This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Pharmacokinetics of Ceftolozane/Tazobactam in Plasma and Cerebrospinal Fluid (NCT03309657), a na phase 1, phase 2 study. The primary outcome is Unbound Ceftolozane Exposure in the Plasma.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03309657 |
| Phase | Phase 1, Phase 2 |
| Condition | Pharmacokinetics |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 10 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Royal Brisbane and Women's Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Critically ill patients with an infection and an existing external ventricular drain. The registry record lists an enrollment of 10. It does not report further eligibility details or a description of the patients included in the endpoint analysis.
Intervention
A single dose of ceftolozane/tazobactam, described as 3000mg administered over 1 hour. Blood, cerebrospinal fluid, and urine sampling was planned at specified times over an 8 hour period.
Comparator
There was no separate control group or comparator treatment. The study is recorded as single-group, with allocation listed as not applicable and masking listed as none. The patients’ plasma and cerebrospinal fluid concentrations are described rather than compared between randomized treatment groups.
Primary question
What unbound ceftolozane exposure is observed in plasma after a single dose in this patient group? The primary endpoint is the area under the unbound plasma concentration-time curve from time zero to infinity. The numerical endpoint result is not reported in the registry record.
The study’s broader objective was to describe ceftolozane/tazobactam concentrations in blood and cerebrospinal fluid in critically ill patients with an external ventricular drain. The registry rationale notes that information about penetration into the central nervous system was limited and that achieving adequate antibiotic concentrations in critically ill patients can be challenging. The study was intended to characterize concentrations after a single dose, not to compare treatment strategies or measure clinical efficacy.
The distinction between the broad objective and the primary endpoint matters. The listed primary endpoint concerns unbound ceftolozane exposure in plasma. Although cerebrospinal fluid sampling is part of the study description, a numerical cerebrospinal fluid result is not reported in the registry record. Nor does the record give a target concentration or a clinical outcome against which concentrations could be judged.
3. Trial Design
This is a prospective pharmacokinetic study recorded as Phase 1 and Phase 2, with a single-group model, no allocation, and no masking. Its completed status and registry enrollment of 10 describe the study record, but do not establish how many participants contributed usable samples to each endpoint. The analysis population and endpoint-specific sample counts are not reported in the registry record.
Participants are described as infected critically ill patients with an indwelling external ventricular drain. The intervention description specifies a single ceftolozane/tazobactam dose of 3000mg infused over 1 hour. Blood, cerebrospinal fluid, and urine sampling is described over an 8 hour period. The primary endpoint refers to samples collected at 0, 1, 2, 4, 6, and 8 hours post dose, used to estimate exposure from time zero to infinity by non-compartmental analysis.
Because there is no comparator group, this design can describe concentrations observed after the dose in the studied group, but it cannot estimate a between-group treatment contrast. The single-group design also does not separate the effect of the drug from other factors that may influence concentrations in critically ill patients. There is no basis in the registry record for interpreting the study as a randomized comparison.
The record lists a start date of 2018-02-01 and a primary completion date of 2020-05-01. It does not report the detailed protocol, eligibility criteria, dose-adjustment rules, sample handling procedures, or a statistical analysis plan. The enrollment figure is not a sample-size justification, and the reason for choosing this enrollment is not reported in the registry record.
A sample-size planning illustration is not the same as this study’s design. The record describes generic planning assumptions involving two arms and equal allocation, whereas this trial is single-group. Those assumptions should not be read as evidence that the study had two treatment arms, or as an observed estimate of statistical power for the study as conducted.
