Pharmacodynamic of Ceftaroline and Levofloxacin Against Pathogens Associated With Community Acquired Bacterial Pneumonia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacodynamic of Ceftaroline and Levofloxacin Against Pathogens Associated With Community Acquired Bacterial Pneumonia (NCT01524302), a randomized phase 4 study. The primary outcome is Serum Cidal Activity as Tested Against Staphylococcus Aureus Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth).

2. Clinical Question

The primary outcome concerns serum collected from patients and tested against methicillin-sensitive Staphylococcus aureus isolates. The registry specifies testing levofloxacin serum at 2 hour and ceftaroline serum at 12 hour after receiving the drug. The reported measure is log inhibition of growth, a logarithmic measure of the decrease in microbiological growth.

This is a pharmacodynamic question about activity in a laboratory assay, rather than a direct comparison of patient-centered clinical outcomes. The registry’s study summary also describes the investigation as comparing the potential to eradicate bacterial pathogens, but it does not give a numerical primary-outcome result or a conclusion about that comparison. The record therefore identifies the question and measurement approach without establishing which drug had greater measured activity.

The isolate MICs listed for levofloxacin are 0.5, 1.0, 2.0, and 4.0. The corresponding ceftaroline MICs are 0.125, 0.19, 0.094, and 0.094, respectively. These values describe the isolates’ reported minimum inhibitory concentrations; they are not the study’s serum cidal activity results.

3. Trial Design

The registry describes a randomized, parallel-group phase 4 study with no masking. Enrollment was 12. The study is marked completed, with a start date of 2012-02 and a primary completion date of 2014-05. Gary E. Stein, Pharm.D. is named as sponsor in the registry record.

The two interventions are ceftaroline and levofloxacin. The arm descriptions identify pharmacodynamics for both groups. Random allocation means that treatment assignment was intended to be determined by chance, while a parallel design means the groups received their assigned intervention rather than switching between interventions as part of the described design. The record does not report the allocation sequence method or the ratio used for assignment.

The primary endpoint is an ex-vivo laboratory measure of serum cidal activity against Staphylococcus aureus isolates. The specified sampling times differ by treatment: 2 hour for levofloxacin and 12 hour for ceftaroline after receiving the drug. This distinction matters when interpreting the comparison, because the endpoint is tied to drug-specific collection times rather than a shared sampling time stated for both groups.

The registry lists secondary pharmacokinetic outcomes, including volume of distribution and half life for ceftaroline and levofloxacin, as well as doripenem clearance and area under the serum curve. Doripenem is not listed among the interventions. The record does not explain this distinction, so the listed outcome descriptions should be read as recorded rather than as evidence that doripenem was an assigned treatment.

Further details about doses, eligibility criteria, treatment duration, study setting, participant characteristics, and the randomization procedure are not reported in the registry record. Nor does the record explain the rationale for the enrollment target. Those omissions limit how fully the trial conduct and the representativeness of its participants can be assessed.

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 Serum Cidal Activity as Tested Against Staphylococcus Aureus Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth), measured over 2 hour (levofloxacin) and 12 hour (ceftaroline) after receiving the drug.

The primary endpoint is serum cidal activity against Staphylococcus aureus isolates, expressed as log inhibition of growth. Serum collected from patients is tested outside the body against the isolates, and the result represents the logarithmic measurement of the decrease in microbiological growth. This makes the endpoint a laboratory measure of antimicrobial activity in patient serum, not a direct measure of symptom improvement, pneumonia resolution, or another clinical outcome.

The registry specifies levofloxacin sampling at 2 hour and ceftaroline sampling at 12 hour after receiving the drug. Because the collection times differ by treatment, the endpoint comparison is also a comparison at those specified time points; it is not described as a same-timepoint comparison.

The isolates are reported to have levofloxacin MICs of 0.5, 1.0, 2.0, and 4.0, with corresponding ceftaroline MICs of 0.125, 0.19, 0.094, and 0.094, respectively. In general, an MIC is a laboratory measure of the concentration that inhibits visible microbial growth under test conditions. MIC values characterize the isolates and do not replace the serum cidal activity endpoint. The registry record gives the endpoint definition and isolate MICs but does not report the observed log-inhibition values.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

In general, randomization assigns participants to treatment groups by chance. When implemented as planned, it can reduce systematic differences between groups at the start of a study. It does not ensure that groups are identical, especially in a study with limited enrollment, and it does not correct problems in measurement or analysis. The registry labels this study randomized but does not report the sequence-generation method, allocation concealment, or other implementation details.

The parallel design means that the record describes separate ceftaroline and levofloxacin groups. No masking was used. In general, lack of masking can affect expectations and behavior, particularly for subjective assessments. The primary outcome is a laboratory measurement of serum tested against isolates, but the registry does not describe laboratory masking or procedures intended to reduce measurement bias. It would therefore be inappropriate to assume that assessors were blinded.

What does the primary measure represent?

