Statins for the Early Treatment of Sepsis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Statins for the Early Treatment of Sepsis (NCT00528580), a randomized phase 2 study. The primary outcome is Time to Clinical Stability.

2. Clinical Question

3. Trial Design

This was a randomized, placebo-controlled Phase II trial with a parallel-group design. The registry records quadruple masking, meaning it identifies the study as masked at that level, but does not specify in the registry record which roles were masked or how masking was maintained. The sponsor was the University of Chicago. The condition listed was sepsis.

The registry lists enrollment of 68 participants. The posted outcome results include 34 participants in the treatment group and 34 in the control group. Participants assigned to treatment received simvastatin 80 mg once daily, by mouth or through a nasogastric or gastrostomy tube; participants assigned to control received an identical-appearing placebo by the same routes. The record does not give further details about allocation procedures or treatment duration.

The trial began in 2008-02, and its primary completion date is listed as 2011-09. Its current status is recorded as terminated. The reason for termination, whether recruitment ended as planned, and whether the posted enrollment represents the full intended enrollment are not reported in the registry record. The trial was described as a Phase II study intended to assess the feasibility of a larger investigator-initiated translational research protocol involving multiple clinical services. The registry does not provide a sample-size justification or a detailed account of the study’s operational feasibility findings.

The registry posts one primary outcome measure and no secondary outcomes. Its primary outcome is time to clinical stability, with a stated timeframe of 24 hours. The record does not provide a detailed statistical analysis plan, explain the relationship between that timeframe and the time measured in days, or identify any additional analysis populations.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Time to Clinical Stability, measured over 24 hours.

The primary outcome, time to clinical stability, is a continuous measure reported in days. The registry defines clinical stability as normalization of vital signs for each enrolled subject. It describes the group result as a mean time to normalization with a standard error. The posted results give a mean of 3.0 days and a standard error of 1.0 in each group.

As a general statistical concept, a time-to-stability measure can summarize how quickly a group reaches a stated clinical condition. A mean expresses the average observed time, while the standard error describes the precision of the estimated group mean. These are different quantities: the standard error is not a description of how widely individual participants’ times varied. The registry does not post a standard deviation for the outcome.

The outcome’s stated timeframe is 24 hours, while its unit is days and its definition refers to time until vital signs normalize. The registry record does not clarify how the 24-hour timeframe applies to this time-to-event description, including whether it refers to the period for assessing the outcome or another aspect of its measurement. That ambiguity matters when interpreting the endpoint’s operational definition. The record also does not report which vital signs were required to normalize, how normalization was determined, or how participants without observed normalization were handled.

Clinical stability was selected as the primary measure in a study focused on early treatment of sepsis and clinical outcomes. The posted record identifies the endpoint but does not explain why it was chosen over other possible measures or establish how it relates to longer-term outcomes.

7. Results Posted in the Registry

• Treatment Group: mean 3.00 versus 3.00 on control; difference 0.00 (95% CI -2.77 to 2.77), standardized effect d = 0.00; z-test p = 1.000.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint as continuous and reports it using a mean and standard error. The posted comparison gives a mean difference, a confidence interval, and an unadjusted p-value. It does not describe the statistical test, model, assumptions, or analysis population used to obtain them. The explanations below describe general statistical concepts, not a claim about undocumented choices in this trial.

What does a mean summarize?

In general, the arithmetic mean summarizes the average value across observations. For a time measure, it reflects the average recorded time in the analyzed group. It does not show the full distribution: different patterns of individual times can produce the same mean. A mean may also be affected by particularly high or low observations. The registry record does not provide individual outcome values, medians, ranges, or a distributional plot, so the shape and spread of participant-level times cannot be assessed.

What is a standard error?

In general, a standard error describes the sampling precision of an estimated statistic, such as a group mean. It is not the standard deviation of individual outcomes and should not be interpreted as the typical distance between a participant’s result and the group mean. The posted standard error is 1.0 for each group. The registry does not explain how it was calculated or whether any adjustment was used.

What does the mean difference represent?

A difference between group means expresses the contrast in average outcomes on the endpoint’s original scale. Here, the reported mean difference is 0.0 days, matching the identical posted means of 3.0 days in each group. This is a point estimate: it summarizes the observed contrast but does not alone show how precisely that contrast has been estimated. The record labels the comparison as a mean difference but does not state the direction convention. Since the estimate is zero, the sign convention does not alter the point estimate; it would matter when describing the direction of nonzero values in the confidence interval.

How should the p-value be read?

In general, a p-value describes how incompatible the observed data, or data more extreme, are with a specified null hypothesis under the assumptions of a statistical test. The posted unadjusted p-value is 1.0. The registry record does not name the test or state its assumptions, so the value cannot be independently interpreted as the output of a particular method. A p-value does not quantify the probability that treatment has no effect, and it does not measure clinical relevance. The estimate and confidence interval provide complementary information about the magnitude and precision of the observed comparison.

