Efficacy and Safety of Ceftaroline Versus Linezolid in Subjects With Complicated Skin and Skin Structure Infections: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Ceftaroline Versus Linezolid in Subjects With Complicated Skin and Skin Structure Infections (NCT00633152), a randomized phase 2 study. The primary outcome is Clinical Response at the Test of Cure (TOC) Visit in the Modified Intent-to-treat (MITT) Population.

2. Clinical Question

The Test of Cure (TOC) visit was scheduled 8 to 15 days after the end of therapy. The registry description calls the CE and MITT cure rates coprimary efficacy outcomes, while the posted primary result is for the MITT Population. The Clinical Evaluable (CE) result is not reported in the registry record. The clinical question is therefore best read as a comparison of the posted MITT response percentages at the specified follow-up visit, not as a complete account of every coprimary result or of all outcomes assessed.

3. Trial Design

This was a phase 2, multicenter, randomized, open-label, parallel-group comparative study in adults with complicated skin and skin structure infections. The registry record lists Forest Laboratories as sponsor and gives enrollment as 150. The study is marked completed. Its recorded start was 2008-02, and primary completion was 2008-07.

The treatment groups differed in both the study drug and the route described in the arm records. Ceftaroline was given intramuscularly every 12 hours. The comparator was intravenous linezolid every 12 hours, with or without optional aztreonam. The registry record does not report the criteria for adding aztreonam, nor does it describe further treatment details such as duration.

Open-label means that masking was recorded as none. In general, an open-label design means participants and study personnel know which treatment is being administered. That can matter when outcomes involve clinical judgments, although the record does not establish that it affected these results. Randomization assigns participants to treatment groups using a chance-based process; the registry identifies the study as randomized but does not report the sequence-generation or allocation-concealment methods.

The MITT outcome denominators were 98 for ceftaroline and 45 for linezolid with or without aztreonam. The MITT definition includes randomized subjects who received any amount of study drug. The registry record does not explain the relationship between these reported denominators and the enrollment figure, or provide a participant-flow account. It also does not report the trial's original sample-size assumptions, masking procedures beyond the open-label designation, or other design details that would be needed for a fuller appraisal.

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: Modified-Intent-to-Treat (MITT) Population - Any randomized 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.

6. Primary Endpoint

The registry lists the primary outcome as Clinical Response at the Test of Cure (TOC) Visit in the Modified Intent-to-treat (MITT) Population, measured over Test of Cure Visit (8 to 15 days after end of therapy).

The primary posted endpoint is the percentage of participants in the MITT Population who had a clinical response at the Test of Cure (TOC) visit. The visit took place 8 to 15 days after the end of therapy. The registry's endpoint description defines clinical cure as total resolution of all signs and symptoms of the baseline infection, or improvement to the extent that further antimicrobial therapy was not necessary.

This is a patient-level clinical outcome: each participant is classified according to whether the stated cure criteria were met at the assessment. Reporting the percentage gives the proportion meeting those criteria in each treatment group. It makes the result interpretable as a rate of clinical response, while the confidence interval conveys uncertainty around each group estimate.

A clinical cure endpoint is useful for assessing the status of the infection at a defined follow-up point, because it incorporates the recorded signs and symptoms and whether further antimicrobial therapy was considered necessary. It is distinct from the registry's listed microbiological outcomes, which concern responses assessed by pathogen or in microbiological analysis populations. The clinical definition does not by itself describe longer-term outcomes: the registry separately lists relapse at Late Follow-up as a secondary outcome.

The endpoint description calls the CE and MITT cure rates coprimary, but the posted primary result summarized in the record is for MITT. The CE cure result is not reported in the registry record. The record does not report additional details about how clinical assessments were adjudicated or how uncertain assessments were classified.

7. Results Posted in the Registry

• Linezolid (With or Without Aztreonam): 88.9% (40/45) versus 84.7% (83/98) on control; risk difference 4.2 percentage points (95% CI -7.4 to 15.8), risk ratio 1.05 (0.92–1.20); unadjusted two-proportion z-test p = 0.502.

8. Statistical Interpretation

9. Statistical Methods Explained

The main reported outcome is binary at the participant level: a participant either met the clinical cure definition at the TOC visit or did not. The displayed percentages represent the proportion classified as having a response in each group. The MITT population includes randomized subjects who received any amount of study drug. The registry does not report how missing TOC assessments or participants without an evaluable response were handled.

What does a confidence interval describe?

