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 Comparative Study of Ceftaroline vs. Vancomycin Plus Aztreonam in Adult Subjects With Complicated Skin Infections (NCT00423657), a randomized phase 3 study. The primary outcome is Clinical Cure Rate at Test of Cure (TOC) (MITT Population).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00423657 |
| Phase | Phase 3 |
| Condition | Bacterial Infections |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 680 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Forest Laboratories |
| Results posted | Yes |
2. Clinical Question
Population
Adults with complicated skin and skin structure infection were the intended population. The primary endpoint used the MITT population, defined in the registry record as all subjects who received any amount of study drug. The record lists bacterial infections as the condition and gives total enrollment as 680.
Intervention
The ceftaroline arm received ceftaroline fosamil 600 mg intravenously over 60 minutes every 12 hours, followed by placebo over 60 minutes every 12 hours. The registry record describes this as a randomized, quadruple-masked study.
Comparator
The active comparator was intravenous vancomycin plus intravenous aztreonam. The recorded regimen was vancomycin 1 g over 60 minutes every 12 hours, followed by aztreonam 1 g over 60 minutes every 12 hours. The record lists placebo as an intervention, but does not describe a separate placebo-only arm.
Primary question
The primary endpoint was clinical cure at the test-of-cure visit, assessed 8-15 days after the last dose of study drug administration. The clinical question is how the recorded cure outcomes compare between the two active treatment groups in the MITT population. The registry record does not report the outcome counts or a comparative estimate, so it does not establish the direction or precision of any treatment difference.
3. Trial Design
The registry record describes a Phase 3, multicenter, randomized, double-blind, comparative study of ceftaroline versus vancomycin plus aztreonam in adults with complicated skin and skin structure infection. It also records quadruple masking and a parallel-group model. These design labels describe the intended conduct, but the record does not explain which people were masked or how masking was maintained.
Total enrollment was 680. The record gives the study start as 2007-03, primary completion as 2007-12, and status as completed. Forest Laboratories is listed as the sponsor. The record does not give a recruitment flow, the number analyzed for the primary endpoint, or reasons participants may have been excluded from an analysis.
The ceftaroline arm is described as receiving ceftaroline fosamil 600 mg intravenously over 60 minutes every 12 hours, followed by placebo over 60 minutes every 12 hours. The comparator arm is described as receiving vancomycin 1 g over 60 minutes every 12 hours, followed by aztreonam 1 g over 60 minutes every 12 hours. No treatment duration is reported in the registry record.
The primary endpoint was clinical cure at test of cure, with assessment scheduled 8-15 days after the last dose of study drug administration. The primary population was MITT, defined as all subjects who received any amount of study drug. The record lists several secondary aims, including microbiological success at test of cure, clinical response at end of therapy, outcomes by pathogen, relapse, reinfection or recurrence at late follow-up, and safety. Detailed secondary-outcome results are not reported in the registry record.
Although the record lists placebo as an intervention, it gives no separate placebo-only arm description. The available arm descriptions support an active-treatment comparison with placebo included after ceftaroline; further details of allocation concealment, study-drug preparation, site conduct, and adherence are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Patients were screened for up to 24 hours
Overall Study
| Stage | Ceftaroline for Injection | IV Vancomycin Plus IV Aztreonam |
|---|---|---|
| STARTED | 342 | 338 |
| COMPLETED | 316 | 313 |
| NOT COMPLETED | 26 | 25 |
Reasons for not completing this period:
| Reason | Ceftaroline for Injection | IV Vancomycin Plus IV Aztreonam |
|---|---|---|
| Withdrew consent | 10 | 8 |
| Non-compliance | 0 | 1 |
| Other | 15 | 16 |
| Request of sponsor/investigator | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: MITT (Modified Intent to Treat) - all subjects that received any amount of study drug
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 | Ceftaroline for Injection | IV Vancomycin Plus IV Aztreonam | Total |
|---|---|---|---|---|
| Participants analysed | 342 | 338 | 680 | |
| Age, Customized: <=18 years | participants | 0 | 0 | 0 |
| Age, Customized: >18 and < 65 years | participants | 281 | 291 | 572 |
| Age, Customized: >=65 years | participants | 61 | 47 | 108 |
| Age, Continuous | years | 47.8 (SD 16.98) | 47.5 (SD 16.07) | 47.7 (SD 16.52) |
| Sex: Female, Male: Female | Participants | 118 | 137 | 255 |
| Sex: Female, Male: Male | Participants | 224 | 201 | 425 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 63 | 59 | 122 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 279 | 279 | 558 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Clinical Cure Rate at Test of Cure (TOC) (MITT Population), measured over 8-15 days after last dose of study drug administration.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was clinical cure at the test-of-cure visit in the MITT population. The visit was scheduled 8-15 days after the last dose of study drug administration. Cure was defined as total resolution of all signs and symptoms of the baseline infection, or improvement such that no further antimicrobial therapy was necessary.
