A Study of Avycaz (Ceftazidime/Avibactam) Pharmacokinetics/Pharmacodynamics (PK/PD) in Critically Ill Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Avycaz (Ceftazidime/Avibactam) Pharmacokinetics/Pharmacodynamics (PK/PD) in Critically Ill Patients (NCT02822950), a na phase 1 study. The primary outcome is Mean (SD) Ceftazadime/Avibactam Pharmacokinetic (PK) Volume of Distribution Parameter in Intensive Care Patients.

2. Clinical Question

The study description also states an interest in variable pharmacokinetic parameters, ex vivo time-kill activity against relevant clinical isolates, and Monte-Carlo simulations to help examine dosing schedules. These are stated objectives, not reported findings. The registry record does not report the results of those analyses, the isolates tested, or a numerical pharmacodynamic result. The central clinical research question is therefore descriptive and pharmacokinetic: it concerns drug disposition in a critically ill population, rather than whether the drug outperforms another treatment.

3. Trial Design

This completed Phase 1 study is registered as a single-group investigation sponsored by Michigan State University. The registry lists an enrollment of 10 and identifies no random allocation and no masking. The intervention is ceftazidime/avibactam, with the arm description specifying intravenous administration and a regimen adjusted for the stated CrCl range. Other antibiotics could also be administered as needed. Patients were to receive at least 3 doses before serum sampling.

The intended setting was the intensive care unit, including medical and post-surgical patients who developed an infection for which Avycaz could be used. The brief summary emphasizes that pharmacokinetic parameters might vary among critically ill patients. It describes serum concentration analysis and ex vivo time-kill testing against relevant clinical isolates, as well as Monte-Carlo simulations against ICU isolates. Those plans place the study in a pharmacokinetic/pharmacodynamic framework: drug concentrations are the pharmacokinetic component, while laboratory activity against isolates is a pharmacodynamic component.

The registry gives a start date of 2017-01, a primary completion date of 2017-12, and a completed status. It lists 5 outcome measures, but numerical outcome findings and a detailed analysis plan are not reported in the registry record. The primary outcome is described as mean (SD) volume of distribution, with units of Liter and measurements at 2,4,6, 8 hours after receiving the drug.

Because there is no separate comparator group, the design can describe observations within the treated group but cannot directly estimate a treatment difference against a control. The registry record does not report a protocol justification for the enrollment, a sample-size rationale, or further details about sampling procedures.

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.

6. Primary Endpoint

The registry lists the primary outcome as Mean (SD) Ceftazadime/Avibactam Pharmacokinetic (PK) Volume of Distribution Parameter in Intensive Care Patients, measured over 2,4,6, 8 hours after receiving the drug.

The primary endpoint is the mean (SD) ceftazidime/avibactam pharmacokinetic volume of distribution parameter in intensive care patients. Volume of distribution is a pharmacokinetic measure describing the apparent extent to which a drug is distributed beyond the bloodstream. It is used to characterize drug disposition and can contribute to pharmacokinetic models. It is not, by itself, a measure of clinical benefit or microbiologic success.

The registry specifies Liter as the unit and identifies measurements at 2,4,6, 8 hours after receiving the drug. Reporting a mean describes the central value of the measured parameter; the standard deviation describes variation among measurements or participants, depending on the analysis used. The registry record does not specify the exact calculation or aggregation method, nor does it report the mean or standard deviation. The numerical endpoint result, its precision, and any interpretation of differences across measurement times are therefore not reported in the registry record.

The endpoint is relevant to a pharmacokinetic study because it characterizes how the drug is distributed in the population under study. The registry’s broader description links variable pharmacokinetic parameters with ex vivo activity and simulation work, but the primary endpoint alone does not establish a dosing schedule, clinical response, or comparative effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

For a continuous measurement such as volume of distribution, a mean gives a central summary of the observed values. The standard deviation describes how dispersed those values are around the mean. They answer different questions: the mean concerns the typical level, while the standard deviation concerns variability. Neither alone tells the reader how precisely the mean has been estimated. Precision is commonly conveyed with an interval estimate, but such an estimate is not reported in the registry record.

The primary outcome is labeled mean (SD), with Liter as its unit and a specified timeframe of 2,4,6, 8 hours after receiving the drug. The record does not state whether the measure is reported separately at each time, how measurements are combined, or how missing measurements would be handled. Those details matter because repeated observations from the same participant are related, rather than independent measurements.

What does the pharmacokinetic focus mean?

Pharmacokinetics concerns drug concentrations over time and the processes that influence drug disposition. Volume of distribution is one parameter used to characterize distribution. In general, pharmacokinetic parameters can help describe exposure, but interpreting them requires clarity about sampling times, dose administration, participant characteristics, and the model or calculation used. The registry gives the intended dosing regimen and broad sampling timeframe, but detailed sampling methods and a model specification are not reported in the registry record.