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
| Stage | Ceftolozane Tazobactam |
|---|---|
| STARTED | 10 |
| COMPLETED | 10 |
| NOT COMPLETED | 0 |
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.
| Characteristic | Unit | Ceftolozane Tazobactam |
|---|---|---|
| Participants analysed | 10 | |
| Age, Continuous | years | 60.5 (53.5 to 64.75) |
| Sex: Female, Male: Female | Participants | 7 |
| Sex: Female, Male: Male | Participants | 3 |
| Race and Ethnicity Not Collected | Participants | — |
| Region of Enrollment: Australia | participants | 10 |
| Weight | kg | 75 (65 to 87) |
| Serum Creatinine | micro-mole/litre | 48.5 (42.25 to 57.75) |
| Albumin | g/L | 24 (21.25 to 25.75) |
| Acute Physiology and Chronic Health Evaluation (APACHE) II | units on a scale | 17.5 (14 to 22.5) |
6. Primary Endpoint
The registry lists the primary outcome as Unbound Ceftolozane Exposure in the Plasma, measured over Samples collected from 0 to 8 hours post dose at "0, 1, 2,4,6, & 8 h post dose were use estimate area under the curve from time zero to infinity estimated by non-compartmental analysis.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | mg*h/L |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is unbound ceftolozane exposure in plasma, expressed as the area under the unbound concentration-time curve from time zero to infinity, or AUC0-inf. It is reported in mg*h/L, with the planned summary described as a median and inter-quartile range. The numerical median and inter-quartile range are not reported in the registry record.
In general, an area under a concentration-time curve summarizes drug exposure across time. For this endpoint, concentrations sampled after dosing contribute to an estimate of the concentration curve over the specified interval and beyond it. The record states that concentrations at 0, 1, 2, 4, 6, and 8 hours post dose were used to estimate AUC from time zero to infinity by non-compartmental analysis. The registry does not provide further details on how the portion beyond the last sampling time was estimated.
Unbound concentration refers to the portion of a drug concentration not bound to proteins in the sampled fluid. In general, pharmacokinetic studies may measure unbound exposure because it characterizes that portion of drug present over time. The endpoint is a measure of exposure, not a direct measure of clinical response, infection resolution, or drug penetration into cerebrospinal fluid.
The study description includes cerebrospinal fluid and urine sampling, but the primary endpoint listed in the record is plasma exposure. Numerical cerebrospinal fluid and urine results, and their analysis methods, are not reported in the registry record. The endpoint therefore cannot by itself answer how much drug reached cerebrospinal fluid.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary endpoint and the planned way of summarizing it, but does not report its numerical result. As a result, readers cannot use this record to assess the observed median plasma exposure, the spread of individual values, or the precision of the estimate. No confidence interval or other uncertainty interval for the primary endpoint is reported in the registry record.
The endpoint is a pharmacokinetic measure following a single dose in a specific clinical setting: infected critically ill patients with an external ventricular drain. The design is prospective and single-group. Its role is descriptive; it does not provide a randomized treatment contrast, and the record does not report a clinical efficacy comparison. The exposure endpoint should not be interpreted as evidence about whether a treatment succeeds or fails in treating an infection.
The stated objective includes describing cerebrospinal fluid concentrations, but the primary endpoint is unbound plasma exposure. Numerical cerebrospinal fluid concentration results are not reported in the registry record. Consequently, the record does not allow a quantitative assessment of central nervous system penetration, nor does it show whether measured concentrations met a target. No target concentration or concentration-response relationship is reported.
The registry lists 10 enrolled participants and a completed status. Those details do not establish the number with evaluable samples at each time point or the number included in the primary endpoint summary. These analysis-population details, as well as missing-sample counts, are not reported in the registry record. The planned sampling times do not guarantee that every participant contributed every measurement.
The primary endpoint is described using a median and inter-quartile range. In general, a median describes the central value of a distribution, while the inter-quartile range describes the spread of the middle portion of that distribution. Neither summary can be evaluated because the numerical values are absent. A confidence interval, if reported, would convey uncertainty in an estimate; no such interval is reported for this endpoint.
The registry lists four outcome measures and no analyses. That does not supply enough detail to reconstruct the study’s statistical analysis or to determine whether all planned analyses were completed. A full analysis plan, handling of values below assay limits, approach to missing samples, and any adjustments are not reported in the registry record.
