Nutritional Status and Enteral Absorption Capability After Brain Death: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Nutritional Status and Enteral Absorption Capability After Brain Death (NCT00858390), a randomized na study. The primary outcome is Primary Outcome Measure is IL-6 Level.

2. Clinical Question

3. Trial Design

The registry classifies this study as randomized, with a parallel-group model and no masking. It lists the condition as brain death and describes a comparison between standard care and enteral feeding. The record gives an enrollment of 36 and reports 18 participants in each primary-outcome group. The trial status is completed. Its recorded start is 2009-02, and its primary completion is 2012-08.

The enteral-feeding arm is described as receiving Oxepa® and RESOURCE® GLUTASOLVE®. The brief summary refers to assessing nutritional status with prealbumin and resting energy expenditure, nutrient intestinal absorption through 13Curacil breath tests, and serum IL-6 and TNFalpha. However, only one outcome measure is posted in the results, and it is IL-6. No secondary outcomes are posted in the registry record.

Random allocation can support a fair comparison by reducing systematic differences between groups, but the record does not describe the allocation sequence, how allocation was concealed, or whether any stratification was used. Masking is listed as none. The record does not explain whether outcome measurement or data analysis was blinded. The trial phase is listed as NA.

The registry record does not report the trial's original sample-size assumptions, its statistical analysis plan, or a detailed protocol for the interventions. It also does not explain how standard care was defined, whether participants received other nutritional interventions, or how treatment adherence was assessed. Those omissions limit how fully the design can be reconstructed from the posted 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.

Before assignment: Inclusion criteria: consented brain-dead organ donors age 14 to 70 years; may have received parenteral/enteral nutrition prior, but were excluded for prior gastric/bowel resections, GI malabsorption, bariatric procedures, vagotomy, pyloroplasty, or pancreatitis. Donors were excluded if a FiO2 greater than 60% was required (REE).

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 Primary Outcome Measure is IL-6 Level, measured over 12+/-2 hours.

The primary outcome is the plasma level of IL-6, reported as a continuous measure in pg/ml. The stated measurement method is ELISA, and the measurement time is 12+/-2 hours before organ explantation. Results are expressed as a mean and standard deviation for each arm.

IL-6 is an inflammatory marker. In the context described by the registry, investigators planned to assess it alongside nutritional status and intestinal absorption to examine the response to continuing or initiating enteral feeding and nutritional supplementation. The posted primary endpoint, however, is specifically the IL-6 concentration. It is not itself a direct measurement of nutritional status or intestinal absorption.

A continuous measurement preserves differences in the measured concentration rather than reducing the outcome to a category. Reporting a group mean describes the central level in each group, while the standard deviation describes the spread of participant values around that mean. A comparison of means estimates the average difference between groups. Such a summary does not show the full distribution, whether the values were skewed, or how any individual participant's level changed.

The registry record does not report additional details about the timing of blood collection beyond the stated timeframe, assay performance, or handling of measurements outside that timeframe. It also does not post results for prealbumin, resting energy expenditure, breath tests, or TNFalpha, despite mentioning these measures in the brief summary.

7. Results Posted in the Registry

• 2 Enteral Feeding: mean 264.90 versus 565.50 on control; difference -300.60 (95% CI -785.48 to 184.28), standardized effect d = -0.41; z-test p = 0.224.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry posts group means, standard deviations, a mean-difference estimate, a confidence interval, and an unadjusted p-value for IL-6. These are descriptive and comparative summaries of a continuous outcome. Understanding what each statistic represents helps distinguish the observed difference from the uncertainty around it.

What does a mean difference represent?

A mean is the arithmetic average of measured values within a group. The posted means are 565.5 pg/ml for standard care and 264.9 pg/ml for enteral feeding. The mean difference is reported as the enteral-feeding mean relative to the standard-care mean, with an estimate of -300.6 pg/ml. Its sign therefore gives the direction of the comparison: negative values indicate a lower mean in the intervention group under this definition. The estimate describes the difference between group averages; it does not imply that every participant had a lower value or that the same change occurred within individuals.

In general, a mean difference is easiest to interpret when the measure has a meaningful common scale, as IL-6 does in pg/ml. It retains that scale, unlike a standardized effect. The record also gives a standardized estimate of -0.405, based on a pooled standard deviation of 742.2. A standardized difference expresses the contrast relative to the spread of measurements and can help describe magnitude across scales, but it does not replace the clinical interpretation of the original units.

Why report a standard deviation?

A standard deviation describes how dispersed measurements are around the group mean. The reported standard deviations are 1010.0 pg/ml for standard care and 285.6 pg/ml for enteral feeding. Greater spread means individual measurements vary more widely around their group's average. The standard deviation is not the uncertainty in the estimated mean difference; that uncertainty is represented by the confidence interval. It is also not the range containing every participant's value.

