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 A Study of Ceftobiprole in Patients With Fever and Neutropenia. (NCT00529282), a randomized phase 3 study. The primary outcome is Clinical Cure Rate of Ceftobiprole vs Comparator in Patients With Fever and Neutropenia..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00529282 |
| Phase | Phase 3 |
| Condition | Fever, Neutropenia, Gram-positive Bacterial Infections |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Basilea Pharmaceutica |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with fever and neutropenia. The registry also lists gram-positive bacterial infections and Pseudomonas infection among the conditions associated with the study. The primary outcome description refers to patients in the population, but the record does not report an analyzed population because no outcome measures were analyzed.
Intervention
The intervention was ceftobiprole medocaril. The arm description specifies 500 mg every 8 hours, given by a 120-minute infusion. The registry record describes the study purpose as assessing safety and efficacy relative to a comparator in patients with fever and neutropenia.
Comparator
The comparator was cefepime with or without vancomycin. The arm description gives cefepime as 2 g every 8 hours with a 30-minute infusion, and vancomycin as 1 000mg every 12 hrs with a 60-minute infusion. The record does not report how many comparator participants received vancomycin.
Primary question
The intended primary question was whether the clinical cure rate with ceftobiprole differed from the comparator at the specified post-therapy assessment. Cure required resolution of fever and clinical signs and symptoms such that further anti-infective therapy was unnecessary, and eradication of infecting organisms identified at baseline. No comparative cure result is reported.
3. Trial Design
The registry identifies this as a Phase 3, randomized, quadruple-masked, parallel-group study sponsored by Basilea Pharmaceutica. Its official title describes a multicenter comparison of ceftobiprole with comparators in patients with fever and neutropenia. The listed study status is terminated. The registry gives an enrollment of 2; that entry does not establish how many participants were assigned to each arm or contributed to any particular analysis.
The intervention was ceftobiprole medocaril. The comparator regimen was cefepime with or without vancomycin. The record gives dosing and infusion descriptions for the arms, but it does not report the allocation sequence, the method used to conceal assignments, or the operational details of masking. The masking designation indicates quadruple masking; the identities of the masked roles are not reported in the registry record.
The study began in 2007-10, and the primary completion date is listed as 2008-01. No reason for termination is reported in the registry record. Nor does the record explain whether termination followed a planned decision, recruitment difficulty, a safety concern, or another circumstance. Those possibilities should not be inferred from the status alone.
The planned comparison was clinically framed around cure after treatment, alongside secondary outcomes concerning clinical cure with therapy modification, clinical success at 72 hours, and cure without prophylactic antibiotics after the end-of-treatment visit up to 28 days of study drug. However, the registry explicitly states that no outcome measures were analyzed because the study ended early. Consequently, randomization and masking describe the intended design, not a completed comparative analysis with interpretable efficacy estimates.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Ceftobiprole Medocaril | Cefepime With or Without Vancomycin |
|---|---|---|
| STARTED | 0 | 2 |
| COMPLETED | 0 | 2 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: No outcome measures were analyzed due to early termination of the 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.
| Characteristic | Unit | Ceftobiprole Medocaril | Cefepime With or Without Vancomycin | Total |
|---|---|---|---|---|
| Participants analysed | 0 | 2 | 2 | |
| Age Categorical: <=18 years | participants | — | 0 | 0 |
| Age Categorical: Between 18 and 65 years | participants | — | 2 | 2 |
| Age Categorical: >=65 years | participants | — | 0 | 0 |
| Gender: Female | participants | — | 1 | 1 |
| Gender: Male | participants | — | 1 | 1 |
| Region of Enrollment: United States | participants | — | 2 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Clinical Cure Rate of Ceftobiprole vs Comparator in Patients With Fever and Neutropenia., measured over 7 to 10 days after end of therapy or before 24 hours of the initiation of the next course of chemotherapy, whichever is shorter..
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the clinical cure rate of ceftobiprole versus the comparator in patients with fever and neutropenia. The stated assessment was 7 to 10 days after the end of therapy or before 24 hours of the initiation of the next course of chemotherapy, whichever was shorter. The endpoint was defined as the ratio of clinically cured patients to the total number of patients in the population.
For the definition of cure without modification, the investigator was to judge whether fever and clinical signs and symptoms had resolved to the extent that further anti-infective therapy was unnecessary. Any infecting organisms identified at baseline also had to be eradicated. Thus, the endpoint combined a clinical assessment with a microbiological condition; it was not simply a temperature measure or a count of identified organisms.