General statistical explanation: A confidence interval gives a range of values compatible with the observed data under the method used to construct it. It reflects sampling uncertainty; it is not a guarantee that the true value lies in the interval, and it is not a range containing a specified share of individual participants. For a treatment-group response percentage, the interval describes uncertainty around that group's estimated response rate. For a difference between groups, it describes uncertainty around the estimated contrast.

The group response intervals are 76.0% to 91.2% for ceftaroline and 75.9% to 96.3% for linezolid with or without aztreonam. The comparison is reported as a risk difference of 0.042, with an interval extending from a negative to a positive value. Because that interval spans zero, the posted estimate does not establish a direction of difference at the interval's stated confidence level. The registry identifies the group dispersion as a 95% Confidence Interval.

How do the effect measures differ?

General statistical explanation: The risk difference compares the response proportions by subtraction and is expressed on an absolute scale. A risk ratio compares them by division and is relative to the response proportion in the reference group. An odds ratio compares the odds of response, rather than the response probabilities themselves. These measures answer related but distinct questions and can have different numerical magnitudes.

The posted comparison gives a risk ratio of 1.05, with an interval from 0.919 to 1.199, and an odds ratio of 1.446, with an interval from 0.491 to 4.258. Each interval includes the null value for its measure: zero for a risk difference and one for a ratio. The posted unadjusted p-value is 0.502. A p-value describes how unusual data at least as incompatible with a specified null model would be if that model were correct, under the assumptions of the test. It is not the probability that the null hypothesis is true, nor does it quantify the clinical importance of an effect.

What can randomization and open-label conduct tell us?

General statistical explanation: Randomization is intended to make treatment-group comparisons less vulnerable to systematic differences in participant characteristics at baseline. It does not ensure that every relevant characteristic is balanced in a particular trial, and it does not eliminate uncertainty from the observed sample. The record identifies random allocation but does not report its implementation details. Open-label conduct means masking was absent. Because clinical cure involves assessment of signs, symptoms, and whether additional antimicrobial therapy is needed, awareness of treatment assignment could be relevant in principle. The registry record does not report whether assessment procedures were blinded or independently adjudicated.

The registry describes the CE and MITT cure rates as coprimary outcomes. The primary result available in the record is the MITT estimate; the CE estimate is not reported in the registry record. The record lists 9 outcome measures and 7 secondary outcomes, but reports no analysis entries. It does not report whether or how multiplicity across outcomes was addressed. The p-value is specifically described as unadjusted, and it should not be interpreted as evidence that any familywise error or multiple-comparison procedure was applied.

Some statistical features that would clarify interpretation are not reported in the registry record, including the original statistical analysis plan, the method used for the confidence intervals and hypothesis test, covariate adjustment, missing-data procedures, and handling of protocol deviations. Without those details, the posted summary supports a descriptive comparison and a cautious reading of the reported uncertainty, but not a reconstruction of every analytical decision.

10. Confidence Intervals and Precision

Precision concerns how tightly an estimate is determined by the observed data. The ceftaroline response estimate was 84.7%, with a 95% confidence interval from 76.0% to 91.2%. The estimate for linezolid with or without aztreonam was 88.9%, with a 95% confidence interval from 75.9% to 96.3%. The intervals cover a wide range of plausible response percentages, so neither group rate is estimated with narrow precision.

The denominators differ: 98 participants contributed to the ceftaroline estimate and 45 to the linezolid estimate. The confidence interval for linezolid is wider, consistent with greater uncertainty in an estimate based on a smaller reported denominator. In general, confidence intervals tend to be wider when the data contain less information about an estimate. This general principle does not explain every feature of an interval; the interval method and data distribution also matter.

For the between-group comparison, the estimated risk difference was 0.042, and its confidence interval extends from below zero to above zero. The interval therefore includes no difference as well as values pointing in either direction. It does not demonstrate equivalence. Equivalence requires a prespecified margin and an analysis designed to assess whether the entire uncertainty range falls within that margin; such a margin is not reported in the registry record. The record also does not report a noninferiority margin or a corresponding analysis.

The confidence intervals describe statistical uncertainty for the estimates under the method used. They do not account automatically for every possible source of bias, such as open-label assessment, missing outcome information, or differences in treatment implementation. The registry record does not report enough detail to evaluate those issues fully. The precision of the estimates should therefore be distinguished from the broader certainty of any causal or clinical conclusion.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are illustrations based on the observed effect, not a report of the original trial design. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect.