In general, an ex-vivo assay tests a biological sample outside the body. This study’s primary outcome uses serum collected from patients and measures its cidal activity against Staphylococcus aureus isolates as log inhibition of growth. The result, if reported, would describe activity under the assay conditions. It would not by itself establish a clinical effect in patients, because laboratory activity and patient outcomes are distinct kinds of evidence.

The registry assigns different post-dose sampling times to the two drugs: 2 hour for levofloxacin and 12 hour for ceftaroline. The timing is part of the endpoint definition and should accompany any interpretation of the measurements. The record does not state why these sampling times were selected, whether they represent peak or other drug concentrations, or whether the timing was chosen before data collection.

The MIC values listed for the isolates provide context about their susceptibility measurements. In general, an MIC is an in-vitro measure and does not describe the concentration of drug in a patient’s serum. The listed values are not serum activity results, and the registry does not report how the isolate MICs were incorporated into the primary analysis, if at all.

What would an estimate and confidence interval show?

In general, an estimate summarizes the observed difference or value in a study, while a confidence interval describes the uncertainty around an estimate under the assumptions of the statistical method. A narrow interval indicates greater precision than a wide interval, although interpretation also depends on the outcome scale and the question being asked. Neither an estimate nor an interval can be reconstructed from the design description alone.

The registry record does not report observed primary-endpoint values, a treatment contrast, or a confidence interval. It therefore supplies no basis for describing the magnitude or precision of a primary comparison. A p-value is also not reported. In general, a p-value is not a measure of effect size and does not, by itself, describe the uncertainty or clinical importance of a result.

How should multiple outcomes be considered?

The record lists a primary endpoint and secondary pharmacokinetic outcomes. In general, evaluating multiple outcomes can increase the chance that at least one apparently notable result occurs by chance when many statistical tests are performed. Methods such as prespecifying a primary endpoint or adjusting inference for multiple comparisons can address different aspects of this issue. The registry does not report a multiplicity strategy, the statistical tests used, or the analysis plan for the listed outcomes. No particular adjustment should therefore be attributed to the study.

The secondary descriptions include mean and standard deviation measures for pharmacokinetic parameters. In general, a mean describes a center of a distribution and a standard deviation describes spread around that mean. These summaries can be informative when the data are suitably represented by them, but they do not show the full distribution. The registry does not report the observed values, the number contributing data to each measure, or the method used to calculate the summaries.

What statistical details are unavailable?

The registry reports no analysis entries. It does not report the model or test used for the primary endpoint, how repeated or isolate-level observations were handled, or whether any covariates were included. It also does not report an analysis population, missing-data approach, protocol deviations, or sample-size justification. These are distinct decisions: an analysis model describes how outcomes are compared, an analysis population defines which participants contribute, and missing-data methods specify how unavailable measurements are treated.

In general, small studies can yield unstable estimates and wide uncertainty, particularly when outcomes vary substantially. The enrollment of 12 describes the study’s scale but does not determine the precision of the endpoint estimate by itself. Precision also depends on the observed variation and the analysis structure, neither of which is reported for the primary outcome. The record’s description is therefore adequate to identify the question and outcome, but not to reproduce or evaluate a statistical analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures, including the primary serum cidal activity outcome and secondary pharmacokinetic measures. The secondary outcome descriptions include volume of distribution and half life for ceftaroline and levofloxacin, and clearance and area under the serum curve for doripenem. The record does not report how many formal comparisons were made or whether the outcomes were analyzed jointly or separately.

In general, testing several outcomes can increase the chance of a nominally notable result arising by chance. A prespecified primary outcome can help distinguish the main question from exploratory outcomes, while multiplicity adjustments can change how statistical evidence is evaluated across a family of comparisons. The registry does not report a multiplicity procedure, a hierarchy of secondary outcomes, or an analysis plan that clarifies how such comparisons were to be interpreted.

The registry does not report missing primary measurements, the number of participants contributing endpoint data, or how incomplete observations were handled. It also does not define an analysis population, such as whether all randomized participants were included in the primary analysis. These details are important because exclusions and missingness can affect both the estimated comparison and its uncertainty.

No analysis entries are reported in the record. The statistical model, handling of isolate-level measurements, and approach to any repeated observations are not described. Consequently, it is not possible to determine from the record whether analyses accounted for the structure of the serum and isolate measurements. These omissions concern reporting; they do not establish that the study did or did not use a particular method.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 6 participants at risk for serious adverse events in the levofloxacin arm and 6 in the ceftaroline arm. It records 0 participants with a serious adverse event in each arm. It also records 0 participants with other adverse events in each arm.

These counts describe what is entered in the registry for the listed at-risk groups. In general, an observed count of zero does not establish that an event is impossible or that the treatment has no risk. With limited enrollment, uncommon events may not appear in the observed study data. The record does not provide event descriptions, follow-up duration for safety, or further detail about how adverse events were collected.

Deaths are not reported as a count in the record. That is different from a reported count of zero, so the death fields should not be interpreted as evidence that no deaths occurred. The safety information supports a narrow description of the recorded counts, not a broad conclusion about comparative safety.