Why can precision be limited?

General statistical reasoning links precision to the amount and variability of information available for an estimate. This trial’s posted results include 34 participants per group and standard errors of 1.0 for both group means. The confidence interval for the mean difference extends from -2.772 to 2.772 days. Those reported values describe uncertainty in the group comparison. The registry does not provide a standard deviation or other account of variability, and no independent calculation of the comparison is warranted from the posted summary alone.

For continuous outcomes, the choice of analysis can depend on the outcome distribution and the assumptions of the method. As a general matter, a skewed distribution or influential observations may affect a mean-based analysis. The registry does not report a distributional assessment, robust method, transformation, or sensitivity analysis. It also does not state whether the comparison adjusted for baseline characteristics or other factors.

What does the design contribute?

In general, random assignment aims to make comparison groups similar with respect to both measured and unmeasured factors, on average, before treatment. Masking can reduce certain sources of bias in treatment delivery or outcome assessment. The registry describes this study as randomized and quadruple-masked, but does not detail the procedures used. These design labels do not remove uncertainty due to the number of observed outcomes, missing data, measurement choices, or analysis decisions.

The record identifies a parallel-group comparison of simvastatin and placebo and posts one primary endpoint. It does not report the planned statistical methods or a sample-size justification. Although the registry includes a planning illustration based on the observed effect, such planning values are not observed power and do not document the trial’s own design rationale. No claim about the trial’s intended power or its prospective assumptions can be made from the posted record.

10. Confidence Intervals and Precision

The reported mean difference in time to clinical stability is 0.0 days, with a confidence interval from -2.772 to 2.772 days. This interval communicates uncertainty around the estimated contrast. It includes the null value of zero and also includes negative and positive values. Because the registry record does not state the sign convention, the direction associated with each side of the interval should not be assigned to a particular group without qualification.

As a general statistical concept, a confidence interval is a range produced by a method intended to have a stated coverage rate over repeated samples when its assumptions hold. It is not a guarantee that the true value lies in this particular interval, nor does it assign probabilities to individual values within the interval. The registry does not state the confidence level or the method used to construct this interval, so those details are not reported in the registry record.

The interval is broad enough to include differences in either direction, despite the zero point estimate. That means the equal observed means should not be mistaken for a highly precise estimate of no difference. The interval gives a clearer view of uncertainty than the p-value alone, but it does not establish which values would be clinically important. A threshold for a clinically meaningful difference is not reported in the registry record.

Both groups have 34 participants in the posted results, and each reported standard error is 1.0. These figures describe the posted summaries, but they do not explain whether all randomized participants contributed an outcome or how missing observations were treated. The registry does not report further precision measures, subgroup intervals, or sensitivity analyses for the primary outcome.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no posted secondary outcomes. It also records zero listed analyses. The primary comparison has an unadjusted p-value of 1.0, but the registry record does not state whether any multiplicity procedure was planned or applied. Without a fuller statistical plan, it is not possible to determine how the primary comparison fits into any broader set of planned analyses or hypotheses.

Multiplicity is a general concern when several outcomes, time points, subgroups, or statistical tests are examined. Testing many hypotheses can increase the chance of finding an apparently notable result by chance. The registry’s lack of posted secondary outcomes does not establish whether the investigators considered additional outcomes or analyses; those details are not reported in the registry record. No adjustment for multiple comparisons should be assumed.

The record gives 34 participants in each group for the posted outcome but does not state whether these are all randomized participants, all participants with available endpoint data, or a different analysis population. It does not identify an intention-to-treat, per-protocol, or safety population. The handling of participants who withdrew, had incomplete follow-up, or lacked a measurable time to stability is not reported in the registry record.

Missing-data methods can affect both the estimate and its uncertainty, depending on how much data are missing and why. Those details are not posted for this outcome. The record also does not report imputation, censoring rules, exclusions, or sensitivity analyses. Consequently, the reported means and comparison can be described as posted, but the population and data-processing choices behind them cannot be fully assessed.

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.

The adverse-event results list 34 participants at risk for serious adverse events in the simvastatin group and 34 in the placebo group. The number affected is recorded as 0 in each group. The same at-risk counts and zero affected participants are listed for other adverse events. Death counts are not reported in the registry record, and no serious adverse-event terms are listed.

These figures describe what the registry posts; they do not establish that no adverse events occurred outside the registry’s definitions, collection period, or reporting process. The record does not specify the event-collection period, severity criteria, relatedness assessment, or detailed safety-analysis population. It also does not provide information about missing safety observations.

Zero affected participants in the posted categories should therefore be read as a registry result, not as proof that risk was absent. With no event counts beyond those posted, the record cannot characterize the types, timing, or causes of adverse events. The safety information is limited to the group counts and categories recorded above.