A cure endpoint is used to represent whether the clinical and microbiological criteria specified by the study have been met at a defined assessment. Its interpretation depends on the definition, assessment timing, and population used. Here, the registry supplies the endpoint definition and timing but no analyzed cure counts, rate estimates, or uncertainty measures. The primary outcome therefore describes the intended measurement, not an observed comparison between treatment groups.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive fact is that the study was terminated and no outcome measures were analyzed. The registry therefore provides no primary clinical cure estimate and no secondary outcome results. There is no reported treatment contrast, confidence interval, hypothesis-test result, or analysis population for those outcomes. It is not possible to determine from this record whether the groups differed in clinical cure, or how precisely any difference might have been estimated.
The enrollment entry is 2, but it should not be treated as an efficacy denominator. The record does not state how participants were distributed between arms, whether all enrolled participants received study treatment, or whether any participant reached the primary assessment. In particular, the enrollment entry cannot substitute for analyzed outcome data. The adverse-event group entries are separate safety information and do not provide a clinical cure comparison.
Randomization is a design feature intended to support fair comparison by reducing systematic differences between treatment groups. It does not itself produce a reliable treatment estimate when outcome data are not analyzed. Similarly, quadruple masking describes the intended masking arrangement, but it cannot compensate for the absence of reported outcome analyses. The registry record does not report the randomization procedure, masking roles, or steps taken to maintain masking.
The study's termination means the planned clinical question remains unanswered by the posted results. This is not evidence that the treatments are equivalent, that either treatment is superior, or that either is ineffective. It is also not evidence of a particular safety profile. The record contains limited adverse-event counts, but they do not resolve the efficacy question and should be read separately.
Statistical precision cannot be assessed without an estimate and its uncertainty. A confidence interval, in general, describes a range of values compatible with the data under the analysis assumptions; a narrow interval indicates greater precision than a wide one. No confidence interval is reported for the primary endpoint, so the registry record offers no basis for judging the precision of a cure comparison. A missing estimate is not an estimate centered at no difference.
The posted information is best understood as a description of a randomized study that did not yield analyzed outcome measures in the registry record. Its protocol-level question, endpoint definition, and design features can be described, but comparative efficacy conclusions cannot be drawn from them. Any stronger interpretation would require results that are not reported in the registry record.
9. Statistical Methods Explained
Randomization, masking, endpoint definition, and analysis are different parts of a trial's statistical framework. The registry describes a randomized parallel-group design with quadruple masking. Random allocation is generally intended to make treatment groups comparable with respect to measured and unmeasured characteristics, on average. Masking is generally intended to limit the influence of treatment knowledge on care, assessments, or reporting. These are general purposes of the design features; the record does not report the exact randomization or masking procedures used in this study.
What would the primary comparison estimate?
The primary endpoint is a clinical cure rate, defined according to clinical resolution and eradication of baseline organisms at the stated assessment. A comparison of rates would ordinarily summarize the observed frequency of meeting that definition in each treatment group and express the contrast using a prespecified measure. The registry does not report analyzed group counts or rates, so no such contrast can be described. The endpoint definition alone cannot establish the result.
The specified assessment was 7 to 10 days after the end of therapy or before 24 hours of the initiation of the next course of chemotherapy, whichever was shorter. Timing matters because a clinical state can change during follow-up, and an endpoint assessed at a different time may answer a different question. The record names the intended assessment rule but does not report how many participants were assessed at that point or how timing was handled in any analysis.
Why does the absence of an estimate matter?
An effect estimate is a summary of the observed treatment contrast. A confidence interval conveys uncertainty around such an estimate, conditional on the data and statistical assumptions. A hypothesis test, when used, assesses compatibility between the data and a specified null hypothesis; its result does not measure the probability that a treatment is effective. These are general statistical concepts. No effect estimate, confidence interval, or hypothesis-test result for the primary outcome is reported in the registry record, because no outcome measures were analyzed.
Precision depends on the amount and pattern of usable information, not merely on a study's randomized label or its planned enrollment. A small amount of outcome information can yield unstable estimates, while absent outcome analysis yields no estimate to assess. The enrollment entry of 2 does not show the number of participants analyzed or the data available for the endpoint. No account of endpoint availability or missing observations is reported in the registry record.
What do the planning assumptions mean?
The registry describes a planning illustration framework using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. These are assumptions for planning illustrations, not a reported analysis plan for the trial. The registry does not report an observed primary effect, and it does not provide numerical planning estimates in this record. Any sample-size illustration based on an observed effect should be read as a planning scenario, not as observed power or as evidence about the trial's results.
In general, a sample-size calculation asks how much information a future study might need under specified assumptions about the effect, variability, allocation, and error rates. Changing those assumptions changes the planning result. Such a calculation does not show that the original study had adequate power, and it cannot recover a treatment effect from an unanalysed trial. The record does not report the trial's own sample-size justification or statistical plan.
How should multiple outcomes be considered?
