Statin Therapy in the Treatment of Sepsis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Statin Therapy in the Treatment of Sepsis (NCT00676897), a randomized phase 2, phase 3 study. The primary outcome is Time to Shock Reversal.

2. Clinical Question

The registry record describes the study as examining statin therapy in the treatment of sepsis and lists inflammatory marker levels as a secondary outcome. Its brief summary states an expectation about IL-6 levels and more rapid shock reversal. That stated expectation is a rationale, not a result: the posted primary outcome values alone do not establish that one assigned treatment caused a difference in shock reversal time.

3. Trial Design

This was a randomized, parallel-group trial recorded as quadruple masked. The registry lists both Phase 2 and Phase 3. Beth Israel Deaconess Medical Center is named as the sponsor, and the trial status is completed. The recorded enrollment is 18 participants. The registry dates the study start as 2008-02 and primary completion as 2010-12.

Participants were assigned to a Statin Group or a Placebo Group. The Statin Group is described as receiving simvastatin 40 mg by mouth or through a nasogastric tube; the comparison group received placebo. The posted outcome counts are 8 for the Statin Group and 10 for the Placebo Group. The record does not report the randomization sequence, allocation concealment procedures, or the roles covered by quadruple masking. It also does not state whether the treatment was administered in any other way.

The primary outcome was time to shock reversal, reported as a mean in hours with standard deviation, over a timeframe of up to 7 days. In the posted results, the Statin Group mean is 44.4 hours with a standard deviation of 57.3, and the Placebo Group mean is 28.6 hours with a standard deviation of 34.5. No confidence interval, p-value, or other two-group estimate is reported in the registry record.

The record lists inflammatory marker levels as a secondary outcome and indicates two outcome measures. It does not report a detailed protocol, statistical analysis plan, eligibility criteria, or treatment-duration schedule. These omissions limit how fully the design and conduct can be reconstructed from the registry record.

4. Participant Flow and Accounting

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

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 Shock Reversal, measured over up to 7 days.

Time to shock reversal measures the elapsed time until shock reversal, recorded in hours. A time-based endpoint can describe how quickly an event occurs, rather than simply whether it occurred by a particular point. The registry specifies a timeframe of up to 7 days. It does not give a more detailed operational definition of shock reversal, including the exact criteria used to decide when reversal had occurred.

The endpoint is relevant to the trial’s stated question because the study summary expresses an interest in more rapid shock reversal. Interpreting this measure requires attention to both its group averages and the spread of individual observations. The posted mean is 44.4 hours in the Statin Group and 28.6 hours in the Placebo Group. The corresponding standard deviations are 57.3 and 34.5.

These values describe the reported groups, but they do not by themselves provide an estimate of the uncertainty in the difference between groups. The registry record does not report a confidence interval or a statistical test for the primary outcome. Nor does it specify in the endpoint description how participants who did not experience shock reversal within the timeframe were handled. That detail is important for interpreting a time-based measure and is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous: it is measured on a numeric scale, in hours. The registry summarizes it using the mean and standard deviation. The mean is the arithmetic average of observed values. The standard deviation describes how far observations tend to vary around that average. These summaries give information about the center and spread of the recorded times, but neither is a direct measure of uncertainty in the difference between treatment groups.

What does a confidence interval add?

General explanation: a confidence interval gives a range of values compatible with the data and the assumptions of the statistical method used. For a difference between group means, it conveys both the estimated direction and the precision of that estimate. A narrow interval indicates greater precision than a wide interval, while an interval that includes no difference can be consistent with a range of possibilities. The registry record does not report a confidence interval for time to shock reversal, so the precision of a comparative estimate cannot be assessed from the posted summaries alone.

Why is a group comparison more than a comparison of means?

General explanation: observed group means can differ because of a true underlying treatment contrast, random variation, or both. A statistical comparison accounts for sample size and variability under a specified analysis. Here, the registry reports means, standard deviations, and outcome counts, but no inferential two-arm result. The record’s note that values were missing or not estimable for a two-arm comparison indicates that a comparative result is not available in the posted registry information. The reason for that status is not reported in the registry record.

How should the spread be understood?

General explanation: a standard deviation is a descriptive measure of dispersion, not a confidence interval and not the standard error of a treatment contrast. A large spread relative to the mean can reflect substantial variation among observations. For time outcomes, distributions can also be asymmetric, but the distribution of participant-level times is not reported in the registry record. No assumption about that distribution should be treated as a documented feature of this trial.

General explanation: over-dispersion means that observations vary more than a particular statistical model expects. When a model assumes less variability than is present, standard errors and uncertainty estimates can be too small. Appropriate methods depend on the outcome’s distribution and design. The registry does not identify the method intended for this endpoint or describe any checks of model assumptions, so it is not possible to say whether over-dispersion was assessed.

