part of that broader objective. The registry record does not report a numerical threshold for what would count as comparable, or a formal equivalence or non-inferiority margin. Without such a threshold and the corresponding analysis plan, a difference that is or is not statistically distinguishable from zero cannot automatically be interpreted as evidence of equivalence.

Why use a continuous concentration measure? General statistical explanation: a continuous endpoint retains information about the measured amount rather than reducing it to categories. A group mean gives a summary of the average level, while a standard error describes the uncertainty in estimating that mean under the analysis assumptions. The comparison of group means then describes the estimated average difference. These summaries do not show the full distribution of individual measurements; the registry record does not report participant-level values or a distribution plot.

The posted group summaries are 23.65 ug/mL for the IV control group and 9.79 ug/mL for the IO group. Interpretation should stay tied to the measured compartment and timepoint: the result is about systemic levels at 24 hours, not total drug exposure over time, tissue penetration, or subsequent clinical complications.

7. Results Posted in the Registry

• Intervention - Intraosseous (IO) Administration of Vancomycin: mean 9.79 versus 23.65 on control; difference -13.86 (95% CI -21.47 to -6.25), standardized effect d = -1.19; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The posted endpoint is a continuous measurement, and the registry summarizes each group with a mean and standard error. The comparison is an unadjusted recalculation from those summary statistics. The record lists the control mean as 23.65 ug/mL and the intervention mean as 9.79 ug/mL, with standard errors of 3.85 and 0.52 ug/mL, respectively. The recalculated mean difference is -13.86 ug/mL, with a 95% confidence interval from -21.47 to -6.246 ug/mL and an unadjusted p-value of <0.001.

What does a mean difference represent?

General statistical explanation: a mean difference is the first group's average minus the reference group's average, according to the stated comparison order. Here, the displayed comparison is intervention minus control. A negative estimate therefore indicates that the intervention group's reported mean is lower than the control group's. The estimate is expressed in the endpoint's measurement unit, ug/mL, so its scale remains interpretable in the units used for the laboratory measure.

A mean difference summarizes groups, not individual responses. It does not indicate that every participant in one group had a lower value than every participant in the other group. Without participant-level data or additional distribution summaries, the degree of overlap between individual measurements cannot be established from the group means alone.

What does the standard error describe?

General statistical explanation: the standard error describes the uncertainty of an estimated statistic, such as a group mean, under a statistical model. It is distinct from the standard deviation, which describes variation among observations. The registry reports standard errors for the group means, not standard deviations. The comparison record also gives a pooled standard deviation of 11.67 for its planning calculation. That pooled value is used by the planning illustration and should not be confused with either posted group standard error.

Standard errors depend on the observed data and the analysis assumptions. The record does not report participant-level values, distributional checks, or the method used to calculate the sponsor's own standard errors, if any. Therefore, this explanation concerns the summaries posted for the endpoint rather than an independently verified reconstruction from raw measurements.

How should the confidence interval be read?

General statistical explanation: a confidence interval gives a range of estimates compatible with the data and the procedure used to construct it. Its width communicates precision: a narrower interval indicates greater precision on the scale being estimated, while a wider interval leaves more uncertainty about the magnitude. A 95% confidence interval is not a statement that there is a 95% probability that this particular fixed interval contains the true value. Under repeated use of the same method and its assumptions, intervals constructed in this way would cover the target value at the stated rate.

For this comparison, the interval runs from -21.47 to -6.246 ug/mL. Its limits are both below zero, aligning with the direction of the estimated mean difference. The interval describes uncertainty in the average difference, not a range of individual participant concentrations, and not a prediction interval for a future participant.

What does the p-value say?

General statistical explanation: a p-value is calculated under a null hypothesis and a specified statistical model. It measures how incompatible the observed data, or more extreme data, are with that null model. It is not the probability that the null hypothesis is true, nor does it quantify clinical importance. The posted unadjusted p-value is <0.001. “Unadjusted” means the value shown is not identified as corrected for multiple testing; the registry record does not report a multiplicity procedure for this result.

The p-value and confidence interval are two ways of expressing information about the comparison under its assumptions. Neither answers whether the difference should be considered important for a clinical decision. The registry record does not report a threshold for a meaningful difference or a formal equivalence margin.

