Pharmacokinetics of Ceftolozane/Tazobactam in Patients With Burns: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetics of Ceftolozane/Tazobactam in Patients With Burns (NCT03002506), a na phase 4 study. The primary outcome is Ceftolozane Clearnace.

2. Clinical Question

The clinical and statistical question is descriptive rather than comparative. The study was intended to characterize how patients with burns handle ceftolozane and tazobactam after a dose, using blood and urine sampling over 24 hours. Its registered primary endpoint focuses specifically on ceftolozane clearance; the endpoint does not itself compare dosing strategies or establish whether one treatment is better than another.

The registry summary describes using pharmacokinetic information alongside previously published microbiology information for simulations intended to inform dosing recommendations. That intended use is distinct from a direct clinical outcome question: the primary endpoint is a measure of drug disposition, not a measure of infection response or another patient outcome. The registry record does not report the clearance results, the concentration measurements, or any simulations. It therefore does not establish what clearance was observed or what dosing recommendations those analyses might support.

3. Trial Design

This is a phase 4, single-group study of ceftolozane/tazobactam in patients with burns. The registry records no allocation to different study groups and no masking. One intervention is listed: ceftolozane/tazobactam. The arm description specifies a planned single dose of 3 grams for each participant. With no comparator group, the design is not a randomized treatment comparison.

The registry summary describes collecting blood and urine samples at various times over 24 hours to measure how much of each antibiotic is in the body and urine. The primary endpoint is ceftolozane clearance, expressed in liters per hour and described as a continuous measure. The registry lists the mean and standard deviation as the endpoint summary measures. This design is suited to describing pharmacokinetic characteristics in the enrolled group, but the posted record does not report the endpoint values.

The recorded enrollment is 6. The brief summary refers to 12 patients completing the study as a planned number, which is not the same as the registry's recorded enrollment. The study status is terminated. The record does not say how many participants completed the planned procedures, whether all enrolled participants received the dose, or why the study was terminated.

Study start is recorded as 2017-08-21, and primary completion as 2020-06-01. These registry dates describe the study timeline; they do not establish that endpoint data were collected from every enrolled participant or that the planned analyses were completed. The registry lists one outcome measure and no analyses. A trial-specific statistical analysis plan, sample-size justification, and interim-analysis plan 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

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: All participants who provided informed consent and received ceftolozane/tazobactam.

6. Primary Endpoint

The registry lists the primary outcome as Ceftolozane Clearnace, measured over 24 hours.

The primary endpoint is titled “Ceftolozane Clearnace” in the registry and is described as a continuous measure in liters per hour over 24 hours. The intended quantity is ceftolozane clearance. In general, clearance describes the volume of plasma from which a drug is removed per unit of time. It is a pharmacokinetic measure of drug disposition, not a direct measure of infection response or clinical benefit.

The registry specifies the mean as the endpoint parameter and standard deviation as the measure of dispersion. The mean describes the average clearance in the group; the standard deviation describes how much individual measurements vary around that average. In general, these summaries can help characterize drug handling in the population studied. Their usefulness depends on having measured values and sufficient information about how those measurements were obtained and analyzed.

The stated 24-hour timeframe corresponds to the planned period for blood and urine sampling described in the study summary. However, the registry record does not report the actual clearance mean, standard deviation, individual observations, or an uncertainty interval. It also does not explain whether the endpoint calculation used a particular sampling or pharmacokinetic modeling procedure. Those details are not reported in the registry record, so the endpoint definition can be described, but its empirical result cannot be interpreted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study uses a single-group pharmacokinetic design. In general, a single-group design describes measurements within one enrolled group rather than estimating a contrast between randomized treatments. That distinction matters: the primary endpoint can describe ceftolozane clearance among participants with burns, but the design does not separate treatment effects from other influences through a control-group comparison. No comparator or randomized allocation is listed in the registry record.

What does the mean describe?

The endpoint parameter is the mean. In general, the mean is calculated by combining the observed values and dividing by the number of observations included. It provides a measure of the group's central tendency, but it can be influenced by unusually high or low values. The registry record does not post the individual clearance values or the mean, so no numerical interpretation of the group average is possible.

The endpoint is continuous and measured in liters per hour. Continuous measures can take values across a scale rather than being limited to categories. A pharmacokinetic endpoint such as clearance is used to describe drug disposition. Here, the registry's stated purpose is to understand how patients with burns handle ceftolozane and tazobactam after a dose. The primary endpoint specifically concerns ceftolozane clearance, not a clinical outcome or a comparison of treatment effects.

What does the standard deviation add?

The registry specifies standard deviation as the dispersion measure. In general, standard deviation describes the spread of observations around their mean. A smaller standard deviation indicates that observations are more closely grouped around the mean, while a larger one indicates greater spread. It is different from a confidence interval: standard deviation describes participant-level variation, while a confidence interval describes uncertainty about an estimated quantity. Neither the standard deviation nor a confidence interval for the endpoint is reported in the registry record.