The endpoint also specified failure and indeterminate outcomes. Failure included a need for alternative antimicrobial therapy for the primary infection because of inadequate response, recurrence, or new infection at the same site; a treatment-limiting adverse event; surgery because of study-drug failure; a diagnosis of osteomyelitis after Study Day 8; or death caused by cSSSI. An outcome was indeterminate when it could not be determined.
Clinical cure is used as a patient-level summary of whether the baseline infection has resolved or improved sufficiently under the endpoint definition. It combines signs and symptoms with the need for further antimicrobial therapy, while the failure criteria also capture specified clinical events. General statistical consideration: a clearly defined endpoint helps make outcome classification consistent across participants and treatment groups. However, interpretation depends on how outcomes were assessed and how indeterminate cases were handled; those details are not reported in the registry record. The record gives no cure counts, comparison estimate, or confidence interval for this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted results include safety counts, but the registry record does not report the primary clinical-cure result. It therefore does not support a numerical estimate of the difference in cure outcomes between ceftaroline and vancomycin plus aztreonam. No confidence interval or p-value for the primary endpoint is reported in the registry record. Without these, the direction, magnitude, and statistical precision of the primary comparison cannot be assessed from the record.
The primary outcome description specifies cure, failure, and indeterminate outcomes, but no counts for these categories are reported. The registry record also does not provide a treatment-effect estimate adjusted for any covariates, or an unadjusted estimate. The record lists one analysis, but that entry does not supply a result or explain the analysis method. It should not be treated as evidence that a particular comparison was statistically significant or nonsignificant.
The listed safety counts are descriptive. For ceftaroline, 14 participants are recorded as affected by serious adverse events among 341 at risk; for vancomycin plus aztreonam, 16 are recorded as affected among 339 at risk. Other adverse events are listed for 144 of 341 at risk in the ceftaroline group and 159 of 339 at risk in the comparator group. These counts do not by themselves establish whether the groups differ beyond chance. The registry record does not provide confidence intervals, formal comparative tests, event definitions, or a detailed accounting of event severity and duration.
General statistical consideration: an estimate describes the observed difference, while a confidence interval conveys the range of values compatible with the data under the analysis assumptions. A p-value, when reported, addresses compatibility with a specified null hypothesis; it does not measure clinical importance. Here, the primary estimate and its uncertainty are not reported, so neither statistical significance nor the size of any clinical difference can be evaluated from the registry record.
The record identifies the intended endpoint, population, treatment groups, and some safety counts. It does not report the outcome information needed to establish comparative efficacy or to judge the precision of an efficacy comparison. The appropriate interpretation is therefore limited to the trial design and descriptive safety figures that are actually recorded.
9. Statistical Methods Explained
Clinical trial results depend on the population analyzed, the definition of the outcome, the comparison method, and how uncertainty is expressed. The registry record identifies a randomized, parallel-group study and names the MITT population for the primary endpoint. It does not report the statistical analysis details or the primary outcome results, so the methods below explain general concepts rather than reconstructing the study's analysis.
What does randomization contribute?
In general, randomization assigns participants to treatment groups using a chance-based process. Its purpose is to reduce systematic differences between groups at the start of the study, including differences that may not be known to investigators. It does not guarantee that the groups will be identical, and it does not replace careful outcome assessment or analysis. The registry record states that allocation was randomized, but the sequence-generation and allocation-concealment procedures are not reported in the registry record.
What does masking mean?