For planning at 100% of the observed effect, the figures are 1,022 participants per arm for 80% power and 1,367 participants per arm for 90% power. For planning at 75% of the observed effect, the figures are 1,878 participants per arm for 80% power and 2,513 participants per arm for 90% power. For planning at 50% of the observed effect, the figures are 4,361 participants per arm for 80% power and 5,838 participants per arm for 90% power.

In plain terms, 80% power is the probability of detecting an effect of the specified size under the planning assumptions when that effect is present. The 90% power column describes a higher planned chance of detecting that same specified effect, and therefore calls for more participants per arm. The rows illustrate that smaller effects require more participants to detect under the stated assumptions. These figures are not observed power. The registry record does not report the trial's own original sample-size justification or assumptions.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.847; treatment proportion p₁ = 0.889; average p̄ = 0.868.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4788 = 0.9385.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4779 = 0.4022.
4. n = (0.9385 + 0.4022)² / (0.0420)² = 1,021.4, rounded up to 1,022 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.846938775510204                          # control proportion
p1 <- 0.888888888888889                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(633152)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 1,022 (80% power), 1,367 (90% power)
 75% of observed effect: n per arm = 1,878 (80% power), 2,513 (90% power)
 50% of observed effect: n per arm = 4,361 (80% power), 5,838 (90% power)
power.prop.test: 1021.4 
Simulated power at n = 1,022 per arm: 0.798 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry identifies the CE and MITT clinical cure rates as coprimary efficacy outcomes. The posted primary result is for the MITT Population; the CE result is not reported in the registry record. The record also lists 7 secondary outcomes, including clinical response at end of therapy, microbiological response, pathogen-specific response, clinical relapse, microbiological reinfection or recurrence, and safety. There are 9 outcome measures in total, but the record does not include analysis entries.

When a study evaluates multiple outcomes or conducts multiple statistical tests, the chance of at least one false-positive finding can increase if each test is interpreted separately. Statistical procedures can address this issue, but which procedure is appropriate depends on the study's objectives and analysis plan. The registry record does not report whether multiplicity was addressed, how coprimary outcomes were combined for interpretation, or whether any hierarchy or adjustment was planned. The posted p-value is unadjusted; it does not indicate that a multiplicity adjustment was made.

Missing-data handling is not reported in the registry record. The MITT definition includes randomized subjects who received any amount of study drug, but the record does not state how participants without a TOC assessment were treated in the response analysis, whether outcome data were imputed, or whether sensitivity analyses were conducted. The reported group denominators are 98 for ceftaroline and 45 for linezolid with or without aztreonam, but no participant-flow details explain how these denominators arose relative to enrollment.

The record also lists CE, MITT, mMITT, and ME populations across primary and secondary outcomes, but does not provide all corresponding analysis results or detailed population definitions. Those omissions limit comparison across analysis populations and make it difficult to assess the robustness of conclusions to population choice or missing observations. The registry record does not report the full statistical analysis plan.

14. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cellulitis (1.0%), necrotizing fasciitis (1.0%), postoperative wound infection (1.0%), skin infection (1.0%).

The serious adverse event figures describe 4 affected participants among 98 at risk in the ceftaroline group and 0 among 45 at risk in the linezolid group. The registry lists Cellulitis, Necrotizing fasciitis, Postoperative wound infection, and Skin infection among the top serious terms, each at 1.0%. The record does not identify the treatment group for each listed term in this summary.

The record also reports 35 participants affected by other adverse events among 98 at risk with ceftaroline, and 15 among 45 at risk with linezolid. These are participant counts, not counts of distinct event episodes. The registry record does not report death counts. It also does not provide enough detail to determine event duration, severity beyond the serious classification, timing, or whether an event was considered related to treatment.

These figures are descriptive safety counts. They should not be read as a complete comparison of safety or as proof that the groups differ. The groups have different reported denominators, and the registry record does not include the analysis methods or detailed adverse-event listings needed for a more extensive comparative assessment.

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

The posted MITT results show clinical response at the TOC visit in 84.7% of participants in the ceftaroline group and 88.9% in the linezolid group, with or without aztreonam. The risk-difference estimate was 0.042, and its confidence interval extended across zero. The corresponding unadjusted p-value was 0.502. Taken together, these summaries describe the observed response proportions and indicate substantial uncertainty about the between-group contrast.

The results do not establish that the treatments are equivalent, nor do they establish that one is superior. A nonsignificant p-value is not proof of no difference. Equivalence or noninferiority conclusions require a prespecified margin and an appropriate analysis; those are not reported in the registry record. The confidence interval's breadth also means that the data remain compatible with a range of possible differences.

