Evaluation of Safety, Pharmacokinetics and Efficacy of Ceftazidime and Avibactam (CAZ-AVI ) Compared With Cefepime in Children From 3 Months to Less Than 18 Years of Age With Complicated Urinary Tract Infections (cUTIs): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Safety, Pharmacokinetics and Efficacy of Ceftazidime and Avibactam (CAZ-AVI ) Compared With Cefepime in Children From 3 Months to Less Than 18 Years of Age With Complicated Urinary Tract Infections (cUTIs) (NCT02497781), a randomized phase 2 study. The primary outcome is Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs).

2. Clinical Question

The trial’s stated purpose was to assess safety, tolerability and efficacy of CAZ-AVI compared with cefepime in the specified pediatric population. Its recorded primary outcome concerns adverse events, rather than a single efficacy measure. Secondary outcomes included plasma concentrations of ceftazidime and avibactam and clinical response at several treatment or follow-up times, using different analysis populations.

That distinction matters when interpreting the clinical question. A comparison of adverse-event counts addresses observed safety events in the safety analysis set; it does not by itself answer every question about efficacy, tolerability, or drug exposure. The registry record lists clinical response outcomes, but does not report their results in the information available for this analysis. It also does not report a single combined estimate that summarizes the primary outcome across its categories or time points.

3. Trial Design

This was a phase 2, randomized, single-blind, parallel-group, active-controlled trial. It compared CAZ-AVI with cefepime in children with complicated urinary tract infections. The registry record describes the study as multicenter. The recorded enrollment was 97. The study status is completed; its recorded start date was 2015-09-24, and its primary completion date was 2017-09-15.

Random assignment was used to allocate participants to treatment groups, but the registry record does not report the allocation ratio or the method used to generate or conceal the random sequence. It identifies the trial as single blind without specifying in the record which people were blinded or how blinding was maintained. Those details should not be inferred from the design label alone.

The CAZ-AVI regimen was an intravenous infusion every 8 hours over 2 hours, with dose and frequency depending on body weight and renal function. For cefepime, dose, schedule and infusion duration followed local prescribing information or the investigator’s prescription, with a maximum single infusion dose of 2000 mg. The treatment regimens were therefore described differently in the registry record; it does not provide additional information about how regimen variation was handled in the analysis.

The primary safety outcome covered treatment-emergent adverse events from baseline until the late follow-up visit, up to a maximum study duration of 50 days. The safety analysis set included randomized participants who received any amount of intravenous study medication. Several secondary outcomes concerned clinical response at defined assessment points, in specified analysis populations, while another concerned plasma concentrations. The registry record does not report a planned sample-size justification, a detailed statistical analysis plan, or the number of participants included in each efficacy analysis population.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety analysis set included all randomized participants who received any amount of IV study medication (CAZ-AVI or Cefepime).

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Safety analysis set included all randomized participants who received any amount of IV study medication.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over Baseline until the LFU visit (up to a maximum study duration of 50 days).

The primary outcome is the percentage of participants with treatment-emergent adverse events and serious adverse events. The registry definition counts an adverse event as an untoward medical occurrence in a participant who received study drug, without regard to whether it was considered causally related to treatment. Serious adverse events are events resulting in outcomes such as death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability or incapacity, or a congenital anomaly, or events deemed significant for another reason.

A treatment-emergent event is defined by its timing and change from pretreatment status: it occurred between the first dose and the late follow-up visit, 20 to 36 days after the last dose of study treatment, and was absent before treatment or worsened relative to the pretreatment state. The definition includes both serious and non-serious adverse events. The recorded outcome timeframe is baseline until the late follow-up visit, with a maximum study duration of 50 days.

Tracking adverse events is a way to describe the safety experience during and after treatment. The percentage format expresses how many participants in an analysis population experienced an event, rather than how many event episodes occurred. The registry record defines the safety population as randomized participants who received any amount of intravenous study medication. It does not provide a single reduced comparison for this primary outcome, so the recorded event counts should not be treated as a complete, adjusted estimate of comparative risk.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization assigns participants to treatment groups by chance, reducing the influence of participant or clinician choice on allocation. In general, randomization can help make groups comparable with respect to measured and unmeasured characteristics, but it does not guarantee identical groups, particularly in a modest-sized trial. The registry identifies this study as randomized, but does not report the sequence-generation or allocation-concealment procedures. Those methods are not reported in the registry record.