Why can variance and over-dispersion matter?

General statistical explanation: statistical methods rely on assumptions about the variability and distribution of observations. If observations are more variable than a model allows, uncertainty can be understated and inferential results can become too optimistic. This issue is often called over-dispersion in settings where a model specifies a particular variance structure. Over-dispersion is not reported as a finding in this record, and the endpoint is a continuous concentration measure. The general lesson is that uncertainty estimates should be considered alongside the model and the data structure; the registry record does not report diagnostics that would allow those assumptions to be assessed.

The record identifies the trial as randomized and double masked, but it does not detail implementation or the analysis set. The posted primary endpoint population note says one sample was unusable after a laboratory processing error. The record does not describe imputation or another method for handling that unavailable measurement. The comparison should therefore be understood as based on the posted endpoint summaries, rather than assumed to include a value for every enrolled participant.

The registry record lists no formal analysis entries, and it does not report a full statistical analysis plan, the original sample-size justification, or whether interim analyses were planned. Those details cannot be inferred from the recalculation. The comparison is a simple unadjusted recalculation from posted summaries; it is not a substitute for a prespecified sponsor analysis if one exists outside the registry record.

10. Confidence Intervals and Precision

The estimate of the mean difference is -13.86 ug/mL, with a 95% confidence interval from -21.47 to -6.246 ug/mL. The interval expresses uncertainty in the estimated difference between the group means at the 24-hour measurement. It does not describe the spread of individual concentrations, and it should not be read as a range in which most participants' values fall.

General statistical explanation: precision concerns how tightly the data and analysis procedure locate an estimated quantity. A confidence interval presents that uncertainty on the original measurement scale. A narrow interval can support a more precise estimate than a broad interval, while even a precisely estimated difference may not be clinically meaningful. The registry record does not report a threshold for a meaningful systemic-level difference, so the interval cannot be judged against such a threshold from the posted information.

The interval's limits are below zero, consistent with the negative mean difference for IO minus IV. The associated unadjusted p-value is <0.001. Statistical compatibility with a difference does not show whether the result generalizes beyond this study or whether it predicts infection complications. The registry record does not report confidence intervals for infection outcomes.

The number of endpoint observations is limited to the group counts posted for this outcome, and the registry notes a sample lost because of a processing error. That loss contributes to uncertainty and makes transparent reporting of the analysis population important. The record does not report participant-level data, additional precision measures, or an analysis that accounts for the unavailable sample. Precision should therefore be understood as represented by the posted interval and not as a complete description of all sources of uncertainty.

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 sample-size table and curve are planning illustrations based on the observed effect, not the trial's original design calculation. The figures are participants per arm for 80% power and participants per arm for 90% power. They are not total event counts: the exception for time-to-event outcomes does not apply to this continuous endpoint.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set in turn to 100%, 75%, or 50% of the observed effect. These are illustrative target effects, not claims about effects that will occur in another study. The planning table gives one column for participants per arm for 80% power and another for participants per arm for 90% power. In plain language, those columns show the planned per-group sample size associated with those respective power targets under the listed assumptions.

General statistical explanation: power is the probability, under a specified assumed effect and analysis model, of detecting an effect at the chosen significance threshold. Higher power generally requires more information, and smaller effects are harder to distinguish from random variation than larger effects. For that reason, the table and curve show that planning for a smaller fraction of the observed effect requires more participants. The curve is a visual representation of that planning relationship; it does not describe observed outcomes or the trial's actual power.

This is not observed power. The registry record does not report the assumptions used for the trial's own original design or sample-size justification, so the illustration should not be presented as the study's planned enrollment target or as evidence that the completed study had a particular probability of detecting an effect.

