Impact of SPN on Infection Rate, Duration of Mechanical Ventilation & Rehabilitation in ICU Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Impact of SPN on Infection Rate, Duration of Mechanical Ventilation & Rehabilitation in ICU Patients (NCT00802503), a randomized phase 3 study. The primary outcome is Documented Infection Rate.

2. Clinical Question

3. Trial Design

The registry describes a prospective, controlled, randomized clinical study with a parallel-group design and no masking. It lists the study as Phase 3 and completed. The sponsor was University Hospital, Geneva, and the study site was the intensive care service at Geneva University Hospital. The recorded enrollment is 305. The brief study summary separately describes an intention to include 220 ICU patients; the registry does not explain the difference between that planned figure and the recorded enrollment.

Participants were assigned to enteral nutrition alone or enteral nutrition plus supplemental parenteral nutrition. The summary says patients were randomized at day 3 if energy input was below 60% of predicted needs. The intervention description says SPN was started from ICU day 4 when enteral intake was below that threshold. These descriptions indicate the intervention’s energy-target rationale and timing, but the registry does not give a fuller account of allocation procedures or clarify the difference in the timing language.

The posted arm counts are 152 in the control group and 153 in the SPN group. The primary endpoint description covers infections during ICU and hospital stays from day 9 through day 28, while the timeframe is recorded as 20 days. Several secondary outcomes concern energy and protein delivery over the intervention period, mortality at 28 days, mechanical ventilation, antibiotic-free days, and time in the ICU or hospital. The registry lists eight secondary outcomes, but only three have posted results in the record. It does not report a detailed protocol, allocation-concealment method, or a complete statistical analysis plan.

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 Documented Infection Rate, measured over 20 days.

The primary endpoint is the number of documented infections. An infection is defined according to CDC criteria during the ICU and hospital stay, with the relevant occurrence window recorded as between day 9 and day 28. The registry gives a timeframe of 20 days. This outcome is intended to capture infections arising during a specified period of critical care and hospitalization, rather than an energy-delivery measure or a single laboratory value.

The registry reports 58 infections for the control group and 41 for the SPN group. These are counts, not infection rates or participant-level risks. The record does not provide a dispersion measure, confidence interval, or reported analysis for comparing the counts. It also does not state how recurrent infections within a participant were handled, or provide a primary-outcome population description. Consequently, the counts describe what was posted for each arm, but the registry record does not support a quantified estimate of the comparative effect or its precision.

For count outcomes, interpretation can depend on whether the count represents events or people with at least one event, the amount of follow-up, and the variability of counts across participants. Those details are not reported for this endpoint. A count comparison would ordinarily need an analysis suited to the outcome’s structure and an explicit account of its assumptions; the registry record does not report such an analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help distinguish the different kinds of results in the registry. The primary endpoint is a count, whereas the posted energy outcome is a continuous measure and the mortality outcomes are binary. These outcome types require different summaries and may call for different models. The registry does not report a formal analysis for the primary count endpoint, so the comparison of infection counts remains descriptive.

What does a confidence interval communicate?

A confidence interval describes uncertainty around an estimated effect under the assumptions of the analysis. For a difference, zero represents no difference between groups. An interval that crosses zero includes values corresponding to either direction of difference and no difference; it therefore does not pinpoint a single conclusion. An interval that excludes zero indicates that the data are less compatible with a zero difference under that model, but it does not establish clinical importance, eliminate bias, or show that the estimate applies to every outcome.

The energy-intake comparison reports a mean difference of 26.0 percentage points, with a confidence interval that excludes zero, and an unadjusted p-value of <0.001. The outcome is the percentage of the energy target delivered during the intervention period between day 4 and day 8. The groups’ reported means are 77% and 103%, with standard deviations of 27 and 18. A standard deviation describes variation among observations; it is not the same as the uncertainty around the group mean. The confidence interval for a mean difference incorporates the sample sizes and variability, subject to the analysis assumptions.

How should the mortality comparisons be read?

For a binary outcome, a risk difference expresses the difference between the proportions experiencing the outcome in the groups. The registry reports risk differences for general mortality and ICU mortality, along with confidence intervals and unadjusted p-values. In both cases, the intervals cross zero. This means the estimates are not precise enough to rule out no difference under the reported analysis. The intervals also extend to effects in either direction, so the results should not be described as establishing equivalence. The reported p-values are 0.2 for general mortality and 0.347 for ICU mortality.

A p-value is calculated relative to a specified statistical model and null hypothesis. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The registry labels these secondary p-values as unadjusted. They should therefore be interpreted with caution in the context of multiple outcomes and without an adjustment plan reported in the record.