The study is described as double-blind and quadruple-masked. In general, masking is intended to reduce the influence of expectations on care, assessment, or reporting. Different records may use masking labels to describe different groups of people involved in a trial, but the registry record does not say which roles were masked or how the masking was implemented. The ceftaroline arm description includes placebo administration after ceftaroline; the record does not provide further operational details.
Why does the analysis population matter?
The named primary population is MITT, defined as all subjects who received any amount of study drug. The population used for analysis determines which participants contribute to the reported result. In general, analyses that retain participants in their assigned groups can preserve the benefits of randomization, while exclusions or missing outcomes can affect interpretation. The registry record does not report the number of participants contributing to the primary endpoint, the handling of participants with missing assessments, or whether other analysis populations were used.
How should a binary endpoint be compared?
The endpoint classifies each participant's status at test of cure as cure, failure, or indeterminate. For a binary comparison, an analysis typically summarizes the number or proportion meeting an outcome in each group and estimates a between-group contrast. A confidence interval communicates uncertainty around that estimate. The record does not report the primary category counts, a comparative estimate, a confidence interval, or a test result. The record's analysis listing does not identify which statistical model or contrast was used.
What does a confidence interval tell the reader?
General explanation: a confidence interval reflects the statistical uncertainty around an estimate under the assumptions of the method used. A narrower interval indicates greater precision than a wider interval, but precision alone does not determine clinical importance. Whether an interval includes a no-difference value can be relevant to a statistical test, yet the interval must be interpreted alongside the endpoint, analysis plan, and clinical context. No primary-outcome confidence interval is reported in the registry record.
How do planning calculations differ from trial results?
General explanation: a sample-size calculation is a planning exercise about the amount of information a study might need under specified assumptions. It is not an observed treatment effect and is not a measure of the probability that a result is true. The planning description associated with the record refers to a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. It distinguishes participant-per-arm calculations from total-event calculations for time-to-event settings. The specific planning values and any trial-specific sample-size justification are not reported in the registry record. These assumptions should not be mistaken for evidence about the study's observed efficacy or precision.
Why can outcome categories matter?
The endpoint definition includes cure, failure, and indeterminate outcomes. General explanation: combining categories, excluding indeterminate outcomes, or treating them as failures can change the interpretation of a comparison. The appropriate approach depends on the analysis plan and the clinical meaning of each category. The registry record does not report how indeterminate outcomes were handled in the analysis, so no such choice can be attributed to the trial from this record.
The record identifies eight outcome measures and one analysis, but it does not state the model, covariates, treatment contrast, handling of missing data, or multiplicity procedure. No statistical method should be inferred from those labels alone. The primary endpoint result and its uncertainty remain unavailable in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists several secondary outcomes: microbiological success at the test-of-cure visit; clinical response at end of therapy; clinical and microbiological response by pathogen at test of cure; clinical relapse at late follow-up; microbiological reinfection or recurrence at late follow-up; and safety. It also records eight outcome measures and one analysis. The record does not explain how many hypotheses were formally tested, which outcomes were designated for confirmatory inference, or whether any adjustment for multiple comparisons was planned or used.
General statistical consideration: when many outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase. A prespecified multiplicity strategy can help control that concern. Because no strategy is reported in the registry record, the status of any secondary-outcome findings cannot be assessed for multiplicity control. Detailed secondary results are not reported in the registry record.
The primary endpoint allows an indeterminate classification, defined as inability to determine an outcome. The record does not say how indeterminate outcomes or other missing assessments were treated in the analysis. It also does not report reasons for missingness, follow-up completeness, or sensitivity analyses. These details matter because missing outcomes can affect estimates, particularly if missingness differs between groups or is related to outcome status.
The MITT population is defined as all subjects who received any amount of study drug. The registry record does not report the number analyzed for the primary endpoint or describe whether additional populations were used. It also does not report a statistical analysis plan or explain the relationship between the stated analysis count and the listed outcome measures. Consequently, the analysis population, missing-data approach, and multiplicity handling cannot be fully evaluated from the registry record.