The estimate applies to the posted MITT outcome and its defined population: randomized participants who received any amount of study drug. It does not automatically describe all enrolled participants, the CE population, or the secondary outcome populations. The registry describes CE and MITT cure rates as coprimary, but the CE result is not reported in the registry record. The listed secondary outcomes are not all accompanied by results in the record.

The open-label design and missing details about outcome assessment, analysis methods, and missing-data handling are relevant limits on interpretation. The trial's enrollment was 150, while the reported MITT denominators were 98 and 45; the registry does not provide participant flow to explain this. This statistical summary describes what the recorded outcomes show and how uncertain the estimates are. It is not medical advice and does not determine which treatment should be used.

16. Why This Trial Matters Statistically

This study illustrates why an observed difference between response percentages needs to be interpreted alongside its uncertainty. The group estimates are 84.7% and 88.9%, but the comparison interval extends across zero. A point estimate gives one summary of the observed contrast; the confidence interval shows that the data do not determine its direction precisely. A p-value alone would not convey that range of uncertainty or the size of effects compatible with the data.

The registry's description of CE and MITT outcomes as coprimary also makes analysis-population reporting important. The posted result covers MITT, defined as randomized subjects who received any amount of study drug, while the CE result is not reported in the registry record. If populations differ in who is included, their results can address related but distinct estimands. Without the CE result and fuller population definitions, readers cannot compare those views of the outcome.

Open-label conduct is another statistically relevant feature because the primary outcome is a clinical assessment. Randomization can support a fair comparison, but it does not remove all potential measurement concerns or replace transparent reporting of assessment procedures. The registry does not report whether clinical assessments were blinded or adjudicated.

Finally, the record does not report multiplicity procedures, missing-data handling, or the original sample-size justification. Those omissions matter when interpreting a result among multiple outcomes and populations. The planning illustrations based on the observed effect are distinct from the trial's own design assumptions. This record therefore offers a useful example of the difference between a descriptive result, an inferential comparison, and a claim of equivalence or superiority.

17. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record contains limited information about several design and analysis features needed for a complete appraisal. Although the study is identified as randomized and open-label, the randomization sequence and allocation-concealment methods are not reported. The registry does not report how clinical cure was assessed, whether assessors were independent, or whether any adjudication procedure was used.

The reported MITT denominators are 98 for ceftaroline and 45 for linezolid with or without aztreonam, while enrollment is recorded as 150. Participant flow, reasons for exclusion from the outcome analysis, and handling of participants who did not attend the TOC visit are not reported in the registry record. Missing-data methods and sensitivity analyses are also not reported.

The primary outcome description calls CE and MITT cure rates coprimary, but the CE result is not reported. The record lists secondary outcomes but does not provide results for all of them in the information recorded. The registry record does not report a complete analysis plan, multiplicity handling, an equivalence or noninferiority margin, covariate adjustment, or the method used to calculate the reported confidence intervals and p-value.

The comparator allowed linezolid with or without optional aztreonam, but criteria for using aztreonam are not reported. The duration of treatment and further protocol details are also not reported in the registry record. These gaps limit assessment of treatment implementation, the exact analyzed populations, and the extent to which the outcome estimates can be generalized beyond the participants and conditions represented by the recorded study.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Efficacy and Safety of Ceftaroline Versus Linezolid in Subjects With Complicated Skin and Skin Structure Infections — NCT00633152.
• Registry record last updated 2017-03-14; status last verified 2017-02.
• Results first posted 2012-08-31.
• 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.

21. Record Summary

The registry record describes a completed, randomized, open-label, parallel-group phase 2 study sponsored by Forest Laboratories. It lists 150 enrolled adults with complicated skin and skin structure infections. Ceftaroline was administered intramuscularly every 12 hours; the comparator was intravenous linezolid every 12 hours, with or without optional aztreonam.

The posted primary result is clinical response at the TOC visit in the MITT Population, assessed 8 to 15 days after the end of therapy. Response was reported for 84.7% of the ceftaroline group and 88.9% of the linezolid group, with or without aztreonam. The risk-difference estimate was 0.042, with an interval extending across zero, and the unadjusted p-value was 0.502.

The registry describes CE and MITT cure rates as coprimary, but the CE result is not reported in the registry record. Important details about missing data, multiplicity, analysis procedures, and the original sample-size justification are also not reported. The estimates are therefore best read as descriptive posted results with substantial uncertainty around the comparison.