How should the timeframe be understood?

The endpoint timeframe is 24 hours. The study summary describes planned blood and urine collection at various times over that period. Pharmacokinetic measurement generally relies on the timing and pattern of drug measurements, because those observations describe concentrations over time. The registry record does not provide the sampling schedule, concentration data, endpoint calculation details, or a pharmacokinetic model. It is therefore possible to identify the intended observation period, but not to evaluate the measurement procedure or reconstruct the clearance estimate.

What does the study size tell us?

The registry records enrollment of 6, while the study summary describes 12 patients completing the study as a plan. These figures serve different purposes: enrollment is the registry's recorded study count, whereas the completion figure is part of the planned description. The record does not state how many participants completed sampling or contributed usable primary-endpoint data. In general, the amount of information available for estimating a mean depends on the number and quality of observed measurements, not merely on a planned completion target.

Sample-size calculations are planning tools, not results. The registry record does not report a trial-specific sample-size justification. Any planning illustration should not be mistaken for the actual design rationale, the number enrolled, or observed power. In general, observed power is not a substitute for reporting the estimate and its uncertainty; the key evidence for interpreting the endpoint would be the observed clearance summary and its precision. Neither is posted.

What can be inferred from the analysis record?

The registry lists one outcome measure and no analyses. This means the record does not give a reported statistical analysis for the endpoint. The statistical test, if any, is not reported in the registry record. A model, transformation, handling of repeated observations, and method for calculating uncertainty are also not reported. Those omissions prevent readers from assessing whether the reported endpoint, if later posted, would be based on a simple summary or a more involved pharmacokinetic analysis.

In general, over-dispersion means that observed variability is greater than a model assumes. When relevant, it can affect standard errors and the reliability of confidence intervals or tests. The registry record does not report a model or variability analysis that would allow over-dispersion to be assessed in this study. It would therefore be speculative to claim that this issue was present or that a particular correction was used.

Likewise, a confidence interval is useful because it expresses uncertainty about an estimated mean, while a p-value is tied to a stated hypothesis and analysis. Neither is available for the primary endpoint. Without the estimate, variability, analysis population, and analysis method, the registry record supports a description of the planned statistical target but not a quantitative conclusion about clearance or its precision.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Ceftolozane/Tazobactam")
n   <- c(6)
m   <- c(7.79)
sp  <- c(2.3)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Ceftolozane/Tazobactam  6  7.790  2.300  5.376  10.204

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, ceftolozane clearance, and no analyses. It does not report a statistical analysis plan, a prespecified family of hypotheses, or a multiplicity adjustment. Multiplicity concerns the increased chance of false-positive findings when multiple hypotheses are tested; in general, adjustment methods account for the number and structure of those tests. The record does not establish that multiple inferential tests were conducted, so neither a multiplicity concern nor an adjustment should be assumed.

Missing-data handling is not reported in the registry record. The status is terminated, and recorded enrollment is 6, while the brief summary describes 12 completers as a plan. The record does not say how many participants completed the planned sampling, whether any measurements were missing, how incomplete concentration profiles were handled, or whether any participants were excluded from endpoint analysis. It also does not report reasons for missingness or a sensitivity analysis.

The analysis population is not defined in the registry record. It is not stated whether the endpoint was to include all enrolled participants, only those who received the dose, only those with complete sampling, or another group. The number contributing to the primary endpoint is not reported. These details matter because the estimate and its precision depend on which participants and observations are analyzed.

In general, missingness can affect interpretation when the availability of measurements is related to participant characteristics or outcomes. Without information on completion and analysis populations, readers cannot assess that possibility for this study. The posted record therefore does not support a judgment about the impact of missing data or the adequacy of any analysis strategy.

12. 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 0 serious adverse events among 6 participants at risk, 0 other adverse events among 6 participants at risk, and 0 deaths. These are counts for the ceftolozane/tazobactam group recorded in the registry. No serious adverse-event terms are listed.

These counts are descriptive, not a comparison between groups. The study has a single group and no randomized control arm, so the adverse-event figures cannot estimate a difference in event frequency between treatments. The record also does not report event-level detail, timing, severity definitions, or a causal assessment beyond the registry's categories.

In general, a count of zero means that no events in that category are recorded for the participants at risk in the registry entry. It does not prove that an event is impossible or that the treatment has no safety risks. The study's recorded enrollment is 6, its status is terminated, and the number completing follow-up is not reported in the registry record. The safety counts should therefore be interpreted as limited descriptive observations, not as a definitive characterization of safety.

