Trial of Supplemental Parenteral Nutrition in Under and Over Weight Critically Ill Patients (TOP-UP): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial of Supplemental Parenteral Nutrition in Under and Over Weight Critically Ill Patients (TOP-UP) (NCT01206166), a randomized phase 3 study. The primary outcome is Calorie & Protein Intake 7 Days Post Randomization.

2. Clinical Question

The TOP-UP trial asked whether adding parenteral nutrition to enteral nutrition changed the amount of calories and protein critically ill participants received relative to what was prescribed. The registry describes this as a pilot study, with aims that included assessing whether the groups could achieve a clinically significant difference in calorie and protein intake. It also describes aims related to recruitment, safety, tolerance, and the logistics of conducting a multicenter study. A secondary aim was to explore differential effects of calorie and protein delivery on muscle and mass function.

The primary question is about intake during the specified period, rather than a direct comparison of mortality or duration of care. Those outcomes appear among the listed secondary outcomes. The registry record does not report group-level primary outcome values or a statistical comparison, so the magnitude and precision of any difference in intake cannot be described.

3. Trial Design

The registry lists TOP-UP as a randomized, parallel-group study with no masking. Its phase is listed as PHASE3, while the official title and study summary describe it as a pilot trial. Those labels are both part of the record; the registry does not explain their relationship. The sponsor is the Clinical Evaluation Research Unit at Kingston General Hospital.

The two groups were enteral nutrition plus parenteral nutrition and enteral nutrition only. The intervention description names Olimel (5.7%E / N9E) as the parenteral supplement. Because masking is listed as none, the recorded design was open label. The registry does not describe the randomization sequence, allocation concealment, or any procedures used to limit bias in outcome assessment.

The study summary describes an intended pilot involving 160 critically ill lean and obese patients at 11 sites in Canada, the United States of America, Belgium, and France. The registry enrollment is 125. The study start is recorded as 2011-06, primary completion as 2015-03, and status as terminated. The reason for termination and the relation between the intended and recorded enrollment are not reported in the registry record.

The summary identifies feasibility and implementation aims, including recruitment, intake separation between groups, glycemic control, metabolic consequences, protocol compliance, and completion of case report forms. It also describes an exploratory aim concerning muscle and mass function. These objectives provide context for the pilot designation, but the registry does not report results for those aims in the information.

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: ICU patients

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 Calorie & Protein Intake 7 Days Post Randomization, measured over 7 days post randomization.

The primary endpoint is titled “Calorie & Protein Intake 7 Days Post Randomization.” It measures the amount of calories and protein received as a percentage of the amount prescribed, at 7 days post randomization. The registry classifies the measure as continuous and specifies a mean with standard deviation as the summary.

Expressing intake as a percentage of prescribed intake relates what participants received to the nutritional amount intended for them. In general, such a measure can help assess whether the assigned feeding strategies produced different levels of nutritional delivery during the stated period. It is an intake measure, not itself a measure of survival, infection, length of stay, or functional recovery.

The summary presents the endpoint as a combined title referring to calorie and protein intake, and the registry indicates that the primary outcome has several categories or time points and was not reduced to one comparison. The available record does not give the separate category or time-point results, group means, standard deviations, or a comparison estimate. Consequently, the endpoint’s direction, size, and statistical precision cannot be evaluated from this record alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group study. In general, random assignment is intended to make the groups comparable at the start of a trial, on average, so that differences in outcomes can be interpreted in relation to the assigned strategies. Randomization does not guarantee identical groups, and its value depends on how it was generated and implemented. The registry does not report the sequence-generation method or allocation concealment for this study.

What does the primary measure summarize?

The primary measure is continuous: calorie and protein intake as a percentage of prescribed intake. The record specifies a mean and standard deviation. In general, the mean summarizes the average level within a group, and the standard deviation describes variation among participants. A comparison of means is one way to express an average difference between groups. The registry does not report the group means, standard deviations, or a comparison estimate for this outcome, so none can be interpreted.

What can a confidence interval show?

In general, a confidence interval gives a range of values compatible with the observed data under the analysis method. Its width conveys precision: a narrower interval indicates greater precision than a wider interval. The interval’s position relative to a meaningful reference can help distinguish the range of effects compatible with the data from effects that are less compatible. No confidence interval for the primary outcome is reported in the registry record, so the precision of the trial’s estimated effect is unavailable.

