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 Tissue Penetration of Ceftolozane/Tazobactam in Diabetic Patients With Lower Limb Infections (NCT02620774), a non-randomized phase 1 study. The primary outcome is Ceftolozane Tissue Penetration.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02620774 |
| Phase | Phase 1 |
| Condition | Diabetes, Wound Infection, Healthy Volunteers |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 16 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hartford Hospital |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled participants with diabetes and a mild to moderate lower-limb wound infection, alongside healthy adult volunteers. The diabetic group was described as having Type 1 or Type 2 diabetes and a Grade 2 or 3 wound infection. The healthy volunteer group was described as having no significant medical or medication history. The registry lists 16 participants overall.
Intervention
Both groups received intravenous ceftolozane/tazobactam. The arm descriptions specify at least 3 doses of 1.5g every 8 hours. Microdialysis catheter insertion was also listed as a procedure, enabling sampling of interstitial tissue fluid.
Comparator
The study compared tissue penetration in participants with diabetic wound infections with tissue penetration in healthy volunteers. This was a non-randomized study, so the groups were not formed by random assignment. Their different health and infection status means they should not be treated as like-for-like treatment groups.
Primary question
The primary endpoint was the median ratio of ceftolozane tissue concentration area under the curve to plasma concentration area under the curve, measured over 16-24 hours after the first dose. The research question was whether the drug’s exposure in sampled tissue could be characterized in the diabetic wound-infection group and compared with exposure in healthy volunteers. The endpoint result is not reported in the registry record.
3. Trial Design
This completed Phase 1 study was registered as a non-randomized, unmasked, parallel-group study. Its sponsor was Hartford Hospital. The registry gives a start date of 2016-02-19 and a primary completion date of 2017-04. Enrollment was 16.
One group consisted of participants with diabetes and a lower-limb wound infection. The other consisted of healthy volunteers. The arm descriptions state that participants in both groups received at least 3 intravenous doses of ceftolozane/tazobactam 1.5g every 8 hours. The endpoint description specifies doses at 0, 8, and 16 hours, with sampling after the final, third dose. The interventions also list microdialysis catheter insertion.
The study focused on tissue and plasma drug concentrations rather than a clinical outcome such as wound healing. Its stated purpose was to determine ceftolozane/tazobactam penetration into extracellular, interstitial fluid of soft tissue in diabetic participants with lower-limb wound infections, and compare penetration with that in healthy volunteers. The healthy volunteer arm description specifies tissue-fluid sampling in the thigh by a microdialysis probe. The diabetic arm description refers to sampling interstitial tissue fluid at the margin of the wound, although the posted description is truncated.
Because allocation was non-randomized and the arms differed by health and infection status, comparisons describe two distinct groups rather than an effect of assigning a treatment. Masking was listed as none. Details of a randomization procedure, a masking procedure, or a more extensive study protocol 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
| Stage | Diabetic Wound Infection | Healthy Volunteer |
|---|---|---|
| STARTED | 10 | 6 |
| COMPLETED | 10 | 6 |
| NOT COMPLETED | 0 | 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 | Diabetic Wound Infection | Healthy Volunteer | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 6 | 16 | |
| Age, Categorical: <=18 years | Participants | 0 | 1 | 1 |
| Age, Categorical: Between 18 and 65 years | Participants | 10 | 5 | 15 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 53 (35 to 64) | 28 (18 to 36) | 44 (18 to 64) |
| Sex: Female, Male: Female | Participants | 1 | 2 | 3 |
| Sex: Female, Male: Male | Participants | 9 | 4 | 13 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: United States | participants | 10 | 6 | 16 |
| Height | centimeters | 182.9 (164.0 to 193.0) | 170.2 (157.5 to 186.7) | 178.1 (157.5 to 193.0) |
| Weight | kilograms | 114.8 (74.6 to 147.0) | 69.1 (50.5 to 102.7) | 97.7 (50.5 to 147.0) |
| Body Mass Index | kg/m^2 | 33.4 (26.6 to 48.0) | 24.0 (20.4 to 29.5) | 29.9 (20.4 to 48.0) |
| Creatinine clearance | mL/min | 108.4 (75.3 to 136.5) | 121.5 (92.5 to 159.2) | 113.3 (75.3 to 159.2) |
6. Primary Endpoint
The registry lists the primary outcome as Ceftolozane Tissue Penetration, measured over 16-24 hours.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | ratio |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the median ratio of ceftolozane tissue concentration area under the curve (AUC) to plasma concentration AUC. It describes how tissue exposure compares with blood exposure across the sampling interval; it is not a clinical measure of infection response. The endpoint description places the assessment at 16-24 hours after the first dose, following the final, third ceftolozane/tazobactam dose.