The registry lists a primary cure outcome and secondary outcomes addressing cure regardless of therapy modification, clinical success at 72 hours, and cure without prophylactic antibiotics after the end-of-treatment visit up to 28 days of study drug. When a study considers multiple outcomes, multiplicity can matter because repeated testing may increase the chance of a false-positive finding if no adjustment or hierarchy is used. This is a general concern, not a claim about the analysis of this trial. No outcome analyses were conducted according to the registry record, and no multiplicity procedure is reported.
Different outcome definitions can also answer different questions. For example, allowing therapy modification in an outcome definition is not equivalent to the primary definition of cure without modification. The secondary outcomes therefore should not be assumed to duplicate or replace the primary endpoint. Because the registry reports no analyses, neither the relative results across outcomes nor any planned prioritization can be assessed.
Finally, the safety entries are descriptive counts rather than an inferential efficacy analysis. General statistical interpretation separates event counts from treatment-effect estimates and considers the group at risk, the event definition, and the observation period. The registry record gives selected serious and other adverse-event counts but does not report follow-up duration or further safety-analysis details. Those limitations restrict what can be concluded from the safety data.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies a primary clinical cure outcome and lists secondary outcomes concerning cure regardless of therapy modification, clinical success at 72 hours, and cure without prophylactic antibiotics after the end-of-treatment visit up to 28 days of study drug. Considering multiple outcomes can raise multiplicity concerns: testing several outcomes may increase the chance of a chance finding unless a suitable strategy is specified. The registry record does not report a multiplicity adjustment, a testing hierarchy, or another approach to this issue. Since no outcome measures were analyzed, there are no reported outcome tests to interpret or adjust.
Missing-data handling is also not reported in the registry record. The entry does not describe how missing assessments, withdrawals, or incomplete outcome information would have been handled. It does not state whether an analysis would use observed cases, imputation, or another method. These methods can affect the interpretation of an outcome estimate, but no method should be attributed to this study without a reported plan.
The analysis populations are not reported in the registry record. There is no stated intention-to-treat, modified intention-to-treat, per-protocol, or safety population for the efficacy outcomes. The enrollment entry does not establish which participants would have been included in a particular analysis. Because no outcome measures were analyzed, neither the population denominator nor the handling of participant exclusions can be assessed.
These omissions do not show that a particular method was or was not used outside the registry. They mean that the registry record does not document it, and no completed outcome analysis is available there to clarify the issue.
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 |
|---|---|---|---|
| Cefepime With or Without Vancomycin | 2 | 2 | 100.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Ceftobiprole Medocaril | 0 of 0 |
| Cefepime With or Without Vancomycin | 2 of 2 |
Most frequent serious adverse event terms
| Event term | Organ system | Ceftobiprole Medocaril | Cefepime With or Without Vancomycin |
|---|---|---|---|
| Bacteraemia | Infections and infestations | 0 of 0 | 1 of 2 |
| Sepsis | Infections and infestations | 0 of 0 | 1 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ceftobiprole Medocaril | Cefepime With or Without Vancomycin |
|---|---|---|---|
| Constipation | Gastrointestinal disorders | 0 of 0 | 2 of 2 |
| Procedural Pain | Injury, poisoning and procedural complications | 0 of 0 | 2 of 2 |
| Anorectal disorder | Gastrointestinal disorders | 0 of 0 | 1 of 2 |
| Diarrhoea | Gastrointestinal disorders | 0 of 0 | 1 of 2 |
| Dyspepsia | Gastrointestinal disorders | 0 of 0 | 1 of 2 |
| Stomatitis | Gastrointestinal disorders | 0 of 0 | 1 of 2 |
| Vomiting | Gastrointestinal disorders | 0 of 0 | 1 of 2 |
| Depression | Psychiatric disorders | 0 of 0 | 1 of 2 |
| Insomnia | Psychiatric disorders | 0 of 0 | 1 of 2 |
| Rash | Skin and subcutaneous tissue disorders | 0 of 0 | 1 of 2 |
Serious events with the highest arm-level rate: bacteraemia (50.0%), sepsis (50.0%).
The serious adverse-event entries are reported by group. For ceftobiprole medocaril, the registry lists 0 at risk and 0 affected in the serious-event fields. For cefepime with or without vancomycin, it lists 2 at risk and 2 affected. The record names Bacteraemia and Sepsis among the top serious terms, with 50.0% for each. These entries are descriptive registry data; they are not a comparative safety estimate.
The record does not report deaths for either group. It also does not provide the event observation period, definitions beyond the serious-event classification, participant-level detail, or an adjusted comparison. The reported group figures are very limited, and the enrollment entry should not be used to infer the denominator for every safety field. The safety counts do not establish whether the treatments differ in risk, and the named terms should not be interpreted as a complete account of all adverse events.
