Effects of Code Sepsis Implementation on Emergency Department (ED) Sepsis Care: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Code Sepsis Implementation on Emergency Department (ED) Sepsis Care (NCT04148989), a non-randomized na study. The primary outcome is Door-to-antibiotic Time.

2. Clinical Question

3. Trial Design

This completed study is registered as a nonrandomized, single-group study of full implementation of the Code Sepsis protocol. The registry lists an enrollment of 180402 and identifies sepsis as the condition. The study dates run from 2018-11-13 to primary completion on 2023-01-23. The registry’s phase category is not applicable.

Although the model is categorized as single group, the arm descriptions distinguish four settings: usual care before implementation at the intervention site, Code Sepsis after implementation at that site, usual care before implementation at control sites, and usual care at control sites after implementation. This structure describes comparisons across time and sites, not random assignment to treatment. The registry explicitly cautions that the arms are not a like-for-like control comparison. Differences between periods or hospitals could therefore reflect factors beyond the protocol; the record does not report enough information to determine how such differences were addressed.

The intervention is labeled as an “other” intervention and named Code Sepsis protocol (full implementation). Its detailed content, implementation fidelity, and any variation in delivery are not reported in the registry record. Masking is recorded as single, but who was masked and how masking was implemented are not reported in the registry record. Allocation concealment is not described.

The primary analysis is restricted to patients meeting sepsis criteria before emergency-department departure. The stated total enrollment should not be assumed to equal the number included in that endpoint analysis; the number meeting the criteria and the analysis-specific group sizes are not reported in the registry record. The registry lists 14 outcome measures and 14 analyses, including secondary outcomes related to mortality, hospital charges, and length of stay. It does not report the statistical analysis plan, a sample-size justification for the study, interim analyses, or outcome results.

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.

Pre-implmentation Period

Post-implmementation Period

Analysis population for the primary outcome, as defined in the registry: Restricted to participants who met sepsis criteria (acute organ failure plus suspected or confirmed infection) before ED departure.

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 Door-to-antibiotic Time, measured over Up to 24 hours from ED arrival (an average of 3 hours).

Door-to-antibiotic time measures the interval from a sepsis patient’s emergency-department arrival until intravenous or equivalent antibiotics are initiated. The registry specifies minutes as the unit and identifies the median and inter-quartile range as the summary measures. The endpoint timeframe is described as up to 24 hours from emergency-department arrival, with an average of 3 hours. The analysis is restricted to participants who met the registry’s sepsis criteria—acute organ failure plus suspected or confirmed infection—before leaving the emergency department.

This timing measure is relevant to the study’s stated focus on reorganizing emergency-department care, because it captures the interval between arrival and initiation of antibiotics. That rationale does not by itself show whether care became faster or whether any change was caused by the protocol. The median describes the middle of the observed time distribution, while the inter-quartile range describes its central spread. These summaries can be useful when times are skewed or include unusually long intervals, since the median is less sensitive to extreme values than the mean.

The registry record does not report the median, inter-quartile range, group-specific endpoint values, an estimated difference, or uncertainty intervals. It therefore does not permit a quantitative reading of the primary endpoint or a judgment about the precision of any group comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies door-to-antibiotic time as the primary endpoint and specifies the median and inter-quartile range as its summary. It does not report the comparison method or the model used for estimation. The concepts below explain how these statistical choices are generally understood; they are not a description of an analysis plan that is absent from the registry record.

What does a median describe?

In general, the median is the middle value when observations are ordered by size. It is a measure of location: it indicates the point that divides an ordered distribution into two halves. It is often used for time measurements because times can be asymmetric, with many shorter observations and a smaller number of much longer ones. In such a distribution, a few unusually long times can pull the arithmetic mean upward, while the median is less affected by extreme values.

The inter-quartile range describes the spread of the central portion of a distribution, from the first quartile to the third quartile. Reporting it alongside a median gives information about both a typical value and variability among observations. It does not show every feature of the distribution, however. Two groups can have similar medians and inter-quartile ranges but differ in their tails or in other respects. The registry record does not provide the actual values or a distribution plot for this endpoint.

What would a group comparison need to show?

In general, a comparison should make clear which groups are being compared, how the contrast is defined, and how uncertainty is represented. A confidence interval is a range of values compatible with the data and the method used to calculate it; it conveys precision as well as the estimated direction and size of an association. A narrow interval indicates greater precision than a wide interval, although precision does not resolve bias from nonrandom group assignment. No endpoint estimate or confidence interval is reported in the registry record, and the planned comparison method is not reported in the registry record.

A p-value, when reported, addresses how compatible the data are with a specified statistical model or null hypothesis. It does not measure the probability that the null hypothesis is true, and it does not quantify clinical importance. The registry record does not report a p-value for the primary endpoint or state which testing procedure was planned. Without an estimate and its uncertainty, a statistical significance claim cannot be evaluated.