The registry says doses were given at 0, 8, and 16 hours. Plasma and dialysate concentrations were determined at hours 16, 17, 18, 19, 20, 21, 22, 23, and 24 after the first dose to determine ceftolozane AUC in blood and tissue. The ratio makes the two exposure summaries interpretable in relation to one another, rather than describing tissue concentration alone.
In general, AUC represents drug exposure over a period, using concentrations measured across time. Tissue sampling is relevant to a study whose stated question concerns penetration into interstitial fluid. The registry specifies the endpoint’s summary as a median and its dispersion as the full range, which would describe the central value and the observed spread without implying a normally distributed set of values. The actual median, range, and group-specific endpoint results are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a tissue-penetration question and describes the endpoint used to address it, but it does not report the primary endpoint values. There is therefore no posted median ratio or full range to interpret, and the record does not establish the magnitude or precision of tissue penetration in either group. The listed outcome and sampling details are not a substitute for the numerical outcome results.
Enrollment was 16, divided between a diabetic wound-infection group and a healthy volunteer group. The adverse-event record lists 10 participants at risk in the diabetic group and 6 in the healthy volunteer group. Those group sizes are small, so even if a summary estimate were reported, its precision and the stability of its range would need careful consideration. The registry does not give confidence intervals for the primary endpoint.
The design also limits what a between-group contrast could mean. Allocation was non-randomized, and the groups were defined by different health conditions: one had diabetes and a wound infection, while the other comprised healthy volunteers. Thus, any observed difference could reflect differences between the groups beyond the tissue setting of interest. The registry itself flags that the arms are not a like-for-like control comparison. The study can be read as a comparison of measured exposure in these groups, not as a randomized estimate of a treatment effect.
The record lists seven outcome measures and no analyses. It does not report a statistical analysis plan, adjustment for covariates, inferential tests, or confidence intervals. Without those details and the endpoint values, no conclusion about statistical significance or uncertainty can be drawn. The study status is completed, but completion alone does not supply the missing outcome estimates.
In general, a confidence interval describes a range of values compatible with an estimate under a specified statistical method. It would help readers assess how precisely a tissue-to-plasma ratio was estimated, but such an interval is not reported in the registry record. Likewise, a p-value would address a specified statistical test, not the clinical importance of an exposure ratio; no p-value or inferential comparison is reported. The posted data should therefore be interpreted as a description of study design and recorded safety counts, rather than evidence for a quantified difference in tissue penetration.
9. Statistical Methods Explained
The registry record gives a descriptive primary endpoint: the median ceftolozane tissue-to-plasma AUC ratio, with dispersion described by the full range. It does not report an analysis method beyond those summaries, and it lists no analyses. The explanations below describe general statistical concepts relevant to this endpoint, not additional methods documented for this study.
What does an AUC ratio describe?
In general, an area under the curve combines concentration measurements across time into a summary of exposure during a defined interval. The study measured plasma and dialysate concentrations during the interval after the third dose, using samples at the listed hours from 16 through 24 after the first dose. The tissue-to-plasma ratio relates the two AUC summaries. A ratio above or below a reference value could have a particular interpretation only when the actual estimate and its definition are available; the registry does not report the estimate.
The ratio is an exposure measure, not a direct measure of clinical benefit or harm. It describes the distribution of drug in sampled tissue relative to plasma under the study conditions. It does not, by itself, establish whether an infection improved, whether an individual participant had a particular clinical outcome, or how the exposure relates to an outcome. Such links would require relevant measurements and analyses, which are not reported in the registry record.
Why report a median and full range?
In general, the median is the middle value in an ordered set of observations. It can be a useful summary when data are skewed or when extreme observations make the arithmetic mean less representative of a typical observation. The full range describes the lowest and highest observed values, showing the extremes rather than the distribution’s detailed shape. A range can be sensitive to unusual observations and does not show how densely values cluster between its endpoints.
These summaries do not convey the same information as a confidence interval. A range describes observed data; a confidence interval is an inferential summary of uncertainty about an estimated quantity under a statistical model. Neither a confidence interval nor the underlying participant-level endpoint observations are reported in the registry record. The record also does not describe how the ratio was calculated for each participant or how missing concentration samples, if any, were handled.
What can a group comparison establish?
In general, random allocation can help balance measured and unmeasured characteristics between comparison groups, on average, when a study is designed and conducted appropriately. This study was non-randomized. The diabetic wound-infection group and healthy volunteer group differed by design, so an observed exposure contrast would not isolate the effect of wound infection or diabetes from other group differences. The registry flags that the arms are not a like-for-like control comparison. This is important when interpreting descriptive differences and especially when considering causal explanations.
