Safety and Efficacy of Daptomycin for the Treatment of Complicated Skin and Skin-structure Infections: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Daptomycin for the Treatment of Complicated Skin and Skin-structure Infections (NCT00463801), a non-randomized phase 4 study. The primary outcome is Proportion of Participants With Clinical Success at the Day 7 (D7) and Day 14 (D14) Visit After Treatment Start.

2. Clinical Question

3. Trial Design

This was a Phase 4, multicentre, open-label, uncontrolled clinical trial with a non-randomized, single-group design. The registry lists an enrollment of 52 and identifies daptomycin as the intervention. The study addressed complicated skin and skin-structure infections caused by MRSA. Its stated primary objective was to evaluate efficacy, with safety also assessed.

Because all participants were treated within a single study group, the design does not provide a contemporaneous control for estimating what would have happened without daptomycin or under a different treatment. The study can describe outcomes among the treated participants, but it cannot use random allocation to balance differences in patient characteristics or other influences across treatment groups. Open-label conduct also means that treatment assignment was not masked; the registry record does not describe additional steps to limit possible assessment bias.

The registry records a study start of 2007-01 and a primary completion of 2007-11. Its status is terminated. The reason for termination and the circumstances of ending the study are not reported in the registry record, so the status alone does not establish why the trial stopped or whether it stopped before reaching its planned enrollment.

The intervention description identifies intravenous daptomycin. The available treatment description does not provide enough detail to establish the complete regimen and duration. The registry lists secondary outcomes covering clinical success at other visits, bacteriological success, treatment duration, time to resolution, laboratory and safety monitoring, and resource use and treatment cost. The record does not describe a comparator or a randomized allocation process.

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: Intention to treat (ITT) and safety population: all patients who received at least one dose of study medication.

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 Proportion of Participants With Clinical Success at the Day 7 (D7) and Day 14 (D14) Visit After Treatment Start, measured over at Day 7 and 14.

The primary endpoint is the proportion of participants with clinical success at the Day 7 and Day 14 visits after treatment start. The registry defines success as complete resolution of infection signs and symptoms, or clinical improvement that leaves no need for further antibacterial treatment. This is a clinical endpoint: it concerns the participant’s signs, symptoms, and need for additional treatment rather than only a laboratory measurement.

Assessing the endpoint at both visits provides a way to describe clinical status at two specified points during treatment. A proportion expresses how many participants in the stated analysis population met the success definition relative to that population. To interpret such an estimate, readers need the numerator, denominator, and an indication of uncertainty. Those endpoint counts and estimates are not reported in the registry record.

Clinical success is used because it translates changes in infection into an outcome with direct clinical meaning. The definition also sets a threshold for what counts as improvement: partial resolution qualifies only when further antibacterial treatment is not required. Results depend on applying that definition consistently. The record does not report the assessment procedures, adjudication process, or endpoint results, so the extent to which assessments were standardized cannot be determined from the registry entry.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary outcome as a binary clinical-success measure at the Day 7 and Day 14 visits. A binary outcome assigns each assessed participant to a category such as success or not success according to the stated definition. Reporting the number who meet the definition alongside the number assessed would allow readers to understand the observed proportion and its denominator. The registry record does not report these endpoint counts or proportions.

What does a proportion describe?

A proportion describes the share of an analysis population that meets an outcome definition. It is a summary of observed data, not by itself a comparison or causal effect. In a single-group study, a success proportion would describe the experience of the treated group. It would not tell readers how much higher or lower the proportion was than it would have been under another treatment, because no control group was included.

Uncertainty matters as well as the point estimate. In general, a confidence interval gives a range of values compatible with the observed data under the statistical procedure used. A narrower interval indicates greater precision under that procedure, while a wider interval indicates less precision. An interval does not remove limitations in study design, correct for bias automatically, or establish that the observed outcome was caused by treatment. The registry record does not report a confidence interval for the primary endpoint.

What can an uncontrolled design establish?

A single-group design can describe outcomes and safety events observed among participants who received the intervention. It cannot make a like-for-like treatment comparison. Random allocation, when used in a controlled trial, is intended to make treatment groups comparable in expectation with respect to both measured and unmeasured characteristics. There is no such allocation: the registry identifies the trial as non-randomized and single group. Therefore, a difference from an external benchmark, if one were considered, could reflect differences in populations, care, outcome definitions, or timing rather than a treatment effect. No external comparison is reported.

Open-label conduct means that treatment was not masked. In general, knowledge of treatment may influence reporting, care decisions, or outcome assessment. The clinical-success definition offers a stated criterion, but the registry record does not report whether assessments were independently reviewed or otherwise protected from knowledge of treatment. These missing details limit what can be said about the measurement process without demonstrating that any particular assessment was inaccurate.