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 |
|---|---|---|---|
| Ceftaroline for Injection | 14 | 341 | 4.1% |
| IV Vancomycin Plus IV Aztreonam | 16 | 339 | 4.7% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Ceftaroline for Injection | 144 of 341 |
| IV Vancomycin Plus IV Aztreonam | 159 of 339 |
Most frequent serious adverse event terms
| Event term | Organ system | Ceftaroline for Injection | IV Vancomycin Plus IV Aztreonam |
|---|---|---|---|
| Bradycardia | Cardiac disorders | 1 of 341 | 1 of 339 |
| Myocardial infarction | Cardiac disorders | 1 of 341 | 1 of 339 |
| Anemia | Blood and lymphatic system disorders | 0 of 341 | 1 of 339 |
| Coagulopathy | Blood and lymphatic system disorders | 0 of 341 | 1 of 339 |
| Sinoatrial block | Cardiac disorders | 0 of 341 | 1 of 339 |
| Abdominal pain | Gastrointestinal disorders | 1 of 341 | 0 of 339 |
| Ileus | Gastrointestinal disorders | 0 of 341 | 1 of 339 |
| Multi-organ failure | General disorders | 1 of 341 | 0 of 339 |
| Condition aggravated | General disorders | 0 of 341 | 1 of 339 |
| Hepatitis | Hepatobiliary disorders | 0 of 341 | 1 of 339 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ceftaroline for Injection | IV Vancomycin Plus IV Aztreonam |
|---|---|---|---|
| Pruritus | Skin and subcutaneous tissue disorders | 13 of 341 | 28 of 339 |
| Nausea | Gastrointestinal disorders | 21 of 341 | 19 of 339 |
| Diarrhea | Gastrointestinal disorders | 22 of 341 | 15 of 339 |
| Headache | Nervous system disorders | 18 of 341 | 18 of 339 |
| Rash | Skin and subcutaneous tissue disorders | 11 of 341 | 10 of 339 |
| Constipation | Gastrointestinal disorders | 10 of 341 | 11 of 339 |
| Insomnia | Psychiatric disorders | 12 of 341 | 8 of 339 |
| Vomiting | Gastrointestinal disorders | 11 of 341 | 9 of 339 |
| Hypokalemia | Metabolism and nutrition disorders | 5 of 341 | 9 of 339 |
| Alanine aminotransferase increase | Investigations | 5 of 341 | 7 of 339 |
Serious events with the highest arm-level rate: anemia (0.3%), coagulopathy (0.3%), bradycardia (0.3%), myocardial infarction (0.3%), sinoatrial block (0.3%).
The registry record reports serious adverse events for two treatment groups. In the ceftaroline group, 14 participants were affected among 341 at risk. In the intravenous vancomycin plus intravenous aztreonam group, 16 participants were affected among 339 at risk. These are counts with corresponding at-risk group sizes, not a formal comparison of treatment effects.
The record also lists other adverse events affecting 144 participants among 341 at risk in the ceftaroline group and 159 among 339 at risk in the comparator group. The registry record does not provide a definition for this other-event category, event-level details, confidence intervals, or a statistical test comparing groups. The counts therefore describe what was recorded but do not establish whether a difference is meaningful or attributable to treatment.
Six serious adverse-event terms are listed, each with a reported frequency of 0.3%: anemia, coagulopathy, bradycardia, myocardial infarction, sinoatrial block, and ileus. The record does not give further event counts or explain the denominator used for these percentages. Death counts are not reported in the registry record. General statistical consideration: safety counts are most informative when read with consistent definitions, follow-up, denominators, and enough detail to understand event timing and severity; those details are not available.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this was a randomized, masked Phase 3 comparison of ceftaroline with vancomycin plus aztreonam in adults with complicated skin and skin structure infection. It identifies clinical cure at test of cure as the primary endpoint and defines the MITT population. It also records several secondary aims and descriptive adverse-event counts. These registry entries describe the study's question and some of its reported safety information.
The record does not report the primary clinical-cure counts, a treatment-effect estimate, a confidence interval, or a p-value. It therefore cannot show how the treatment groups compared on the primary endpoint, how large any difference may have been, or how precisely any difference was estimated. It also cannot support a conclusion that one treatment was superior, inferior, or equivalent to the other.
The serious adverse-event and other adverse-event counts provide a descriptive account of participants affected in each group. Without formal comparisons and additional event-level information, they do not establish a causal safety difference. The listed serious-event terms and their reported percentages do not supply a complete account of all safety outcomes, and death counts are not reported in the registry record.