What does randomization contribute?

General explanation: random assignment is intended to make treatment groups comparable, on average, with respect to factors measured and unmeasured at baseline. It does not guarantee exact balance in a small trial. The record identifies the study as randomized but does not report baseline characteristics or the sequence-generation and allocation-concealment procedures. Therefore, the registry information does not permit a detailed evaluation of balance or implementation.

The trial is recorded as parallel-group and quadruple masked. In general, masking can reduce the influence of knowledge of treatment assignment on care, outcome assessment, or reporting, depending on which people are masked. The registry does not identify those roles or report whether masking was maintained. The design labels alone cannot establish how masking operated in practice.

What does the planning illustration represent?

The planning illustration is described as using the observed effect, two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation. It considers an effect defined as a stated fraction of the observed effect. These are planning assumptions, not evidence about what was achieved in the trial. Any resulting sample-size figures represent participants per arm for a chosen planning scenario, not observed power. The planning assumptions do not show that the trial was designed using those assumptions; the trial’s own sample-size justification is not reported in the registry record.

General explanation: planned sample size depends on the effect worth detecting, the chosen error rate, allocation, variability, and the method used. A planning calculation based on an effect estimated from a small study can be uncertain because that estimate may itself be imprecise. The registry record does not report the original design assumptions, any target enrollment rationale, or whether the planned sample size changed during the trial.

The posted record also gives no analysis plan describing covariate adjustment, transformations, handling of censoring, or sensitivity analyses. These methods can affect how time outcomes are estimated, particularly if some participants do not experience the event during the specified timeframe. Without the endpoint definition and analysis details, no particular model or interpretation should be attributed to the trial.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Statin Group", "Placebo Group")
n   <- c(8, 10)
m   <- c(44.4, 28.6)
sp  <- c(57.3, 34.5)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Statin Group  8  44.400  57.300  -3.504  92.304
CARM  Placebo Group  10  28.600  34.500  3.920  53.280

11. Multiplicity, Missing Data and Analysis Populations

The registry lists inflammatory marker levels as a secondary outcome and indicates two outcome measures. It does not report a multiplicity strategy, such as a prespecified approach to controlling the chance of false-positive findings across multiple outcomes or analyses. It also does not describe a hierarchy of outcomes or distinguish confirmatory from exploratory analyses. The analysis plan for secondary outcomes is not reported in the registry record.

The record reports no analyses and does not give a comparative statistical result for the primary endpoint. It notes that values were missing or not estimable for a two-arm comparison of the continuous endpoint. The reason for this and whether any analyses were conducted outside the registry record are not reported in the registry record. A count of analyses in the registry does not establish what analysis was planned or performed.

Although the posted outcome counts are 8 and 10, the record does not specify the analysis population, such as whether all randomized participants were intended to be included. It does not state whether the primary analysis followed assigned treatment, whether participants were excluded, or how protocol deviations were handled. The counts therefore should not be taken as confirmation of a particular analysis population.

Missing-outcome methods are also not described. The record does not report how participants without an observed shock-reversal time, or with incomplete follow-up, were handled. It does not state whether data were censored, imputed, or excluded from an analysis. The endpoint timeframe is up to 7 days, but the way that limit was incorporated into the analysis is not reported in the registry record. These gaps make it difficult to assess how missing data might affect the group summaries or a potential comparison.

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 0% reporting threshold.

The posted serious adverse event counts are 0 among 8 participants at risk in the Statin Group and 0 among 10 participants at risk in the Placebo Group. The record also lists 0 other adverse events in each group, with the same respective numbers at risk. These are counts of events recorded in the registry, not estimates of comparative safety.

A zero count means no events of that category were posted for those participants; it does not show that the underlying risk is zero. With a small number of participants, uncommon events may not occur during observation even when a risk exists. The registry record does not provide a statistical comparison or confidence interval for adverse events, so the precision of any difference cannot be assessed.

Deaths are not reported in the registry record: the death fields have no value. This is different from a reported count of zero. The record lists no top serious-event terms and does not provide a detailed account of event definitions, ascertainment, or follow-up duration for safety outcomes. These safety counts should therefore be interpreted as limited registry reporting, not as a complete characterization of possible harms.

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

The posted results establish that the registry reports mean time to shock reversal of 44.4 hours in the Statin Group and 28.6 hours in the Placebo Group, with standard deviations of 57.3 and 34.5, respectively. They also establish that the outcome counts were 8 and 10. These descriptive values summarize the recorded groups; they do not show the individual participants’ times or the uncertainty in a between-group contrast.