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

The record establishes that the study was intended to characterize ceftolozane/tazobactam pharmacokinetics in patients with burns, with ceftolozane clearance as the primary endpoint. It also documents a single-group design, planned single-dose administration, a 24-hour observation period, recorded enrollment of 6, and terminated status. These registry entries describe the study's scope and its status in the registry.

The record does not report the numerical clearance result, its standard deviation, a confidence interval, or an analysis. It therefore does not show the average clearance observed in the participants or how precisely that average was estimated. Nor does it provide the concentration data or simulation outputs described as part of the study's intended use. The intended goal of informing dosing recommendations should not be mistaken for a posted dosing result.

Because there is no control group, the study cannot provide a randomized comparison of ceftolozane/tazobactam against another treatment. Its registered pharmacokinetic objective is different from establishing a comparative treatment effect. The record also does not report clinical efficacy outcomes, so no conclusion about infection outcomes can be drawn from the endpoint description.

The adverse-event counts describe the registry entry but do not establish that the treatment is free of risk. They are not comparative estimates, and the study size and completion details limit what can be inferred about event frequency. More generally, absence of a reported endpoint analysis is not evidence that the endpoint had a particular value, was statistically significant, or was not statistically significant.

The appropriate interpretation is therefore narrow: the registry documents a terminated pharmacokinetic study with a defined primary measure and limited recorded enrollment, but it does not supply the results needed to answer that measure's numerical question. Claims about clearance, precision, dose suitability, or clinical benefit would require information not reported in the registry record.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a registered research question and an interpretable result. The registry identifies a continuous pharmacokinetic endpoint, its units, summary parameter, dispersion measure, and timeframe. Those details make the intended measurement understandable. However, without a posted estimate, variability measure, or analysis, readers cannot quantify the endpoint or judge its precision.

The design also determines what kind of inference is possible. A single-group pharmacokinetic study can be used to describe drug handling in its enrolled participants. It does not, by itself, estimate a randomized contrast with a control group. Keeping that distinction clear prevents a descriptive study objective from being read as evidence of comparative treatment effects.

The record's enrollment and completion descriptions also show why planning and observed data must be separated. Enrollment is recorded as 6, while 12 patients completing the study appears in the brief summary as a planned figure. Since the status is terminated and completion is not reported, the planned target cannot be treated as the number with observed endpoint data. A sample-size illustration is likewise not a report of the study's actual information or an explanation of its design rationale.

Finally, reporting the analysis population, missing-data approach, measurement procedures, and uncertainty would be essential for evaluating a pharmacokinetic mean. These details are not reported in the registry record. The case therefore underscores that a clearly named endpoint is not sufficient for statistical interpretation: the estimate, its precision, and the analysis context are also needed.

15. 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 main limitation for interpreting the primary question is that the registry record does not report a ceftolozane clearance estimate or its variability. Although it defines the endpoint as a mean with standard deviation over 24 hours, the numerical results are absent. No confidence interval or p-value is reported, and no analysis is listed. The observed magnitude and precision of clearance therefore cannot be evaluated.

The study is recorded as terminated, with enrollment of 6. The brief summary describes 12 patients completing the study as a plan, but the record does not state how many participants completed the procedures or contributed analyzable measurements. The reason for termination is not reported in the registry record. These unknowns make it difficult to determine the amount of endpoint information available and whether the planned sampling was completed.

The single-group design has no like-for-like control comparison. This is consistent with a descriptive pharmacokinetic objective, but it limits comparative inference. The registry also does not report the sampling schedule, concentration results, endpoint calculation details, pharmacokinetic model, statistical analysis plan, or trial-specific sample-size justification. The analysis population and missing-data methods are not reported.

Finally, the adverse-event counts are limited descriptive figures for the recorded group. The registry does not provide event-level detail or a comparison group. These limitations do not negate the study's stated objective, but they restrict what can be concluded from its registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pharmacokinetics of Ceftolozane/Tazobactam in Patients With Burns — NCT03002506.
• Registry record last updated 2021-03-02; status last verified 2021-03.
• Results first posted 2021-03-02.
• 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.

19. Record Summary

NCT03002506 is a phase 4, single-group study titled “Pharmacokinetics of Ceftolozane/Tazobactam in Patients With Burns,” sponsored by Texas Tech University Health Sciences Center. The registry records no masking, enrollment of 6, and terminated status. The study dates are 2017-08-21 for start and 2020-06-01 for primary completion.

The intervention is ceftolozane/tazobactam, with a planned single dose of 3 grams. The primary endpoint is ceftolozane clearance, a continuous measure in liters per hour over 24 hours, summarized by mean and standard deviation. The study summary describes planned blood and urine sampling to characterize drug disposition.

The registry lists one outcome measure and no analyses. It does not report the primary endpoint result, analysis population, missing-data approach, or reason for termination. The adverse-event record reports 0 serious adverse events, 0 other adverse events, and 0 deaths, among 6 participants at risk in the listed group.