The study description also mentions pharmacodynamics, including ex vivo time-kill testing against clinical isolates, and Monte-Carlo simulations. In general, ex vivo testing evaluates activity in a laboratory setting, while simulations use a model to explore expected outcomes under specified assumptions. These analyses do not automatically establish patient-level clinical outcomes. The registry record does not report numerical results, model assumptions, or the isolate-level findings for these planned analyses.

Why does a single-group design matter?

A single-group study can characterize measurements among participants who received the studied intervention. Without a concurrent comparison group, it cannot estimate a between-group difference. This limits causal interpretation and makes it inappropriate to read the study as a comparative trial. The registry lists allocation as not applicable and masking as none; it identifies the model as single group.

Randomization, when used, helps balance prognostic factors across groups on average. Masking can reduce some forms of knowledge-related bias. Neither feature is listed for this study. That does not make descriptive pharmacokinetic measurement impossible, but it means the design does not provide the protections or comparisons associated with a randomized, masked trial. The record does not report further procedures that might address measurement or selection bias.

How should uncertainty and modeling be read?

A confidence interval, in general, expresses a range of values compatible with an estimate under the assumptions of the analysis. Its width reflects precision: a wider interval indicates greater uncertainty than a narrower one. No confidence interval is reported for the primary endpoint, so its precision cannot be quantified from the registry record. A standard deviation is not a substitute for a confidence interval; it describes spread in the observations rather than uncertainty in the estimated mean.

Over-dispersion, in general, occurs when observed variability exceeds what a statistical model assumes. If a model ignores excess variability, uncertainty can be understated. This concept may be relevant to variable drug concentrations or laboratory responses, but the registry record does not report a fitted model or a finding of over-dispersion. It would be speculative to claim that this study detected or adjusted for it.

The registry includes a planning illustration based on a two-arm, equal-allocation assumption, a two-sided significance level of 0.05, a normal approximation, and fractions of an observed effect. Such planning quantities are not observed power. They are hypothetical planning illustrations, and their two-arm framing does not match this study’s registered single-group design. The registry does not report that these assumptions were used to design the study, nor does it report a sample-size justification. No numerical planning result is stated in this explanation.

Finally, a completed status is an administrative description of study status, not a statement that every planned analysis is reported. The registry lists 5 outcome measures and 0 analyses, but the primary numerical findings and the methods used to estimate them are not reported in the registry record. Interpretation should therefore distinguish the study’s stated objectives from results that are actually available.

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("Ceftazadime/Avibactam")
n   <- c(10)
m   <- c(34)
sp  <- c(12)
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  Ceftazadime/Avibactam  10  34.000  12.000  25.416  42.584

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures, while identifying mean volume of distribution as the primary outcome. It does not describe a multiplicity strategy, such as a prespecified ordering of outcomes or an adjustment for testing several hypotheses. The number and nature of statistical comparisons are not reported in the registry record. Without those details or numerical results, the risk of chance findings across multiple analyses cannot be assessed.

Missing-data methods are also not reported in the registry record. The record does not state whether all enrolled participants contributed to the primary endpoint, how incomplete concentration measurements were handled, or whether any imputation or other approach was used. It also does not describe exclusions from analysis or the handling of measurements that could not be obtained at a specified time.

The analysis population is not described beyond the registered enrollment of 10 and the safety counts. It is not clear from the registry record whether the primary analysis included every enrolled participant, only participants with usable samples, or another defined group. These distinctions can affect how a mean and standard deviation should be interpreted.

The record does not report an analysis plan, interim analyses, or a protocol-based sample-size justification. The planning illustration’s two-arm assumptions should not be treated as the study’s design rationale or as observed power. Since numerical endpoint results and analysis details are absent, neither multiplicity nor missing-data sensitivity can be evaluated from the registry record.

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 lists the ceftazidime/avibactam group with 10 at risk for serious adverse events and 0 affected. It also lists 10 at risk for other adverse events and 0 affected. The death count is 1. These entries are descriptive counts in the registry record; they do not establish whether any event was caused by the study drug or how an event was classified clinically.

The record does not report the timing or cause of the death, its relationship to treatment, or additional details about follow-up. It also does not list serious adverse event terms. Without a comparator group, these figures cannot show whether event occurrence differed from another treatment or from an untreated course. The counts should be read as registry-reported safety information, not as a comparative safety estimate.

Zero recorded events in a group does not establish that the risk of an event is absent. Interpretation depends on follow-up, event definitions, ascertainment, and completeness of reporting, details that are not reported in the registry record. The death entry likewise cannot be interpreted as treatment-related without attribution information.