Single blinding means that some aspect of treatment assignment was concealed, but the label alone does not identify who was blinded. For example, the designation does not establish whether participants, investigators, outcome assessors, or another group were unaware of treatment allocation. The registry does not specify this detail or describe the practical steps used to maintain blinding. The study is also recorded as parallel-group and active-controlled: participants were assigned to one of the treatments, and the comparator was another active drug rather than an untreated control.

The primary outcome is expressed as a percentage of participants with events. In general, a percentage summarizes the proportion of an analysis population that experienced the defined outcome over the specified observation period. A proportion of participants with at least one event is different from a count of event episodes: one participant may have more than one event, while still counting as one participant with an event for a participant-level percentage. The registry’s displayed safety figures include counts and denominators, but it does not provide a single reduced comparison for the primary endpoint.

What does a confidence interval describe?

In general, a confidence interval communicates the precision of an estimated effect and the range of values compatible with the data under the analysis assumptions. A narrow interval indicates greater statistical precision than a wide interval; an interval that includes no difference may be compatible with both little difference and some differences in either direction. The registry record does not report confidence intervals for the posted safety counts or a comparative primary-outcome estimate. Therefore, the precision of a treatment difference cannot be assessed from those counts alone.

Why can event rates be difficult to compare?

In general, event comparisons depend on both the number of participants who experienced an event and the number observed in each group. Follow-up duration and completeness also matter: participants observed for different lengths of time may have different opportunities for an event to be recorded. This trial’s timeframe is specified as baseline to the late follow-up visit, up to a maximum study duration of 50 days, and the adverse-event definition refers to a follow-up visit 20 to 36 days after the last dose. The registry does not provide participant-specific follow-up time or a detailed account of completeness, so no person-time comparison can be inferred.

The record gives event counts for the safety groups, but does not report a relative risk, risk difference, model-based estimate, or uncertainty interval. Recalculating a percentage or contrast from summary counts would be an unadjusted calculation, not the sponsor’s full analysis. No such recalculation is needed to interpret the central limitation: the registry does not report one primary comparison. The sponsor’s own analysis takes precedence if it is available, and a simple calculation from counts would not replace it.

What is over-dispersion, and is it relevant?

In general, over-dispersion occurs when observed variation exceeds what a statistical model assumes. It can matter for outcomes that count event episodes, because repeated events within participants may create more variability than a simple model allows. The primary outcome is described as a percentage of participants with events, while the adverse-event definition includes events at the participant level. The registry does not report a model for recurrent event counts or an over-dispersion assessment. It would therefore be inappropriate to claim that such a method was used or was needed for the posted analysis.

The secondary outcomes use different response definitions, time points, and analysis populations. In general, comparisons across populations or assessment times are not interchangeable: each answers a question about the participants and outcome definition included in that analysis. The registry lists intent-to-treat, microbiological intent-to-treat, clinically evaluable, and microbiologically evaluable populations for some clinical response outcomes, but does not report their sizes or results in the record. No efficacy estimate, confidence interval, or p-value for those outcomes is reported.

Sample-size calculations for future research are planning illustrations rather than evidence about the probability that this completed trial detected an effect. In general, such illustrations depend on assumptions about the effect to detect, the significance level, allocation, and statistical method. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as stated fractions of an observed effect. These illustrations do not establish the trial’s original design rationale or observed power. A sample-size justification and the trial’s own detailed statistical plan are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a range of secondary outcomes: plasma concentrations of ceftazidime and avibactam and clinical response measured in different analysis populations and at different treatment or follow-up points. In general, examining multiple outcomes or time points creates multiple opportunities to observe a result that appears notable by chance. A statistical plan may address this through a prespecified primary comparison, adjustment procedures, or a hierarchy for interpreting outcomes. The registry record does not report whether such procedures were planned or used. It does not report a detailed multiplicity strategy.

