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 Ceftazidime-avibactam Among Critically-ill Patients Receiving CVVHDF (NCT04358991), a registered phase not stated study. The primary outcome is Serum Levels of Ceftazidime and Avibactam Among Critically-ill Patients.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04358991 |
| Phase | Phase not stated |
| Condition | Bacterial Infections |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Pittsburgh |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns critically ill patients receiving ceftazidime-avibactam. The title specifies patients receiving continuous venovenous hemodiafiltration (CVVHDF), while the brief summary also refers to CVVHD. The registry record does not give a more detailed description of the patient characteristics or the number of participants receiving CVVHDF.
Intervention
Patients receiving ceftazidime-avibactam were asked to provide blood samples around a medication dose. The registry describes sampling immediately before administration and at 1, 2, 4, 6, and 8 hours afterward. It characterizes the dosing regimens as standard of care; specific dosing details are not reported in the registry record.
Comparator
No like-for-like control comparison is described. The registry record does not state an allocation method, and it flags the study as not being a randomized comparison. The available description therefore supports a question about measured drug concentrations, not a treatment-effect comparison between randomized groups.
Primary question
The primary outcome is serum levels of ceftazidime and avibactam, expressed in mcg/mL and summarized using the median and inter-quartile range. The question is how these concentrations vary around dosing in the described critically ill population. Although the outcome definition and sampling schedule are recorded, actual concentration results are not reported in the registry record.
3. Trial Design
This completed study is registered as NCT04358991, with the title “Pharmacokinetics of Ceftazidime-avibactam Among Critically-ill Patients Receiving CVVHDF.” The registry lists an enrollment of 20 and identifies bacterial infections as the condition. The sponsor is the University of Pittsburgh. The recorded start date is 2017-01-01, and the primary completion date is 2019-12-31.
The intervention is ceftazidime-avibactam. The arm description says that patients receiving the medication were asked to provide blood samples around a dose for sample analysis. This description does not establish a randomized allocation or a comparison with an untreated or alternative-treatment group. The registry record itself cautions that the arms are not a like-for-like control comparison, and the allocation method is not stated.
The study is classified as “other” rather than as a conventional comparative trial. Its stated purpose is to evaluate the pharmacokinetics of ceftazidime and avibactam among critically ill patients, including those receiving CVVHD in the brief summary. The title instead uses CVVHDF. The record does not clarify the use of these terms or provide subgroup counts.
The primary outcome concerns serum drug levels around standard-of-care dosing. Sampling is described immediately before dosing and at 1, 2, 4, 6, and 8 hours after administration. The registry reports one outcome measure and no analyses. It does not report the measured concentrations, detailed eligibility criteria, protocol dosing, or a statistical analysis plan. Those omissions limit how specifically the design and results can be reconstructed.
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 | Subjects Included |
|---|---|
| STARTED | 20 |
| COMPLETED | 20 |
| 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 | Subjects Included |
|---|---|---|
| Participants analysed | 20 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 18 |
| Age, Categorical: >=65 years | Participants | 2 |
| Sex: Female, Male: Female | Participants | 9 |
| Sex: Female, Male: Male | Participants | 11 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 18 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Serum Levels of Ceftazidime and Avibactam Among Critically-ill Patients, measured over 8 hours.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | mcg/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is serum levels of ceftazidime and avibactam, measured in mcg/mL. The registry specifies the median and inter-quartile range as the summary statistics and gives an 8 hours timeframe. Its description says samples were obtained immediately before dosing and at 1, 2, 4, 6, and 8 hours after administration. Thus, the endpoint is intended to characterize drug concentrations around a dose rather than a clinical outcome such as infection resolution or survival.
As a general statistical explanation, the median describes the center of an observed distribution while the inter-quartile range describes its middle spread. These summaries can be useful for concentration data when values are skewed or when a small number of unusually high or low measurements could pull the mean. They do not, by themselves, show how concentrations changed within individual patients or establish a comparison between dosing strategies.