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

The central statistical result is straightforward but limited: the posted group means for time to clinical stability are both 3.0 days, producing a reported mean difference of 0.0 days. The confidence interval, from -2.772 to 2.772 days, shows that the estimate is not precise enough to rule out differences in either direction under the comparison’s stated uncertainty. The unadjusted p-value is 1.0.

This does not demonstrate that simvastatin and placebo are equivalent. Equivalence requires a defined margin and an analysis designed to assess whether the plausible difference lies within that margin. No equivalence margin or equivalence analysis is reported in the registry record. Nor does the result prove that there is no effect. It reports the observed outcome comparison and its uncertainty among the participants represented in the posted results.

The registry describes a Phase II study intended to assess feasibility for a larger investigator-initiated protocol, as well as to test a hypothesis about statins, inflammatory cytokines, and clinical outcomes. The posted primary outcome is time to clinical stability. No cytokine result or secondary clinical outcome is posted, so those questions cannot be evaluated from these results.

The terminated status is relevant context, but the reason for termination and its implications for outcome collection or interpretation are not reported in the registry record. The record also does not provide the original analysis plan, sample-size justification, missing-data handling, or details needed to assess how closely the posted analysis follows its intended approach.

In practical statistical terms, the result is best read as an estimate centered at zero with substantial uncertainty, rather than as a definitive answer about treatment effects. It describes this trial’s posted primary comparison and cannot by itself settle broader questions about outcomes or populations not measured in the record.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why a point estimate and its precision should be read together. The observed means are equal, and the mean difference is 0.0 days. Taken alone, that point estimate might appear to indicate no contrast. The confidence interval from -2.772 to 2.772 days adds essential context: it spans differences in both directions and therefore leaves considerable uncertainty around the estimate.

The study also illustrates the importance of matching interpretation to the stated purpose. The registry describes a Phase II feasibility study intended to inform a larger investigator-initiated translational research protocol. That context differs from a definitive evaluation designed to establish equivalence or to exclude a clinically meaningful effect. The registry does not report a sample-size justification or a threshold for clinical importance, so the strength of the evidence for any such claim cannot be assessed from the record.

Its posted information also highlights how registry completeness affects statistical interpretation. The record identifies randomization, masking, the primary endpoint, group summaries, and a comparison, but does not provide the detailed analysis plan, missing-data handling, analysis population, or reason for termination. These omissions limit assessment of the methods and the extent to which results reflect the intended analysis.

The lesson is not that the outcome is uninformative. Rather, its value lies in a careful description of what was observed and how uncertain the comparison remains. Avoiding the leap from equal means to proof of no difference is central to sound interpretation of clinical trial results.

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.

Several features of the registry record limit interpretation of this trial’s primary outcome. The study status is terminated, but the reason for termination is not reported in the registry record. Without that context, it is not possible to judge whether termination affected recruitment, follow-up, outcome collection, or analysis. The record also does not state whether enrollment of 68 represents the intended enrollment or the number reached before termination.

The endpoint is described as time to normalization of vital signs and is reported in days, while its stated timeframe is 24 hours. The registry does not clarify how these descriptions fit together. It does not define which vital signs were measured, the criteria for normalization, the assessment schedule, or the handling of participants who did not reach stability during observation.

The record reports group means, standard errors, a mean difference, a confidence interval, and an unadjusted p-value, but does not provide the test or model used. It also does not report an analysis population, missing-data procedures, exclusions, protocol deviations, or sensitivity analyses. Participant-level distributions and standard deviations are absent, limiting assessment of variability and the suitability of a mean-based summary.

The registry posts no secondary outcomes and no adverse-event terms, while death counts are not reported in the registry record. This leaves questions about other outcomes and the scope of safety reporting unanswered. These limitations do not change the posted result, but they constrain the conclusions that can be drawn from it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Statins for the Early Treatment of Sepsis — NCT00528580.
• Registry record last updated 2018-09-05; status last verified 2018-08.
• Results first posted 2018-06-07.
• 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

The registry record describes NCT00528580, Statins for the Early Treatment of Sepsis, as a randomized, placebo-controlled, quadruple-masked, parallel Phase II trial sponsored by the University of Chicago. It lists sepsis as the condition, enrollment of 68, a start date of 2008-02, primary completion in 2011-09, and a terminated status.

The treatment group received simvastatin 80 mg once daily, and the control group received identical-appearing placebo. The primary outcome was time to clinical stability. The posted group means were 3.0 days in each group, with standard errors of 1.0. The mean difference was 0.0 days, with a confidence interval from -2.772 to 2.772 days and an unadjusted p-value of 1.0.

The registry does not report the reason for termination, a detailed analysis plan, missing-data methods, or an analysis population. The posted primary comparison therefore supports a description of the observed result, while leaving important methodological and interpretive details unresolved.