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

The record describes a randomized comparison of ceftaroline and levofloxacin focused on pharmacodynamics in community-acquired bacterial pneumonia. Its primary outcome is ex-vivo serum cidal activity against Staphylococcus aureus isolates, measured as log inhibition of growth. The record also specifies treatment-specific sampling times and lists pharmacokinetic outcomes.

What the record does not provide is the primary endpoint result. There are no numerical log-inhibition observations, treatment-effect estimate, confidence interval, or p-value reported. As a result, the direction, size, and precision of any difference between groups cannot be determined from the registry record. The study summary describes the intended investigation, but it does not substitute for an observed result.

In general, laboratory activity is not equivalent to a clinical outcome. The endpoint measures activity of collected serum against isolates under ex-vivo test conditions. It does not directly report whether participants’ pneumonia improved, whether pathogens were eradicated in patients, or whether one intervention changed a clinical outcome relative to the other.

The randomized design is relevant to a comparative question, but its interpretation also depends on the conduct of randomization, outcome measurement, and analysis. The record does not provide enough detail to assess those features fully. The limited enrollment and absence of endpoint results further prevent an assessment of uncertainty or the range of effects compatible with the data.

The adverse-event counts are also limited in scope. The record lists no serious or other adverse events among the recorded at-risk participants, but death counts are not reported. These entries should not be treated as comprehensive evidence about safety. Overall, the registry record documents the study question and selected design details, but it does not establish comparative efficacy or safety.

13. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between a laboratory pharmacodynamic endpoint and an outcome measured in patients. Serum cidal activity can describe what a patient’s serum does against bacterial isolates in an ex-vivo assay. That measure may inform a pharmacodynamic question, but it is not interchangeable with a clinical endpoint. Statistical interpretation must stay aligned with the outcome actually recorded.

The endpoint is also tied to different post-dose sampling times for the two interventions: 2 hour for levofloxacin and 12 hour for ceftaroline. Timing is part of the estimand in practical terms, because it defines the observations being compared. A statistical result would need to be interpreted in light of those times rather than as a comparison at a common time point.

The study’s randomized, parallel design provides a framework for comparing treatment groups, while the absence of masking and the limited enrollment are relevant features to consider when assessing precision and potential sources of bias. The record does not provide enough analysis detail to determine how the laboratory observations were summarized or modeled.

Most importantly, the registry illustrates the difference between a clearly named endpoint and a reported result. The endpoint definition and isolate MICs are recorded, but numerical primary findings and uncertainty measures are not. Without those, a reader cannot judge the magnitude or precision of any observed treatment contrast. The statistical importance of the study is therefore as much about defining what evidence is missing as about identifying the intended comparison.

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 consequential limitation for interpretation is that the registry record does not report numerical results for the primary endpoint. Without observed log-inhibition values or an estimate of the between-group comparison, the direction and size of any difference cannot be assessed. No confidence interval or p-value is reported, so precision and statistical uncertainty are also unavailable.

Enrollment was 12. This limits the scale of the available study, although the actual precision of an estimate would also depend on the observed variation and analysis method. Neither the primary-outcome distribution nor the number contributing endpoint data is reported. The record therefore does not permit a direct assessment of how stable any estimate would be.

The primary outcome uses different specified sampling times for the two drugs, 2 hour for levofloxacin and 12 hour for ceftaroline. The registry does not explain the rationale for those choices or report measurements at other times. The comparison should therefore be understood as tied to the stated sampling schedule, not generalized to an unspecified common time point.

Important design and analysis details are not reported in the registry record, including eligibility criteria, dosing details, randomization procedures, laboratory masking, statistical methods, missing-data handling, and the analysis population. The record also does not report a sample-size justification or a multiplicity strategy. These gaps limit assessment of internal validity, representativeness, and the reliability of inference.

Finally, the outcome is an ex-vivo laboratory measure rather than a direct clinical outcome. The registry’s adverse-event entries are limited to recorded counts, and death counts are not reported. These features restrict conclusions about both clinical outcomes and safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacodynamic of Ceftaroline and Levofloxacin Against Pathogens Associated With Community Acquired Bacterial Pneumonia — NCT01524302.
• Registry record last updated 2016-04-12; status last verified 2016-03.
• Results first posted 2016-04-12.
• 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

The registry record describes a completed, randomized, unmasked, parallel phase 4 study with enrollment of 12. The study started in 2012-02 and reached primary completion in 2014-05. Ceftaroline and levofloxacin are the listed interventions.

The primary endpoint is serum cidal activity against Staphylococcus aureus isolates, reported as log inhibition of growth. The specified collection times are 2 hour for levofloxacin and 12 hour for ceftaroline after receiving the drug. The record lists pharmacokinetic secondary outcomes and isolate MIC values.

Numerical primary-outcome results, inferential statistics, analysis methods, and sample-size justification are not reported in the registry record. The adverse-event record lists 0 serious and 0 other adverse events among 6 participants at risk in each arm; death counts are not reported.