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

This study addresses a useful descriptive question: how ceftazidime/avibactam pharmacokinetic parameters appear in critically ill intensive care patients. The registry identifies volume of distribution as the primary measure and describes additional intended work on serum concentrations, ex vivo activity, and simulations. Such work can help characterize a study population and frame further pharmacokinetic research.

The registry record does not report the numerical primary endpoint or the results of the additional analyses. It therefore does not establish the observed volume of distribution, the amount of variability, the relationship between drug exposure and laboratory activity, or a modeled dosing schedule. The objectives in the summary are not findings.

The study is single-group, with no randomized comparator. It cannot estimate a comparative effect against another regimen, and it does not answer whether the drug improves clinical outcomes. The primary endpoint is pharmacokinetic rather than a clinical outcome. No clinical efficacy result is reported in the registry record.

The listed enrollment is 10, and the record does not provide an interval estimate or the analysis details needed to judge precision. Nor does it state a sample-size justification. A small or large degree of uncertainty cannot be asserted from enrollment alone in the absence of observed values and an analysis method.

The safety entries should also be kept in proportion: the record lists no serious adverse events, no other adverse events, and 1 death in the intervention group, without reporting timing, cause, or treatment relationship. These entries do not support a comparative safety conclusion. The soundest conclusion is that the registry documents a completed study intended to characterize pharmacokinetics and related activity, while leaving the quantitative results and important interpretive details unreported.

14. Why This Trial Matters Statistically

Critically ill patients can have variable pharmacokinetic parameters, a concern explicitly identified in the study description. Describing drug disposition in this setting can be statistically important because a population average may not capture the spread of individual observations. Reporting both a mean and standard deviation is intended to convey central tendency and variability, although the registry does not report the numerical values.

The planned combination of serum concentration assessment, ex vivo time-kill testing, and simulation work also illustrates how pharmacokinetic and pharmacodynamic questions can be connected. In general, concentration measurements characterize exposure, laboratory testing examines activity under experimental conditions, and simulations explore consequences of model assumptions. Each addresses a different inferential step; none should be mistaken for a direct clinical comparison.

The study is also a useful example of why design and result reporting must be read together. A single-group design can describe observations, but cannot supply a randomized comparator. Further, a stated objective is not equivalent to a reported finding. Here, the registry lists the primary endpoint and its timeframe but does not report its numerical result, the analysis method, or the precision of the estimate.

Safety counts need similar context. Descriptive counts without event details, follow-up information, or comparison data cannot establish causality or comparative risk. The registry’s death entry is especially difficult to interpret because cause and relationship are not reported. This makes transparent reporting of endpoint values, uncertainty, analysis populations, and event context essential for statistical interpretation.

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 primary limitation for interpreting this record is the absence of numerical results. The registry identifies a mean (SD) volume of distribution endpoint but does not report the estimate, standard deviation, or any interval estimate. The results of the additional pharmacokinetic, ex vivo, and simulation analyses are also not reported in the registry record.

The single-group design has no comparator and no random allocation. It therefore supports description rather than a direct treatment comparison. Masking is listed as none. The record does not describe other procedures for reducing measurement or selection bias.

The registry does not explain how the primary endpoint was calculated, whether it was estimated separately at each stated time, or how repeated measurements were modeled. It does not report the analysis population, missing-data handling, multiplicity strategy, or a statistical analysis plan. Those omissions limit assessment of validity and precision.

The enrolled population is described broadly as critically ill medical and post-surgical patients with an infection where Avycaz could be used. Further eligibility criteria and participant characteristics are not reported in the registry record. The enrollment is 10, but no sample-size justification is reported. The record also does not give details about the clinical isolates or simulation assumptions described as planned work.

Safety interpretation is limited by absent event details. The registry lists 1 death but does not report its timing, cause, or relationship to treatment. Follow-up duration and adverse-event ascertainment details are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Avycaz (Ceftazidime/Avibactam) Pharmacokinetics/Pharmacodynamics (PK/PD) in Critically Ill Patients — NCT02822950.
• Registry record last updated 2019-03-06; status last verified 2018-11.
• Results first posted 2019-03-06.
• 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

NCT02822950 is a completed Phase 1, single-group study sponsored by Michigan State University. The registry lists an enrollment of 10, no random allocation, and no masking. The intervention is ceftazidime/avibactam for critically ill intensive care patients.

The primary outcome is mean (SD) pharmacokinetic volume of distribution in Liter, measured at 2,4,6, 8 hours after receiving the drug. The study description also outlines serum concentration analysis, ex vivo time-kill testing, and Monte-Carlo simulations. Numerical primary and additional results are not reported in the registry record.

The safety entries list 0 serious adverse events, 0 other adverse events, and 1 death in the intervention group. The record does not report the death’s cause or relationship to treatment. Analysis methods, missing-data handling, analysis populations, and a sample-size justification are not reported in the registry record.