What is the role of a significance test?

In general, a significance test evaluates how compatible the data are with a specified null hypothesis under a statistical model. A p-value does not measure the size or clinical importance of an effect, and it does not replace an estimate with its uncertainty. The record does not report a p-value or a test for the primary outcome. It also does not report the trial’s analysis plan, so the intended test, covariate adjustment, and handling of repeated or multiple outcome categories cannot be identified.

What do the planning assumptions mean?

The sample-size assumptions describe planning illustrations, not the trial’s own design justification. They specify a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustration is framed around detecting a stated fraction of the observed effect. For time-to-event outcomes, the section describes total events; for other outcomes, it describes participants per arm. These are planning conventions. They are not observed power, and the registry does not report a sample-size justification from the trial protocol.

Because the primary outcome is continuous, an illustration based on a normal approximation concerns a comparison of continuous measures under its stated planning assumptions. In general, such calculations depend on assumptions about the target effect and variability. The registry record does not give the primary outcome’s observed variability or numerical effect, and no numerical planning illustration can be interpreted from the information. The illustrations should not be treated as evidence that the trial had a particular probability of detecting an effect after completion.

Why can variability matter?

In general, greater variability among participants makes an average difference harder to estimate precisely, while lower variability can allow a more precise estimate for the same amount of information. A standard deviation is one way to describe that variability for a continuous measure. The registry identifies standard deviation as the dispersion measure but does not give its value for either group. It also does not report whether the analysis accounted for site, baseline measurements, or other participant characteristics.

The study is listed as unmasked. In general, knowledge of assigned treatment can influence care, adherence, co-interventions, or assessment, depending on the outcome and study procedures. Randomization addresses some sources of bias but does not by itself eliminate these possibilities. The registry does not describe outcome-assessment procedures or steps taken to address the implications of an unmasked design.

These explanations describe statistical concepts, not a reconstruction of the TOP-UP analysis. The registry reports 0 analyses and does not report a statistical analysis plan. The methods actually used to analyze the outcomes, including the treatment of missing values and any adjustments for multiplicity, are therefore not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 30 outcome measures, including the primary intake outcome and secondary outcomes covering mortality, time in care, mechanical ventilation, infections, and physical functioning. When a study assesses multiple outcomes, categories, or time points, the chance of at least one apparently notable result can increase if each is tested without an appropriate strategy. In general, a prespecified hierarchy or a multiplicity adjustment can help clarify how multiple tests should be interpreted. The registry does not report such a strategy.

The primary outcome is flagged as having several categories or time points and is not reduced to one comparison. The record does not identify which category or time point was prespecified as the principal statistical test, or whether any multiplicity adjustment was planned or performed. It reports 0 analyses, so there are no listed tests or model results to evaluate.

Missing data can affect both the estimates and their precision. In general, interpretation depends on how much information is missing, why it is missing, and how the analysis handles it. The registry does not report the amount or pattern of missing primary outcome data, any missing-data method, or whether sensitivity analyses were conducted.

The analysis populations are also not reported in the registry record. In particular, the record does not say which randomized participants were included in each outcome analysis or how protocol deviations were handled. It is therefore not possible to determine whether analyses followed assignment regardless of treatment received, or whether another population was used. These gaps limit assessment of both the primary comparison and the listed secondary outcomes.

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

The record establishes that TOP-UP compared enteral nutrition alone with enteral nutrition plus parenteral supplementation in a randomized, unmasked, parallel-group study. It identifies calorie and protein intake as the primary outcome, measured as a percentage of prescribed intake at 7 days post randomization. These details describe the question and measurement, not the answer.

The registry record does not report the group values, an estimated difference, a confidence interval, or a p-value for the primary outcome. It therefore does not show whether intake differed between the groups, how large any difference was, or how precisely it was estimated. The absence of a reported result is not evidence that the groups were the same, and it is not evidence that they differed.

The study summary describes pilot aims related to recruitment, intake separation, safety, tolerance, logistics, and an exploratory muscle and mass function question. However, the record does not report numerical findings for those aims. The secondary outcomes are listed without results in the information. Their presence in the registry should not be interpreted as a finding about mortality, infections, length of stay, ventilation, or physical functioning.