The registry record does not provide a two-arm statistical comparison, confidence interval, or p-value for the primary outcome. It therefore does not establish whether the observed group summaries represent a statistically distinguishable difference. It also does not report enough information about endpoint handling and the analysis population to determine how all enrolled participants contributed to the primary outcome summaries.

The trial’s brief summary gives an expectation about IL-6 levels and more rapid shock reversal. An expectation is not a finding. The posted values should not be interpreted as proof that simvastatin did or did not cause a change in shock-reversal time. A randomized design can support causal interpretation when properly conducted and analyzed, but the registry information does not report the comparative analysis needed to assess the treatment contrast.

Likewise, the adverse-event counts do not establish an absence of risk. They show zero posted serious and other adverse events in the two small groups, while death counts are not reported. The record does not provide uncertainty estimates or detailed safety follow-up.

In short, the record supports a descriptive account of the reported primary endpoint and adverse-event counts. It does not support a precise estimate of treatment effect, a definitive conclusion about the direction or size of a causal effect, or a comprehensive assessment of safety. Those questions remain unresolved by the statistical information reported in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates the difference between reporting group summaries and reporting a treatment comparison. Means and standard deviations describe the observed outcome within each group. For a clinical question about whether outcomes differ under randomized assignment, a comparative estimate and its uncertainty are also important. Those are not reported for the primary endpoint in this record.

The distinction matters especially when the group sizes are small and the reported measurements are dispersed. In general, the amount of uncertainty in a comparison depends on sample size and variability, among other features. Without a confidence interval or an inferential result, readers cannot tell how precisely the difference between groups has been estimated. The group summaries are informative, but they cannot replace that missing comparison.

The record also demonstrates why analysis details matter for time-based outcomes. Interpretation depends on how shock reversal was defined, how participants without an observed reversal were handled, and which analysis population was used. These details are not reported in the registry record. A stated timeframe alone does not explain how incomplete follow-up or events after the timeframe were treated.

Finally, a small trial’s observed effect can be an uncertain basis for planning later studies. General planning calculations depend on explicit assumptions and should not be confused with observed power or evidence that an effect is established. The planning illustration is described using the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. The trial’s own sample-size justification is not reported in the registry record.

For biostatistical interpretation, the central lesson is to separate observed summaries, inferential evidence, and planning assumptions. Each addresses a different question, and the registry record does not contain enough comparative analysis to treat them as interchangeable.

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 primary endpoint is named as time to shock reversal, but its operational definition is not reported in the registry record. The record does not explain how shock reversal was assessed, whether assessments were scheduled, or how a participant without reversal during the timeframe was represented in the analysis. These details are especially relevant when interpreting a time-based endpoint.

The posted outcome counts are small: 8 in the Statin Group and 10 in the Placebo Group. The registry provides group means and standard deviations, but no comparative estimate or confidence interval. As a result, the precision of any treatment contrast cannot be evaluated. The record’s note that values were missing or not estimable for a two-arm comparison does not explain why a comparative result is unavailable.

The registry does not report baseline characteristics, eligibility criteria, the randomization procedure, allocation concealment, or the roles included in quadruple masking. It identifies the trial as randomized and masked, but the record does not permit an assessment of how those procedures were implemented or whether groups were balanced.

The analysis population, missing-data strategy, and handling of protocol deviations are not reported. The statistical analysis plan, sample-size justification, and multiplicity approach are also not reported. The record lists inflammatory marker levels as a secondary outcome, but does not provide enough detail to assess its analysis alongside the primary endpoint.

Safety reporting is limited to event counts and participants at risk; deaths are not reported. Detailed event definitions and safety follow-up are not reported in the registry record. These limitations concern what can be concluded from the registry information and do not establish what may have been documented elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Statin Therapy in the Treatment of Sepsis — NCT00676897.
• Registry record last updated 2017-06-14; status last verified 2017-05.
• Results first posted 2017-06-14.
• 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 completed trial, sponsored by Beth Israel Deaconess Medical Center, is recorded as a randomized, quadruple-masked, parallel-group study in septic shock. It lists Phase 2 and Phase 3 and an enrollment of 18. The recorded start is 2008-02, and primary completion is 2010-12.

The intervention was simvastatin 40 mg by mouth or nasogastric tube, compared with placebo. The primary endpoint was time to shock reversal in hours over up to 7 days. The Statin Group had 8 participants, a mean of 44.4 hours, and a standard deviation of 57.3. The Placebo Group had 10 participants, a mean of 28.6 hours, and a standard deviation of 34.5. No two-arm statistical comparison is reported in the registry record.

Inflammatory marker levels are listed as a secondary outcome. Serious and other adverse-event counts are 0 in both groups; deaths are not reported. Analysis methods, missing-data handling, and the sample-size justification are not reported in the registry record.