Why does nonrandomized allocation matter?

Random allocation is one way to make comparison groups similar on average in both measured and unmeasured characteristics. This study is labeled nonrandomized, and its groups correspond to periods and sites. General statistical reasoning therefore treats observed differences as associations unless the design and analysis adequately address alternative explanations. For instance, changes over time could occur alongside implementation, and intervention and control hospitals may differ. The registry record does not report the covariates collected, adjustment strategy, or methods used to account for site and time.

The registry labels the model single group, while the descriptions distinguish four site-period groups. Those labels describe different aspects of the record and do not transform the study into a randomized comparison. The registry’s caution that the arms are not a like-for-like control comparison is important when considering any apparent contrast.

What do the planning assumptions mean?

The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is described as a stated fraction of the observed effect. These are planning assumptions, not results, and the illustration is explicitly distinguished from the trial’s own design. The record says time-to-event illustrations use a total event count and other illustrations use participants per arm. Numerical illustration values are not reported in the registry record. Such calculations cannot be treated as observed power or as evidence that the study had adequate precision for its actual comparisons.

A planning calculation estimates the sample size or event count needed under specified assumptions. It does not describe how many participants were actually analyzed, and it does not prove that an observed estimate is precise. Because the assumptions use an observed effect, they also should not be mistaken for an independently established effect size. The study’s own sample-size justification is not reported in the registry record.

What is missing for a full statistical assessment?

The registry record does not report an analysis plan, endpoint estimates, confidence intervals, p-values, covariate-adjusted results, or sensitivity analyses. It also does not describe missing-data methods, the handling of multiple outcomes, or the definitions used for the adverse-event categories. Those omissions limit assessment of both the analysis and the strength of any conclusions. General statistical principles can describe what those methods would mean, but cannot establish which methods were used in this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures and 14 analyses. The primary endpoint is door-to-antibiotic time; listed secondary outcomes include all-cause 30-day mortality, all-cause 1-year mortality, all-cause in-hospital mortality, hospital charges, and hospital length of stay. The other outcome measures and their analysis details are not described in the registry information summarized in this record.

When many outcomes or comparisons are tested, the chance of finding at least one apparently unusual result can increase. General approaches to this issue include designating a primary endpoint in advance, adjusting inference for multiple testing, or clearly treating secondary analyses as exploratory. The registry record does not report whether any multiplicity adjustment was planned or used, how outcome priority was handled beyond naming the primary endpoint, or whether analyses were prespecified.

Missing-data methods are not reported in the registry record. The endpoint population is restricted to participants who met sepsis criteria before emergency-department departure, but the number meeting those criteria and the number with recorded endpoint data are not reported. The registry enrollment of 180402 should not be assumed to be the analysis population for the primary endpoint. Reasons for exclusion, incomplete follow-up, or unavailable outcome measurements are not reported in the registry record.

The registry record also does not report which analysis populations were used for the secondary outcomes, whether analyses were adjusted, or how repeated observations or site-level structure were handled. These details matter because they determine which participants contribute to an estimate and how uncertainty is calculated. Without them and without outcome estimates, multiplicity and missing-data effects on the findings cannot be assessed.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists four groups: pre-implementation usual care at the intervention site, Code Sepsis after implementation at that site, pre-implementation usual care at control sites, and post-implementation usual care at control sites. The recorded serious-event counts affected are 0 for each group. The counts for other events affected are 2, 3, 1, and 2, respectively. The numbers recorded as at risk are 50437, 33415, 56192, and 40358, respectively. The record also lists death counts of 2085, 1426, 2520, and 1760 for those groups, in the same order.

These figures are event counts as recorded, not adjusted comparisons between groups. The record does not identify the “other” event terms, and no serious-event terms are listed. It does not explain whether the death counts are included in or separate from the adverse-event categories, whether deaths were considered related to the intervention, or what event-collection procedures were used. Death counts therefore should not be interpreted as counts of intervention-related harms.

Without defined categories, comparative estimates, and methods for handling differences in group composition, the counts alone do not establish relative safety. The registry record does not report inferential analyses for these figures.

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

The study addresses an operational question: whether reorganizing emergency-department care through full implementation of the Code Sepsis protocol is associated with door-to-antibiotic time among patients meeting the stated sepsis criteria. Its registry record specifies the endpoint, its time unit, and the population restriction. It also identifies several secondary outcomes and describes groups before and after implementation at an intervention site and control sites.

The record does not report primary endpoint values or comparative estimates. It therefore does not show whether door-to-antibiotic time changed, how large any change was, or how precisely it was estimated. Nor does it report results for the listed secondary outcomes. A completed study status and a large enrollment figure do not substitute for outcome estimates or establish that every enrolled person contributed to each analysis.