The primary outcome itself includes treatment-emergent adverse events and serious adverse events, and the record indicates that it has several categories or time points and was not reduced to one comparison. This means the posted primary-outcome information cannot be interpreted as one clearly specified statistical test or one treatment-effect estimate. The registry does not report how multiple categories or time points were handled in the sponsor’s analysis.

Missing data can affect interpretation when participants do not complete follow-up or when outcome information is unavailable. In general, the impact depends on how much information is missing, why it is missing, and how the analysis handles it. The record defines the safety population as randomized participants who received any amount of intravenous study medication, but does not report the number excluded from this population or explain missing outcome data. Reasons for missingness, imputation methods, and sensitivity analyses are not reported in the registry record.

The listed clinical response analyses use several populations, including intent-to-treat and evaluable sets. Such populations can address different estimands: one may include a broad randomized group, while another may restrict analysis to participants meeting defined evaluability criteria. The registry record names these populations but does not state the detailed criteria, their sizes, or their results. Without that information, their consequences for missingness and selection cannot be assessed.

11. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: urinary tract infection (4.5%), cystitis (3.6%), pyelonephritis acute (3.6%), abdominal pain (1.5%), constipation (1.5%).

The registry reports serious adverse events for 8 of 67 participants at risk in the CAZ-AVI group and 2 of 28 participants at risk in the cefepime group. It reports other adverse events for 13 of 67 participants and 9 of 28 participants, respectively. These are participant counts with denominators, not event totals and not an adjusted comparison. The record does not provide confidence intervals or a statistical test for these group figures.

Serious adverse events are defined by specified consequences, including death, hospitalization, life-threatening experience, significant disability or incapacity, and congenital anomaly, or another reason for significance. The registry reports zero deaths in each group. It also lists serious-event terms and percentages: urinary tract infection at 4.5%, cystitis at 3.6%, pyelonephritis acute at 3.6%, abdominal pain at 1.5%, constipation at 1.5%, and viral infection at 1.5%. The listed terms do not identify a treatment group in the record, so they do not support a group-specific comparison.

Adverse events were recorded without regard to a possible causal relationship to study drug. Accordingly, the counts describe events during the defined period, not events established to have been caused by treatment. Serious and non-serious events should not be added together: the primary outcome definition says adverse events include both, and serious events are a category within adverse events. The record does not provide enough detail to infer overlap in the displayed group counts.

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

The registry record documents a randomized, single-blind comparison of CAZ-AVI and cefepime in children with complicated urinary tract infections. It provides safety counts for serious and other adverse events, specifies the safety analysis set, and describes a primary outcome covering treatment-emergent adverse events and serious adverse events. These details help define what was observed and in whom.

The record does not provide a single reduced primary-outcome comparison, a confidence interval, or a statistical test for the posted safety counts. The counts therefore cannot establish the size or precision of a difference between treatments. Nor do they alone establish whether an event was caused by the assigned treatment, because the adverse-event definition explicitly does not require a causal relationship.

The study’s stated purpose also included assessing efficacy and pharmacokinetics. Clinical response and plasma concentration outcomes are listed, but their results are not reported in the registry record. Thus, the available information does not support a conclusion about comparative clinical response or drug concentrations. The title and outcome list describe what the trial intended to evaluate, not the direction or strength of results for every outcome.

Interpretation is further limited by details not reported in the registry record, including the statistical analysis plan, allocation ratio, blinding procedures, analysis population sizes for secondary outcomes, and handling of missing data. The recorded enrollment of 97 should not be substituted for the denominators of the safety groups or treated as the number analyzed for every outcome.

The appropriate reading is descriptive: the posted results state the recorded event counts in the specified safety groups, under the study’s event definitions and follow-up window. They do not, by themselves, provide a complete comparative safety analysis or an efficacy conclusion. Any broader interpretation would require the sponsor’s complete analysis and the unreported methodological details.