How should the safety counts be read?

The safety data are counts for the all-patients group. The registry lists 52 at risk for serious adverse events and 4 participants affected; it also lists 52 at risk for other adverse events and 6 affected. These are event summaries in the registry, not controlled estimates of excess risk. A count alone does not show whether an event was related to treatment, how severe it was beyond the serious classification, or how it compares with background occurrence. The record does not report deaths.

The listed serious adverse-event terms each have a registry percentage of 1.9%. These terms provide descriptions of events recorded as serious, not evidence that daptomycin caused them. The registry does not provide enough information in this record to infer the timing, clinical course, or treatment relationship for each term.

What do planning illustrations mean?

General sample-size planning estimates ask how many participants a future study might require under specified assumptions. The registry’s stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of an observed effect. These are planning assumptions, not a description of this trial’s actual design, which is single group and uncontrolled. Any illustrated sample size is a planning quantity, not an observed result or observed power. The record does not report the trial’s own sample-size justification or statistical analysis plan.

For binary outcomes, planning depends on assumptions about event proportions and the effect a future study is intended to detect. For time-to-event outcomes, planning can instead be based on event counts. The registry’s general note distinguishes those approaches, but the primary endpoint reported for this study is a binary success measure. No trial-specific power calculation, target effect, confidence interval method, or hypothesis test is reported in the registry record.

Why can event variability matter?

In general, over-dispersion means that observed variation is greater than a statistical model assumes. If a model assumes less variability than the data contain, uncertainty may be understated and inferential results can be too optimistic. The registry record does not describe an over-dispersion model or any fitted statistical model for this trial. It is therefore not possible to assess whether such methods were used.

Overall, the registry provides the design, endpoint definition, and selected safety counts, but not the primary outcome analysis or a statistical methods description. Readers should distinguish the information that is explicitly recorded from general statistical considerations that would apply to analyses of this kind.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Daptomycin Intravenous")
n      <- c(52)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Daptomycin Intravenous  52  0  0.0  0.0  6.8  0.0  6.9  0.0  6.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures, including the primary clinical-success endpoint and secondary outcomes that cover clinical, bacteriological, safety, and resource-use topics. When several outcomes or assessment times are examined, the chance of finding an apparently notable result by chance can increase if each is tested separately. General approaches to this issue include prespecifying a primary outcome, adjusting for multiple comparisons, or treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy, adjustment, or hierarchy for interpreting secondary outcomes.

The primary endpoint is assessed at Day 7 and Day 14. Although both visits are part of the stated primary outcome, the record does not explain how the two time points would be analyzed together or separately, or how their results would be interpreted if they differed. Statistical tests, confidence intervals, and analysis results for these visits are not reported in the registry record.

The outcome population is described as the intention-to-treat and safety population, defined as all patients who received at least one dose of study medication. The record does not describe a separate analysis population or explain how participants with missing visit assessments, withdrawals, or incomplete outcome data were handled. Missing-data rules, imputation procedures, and sensitivity analyses are not reported in the registry record. Without those details and the endpoint denominators, readers cannot determine how missing assessments may have affected the reported outcomes.

The registry reports no analyses. This means the entry does not supply an inferential analysis to assess, and it does not establish that analyses were or were not conducted outside the registry. The statistical analysis plan, including any planned adjustments or methods for handling missing data, is not reported in the registry record.

12. 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 (1.9%), device related infection (1.9%), soft tissue infection (1.9%), femur fracture (1.9%).

For the all-patients group, the registry reports 4 participants with a serious adverse event among 52 at risk. It reports 6 participants with another adverse event among 52 at risk. These are descriptive safety counts. They do not provide a comparison with another treatment group, and they do not establish that the events were caused by daptomycin.

The registry lists Cellulitis, Device related infection, Soft tissue infection, and Femur fracture among the top serious adverse-event terms, each with a recorded percentage of 1.9%. These labels describe events recorded in the registry; the listing does not establish their relationship to treatment. The record does not report event timing, participant-level details, or the clinical course associated with each term.

Deaths are not reported in the registry record. That absence should not be interpreted as a reported count of zero. The available safety summaries also do not explain how adverse events were collected, coded, or assessed for relatedness. For these reasons, the counts provide a limited description of recorded safety events, not a full comparative safety evaluation.