The listed serious adverse event figures show zero affected participants in the treatment group, with 10 at risk; the listed other adverse event figures likewise show zero affected participants, with 10 at risk. These counts are descriptive safety entries, not a comparison with another group. The record also lists zero deaths and no top serious terms. The counts should be read as what the registry reports, not as proof that all possible events were absent or that the safety profile is established.
9. Statistical Methods Explained
The registry describes a pharmacokinetic study and identifies a concentration-time endpoint. The primary measure is unbound ceftolozane AUC from time zero to infinity, estimated using non-compartmental analysis. The record gives sampling times and a median with inter-quartile range as the endpoint summary, but does not report the numerical endpoint result or a detailed statistical analysis plan.
What does an area under the curve represent?
In general, a concentration-time curve traces the measured concentration of a substance at successive times after administration. The area under that curve combines concentration and time into an exposure measure. It is not a concentration at one particular sampling time. An AUC from time zero to infinity includes the observed period and an estimated portion extending beyond the final sample, according to the stated endpoint definition.
The record says that samples collected at 0, 1, 2, 4, 6, and 8 hours post dose were used to estimate AUC0-inf. It names non-compartmental analysis as the estimation approach. In general, non-compartmental methods estimate exposure from the observed concentration-time data without requiring a specified compartment model. The registry does not give the computational details, the assay limits, or the method used for the portion of the curve after the last sample.
Why report unbound exposure?
The endpoint specifies unbound ceftolozane in plasma. In general, a total drug concentration may include bound and unbound portions, while an unbound concentration refers to the portion not bound to proteins. Measuring unbound exposure can describe that portion over time. The registry does not report the measurement procedure or whether any samples were unavailable or excluded.
What do the median and inter-quartile range convey?
The primary endpoint is planned to be summarized by a median and inter-quartile range. In general, the median is a measure of the center of observed values that is less influenced by extreme values than the arithmetic mean. The inter-quartile range describes the spread of the middle half of the observations. Reporting both can make the distribution’s center and variability more apparent, but neither communicates uncertainty in the estimate in the same way as a confidence interval. No numerical median, inter-quartile range, or confidence interval is reported in the registry record.
For a small single-group pharmacokinetic study, individual observations and their sampling completeness can be important to interpretation. The registry enrollment is 10, but the number contributing to the primary endpoint and the number with samples at each time are not reported in the registry record. No individual-level results are listed.
What does the design permit statistically?
A single-group design can describe concentrations observed after a dose in the enrolled study population. Without a comparator group, it does not estimate a treatment difference between groups. The study is listed as having no allocation and no masking. There is no reported randomized comparison, and no between-group significance test is identified. The number of analyses listed is zero; the registry does not report inferential tests or model-adjusted estimates.
The record’s sample-size planning assumptions are described as an illustration rather than the study’s own design. They refer to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as a stated fraction of an observed effect. The study itself is single-group, so those two-arm assumptions do not describe its design. Such planning illustrations are not observed power. The registry does not report the trial’s own sample-size justification or a statistical plan that would establish a power calculation for the primary endpoint.
Why can over-dispersion matter in general?
In general, over-dispersion means that observed variability is greater than a statistical model assumes. If a method assumes less variability than the data contain, its uncertainty estimates may be too small. Pharmacokinetic measurements can vary across people and across sampling times, so a sound analysis needs to account appropriately for the data structure and variability. The registry record does not report an over-dispersion assessment or a model that would permit readers to evaluate this issue for the study.
Other methodological details are also not reported in the registry record: the handling of incomplete concentration profiles, missing samples, values below assay limits, exclusions, sensitivity analyses, and multiplicity procedures. Without these details and the numerical results, the endpoint’s precision and robustness cannot be assessed from the registry record alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures but does not list any analyses. It does not report whether the outcome measures were treated as exploratory or confirmatory, whether one endpoint was prioritized for formal inference, or whether any adjustment for multiple testing was planned. The primary endpoint is identified as unbound ceftolozane exposure in plasma, but its numerical result is not reported.