The registry record does not report the actual median concentrations or inter-quartile ranges. It also does not provide separate estimates for each sampling time, the number of samples available at each time, or a model relating concentrations to time. The endpoint definition is therefore available, but the observed pharmacokinetic findings cannot be interpreted from the registry information recorded.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a pharmacokinetic question: what serum levels of ceftazidime and avibactam are observed around dosing in critically ill patients, including those receiving CVVHDF. It describes the sampling schedule and the intended use of medians and inter-quartile ranges. However, it does not give any concentration values. There is consequently no reported estimate of the typical concentration, its spread, or the pattern of concentrations over the recorded sampling times.
The absence of numerical outcome results means that the precision of the estimates cannot be assessed. A median paired with an inter-quartile range would describe the observed distribution, but interpretation would also depend on how many measurements contributed at each time and how complete the sampling was. Those details are not reported in the registry record. No confidence intervals or other uncertainty intervals are listed, so the amount of statistical uncertainty around any concentration estimate is unknown.
The record lists an enrollment of 20, but does not state how many participants contributed usable pharmacokinetic samples or how the analysis population was defined. The enrollment figure should not be treated as proof that every enrolled participant contributed measurements at every time. The record also does not provide the planned or observed number of measurements, or the handling of repeated measurements from the same participant.
This is not described as a randomized comparison. The registry says allocation is not stated and warns that the arms are not a like-for-like control comparison. Therefore, the study description does not support a causal treatment comparison. The available information is framed around concentration measurement following dosing, not a comparison of clinical outcomes between groups.
The record notes sample-size planning illustrations based on an observed effect and assumptions including a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It explicitly distinguishes these illustrations from the trial's own design. No numerical illustration results or specific effect fractions are recorded in the information available. Such planning calculations, in general, describe hypothetical requirements under chosen assumptions; they are not observed power and do not substitute for reported estimates and uncertainty.
In short, the registry defines the pharmacokinetic endpoint and sampling times but does not report the endpoint results or analyses. It is not possible to determine from this record whether measured concentrations were high, low, variable, or different across sampling times. Any conclusion beyond the registered objective and methods would require information that is not reported in the registry record.
9. Statistical Methods Explained
The registered primary outcome is a concentration measure: serum levels of ceftazidime and avibactam in mcg/mL. The registry specifies the median and inter-quartile range, and describes samples around dosing. These choices describe what was intended to be measured and how the distribution was to be summarized. They do not reveal the observed levels, because the numerical endpoint results are not reported in the registry record.
What does a median and inter-quartile range describe?
As a general statistical explanation, the median is the middle value when observations are ordered. The inter-quartile range describes the span between the lower and upper quartiles, covering the middle portion of the observations. Together, they communicate a distribution's center and spread without requiring a symmetric distribution. This can be useful for drug concentrations, which may not be evenly distributed. The registry record does not give the median or inter-quartile range for any sampling time, so these summaries cannot be interpreted numerically for this study.
How should the sampling schedule be understood?
The registry describes blood collection immediately before dosing and at 1, 2, 4, 6, and 8 hours afterward. In general, measurements taken at multiple times can describe how observed concentrations vary around a dose. Measurements from the same participant are related rather than independent, so analyses of repeated measurements often need to account for that within-participant relationship. The registry record lists no analyses and does not report whether a repeated-measures model or another approach was used. It also does not say how the intended summaries were organized by time or whether all participants contributed samples at each time.
What can the stated design establish?
The registry describes patients receiving ceftazidime-avibactam and sampling around standard-of-care dosing. It does not report a randomized comparison, and it states that the arms are not a like-for-like control comparison. In general, descriptive concentration measurements characterize what was observed in the participants sampled. Without a suitable comparison design and a defined analysis, they do not establish that a dosing approach caused a difference in a clinical outcome. The registry's stated pharmacokinetic purpose should therefore be distinguished from evidence about comparative clinical effectiveness.
What do planning illustrations mean?
The record describes sample-size illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. The record says these are planning illustrations and not the trial's own design. In general, a planning calculation explores the sample size implied by assumptions about the effect, variability, allocation, and statistical test. Its output is conditional on those choices; it is not evidence that the study had a particular probability of detecting an effect. The numerical illustrations and specific fractions are not reported in the registry record, so no numerical planning requirement can be interpreted.