13. Why This Trial Matters Statistically

This trial illustrates why an outcome label and its analysis need to be read together. The primary outcome is described as the percentage of participants with treatment-emergent adverse events and serious adverse events, but the registry record does not reduce the outcome to one comparison. Knowing the outcome’s clinical definition is useful; knowing how its categories, follow-up points, and analysis were combined is also necessary to interpret a treatment effect.

The safety figures show why raw counts alone are not a complete comparative result. Counts must be interpreted in relation to their denominators, observation period, and analysis population. Even then, an estimate of a treatment contrast and its precision are needed to judge how compatible the data are with different possible effects. Those inferential quantities are not reported for the primary outcome in the registry record.

The record also distinguishes a safety analysis set from the named populations for clinical response outcomes. This is statistically important because a result in a safety population does not automatically describe the same participants or estimand as an efficacy analysis in an intent-to-treat or evaluable population. The listed outcome populations signal that different analyses were contemplated, but their sizes, definitions and results are not reported.

Finally, this completed phase 2 study includes both safety and efficacy aims, while the available record gives more specific numerical detail for adverse events than for clinical response. That imbalance makes it important to avoid treating the existence of an outcome listing as evidence of its result. A careful statistical reading separates what the record documents from what remains unreported and does not turn descriptive counts into a claim of comparative benefit or harm.

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 main limitation for interpretation is that the registry record does not report one primary-outcome treatment comparison. It gives adverse-event counts and denominators, but no confidence intervals, p-values, or adjusted estimates for those figures. Without a reported comparison and its precision, the magnitude and uncertainty of a between-group effect cannot be assessed from the record.

The safety figures apply to the stated safety analysis set: randomized participants who received any amount of intravenous study medication. The record does not provide a participant flow account or explain why participants may not have contributed to this set. Enrollment is recorded as 97, but that number should not be treated as the number analyzed for each outcome. Secondary analysis population sizes are not reported.

Several design and analysis details are also absent. The allocation ratio, random-sequence method, allocation concealment, identity of the blinded parties, and detailed statistical analysis plan are not reported in the registry record. The record does not describe missing-data methods, multiplicity procedures, or the rationale for the original sample size. Planning assumptions for illustrative sample-size calculations do not fill those gaps or establish the original trial’s design rationale.

The serious-event terms are listed with percentages, but the record does not identify their treatment-group attribution or denominator. The adverse-event definition does not require causal attribution, and the record does not provide an analysis that separates events judged related to treatment from events not judged related. The fixed follow-up description also does not provide participant-level follow-up or event timing.

Finally, the clinical response and plasma concentration outcomes are listed without results in the record. The available information therefore cannot support conclusions about comparative efficacy, pharmacokinetics, or the results across the different clinical response populations and assessment times.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluation of Safety, Pharmacokinetics and Efficacy of Ceftazidime and Avibactam (CAZ-AVI ) Compared With Cefepime in Children From 3 Months to Less Than 18 Years of Age With Complicated Urinary Tract Infections (cUTIs) — NCT02497781.
• Registry record last updated 2018-07-11; status last verified 2018-06.
• Results first posted 2018-04-10.
• 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.

18. Record Summary

NCT02497781 is a completed, randomized, single-blind, parallel-group, active-controlled phase 2 trial of CAZ-AVI versus cefepime in children from 3 months to less than 18 years of age with complicated urinary tract infections. Recorded enrollment was 97. The recorded start date was 2015-09-24 and the primary completion date was 2017-09-15.

The primary outcome concerned treatment-emergent adverse events and serious adverse events, assessed from baseline to the late follow-up visit, up to a maximum study duration of 50 days. Serious adverse events were reported for 8 of 67 participants at risk in the CAZ-AVI group and 2 of 28 in the cefepime group; other adverse events were reported for 13 of 67 and 9 of 28, respectively. The registry record does not report a single primary comparison or its statistical uncertainty.

Secondary outcomes included plasma concentrations and clinical response at specified times in several analysis populations. Their results, the detailed statistical plan, and key information about missing data and allocation procedures are not reported in the registry record.