Even if outcome contrasts were reported, the nonrandomized design would require careful interpretation. Differences between periods or sites could reflect changes other than the protocol. The registry cautions that the arms are not a like-for-like control comparison, and the adjustment methods are not reported. Any observed association would not by itself prove that the intervention caused the difference.

The adverse-event and death counts provide descriptive information recorded for the groups, but the categories and relationships among those counts are not fully explained. They do not support a causal safety conclusion. Likewise, the planning assumptions described in the record are illustrations rather than observed findings or evidence of adequate power.

The defensible conclusion is limited: the registry describes a nonrandomized evaluation of emergency-department sepsis-care reorganization and defines a primary timing endpoint, but the outcome results and key analysis details are not reported in the registry record. The record cannot establish whether the protocol changed the primary endpoint or secondary outcomes.

13. Why This Trial Matters Statistically

This study raises statistical issues common to evaluations of clinical workflow changes. The intervention is implemented in clinical settings, and the registry describes groups defined by both time period and site. This makes the distinction between an observed association and a causal effect especially important. A pre- and post-implementation contrast can reflect the intervention, but it can also reflect concurrent changes or differences between hospitals. The registry’s explicit warning that the arms are not a like-for-like control comparison directs attention to that limitation.

The primary endpoint is a time measurement summarized with a median and inter-quartile range. This choice highlights that outcome distributions need not be symmetric and that a single average may not describe a typical patient’s timing well. Yet a summary statistic alone does not provide a complete comparison: group estimates, an effect contrast, and uncertainty are needed to judge the size and precision of a change. Those results are not reported in the registry record.

The registry also identifies multiple outcomes, spanning timing, mortality, hospital charges, and length of stay. Multiple outcomes can broaden the assessment of a complex intervention, but they make prespecification and transparent reporting important. The record lists 14 outcome measures and 14 analyses, while multiplicity procedures and detailed analysis methods are not reported.

Finally, the record distinguishes study enrollment from planning illustrations based on an observed effect. Keeping design assumptions, sample-size planning, and actual findings conceptually separate is essential. Planning calculations do not demonstrate what happened in the study, and they do not replace estimates with uncertainty. The available information makes the design and its interpretive constraints visible, while leaving the outcome conclusions unresolved.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting the registry record is that it does not report the primary endpoint results or results for the listed secondary outcomes. Group-specific sample sizes for the endpoint analysis, estimates of contrasts, confidence intervals, and significance tests are also not reported in the registry record. The completed status and listed enrollment do not resolve these gaps.

The study is nonrandomized and includes groups defined by site and implementation period. The registry itself cautions that the arms are not a like-for-like control comparison. Methods for controlling confounding, accounting for site differences, or separating implementation effects from other time-related changes are not reported in the registry record. The listed single-group model label alongside four described site-period groups also calls for careful attention to how the analyses were structured; the analysis details are not reported.

The registry does not report the operational details of the Code Sepsis protocol, implementation fidelity, or whether the intervention was delivered consistently. Masking is recorded as single, but the masked party and procedures are not reported. The criteria and procedures used to collect adverse events are not described in enough detail to interpret the categories fully.

The primary analysis is restricted to participants meeting the stated sepsis criteria before emergency-department departure. The number meeting those criteria, exclusions, analysis-specific denominators, and handling of missing data are not reported in the registry record. The generalizability of findings to patients outside that restricted population cannot be assessed from the registry description alone. Multiplicity handling, adjustment methods, and sensitivity analyses are also not reported.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effects of Code Sepsis Implementation on Emergency Department (ED) Sepsis Care — NCT04148989.
• Registry record last updated 2024-03-05; status last verified 2024-02.
• Results first posted 2024-03-05.
• 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.

18. Record Summary

NCT04148989 is a completed, nonrandomized study of full implementation of the Code Sepsis protocol for emergency-department sepsis care. The registry lists enrollment of 180402 and dates from 2018-11-13 to primary completion on 2023-01-23. The study is categorized as single group, while its descriptions identify pre- and post-implementation groups at an intervention site and control sites. The registry cautions that these arms are not a like-for-like control comparison.

The primary endpoint is door-to-antibiotic time, measured in minutes and summarized by median and inter-quartile range among participants meeting the stated sepsis criteria before leaving the emergency department. Secondary outcomes include mortality, hospital charges, and hospital length of stay. The record lists 14 outcome measures and 14 analyses.

Primary and secondary outcome results, statistical analysis details, missing-data methods, and multiplicity procedures are not reported in the registry record. The recorded adverse-event counts are descriptive and do not establish a causal safety comparison.