In general, adverse-event counts are interpreted in relation to the number of participants observed, the duration of observation, and the criteria used to define and collect events. Those details are not reported sufficiently in this registry record to support a broader safety assessment. The figures should therefore be read as the limited safety information recorded, separately from the unanalysed clinical cure outcome.
12. What the Result Does, and Does Not, Mean
The registry record documents the intended comparison of ceftobiprole medocaril with cefepime with or without vancomycin for patients with fever and neutropenia. It also describes a primary clinical cure definition and the planned assessment timing. Those details explain what the investigators intended to evaluate. They do not show what the comparison found.
No outcome measures were analyzed because the study terminated early. As a result, the record gives no analyzed clinical cure rate, treatment contrast, or uncertainty interval. It cannot establish that one regimen had a higher cure rate, that the regimens had similar rates, or that either met a particular efficacy threshold. Absence of a result is not evidence of no effect and does not establish equivalence.
The reported adverse-event fields offer only limited descriptive information and do not fill the efficacy gap. They also do not support a broad comparative safety conclusion because the registry does not report the observation details and analysis needed to interpret risk comparatively. The terms listed as serious events should not be treated as an exhaustive list of events or as a quantified treatment effect.
In general, a trial result is interpreted by considering the endpoint definition, the participants included in the analysis, the estimate of the treatment contrast, and its precision. Here, the endpoint definition is available, but the analysis populations and comparative outcome results are not reported in the registry record. The design features alone cannot supply those missing pieces.
The appropriate conclusion is narrow: the registry describes a randomized, masked study that ended before outcome measures were analyzed. Its clinical question remains unresolved by the posted results. Further conclusions would require results and analysis details not reported in the registry record.
13. Why This Trial Matters Statistically
This study illustrates an important distinction between a trial's design and its evidential result. Randomization, masking, and a clinically defined endpoint can support a rigorous comparison when outcome data are collected and analyzed. They do not themselves provide an effect estimate. Because the registry says that no outcome measures were analyzed, the planned comparison cannot be evaluated statistically from the posted results.
The record also shows why enrollment entries must be interpreted carefully. An enrollment value does not necessarily identify the number assigned to each group, assessed at the endpoint, or included in an analysis. Without analyzed outcome counts and a defined analysis population, even a clearly specified rate endpoint has no reported rate to interpret.
For clinical researchers, the case highlights the value of transparent reporting about termination, analysis populations, missing observations, and statistical methods. The registry records termination but does not state its reason, and it does not report an analysis plan or completed outcome analyses. This limits readers' ability to distinguish what was intended from what was actually evaluated.
For biostatisticians, it is a reminder that statistical interpretation begins with the available evidence, not with the intended design. A planned comparison, an endpoint definition, or a sample-size planning framework cannot be substituted for observed results. The registry record is informative about the question and design, but it does not yield a comparative efficacy conclusion.
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 key limitation is that the registry explicitly reports no analyzed outcome measures because of early termination. There is therefore no primary endpoint result or secondary outcome analysis to assess. The reason for termination is not reported in the registry record, so its implications cannot be evaluated from this entry.
The registry gives an enrollment of 2, but does not report allocation by arm for the efficacy analysis, the number assessed for cure, or the analysis populations. It does not describe missing-data handling, outcome exclusions, or the statistical methods used for an efficacy comparison. Consequently, the endpoint denominator and any potential sources of analysis bias cannot be assessed.
The record specifies the clinical cure criteria and timing, but it does not report whether assessments were completed or how consistently they were applied. The listed safety fields are limited and do not include the observation period or enough analysis detail to support a comparative safety interpretation. Deaths are not reported in the registry record.
Finally, although the registry describes planning assumptions for sample-size illustrations, it does not report the trial's own sample-size justification or statistical plan. No observed outcome effect is available to serve as a basis for interpreting such planning assumptions. These limitations mean the registry can describe the intended study, but cannot answer its comparative clinical question.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Ceftobiprole in Patients With Fever and Neutropenia. — NCT00529282.
- Registry record last updated 2012-08-01; status last verified 2012-07.
- Results first posted 2010-03-29.
- 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
NCT00529282 is a terminated, randomized, quadruple-masked, parallel-group Phase 3 study sponsored by Basilea Pharmaceutica. It compared ceftobiprole medocaril with cefepime with or without vancomycin in patients with fever and neutropenia. The primary endpoint was clinical cure at the specified post-therapy assessment, using clinical resolution and eradication of baseline organisms as criteria.
The registry reports an enrollment of 2 and states that no outcome measures were analyzed because the study ended early. No comparative cure estimate, uncertainty interval, analysis population, or reason for termination is reported. The recorded serious adverse-event information is limited and does not provide a comparative safety analysis. The registry therefore describes the study's design and intended question, but does not report an analyzed answer.