In general, multiplicity arises when several outcomes, time points, or statistical comparisons are examined. Without an analysis plan, readers cannot determine whether multiple tests were conducted or how any resulting uncertainty was handled. The absence of listed analyses does not establish which analyses were or were not performed; details are not reported in the registry record.
The registry describes sampling at several post-dose times, including 0, 1, 2, 4, 6, and 8 hours. It does not report whether all planned samples were obtained from every participant, how missing time points were handled, or how incomplete profiles affected estimation of AUC0-inf. The number of participants contributing to each endpoint and each sampling time is not reported in the registry record.
Likewise, the record does not describe assay limits, treatment of values below those limits, exclusions, or sensitivity analyses. These details matter in general because incomplete or censored concentration measurements can affect an exposure estimate. The endpoint summary is specified as a median and inter-quartile range, but no values or uncertainty intervals are reported. There is therefore no basis in the registry record to assess the influence of missing data or the precision of the summary.
The study’s analysis populations, including any distinction between enrolled participants and those included in pharmacokinetic analyses, are not reported in the registry record. The enrollment figure should not be mistaken for an endpoint-specific denominator.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Ceftolozane Tazobactam | 0 | 10 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Ceftolozane Tazobactam | 0 of 10 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Ceftolozane Tazobactam | 0 of 10 |
The registry lists the Ceftolozane Tazobactam group with 10 participants at risk for serious adverse events and 0 affected. For other adverse events, it also lists 10 at risk and 0 affected. The record lists 0 deaths and no top serious terms. These are the safety figures recorded for this group.
These counts are descriptive. Because the trial has a single group and no comparator, they do not provide a comparative estimate of safety relative to another treatment or to no treatment. The record does not give event definitions, surveillance procedures, duration of safety follow-up, or individual event descriptions. Those details are not reported in the registry record.
A zero count in the registry means that no affected participants are listed in that category; it should not be read as proof that an event is impossible or that risk is absent. The record also does not state whether all enrolled participants had complete safety follow-up. The listed number at risk is not necessarily the denominator for pharmacokinetic analyses, and the endpoint-specific analysis population is not reported in the registry record.
12. What the Result Does, and Does Not, Mean
This record describes a prospective, single-group study designed to measure ceftolozane/tazobactam concentrations after a single dose in infected critically ill patients with an external ventricular drain. The primary pharmacokinetic endpoint is unbound plasma exposure from time zero to infinity. The registry specifies the planned sampling times and a median with inter-quartile range as the summary, but does not report numerical results for that endpoint.
The study’s stated broader aim includes describing concentrations in cerebrospinal fluid and blood. However, numerical cerebrospinal fluid results are not reported in the registry record. Without those data, the record cannot quantify cerebrospinal fluid exposure or establish how concentrations relate to a target. The registry also does not report a concentration-response analysis or clinical outcomes that would connect measured exposure to treatment response.
The single-group design permits descriptive characterization of measurements in the study group, if results are reported. It does not provide a randomized comparison or estimate a treatment effect relative to a control group. The record’s enrollment and completed status do not indicate the precision of the primary estimate, because the endpoint value, uncertainty interval, and endpoint-specific sample count are not reported.
In general, pharmacokinetic concentration data can help describe drug exposure and inform future research. They are not by themselves evidence of clinical benefit or harm. The registry record states that the information was intended to help develop future dosing strategies, but it does not report a dosing comparison or a validated threshold for interpreting exposure.
The safety entries list zero affected participants for serious and other adverse events in the recorded group, and zero deaths. These are registry counts, not comparative safety evidence. Interpretation is limited by the absence of reported follow-up and event ascertainment details.