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 = -13.860; pooled standard deviation σ = 11.674.
2. n = 2 × (1.96 + 0.842)² × 11.674² / -13.860² = 11.1, rounded up to 12 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 <- -13.86                      # observed difference in means
sigma <- 11.6740509964051                     # 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(5831774)
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 = 12 (80% power), 15 (90% power)
 75% of observed effect: n per arm = 20 (80% power), 27 (90% power)
 50% of observed effect: n per arm = 45 (80% power), 60 (90% power)
power.t.test: 12.2 
Simulated power at n = 12 per arm: 0.789 (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 posted statistical comparison concerns systemic vancomycin levels at 24 hours. The registry record lists 10 outcome measures and one posted secondary outcome, post-operative complication (infection) rates. The study summary describes infection comparisons at 30 days and 90 days, but numerical results for those rates are not reported in the registry record. Results for the other outcome measures are also not described.

Multiplicity arises when several outcomes, timepoints, or statistical tests are considered. General statistical explanation: if many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan addresses that issue. Common approaches include specifying a primary hypothesis in advance or applying an adjustment, but the registry record does not report whether any such strategy was planned or used. The p-value shown for the systemic comparison is unadjusted; it should not be assumed to account for tests across all outcomes or timepoints.

The registry record does not report a complete statistical analysis plan, a prespecified hierarchy of outcomes, interim analyses, or a multiplicity adjustment. It also does not report an equivalence margin despite the summary's stated objective of finding comparable levels. Those omissions limit how confidently one can connect the posted result to a prespecified confirmatory claim. The record does not report the trial's original sample-size justification either.

For missing data, the primary outcome description states that one sample from one participant was unusable because of a laboratory processing error, so no value was obtained. The endpoint group counts are 17 for control and 15 for intervention. The registry record does not report imputation, sensitivity analyses, or whether the unavailable measurement was excluded from all analyses. No additional missingness details are reported.

The record identifies the study as randomized, but it does not explain the analysis population, such as whether all randomized participants were included according to assigned group or whether a different population was used. It does not report protocol deviations or the handling of participants with incomplete follow-up. Accordingly, the posted summaries should be read as endpoint results for the stated counts, without assuming an intention-to-treat or per-protocol analysis.

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 adverse-event summary reports zero serious adverse events, zero other adverse events, and zero deaths in both listed groups. The at-risk counts are 18 for standard IV vancomycin and 15 for intraosseous vancomycin. These are the counts attached to the safety summaries; they differ from the endpoint counts, and the registry record does not explain the difference.

These entries mean that no events in those categories are recorded in the registry summary for the listed at-risk groups. They do not prove that no event occurred outside the recorded categories or observation period. The registry record does not report further detail on adverse-event definitions, collection procedures, the duration of safety monitoring, or whether all events were judged related to treatment. No serious adverse-event terms are listed.

General statistical explanation: when event counts are small, observing no events does not establish that the underlying event risk is zero. A zero count is a description of the observed record, not a guarantee about the frequency of rare events. These safety entries should be kept separate from the systemic concentration comparison, and they do not provide results for the secondary infection outcome, which is not reported in the registry record.

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

The posted result describes systemic vancomycin levels measured at 24 hours. The group mean was 23.65 ug/mL for standard IV administration and 9.79 ug/mL for intraosseous administration. The recalculated mean difference, defined as IO minus IV, is -13.86 ug/mL. The 95% confidence interval is -21.47 to -6.246 ug/mL, with an unadjusted p-value of <0.001. These figures show a difference in the posted group means at this timepoint under the assumptions of the recalculation.

That finding does not establish whether the difference is clinically important. The registry record does not report a threshold for a meaningful concentration difference, nor does it report an equivalence margin. The summary describes an objective of comparable levels, but a conventional difference comparison is not the same as a formal equivalence analysis. The result also does not show how concentrations change over time or what levels were present in bone or soft tissue.

The study summary identifies infection complications at 30 days and 90 days as a secondary objective. Those infection-rate results are not reported in the registry record. The systemic concentration result cannot be used as a substitute for those clinical outcomes, and the adverse-event summary is not the same as a report of post-operative infection rates.

The posted result is also limited by the outcome counts and the reported unusable sample. The registry record does not provide participant-level measurements, a full analysis plan, or details of the handling of missing data. Its status is active, not recruiting, but that status does not itself establish that every outcome has been collected or reported.

The appropriate reading is therefore narrow: this is a comparison of two group summaries for systemic vancomycin at 24 hours in this study. It does not establish a preferred treatment approach, prove a clinical benefit or harm, establish equivalence, or answer the unreported infection and tissue-level questions.