The parallel structure means the record presents distinct groups rather than a sequence of treatment periods for the same participants. The registry does not report a paired analysis, covariate adjustment, or another method for accounting for group differences. Those methods should not be assumed. Nor does the record identify a statistical model for the endpoint.
What does the record say about statistical planning?
The registry record does not report the study’s original sample-size justification, assumptions used when planning enrollment, or an inferential analysis plan. Any sample-size figures framed as planning illustrations should be read as hypothetical planning quantities, not as observed power or as proof that the study could detect a particular effect. In general, power calculations depend on assumptions about the target effect, variability, significance level, allocation, and statistical method. Their meaning depends on those assumptions and does not replace reporting the observed estimates and their uncertainty.
The record does not describe interim analyses, stopping rules, or methods for controlling multiple comparisons. It lists seven outcome measures, including the primary endpoint and secondary outcomes, but does not state whether or how testing across outcomes was planned. No p-values, confidence intervals, adjusted estimates, or analysis populations are reported. These omissions leave the inferential framework unclear; they do not justify inferring that a particular method was or was not used beyond what the registry states.
General statistical interpretation should distinguish a descriptive summary from an inferential claim. A median and range can characterize observed measurements, while an inferential comparison requires a defined question, analysis method, and uncertainty assessment. Here, the registry supplies the endpoint definition and time window but not the numerical endpoint result or the analysis details needed to evaluate an inferential claim.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists seven outcome measures: the primary ceftolozane tissue-penetration endpoint and secondary measures covering tissue AUC for ceftolozane and tazobactam, total plasma AUC for both drugs, and participants with adverse events. It reports no analyses. A prespecified approach to handling multiple outcomes or statistical comparisons is not reported in the registry record.
In general, testing multiple hypotheses can increase the chance that at least one result appears notable by chance. A statistical plan may define a primary outcome, distinguish confirmatory from exploratory analyses, or use an adjustment procedure. The registry identifies a primary endpoint, but it does not say whether any multiplicity adjustment was planned or performed. The absence of posted analyses means there are no reported tests to assess for multiplicity.
Methods for missing data are also not reported in the registry record. It is not stated whether all participants contributed to each endpoint, whether concentration samples were incomplete, or how any missing measurements were handled. The analysis populations—such as which participants were included in each outcome analysis—are not reported. Enrollment and the adverse-event groups at risk do not establish the denominator used for the primary endpoint analysis.
In general, missing-data handling matters because an analysis based only on observed measurements can be biased if missingness is related to participant characteristics or outcomes. The registry does not provide enough detail to judge whether missing data occurred or whether any particular approach was appropriate. A detailed statistical analysis plan, participant accounting, and endpoint results would be needed to clarify these issues.
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 |
|---|---|---|---|
| Diabetic Wound Infection | 0 | 10 | 0.0% |
| Healthy Volunteer | 0 | 6 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Diabetic Wound Infection | 0 of 10 |
| Healthy Volunteer | 0 of 6 |
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 |
|---|---|
| Diabetic Wound Infection | 1 of 10 |
| Healthy Volunteer | 0 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Diabetic Wound Infection | Healthy Volunteer |
|---|---|---|---|
| Vertigo | Nervous system disorders | 1 of 10 | 0 of 6 |
The registry records no serious adverse events in either group: 0 of 10 participants at risk in the diabetic wound-infection group and 0 of 6 in the healthy volunteer group. It also records 0 deaths in each group. No serious adverse-event terms are listed.
For other adverse events, the registry records 1 affected participant among 10 at risk in the diabetic group and 0 among 6 at risk in the healthy volunteer group. These are participant counts, not a count of event episodes. The record does not describe the event term, severity, timing, or relationship to study drug, so those details are not reported in the registry record.
In general, zero recorded serious events in a small group does not establish that the risk is absent. Safety counts describe what was recorded among the participants at risk in this study; they do not, on their own, provide a precise estimate of risk in a broader population. The groups were also non-randomized and differed in health status, so their counts should not be treated as a randomized safety comparison.
12. What the Result Does, and Does Not, Mean
The study addresses a pharmacokinetic question: how ceftolozane exposure in sampled tissue compares with plasma exposure in participants with diabetic lower-limb wound infections and healthy volunteers. Its primary endpoint is an AUC ratio, summarized by a median and full range over the specified sampling interval. This design and endpoint describe what the researchers set out to measure.
The registry record does not report the primary endpoint result. It therefore does not support a quantified statement about tissue penetration, the size of a difference between groups, or the precision of either group estimate. The completed status does not change that limitation. A numerical endpoint result, participant accounting, and a clear analysis description would be needed to interpret the measured exposure.