13. Why This Trial Matters Statistically
This study addresses a pharmacokinetic question in a clinical setting that the registry describes as challenging: critically ill patients with an external ventricular drain. Sampling plasma and cerebrospinal fluid can provide information about concentrations in more than one biological compartment. The study’s stated aim was to describe concentrations after a single dose and contribute information relevant to future dosing research.
Statistically, the key distinction is between measuring exposure and evaluating clinical effect. The primary endpoint, unbound ceftolozane AUC0-inf in plasma, is an exposure measure. It summarizes concentration over time rather than comparing clinical outcomes between treatment groups. Its planned median and inter-quartile range would describe the distribution of exposure in the study group, but the numerical summaries are not reported in the registry record.
The single-group design is suited to descriptive pharmacokinetic work, but it limits the questions that can be answered by comparison. There is no control group, randomized allocation, or masking. The design does not estimate a treatment contrast, and the record does not report a clinical outcome analysis. This makes clear why pharmacokinetic findings, when available, should be distinguished from evidence about efficacy or comparative safety.
The record also illustrates the importance of complete reporting. Sample timing and the endpoint definition are stated, but endpoint values, uncertainty estimates, analysis populations, and details about missing samples are not reported. Without those elements, readers cannot assess the observed distribution, precision, or robustness of the exposure estimate from the registry record alone.
The registry’s planning illustration uses generic two-arm assumptions, while the study is single-group. Recognizing that mismatch prevents a planning calculation from being mistaken for the trial’s own design or for observed statistical power.
14. 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 does not report numerical results for the primary endpoint. It identifies unbound ceftolozane plasma exposure as AUC0-inf, with a median and inter-quartile range, but provides neither summary values nor an uncertainty interval. Numerical cerebrospinal fluid concentration results are also not reported, despite their place in the study’s broader objective.
The study is single-group, with no allocation and no masking. It has no comparator for estimating a between-group difference. The record therefore describes a pharmacokinetic evaluation rather than a comparative trial. It does not report clinical efficacy outcomes or a concentration-response analysis.
The registry lists enrollment of 10, but does not report the number included in each endpoint analysis, the number with complete concentration profiles, or how many contributed samples at each time. The handling of missing samples and incomplete profiles is not reported in the registry record. The statistical analysis plan, assay details, treatment of values below assay limits, and sensitivity analyses are also not reported.
The single-dose design and the specified 8 hour sampling period are important context for the exposure estimate. The primary endpoint is defined through time zero to infinity, but the registry does not explain how the portion beyond the last sampling time was estimated. The record does not provide the protocol details needed to evaluate this estimation or the generalizability of the findings to other populations or dosing schedules.
Finally, the record lists four outcome measures but no analyses. It does not report a sample-size justification for the study itself. Generic planning assumptions involving two arms should not be treated as the design or statistical power of this single-group study.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pharmacokinetics of Ceftolozane/Tazobactam in Plasma and Cerebrospinal Fluid — NCT03309657.
- Registry record last updated 2020-09-10; status last verified 2020-08.
- Results first posted 2020-09-10.
- 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.
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18. Record Summary
The registry record describes a completed prospective pharmacokinetic study, listed as Phase 1 and Phase 2, in infected critically ill patients with an external ventricular drain. It records a single group, no allocation, no masking, and enrollment of 10. The intervention is a single 3000mg ceftolozane/tazobactam dose administered over 1 hour, with blood, cerebrospinal fluid, and urine sampling described over an 8 hour period.
The primary endpoint is unbound ceftolozane plasma exposure, AUC0-inf, summarized as a median and inter-quartile range. The record describes sampling at 0, 1, 2, 4, 6, and 8 hours post dose and non-compartmental estimation. Numerical primary endpoint results and numerical cerebrospinal fluid results are not reported in the registry record. The listed safety figures are 0 affected for serious adverse events, 0 affected for other adverse events, and 0 deaths in the group, with 10 at risk for each adverse event category.
The registry lists four outcome measures and no analyses. Endpoint-specific sample counts, missing-data methods, and detailed statistical methods are not reported.