Those assumptions also refer to two arms, while the registry's study description does not establish a randomized, like-for-like comparison. This reinforces the need to treat the planning calculations as hypothetical rather than as a description of the actual design. The registry record does not report the study's own sample-size justification, assumptions about variability, or a formal statistical analysis plan.
What is missing for precision assessment?
Precision is usually assessed from an uncertainty interval around an estimate, interpreted in light of the data contributing to it. As a general explanation, a confidence interval expresses a range of estimates compatible with the data and the method used; it is not a guarantee that the true value lies within that particular interval. The record does not report confidence intervals, numerical concentration summaries, or time-specific sample counts. Accordingly, neither the magnitude of the estimates nor their precision can be evaluated from the recorded results.
The registry lists no analyses. It does not state whether concentrations were analyzed separately by drug, how repeated samples were handled, whether results were adjusted for any participant characteristics, or how missing measurements were treated. These are not details that can be inferred from the endpoint label or sampling schedule. They are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure and no analyses. It does not describe a statistical analysis plan, identify a hierarchy of hypotheses, or state how multiple comparisons were handled. Although the endpoint description includes serum levels of both ceftazidime and avibactam and a schedule of sampling times, the record does not say whether these were treated as separate statistical tests, as descriptive measurements, or in some other way. A multiplicity adjustment therefore cannot be inferred.
The analysis population is not specified in the primary outcome description. The record gives an enrollment of 20, but does not state how many participants had evaluable samples, whether all enrolled participants were included in each analysis, or whether any participants were excluded from an analysis. It also does not state whether the analysis population was defined before data collection or analysis.
Missing data procedures are not reported in the registry record. In general, absent samples can affect descriptive concentration summaries if availability differs across time points or participants. The record does not state whether missing samples occurred, how they were handled, or whether their absence was related to participant condition or sampling circumstances. No imputation or sensitivity analysis is reported.
Because no numerical outcome estimates or analyses are reported, the effect of missing data and multiplicity on the findings cannot be assessed. These are reporting gaps, not evidence that missing data or multiple testing necessarily occurred.
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 |
|---|---|---|---|
| Subjects Included | 0 | 20 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Subjects Included | 3 of 20 |
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 |
|---|---|
| Subjects Included | 0 of 20 |
The registry's safety listing records 20 subjects included. It lists 20 at risk for serious adverse events and 0 affected; for other adverse events, it also lists 20 at risk and 0 affected. The record additionally lists 3 deaths. No top serious-event terms are listed.
These entries should be read as registry counts, not as a complete account of event timing, causes, or clinical context. In particular, the record does not state whether the deaths were considered related to study participation or to ceftazidime-avibactam, nor does it explain their circumstances. The listing of deaths alongside the adverse-event counts does not establish a causal relationship.
The safety information does not give event-level descriptions, follow-up duration, or a narrative explaining how the counts were collected. It also does not report a comparison group suitable for estimating relative safety. The absence of affected entries in the listed adverse-event categories should not be interpreted as proof that no events occurred outside the registry's reporting definitions. The available figures are limited to the registry's recorded categories and counts.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed study registered a pharmacokinetic objective for ceftazidime and avibactam in critically ill patients, including patients receiving CVVHDF. It specifies blood sampling around dosing and identifies serum levels in mcg/mL, summarized by median and inter-quartile range, as the primary outcome. These details describe the research question and intended measurement.
The record does not report the observed serum concentrations, their variability, or the analyses used. It therefore cannot show from the recorded results how concentrations changed across the sampling schedule, how consistent measurements were, or how precisely any estimate was determined. It also does not report the number of evaluable samples at each time or a defined analysis population. Those omissions prevent a quantitative interpretation of the pharmacokinetic findings.
The study is not described as a randomized comparison, and the record cautions that the arms are not a like-for-like control comparison. As a result, the registered description should not be read as a causal comparison of treatment strategies. The endpoint concerns drug levels; no clinical outcome result is reported in the primary outcome information.
The sample-size illustrations are described as planning calculations based on an observed effect and specified assumptions, not as the study's own design. They should not be read as observed power or as evidence that a result was detected. The registry record does not provide the numeric illustrations or the endpoint estimates needed to assess them against actual findings.