Even if group-specific results were available, the non-randomized comparison would remain descriptive. The groups differ by diabetes and infection status, and the record explicitly warns that they are not a like-for-like control comparison. A difference would not, by itself, establish that diabetes, infection, or another factor caused the difference. The study is not described as a trial of clinical effectiveness, and the endpoint does not measure wound healing or another clinical outcome.
The recorded safety data show no serious adverse events or deaths in either group, alongside one participant with an other adverse event in the diabetic group and none in the healthy volunteer group. These counts are useful as a record of events reported for the study, but their small denominators do not establish the absence of risks. The event details are not reported in the registry record.
In general, pharmacokinetic measurements can help characterize where a drug is measured and how exposure varies over time. They do not alone establish clinical benefit, optimal dosing, or safety in populations beyond those studied. Those broader questions require additional evidence and analyses; they cannot be answered from the endpoint description and adverse-event counts alone.
13. Why This Trial Matters Statistically
This study is statistically notable for separating a mechanistic exposure question from a clinical outcome question. Its primary endpoint concerns the ratio of tissue and plasma AUC, not a measure of infection resolution. That distinction helps readers avoid interpreting a pharmacokinetic endpoint as though it were direct evidence about clinical outcomes.
The use of microdialysis to sample interstitial tissue fluid matches the stated interest in extracellular tissue exposure. At the same time, a measurement technique and a well-defined sampling window do not guarantee that an estimate is precise or representative. The registry specifies a median and full range but does not report the endpoint values, confidence intervals, or participant-level data needed to assess the observed variability.
The non-randomized comparison also matters statistically. A healthy volunteer group offers a different context for describing exposure, but it is not a randomized control group for participants with wound infections. Comparing these groups cannot separate the influence of infection and diabetes from other differences between participants. The record’s warning that the arms are not a like-for-like comparison is central to interpreting any contrast.
Finally, the registry record illustrates why an endpoint definition and outcome results are both necessary for statistical interpretation. It documents a completed study, its enrollment, the primary endpoint, and adverse-event counts, yet reports no analyses or primary endpoint values. Without estimates and uncertainty measures, readers cannot judge the observed magnitude, precision, or statistical evidence for a group contrast. Transparent reporting of analysis methods and missing-data handling would also clarify how the measurements were summarized.
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 most direct limitation of the registry record is that it defines the primary endpoint but does not report its numerical result. The median tissue-to-plasma AUC ratio, full range, and any group-specific comparison are not reported in the registry record. No confidence interval or inferential test is listed. As a result, the magnitude and precision of tissue exposure cannot be evaluated from the posted results.
Enrollment was 16, and the adverse-event groups at risk were 10 and 6. These counts indicate a small study, which limits how much can be learned about variability and uncommon events. The record does not report the number included in each primary endpoint analysis, so the enrollment total should not be assumed to be the analytic denominator.
Non-randomized allocation and the contrast between participants with diabetic wound infections and healthy volunteers make causal interpretation especially limited. These groups are not like-for-like controls, and the registry does not report adjustment for differences between them. The masking status was none, and the record does not detail any procedures intended to reduce measurement or assessment bias.
Other important design and analysis details are not reported in the registry record, including the original sample-size justification, a statistical analysis plan, interim analyses, missing-data methods, analysis populations, and handling of multiple outcomes. The diabetic arm description is truncated, limiting detail about its sampling description. The adverse-event record also does not provide the term or clinical details for the one other event in that group. These gaps restrict interpretation of both efficacy-related exposure estimates and safety observations.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Tissue Penetration of Ceftolozane/Tazobactam in Diabetic Patients With Lower Limb Infections — NCT02620774.
- Registry record last updated 2019-01-15; status last verified 2017-10.
- Results first posted 2019-01-15.
- 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
NCT02620774 is a completed Phase 1, non-randomized, unmasked, parallel study sponsored by Hartford Hospital, with enrollment of 16. It examined ceftolozane/tazobactam tissue penetration in participants with diabetic lower-limb wound infections and healthy volunteers. Both groups received at least 3 intravenous doses of 1.5g every 8 hours, with interstitial fluid sampling using microdialysis.
The primary endpoint was the median ratio of ceftolozane tissue AUC to plasma AUC over 16-24 hours. The primary endpoint result and statistical analyses are not reported in the registry record. The record lists 0 serious adverse events and 0 deaths in each group, and one participant with an other adverse event in the diabetic group, compared with none among healthy volunteers. Because the comparison was non-randomized and the groups differed in health status, it is descriptive rather than a like-for-like control comparison.