The structured adverse-event fields display zeros for the listed counts in both groups. The registry record does not explain whether those entries represent complete ascertainment, whether all event types were captured, or whether the zero values reflect missing or unreported information. They cannot, by themselves, establish that no adverse events occurred.

The sample-size illustrations are planning exercises, not observed power and not trial results. The record also does not explain the termination. Accordingly, the posted information is insufficient for a comparative benefit or harm conclusion. It can support a description of the design, aims, and available reporting, while leaving the outcomes and their uncertainty unresolved.

12. Why This Trial Matters Statistically

TOP-UP is statistically interesting because its main question concerns nutritional intake, a continuous measure, within a pilot trial that also had feasibility and implementation aims. The primary endpoint is expressed relative to prescribed intake, while the summary describes a broader set of aims that includes recruitment, safety, tolerance, protocol compliance, and exploratory functional assessment. This makes clear that a pilot can address more than a single treatment-effect question, although the registry does not report results for those aims.

The design also creates important interpretive questions. Randomization is listed, but the record does not describe sequence generation or allocation concealment. Masking is listed as none. These design details matter when considering how groups were formed and how knowledge of assignment might affect care or assessment; they do not, on their own, tell us whether bias occurred.

The primary outcome’s several categories or time points are not reduced to one comparison, and the registry reports no analyses. This illustrates why specifying the principal comparison and analysis plan is important: without those details, readers cannot assess the treatment estimate, precision, or handling of multiple outcomes. The absence of a numerical result also means that the accompanying planning illustrations cannot substitute for an observed effect.

Finally, the record’s pilot description, PHASE3 listing, termination status, and enrollment information all need to be read as registry entries rather than as an explanation of the trial’s conduct or outcome. The record does not explain the phase label or termination. Statistically, the most useful conclusion is therefore about reporting: the available entry establishes the design and intended measures, but does not permit evaluation of the comparative results.

13. 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 registry entry lacks the group-level values needed to interpret the primary endpoint. It gives no means, standard deviations, effect estimate, confidence interval, or p-value for calorie and protein intake. The primary outcome is also flagged as having several categories or time points without a single reported comparison. This prevents assessment of the direction, magnitude, and precision of the primary result.

The record reports 0 analyses and does not describe the statistical analysis plan. It does not report the analysis populations, handling of missing outcome data, covariate adjustment, or an approach to multiplicity. These omissions make it difficult to assess how the reported outcomes were analyzed or whether the intended analysis was followed.

Although randomization and lack of masking are recorded, the registry does not describe the randomization method, allocation concealment, or outcome-assessment procedures. The study summary describes an intended pilot involving 160 participants across 11 sites, while the registry records enrollment as 125. It does not explain that difference, the reason for termination, or whether the planned aims were completed. The record lists PHASE3 while also describing the trial as a pilot, without explaining the labels.

The secondary outcomes and adverse-event fields do not resolve these limitations. Numerical secondary outcome results are not reported, and the displayed zero counts for adverse events lack contextual information about ascertainment and completeness. These are limitations of what the registry record reports; they do not establish what occurred in the study.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Trial of Supplemental Parenteral Nutrition in Under and Over Weight Critically Ill Patients (TOP-UP) — NCT01206166.
• Registry record last updated 2021-03-16; status last verified 2021-02.
• Results first posted 2021-03-16.
• 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.

17. Record Summary

TOP-UP is listed as a randomized, parallel-group, unmasked trial sponsored by the Clinical Evaluation Research Unit at Kingston General Hospital. The registry records a PHASE3 label, enrollment of 125, status as terminated, a start of 2011-06, and primary completion of 2015-03. The study summary describes a pilot comparing enteral nutrition alone with enteral nutrition plus parenteral supplementation.

The primary outcome is calorie and protein intake as a percentage of prescribed intake at 7 days post randomization, summarized as a mean with standard deviation. The registry lists 30 outcome measures and 0 analyses. It does not report numerical primary or secondary outcome results, an analysis plan, or the reason for termination. The record therefore describes the trial’s question and design but does not permit statistical interpretation of its comparative findings.