General statistical explanation: a trial's design and outcome definitions are distinct from its results. Randomization and masking can strengthen a comparison when implemented as intended, but they do not fill gaps in unreported outcome data. Likewise, a completed study status does not itself show whether its primary question was answered. Interpretation must remain limited to the information recorded; missing estimates cannot be recovered from the design description or safety counts.
The main conclusion supported by the record is that the trial was designed to compare clinical cure and safety between the stated regimens. Its posted record does not provide the primary efficacy result needed to judge the comparative clinical-cure outcome.
13. Why This Trial Matters Statistically
This trial is statistically useful as an example of why design information and outcome reporting must be read separately. The record specifies randomization, masking, a parallel-group model, treatment regimens, an endpoint, and an analysis population. Those details help define what comparison was intended. They do not, by themselves, quantify the result.
The primary endpoint also illustrates the importance of operational definitions. Cure, failure, and indeterminate status are described using clinical criteria, including resolution or improvement, the need for further antimicrobial therapy, and specified events such as surgery or death caused by cSSSI. Such definitions determine what the analysis counts as an outcome. The record does not provide category counts or the handling of indeterminate results, leaving key parts of the outcome analysis unknown.
The safety information demonstrates another statistical distinction: counts of affected participants are descriptive, while a comparative estimate addresses the size and uncertainty of a difference between groups. The record includes serious and other adverse-event counts, but no formal comparative estimates or uncertainty measures. Readers should not turn those counts into a treatment conclusion without the analysis and context that are absent from the registry record.
Finally, the record lists multiple secondary aims but does not describe a multiplicity strategy. General statistical practice recognizes that interpretation can change when many outcomes are examined, so prespecified analysis choices are important. The absence of those details limits evaluation of secondary findings. Overall, the trial record shows how a clear design description can coexist with insufficient posted results for assessing the primary 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 principal limitation for statistical interpretation is that the registry record does not report the primary clinical-cure counts or a treatment-effect estimate. It also does not report a confidence interval or p-value for the primary endpoint. As a result, the magnitude, direction, and precision of the primary comparison cannot be evaluated from the record.
The primary population is identified as MITT, but the number analyzed is not reported. The registry record does not provide participant flow, reasons for exclusion, follow-up completeness, missing-outcome handling, or sensitivity analyses. Although the endpoint includes an indeterminate category, its treatment in the analysis is not reported. These omissions prevent assessment of how the endpoint definition was applied to the analyzed participants.
The record describes a randomized, double-blind study and labels masking as quadruple, but does not explain sequence generation, allocation concealment, which roles were masked, or how masking was maintained. It also does not report adherence, treatment duration, or detailed conduct across study sites. These are trial-specific details that could help readers assess implementation but cannot be inferred from the design labels.
The listed secondary outcomes are not accompanied by detailed results or a multiplicity plan. The record does not state the statistical model, analysis covariates, or the purpose of the single listed analysis. It also does not report a trial-specific sample-size justification or the planning values. For safety, event definitions and detailed event-level data are absent, and death counts are not reported. These limitations mean that the available record supports a description of the trial and selected safety counts, but not a complete assessment of efficacy, precision, or comparative safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Comparative Study of Ceftaroline vs. Vancomycin Plus Aztreonam in Adult Subjects With Complicated Skin Infections — NCT00423657.
- Registry record last updated 2017-03-14; status last verified 2017-02.
- Results first posted 2010-11-18.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT00423657 is recorded as a completed, randomized, quadruple-masked, parallel Phase 3 study comparing ceftaroline with intravenous vancomycin plus intravenous aztreonam in adults with complicated skin and skin structure infection. Enrollment was 680. The registry record gives the study start as 2007-03 and primary completion as 2007-12.
The primary endpoint was clinical cure at test of cure, assessed 8-15 days after the last dose of study drug administration in the MITT population. Cure, failure, and indeterminate outcomes are defined in the record. The primary outcome counts and comparative statistical results are not reported in the registry record.
Descriptive safety counts include serious and other adverse events for both treatment groups. The record does not report death counts or a formal comparative safety analysis. It lists secondary outcome aims, but detailed results and the statistical approaches for multiplicity and missing data are not reported in the registry record.