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

This trial’s record documents an evaluation of intravenous daptomycin in adults with complicated skin and skin-structure infections caused by MRSA. It specifies clinical success at the Day 7 and Day 14 visits as the primary endpoint and defines what qualifies as success. It also records selected safety counts and secondary outcome topics. These details clarify what the study intended to assess and the kind of information entered in the registry.

The registry record does not report the primary endpoint results. It therefore does not show how many participants met the success definition at either visit, the size of any estimated success proportion, or the uncertainty around such an estimate. The record’s description of an intended outcome is not a result, and the lack of a reported result should not be mistaken for either success or failure.

Even if outcome estimates were available, the uncontrolled single-group design would limit causal interpretation. An observed outcome among treated participants would not establish what would have occurred under a different treatment or without the intervention. Open-label conduct and the absence of reported assessment procedures also leave questions about how clinical success was measured. These are design and reporting constraints, not proof that the study’s observations are incorrect.

The safety counts indicate that adverse events were recorded, including serious events. They do not establish comparative safety or treatment causation. The registry status of terminated does not explain why the study ended, and it should not be treated as a result about the intervention. In short, the record supports a description of the study design, outcome definitions, and selected safety information, but not a conclusion about the magnitude of clinical benefit or comparative harms.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a clear clinical question can coexist with important limits on inference. The registry identifies a defined population, an intervention, and a clinically interpretable endpoint. It also identifies the absence of randomization and a control group. Those design features determine what conclusions the data could support, regardless of how carefully an endpoint is defined.

The distinction between describing an outcome and estimating a treatment effect is especially important. A single-group success result, if reported, would describe the observed experience of the treated population. A treatment effect requires a basis for comparing outcomes under alternative conditions. Without a concurrent comparator, changes cannot be attributed to the intervention alone. Statistical methods cannot recreate the randomized comparison that the design does not contain.

The record also illustrates why endpoint results and analysis details matter. A defined endpoint is not enough to judge the evidence: readers need the observed counts, denominators, and uncertainty, along with information about missing assessments and planned analyses. Here the primary outcome results, statistical analysis, and missing-data procedures are not reported in the registry record. This leaves the central efficacy question unanswered by the posted information.

Finally, safety summaries require context. Counts and event terms can help describe what was recorded, but a controlled comparison and details on event assessment are needed to interpret differences or attribute events. The trial’s status and limited reporting should be considered separately from any judgment about the intervention. The statistical value of the record lies in clarifying what was planned and reported, as well as what the available evidence cannot establish.

15. 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 important trial-specific limitation is the single-group, uncontrolled design. There is no comparator for separating outcomes during treatment from outcomes that might have occurred under another treatment or usual care. Non-randomized allocation also means the study does not use random assignment to balance possible influences across groups. These limitations restrict causal interpretation.

The study was open label, and the registry does not report whether clinical outcomes were assessed independently or with other safeguards against assessment bias. The primary endpoint depends on clinical signs, symptoms, and whether further antibacterial treatment was required. The registry provides a definition but not the procedures used to apply it.

Primary endpoint results are not reported in the registry record. The record also does not report endpoint denominators, confidence intervals, statistical tests, a sample-size justification, or the statistical analysis plan. The handling of missing assessments and withdrawals is not described. These omissions prevent assessment of the precision and robustness of the primary outcome.

The registry status is terminated, but the reason is not reported. The available entry does not establish whether termination was related to recruitment, safety, efficacy, or another consideration. Treatment details are also incomplete in the available arm description, and the record does not provide additional information on participant characteristics or the clinical course of recorded events.

Safety information is limited to the recorded counts and event terms. There is no comparator, and treatment-relatedness details are not reported. Thus, the safety summaries cannot establish comparative risks or causality. Together, these design and reporting limitations leave the primary efficacy question unresolved by the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy of Daptomycin for the Treatment of Complicated Skin and Skin-structure Infections — NCT00463801.
• Registry record last updated 2011-03-24; status last verified 2011-03.
• Results first posted 2010-12-23.
• 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.

19. Record Summary

NCT00463801 is a Phase 4, multicentre, open-label, uncontrolled, non-randomized, single-group trial of intravenous daptomycin for complicated skin and skin-structure infections caused by MRSA. The registry lists an enrollment of 52, a study start of 2007-01, a primary completion of 2007-11, and a status of terminated.

The primary endpoint was clinical success at the Day 7 and Day 14 visits, defined by resolution or sufficient improvement of infection signs and symptoms without need for further antibacterial treatment. The primary endpoint results and statistical analyses are not reported in the registry record. Safety summaries include 4 participants with a serious adverse event and 6 with another adverse event, each among 52 at risk. The reason for termination, missing-data procedures, and statistical analysis plan are not reported.