Why does the primary count need more than two totals?

Count data can vary differently from continuous or binary data. A count may reflect repeated events for one participant, or it may count participants who experienced an event; those interpretations are not interchangeable. Counts can also be more variable than a simple model assumes, a property often described generally as over-dispersion. If over-dispersion is present, a model that assumes less variability can produce uncertainty estimates that are too narrow. This is a general statistical consideration, not a finding established for this trial. The registry does not report whether infections were counted as events or affected participants, does not provide a dispersion estimate, and does not identify a count model. The posted totals cannot resolve those issues on their own.

What do the planning illustrations mean?

The planning illustrations use the observed effect as a starting point and state assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation. The rows illustrate planning for 100%, 75%, or 50% of an observed effect. For the energy-intake comparison, the illustration for 100% of the observed effect lists 13 participants per arm for 80% power and 17 participants per arm for 90% power. These are hypothetical planning quantities, not the trial’s design rationale and not evidence of observed power. The record does not report the original sample-size justification. Such calculations also depend on the chosen effect, outcome variability, model assumptions, and intended analysis; changing those assumptions changes the planning result.

For the mortality outcomes, the observed differences are small relative to their uncertainty, and the planning illustrations list larger sample sizes for the stated effect fractions. These illustrations should not be read as a recommendation for a future study or as proof that a future study would reproduce the observed effects. They are conditional calculations. Because the primary infection result has no reported comparative estimate, the registry’s planning illustrations for other outcomes do not provide a primary-endpoint sample-size justification.

Finally, the labels and summaries do not describe all analytic choices. The registry does not report the analysis population, missing-data handling, adjustment for baseline characteristics, or a multiplicity procedure. These omissions matter because statistical estimates depend not only on the outcome values, but also on who is analyzed, how missing observations are handled, and which comparisons are considered confirmatory.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary infection endpoint and eight secondary outcomes. It reports results for three secondary outcomes, while the record lists no reported analyses in its analysis field. It does not report a statistical plan describing which outcomes were confirmatory, whether a hierarchy was specified, or whether any correction for multiple comparisons was used. The energy-intake and mortality p-values are explicitly unadjusted. When multiple outcomes are tested, the chance of at least one apparently unusual result can increase; general approaches to this issue include adjusting inference or clearly distinguishing prespecified primary tests from exploratory comparisons. The registry does not say which approach was used.

Missing-data methods are not reported in the registry record. It does not describe missing observations, withdrawals, exclusions after randomization, or whether analyses followed an intention-to-treat or another population definition. The primary endpoint population field is blank. The posted group counts for outcomes do not, on their own, establish how participants with unavailable outcomes were handled or whether the same analysis population was used for every endpoint.

The record also does not report a detailed analysis plan, interim analyses, or a sample-size justification. The planning illustrations are described as calculations based on observed effects, not as the trial’s own design calculations. The brief summary gives an intended inclusion figure of 220, while the recorded enrollment is 305; an explanation is not reported in the registry record. These gaps affect how confidently the results can be interpreted as planned, complete, and confirmatory. They do not establish that analyses were inappropriate; they mean the registry entry does not supply enough detail to evaluate those procedures.

11. 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 adverse-event fields list zero serious adverse events and zero other adverse events for the control group, with 152 at risk, and for the SPN group, with 153 at risk. No top serious adverse-event terms are listed. These registry entries should be read as the event counts recorded in those fields, not as proof that no adverse events occurred or that the interventions have no safety risks. The record does not describe the adverse-event collection period, the definitions used for these categories, or how completeness of reporting was checked.

Deaths are not reported in the adverse-event fields. Mortality is presented separately as a secondary outcome, with general mortality and ICU mortality recorded at 28 days. Those outcome counts are not interchangeable with serious adverse-event counts, and the registry does not explain whether any deaths were also classified as adverse events. The safety information is therefore limited to the recorded categories and should be considered alongside the separate mortality outcomes, without treating the zero entries as a comprehensive safety assessment.

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

The registry records a randomized comparison of enteral nutrition alone with enteral nutrition plus supplemental parenteral nutrition in critically ill ICU patients. It reports fewer documented infection counts in the SPN group than in the control group, but the primary endpoint has no reported comparative estimate, confidence interval, or p-value. The counts alone do not show how precisely the groups differ, whether the counts represent events or affected participants, or how much the result may reflect variability.

The secondary energy-intake result indicates higher average delivery as a percentage of the target in the SPN group, with a reported mean difference of 26.0 percentage points and an unadjusted p-value of <0.001. This is evidence about the measured nutrition-delivery outcome under the reported comparison; it does not by itself establish a difference in infections, mortality, or other clinical outcomes. The mortality comparisons are uncertain: their reported confidence intervals include zero, and the registry does not report multiplicity adjustment.