16. Why This Trial Matters Statistically

This trial raises several statistical questions that are important when interpreting clinical research. First, it distinguishes a laboratory concentration endpoint from a clinical outcome. A measured systemic level at 24 hours can be summarized and compared, but the estimate does not directly answer whether post-operative infection rates differ. The registry's broader objectives include bone and soft-tissue levels and infection complications, while the posted primary result is limited to systemic levels.

Second, the study summary uses the language of comparability, but the registry record does not report a numerical equivalence margin or a formal equivalence analysis. General statistical explanation: showing that two groups differ from zero is not the same as deciding whether they are sufficiently similar for a defined purpose. A prespecified margin and a suitable analysis are needed to make a formal equivalence claim. Without those details, the comparison should be described in terms of its estimated difference and uncertainty.

Third, the confidence interval adds information that a p-value alone cannot convey. The interval communicates the range of mean differences compatible with the calculation and makes the scale and precision visible. Yet statistical precision and clinical importance are separate questions, and the record supplies no clinical threshold for interpreting the magnitude.

Finally, the record illustrates why analysis transparency matters. It notes a laboratory processing error that made one sample unusable, while the safety counts differ from the endpoint counts. The registry record does not explain those differences or detail the missing-data approach. A complete analysis plan, clear analysis populations, and outcome reporting would help readers assess the scope of the conclusions. Until those details are available, the posted comparison supports a focused description of the 24-hour systemic-level summaries, not broader claims about tissue concentrations or infection.

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.

Several trial-specific limitations follow from the registry record. The primary result is restricted to systemic vancomycin levels at 24 hours, although the brief summary also identifies bone and soft-tissue concentrations as objectives. Numerical results for those tissue samples are not reported in the registry record. Infection complications at 30 days and 90 days are described as a secondary objective, but infection-rate results are not reported.

The primary endpoint note says one sample was unusable because of a laboratory processing error and that no value was obtained. The record does not report how missing data were handled, whether sensitivity analyses were performed, or the characteristics of the participant with the unusable sample. The posted outcome counts are 17 in the control group and 15 in the intervention group, while the safety summaries use at-risk counts of 18 and 15. The reason for this difference is not reported in the registry record.

The registry identifies the trial as randomized, double masked, and parallel, but does not describe allocation concealment, who was masked, or how masking was maintained. The original sample-size justification, detailed statistical analysis plan, analysis populations, interim analyses, and multiplicity procedures are not reported in the registry record. It also does not report a prespecified threshold for clinical importance or an equivalence margin, despite the stated objective of finding comparable levels.

The comparison on this page is a recalculation from posted summary statistics, not a reported sponsor analysis. Participant-level data are not reported, so distributions, unusual values, and the analytic treatment of individual observations cannot be assessed. The study status is active, not recruiting, and not all objectives have posted numerical results. These limitations counsel against extending the concentration comparison to clinical outcomes or to questions the registry record does not answer.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: IO Vancomycin in TSA — NCT05831774.
• Registry record last updated 2025-09-22; status last verified 2025-09.
• Results first posted 2025-09-22.
• 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

NCT05831774, titled “IO Vancomycin in TSA,” is a Phase 4 randomized, double-masked, parallel study sponsored by The Methodist Hospital Research Institute. It compares standard IV vancomycin administration with intraosseous vancomycin administration for total shoulder arthroplasty. The registry lists enrollment of 33, a study start date of 2023-06-01, primary completion on 2024-07-15, and status active, not recruiting.

The primary outcome is systemic vancomycin levels in ug/mL at 24 hours, reported as group means with standard errors. The posted means are 23.65 for control and 9.79 for intervention. The unadjusted recalculated mean difference is -13.86, with a 95% confidence interval from -21.47 to -6.246 and p < 0.001. One sample was unusable because of a laboratory processing error.

The record describes infection complications as a secondary objective, but numerical infection results are not reported in the registry record. It also does not report a full statistical analysis plan, original sample-size justification, or formal equivalence margin. The concentration comparison should therefore be interpreted as a result about the posted systemic measurement at the stated timepoint.