Accordingly, the defensible interpretation is limited: the registry records a completed pharmacokinetic study, its planned sampling schedule, and safety counts, but does not report the concentration results or statistical analyses. It cannot establish from these entries whether the measured concentrations were sufficient for any clinical purpose, or whether any dosing approach is preferable.
13. Why This Trial Matters Statistically
Pharmacokinetic studies address the movement of a drug through the body by measuring concentrations over time. This is a statistical problem as well as a clinical one: measurements taken at different times, and repeated measurements from the same participant, need to be described in a way that preserves their timing and dependence. The registry identifies a concentration endpoint and a post-dose sampling schedule, making the intended type of evidence clear.
The study's population is described as critically ill, with the title focusing on patients receiving CVVHDF. The brief summary also uses CVVHD. Such context matters when considering how broadly results might apply, but the registry record does not report subgroup details or the numerical findings needed to assess applicability. The record also does not clarify its use of the two terms.
Statistically, the case illustrates the difference between a registered question and a reportable result. An endpoint definition and a schedule are not enough to judge the size, variability, or precision of a finding. Numerical estimates, information about which measurements contributed, and an analysis description are needed to evaluate the evidence. Those are not reported in this registry record.
The absence of a like-for-like randomized comparison also shapes the interpretation. A descriptive pharmacokinetic study can characterize measured concentrations in its participants, but the record does not support a causal comparison of treatment groups. This distinction helps prevent a concentration question from being mistaken for a clinical effectiveness question.
Finally, the stated sample-size illustrations are planning exercises rather than the trial's design or observed power. Keeping that distinction clear is important when interpreting statistical calculations: their meaning depends on assumptions, and they cannot replace reported endpoint results. In this record, the primary statistical contribution that can be assessed is the measurement plan, not the magnitude or precision of the findings.
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 important limitation for interpretation is that the registry record does not report the numerical primary outcome results. It specifies serum levels, units, summary statistics, and sampling times, but gives no concentration estimates or uncertainty intervals. Consequently, the pharmacokinetic findings cannot be evaluated quantitatively.
The registry lists an enrollment of 20 but does not describe the number of participants with usable samples or the number of measurements at each time. The analysis population, missing-sample handling, and any exclusions are not reported. This makes it impossible to determine how much information supported any potential estimate.
The record lists no analyses and gives no statistical analysis plan. It does not explain how repeated measurements were handled, whether results were separated by drug or sampling time, or whether any adjustment was made. The allocation method is not stated, and the record warns that the arms are not a like-for-like control comparison. The description therefore does not support causal comparisons between arms.
The title refers to CVVHDF, while the brief summary uses CVVHD. The registry record does not clarify this terminology or report the number of participants receiving either form of therapy. It also does not provide detailed participant characteristics or dosing information beyond describing standard-of-care regimens.
Safety reporting is limited to the listed counts, with no event descriptions or explanation of the deaths. The registry's sample-size planning assumptions are not a substitute for a reported design justification or outcome analysis. These limitations concern what the registry record reports; they do not establish what may or may not have been documented elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pharmacokinetics of Ceftazidime-avibactam Among Critically-ill Patients Receiving CVVHDF — NCT04358991.
- Registry record last updated 2020-09-29; status last verified 2020-09.
- Results first posted 2020-05-15.
- 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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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT04358991 is a completed pharmacokinetic study sponsored by the University of Pittsburgh. The registry lists an enrollment of 20, a start date of 2017-01-01, and a primary completion date of 2019-12-31. The study concerns ceftazidime-avibactam in critically ill patients, with the title specifying CVVHDF.
The primary outcome is serum levels of ceftazidime and avibactam in mcg/mL, summarized by median and inter-quartile range. Samples were described immediately before dosing and at 1, 2, 4, 6, and 8 hours afterward. The record lists one outcome measure and no analyses.
Numerical concentration results, uncertainty estimates, analysis-population details, and missing-data methods are not reported in the registry record. The safety listing records 0 affected for serious adverse events and 0 affected for other adverse events, with 3 deaths listed; their circumstances and relationship to treatment are not reported.