These results do not establish that the nutrition strategy improves or worsens clinical outcomes, nor do they establish equivalence between groups. The primary endpoint lacks a formal reported analysis, several listed secondary outcomes have no results in the registry record, and important analytic details—including missing-data handling and analysis populations—are not reported. Interpretation should therefore distinguish the observed arm summaries from an estimate of a treatment effect, and distinguish a process outcome from clinical outcomes. The registry entry describes the recorded results and their limitations; it does not provide enough information to resolve the unanswered questions about the primary endpoint or the broader pattern of outcomes.

13. Why This Trial Matters Statistically

This trial is statistically informative because it places a process measure and clinical outcomes side by side. The energy-intake result shows a reported separation in the delivery measure, while the primary infection endpoint is presented only as arm-specific counts. That contrast illustrates why an intervention can be associated with a clear change in the intended process without the registry record necessarily demonstrating a corresponding change in a clinical endpoint.

It also illustrates the importance of matching analysis to outcome type. Mean energy delivery, binary mortality outcomes, and infection counts do not share a single natural summary or model. The mortality comparisons include uncertainty intervals that cross zero; the primary count outcome has no reported interval or formal comparison. Treating the raw count difference as if it had the same inferential status as the analyzed mean difference would overstate what the registry reports.

The record further demonstrates why statistical significance and practical importance are different questions. An unadjusted p-value of <0.001 for energy intake describes compatibility with a null model under the reported analysis; it does not answer whether the change matters clinically or predicts a benefit in other outcomes. Multiple secondary endpoints, absent reporting of a multiplicity plan, and missing information about analysis populations all affect the strength of confirmatory interpretation.

Finally, the planning illustrations are useful as conditional demonstrations of how sample-size requirements depend on effect assumptions, but they are not observed power and not evidence of the original design rationale. Keeping these distinctions clear helps readers evaluate what the record does report, what it leaves uncertain, and which conclusions require analyses or documentation not reported in the registry record.

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.

Several limitations are specific to the information recorded for this trial. Most importantly, the primary infection outcome is reported as counts of 58 and 41, without a formal comparative analysis, uncertainty interval, or p-value. The registry does not clarify whether the values count infection events or participants with infections, and the primary population field is blank. Thus, the primary endpoint cannot be interpreted as a quantified group effect from the registry entry alone.

The record does not report results for several listed secondary outcomes, including mechanical ventilation, antibiotic-free days, protein delivery, and ICU or hospital duration. The absence of posted results does not establish why those outcomes are missing. The available secondary comparisons are unadjusted, and no multiplicity strategy is reported. Missing-data methods, analysis populations, and the handling of exclusions after randomization are also not reported.

Trial descriptions leave some operational details unclear. The summary describes randomization at day 3 if energy input was below 60%, whereas the intervention description says SPN begins from ICU day 4. The record does not explain this difference in wording. The summary states an intended inclusion of 220, while recorded enrollment is 305; no explanation is reported. The registry does not provide a sample-size justification, a detailed statistical analysis plan, or information on whether interim analyses occurred.

The adverse-event entries list zero events in both categories, but do not specify the observation period or definitions. These limited entries cannot stand in for a full safety assessment. More generally, the registry results should be read as a partial record: they provide some group summaries but not enough analytic detail to resolve all questions about outcome ascertainment, precision, missingness, or confirmatory intent.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Impact of SPN on Infection Rate, Duration of Mechanical Ventilation & Rehabilitation in ICU Patients — NCT00802503.
• Registry record last updated 2013-04-19; status last verified 2013-04.
• Results first posted 2013-04-19.
• 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

NCT00802503 is a completed, Phase 3, randomized, unmasked, parallel-group study sponsored by University Hospital, Geneva. It enrolled 305 participants and compared enteral nutrition alone with enteral nutrition plus supplemental parenteral nutrition in critically ill ICU patients. The primary outcome was documented infections meeting CDC criteria during the ICU and hospital stay, between day 9 and day 28. The registry reports 58 infections in the control group and 41 in the SPN group, but no formal comparison or uncertainty estimate for this endpoint.

Among the posted secondary results, energy intake was higher on average in the SPN group, while the mortality comparisons were uncertain. The registry does not report results for several other listed secondary outcomes, or key details about missing data, analysis populations, multiplicity, and the trial’s sample-size justification. The posted findings therefore support descriptive reading of the primary counts and cautious interpretation of the analyzed secondary outcomes.