As a general statistical point, a mean and standard deviation can be an incomplete description when values are strongly skewed or when a small number of extreme values have substantial influence. The registry record does not post a median, range, distribution plot, or participant-level data for this endpoint. The summaries alone cannot establish whether the normal-model assumptions for the comparison were appropriate.

How should the p-value be read?

The unadjusted p-value is 0.224. In general, a p-value measures the compatibility of observed data with a specified null model, conditional on the analysis assumptions. It is not the chance that the observed difference arose by chance, the probability that a treatment effect exists, or a measure of how large an effect is. The record does not state the significance threshold chosen in the trial's original analysis plan, so the posted p-value should be considered alongside the effect estimate and confidence interval rather than treated as a standalone decision.

The label unadjusted means the posted p-value is not reported as corrected for multiple comparisons. The registry record does not report a multiplicity plan. Since no secondary outcome results or analysis entries are posted, it is not possible to determine from the record how many analyses were conducted or whether other outcomes were considered in the original analysis.

What does a confidence interval add?

The 95% confidence interval for the mean difference extends from -785.5 to 184.3 pg/ml. In general, a confidence interval gives a range of estimates compatible with the observed data under the statistical model and its assumptions. It conveys uncertainty in the estimated contrast more directly than the p-value. The interval crosses zero, so it does not isolate a single direction of difference. Its lower and upper limits indicate that the data are compatible with both a negative and a positive mean difference under the stated comparison.

The width of an interval depends on the amount of information in the data and their variability, as well as the analysis method. High variability and limited group sizes can make estimates less precise. The record reports 18 participants in each group and substantial spread, especially in standard care. The confidence interval reflects uncertainty in the mean contrast, but it does not account for uncertainties that are not represented in the model, such as missing outcome data or bias from unmasked care.

Why can over-dispersion matter?

As a general concept, over-dispersion occurs when observed variability is greater than a model assumes. If a method underestimates variability, its standard errors can be too small and its confidence intervals too narrow. The IL-6 summaries show marked spread, but the registry record does not report a formal dispersion assessment or details sufficient to identify the analysis model. It would therefore be inappropriate to claim that over-dispersion was present or that a particular correction was needed. The general concern is that inference from means depends on whether the method represents the variability reasonably.

The record does not report adjusted analyses, the exact statistical test, treatment of missing measurements, or an analysis population definition. These omissions matter because the posted estimate and uncertainty cannot be independently evaluated against a complete prespecified plan. The numerical results can still be described as posted, but interpretation should remain limited to those summaries and the stated outcome.

10. Confidence Intervals and Precision

The posted 95% confidence interval for the mean difference in IL-6 is -785.5 to 184.3 pg/ml, with the comparison defined as enteral feeding relative to standard care. The point estimate is -300.6 pg/ml. The interval extends across zero, so the observed data do not pin the mean difference to a single direction. Values within the interval represent effect estimates that are compatible with the data under the model used for the interval; the interval is not a guarantee that the true effect lies within its limits.

The interval is wide relative to the point estimate. This indicates uncertainty in the size and direction of the average contrast. The reported group sizes are 18 in each arm, and the standard deviations are 1010.0 pg/ml for standard care and 285.6 pg/ml for enteral feeding. The particularly large spread in standard care contributes to the difficulty of estimating a precise mean contrast from these summaries.

Precision is not the same as whether a result meets a decision threshold. The unadjusted p-value is 0.224, but the registry record does not report the trial's original significance threshold. The confidence interval communicates both the estimated direction and the range of uncertainty, while the p-value condenses evidence relative to a null model. Neither statistic establishes clinical importance.

These precision statements are conditional on the analysis and data represented in the record. The registry does not report the amount of missing outcome data, the method for handling it, or participant-level values. It is not possible to assess whether missingness or unusual observations affected the interval.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are illustrations based on the observed effect, rather than a report of the trial's original design assumptions. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The effect targeted in each row is the stated fraction of the observed effect.

The 80% power column gives the illustrated number of participants per arm for a design with an 80% chance of detecting the specified effect under those assumptions, if the assumed effect and model are correct. The 90% power column gives the corresponding per-arm number for a design with a 90% chance of detecting that effect. These are planning quantities, not probabilities that the trial result is correct, and they do not describe the power achieved by the completed trial.

The displayed planning values are 96 and 129 participants per arm for 100% of the observed effect; 171 and 228 for 75% of the observed effect; and 383 and 513 for 50% of the observed effect, with the first number in each pair corresponding to 80% power and the second to 90% power. Smaller target effects require more participants because they are harder to distinguish from the background variability under the same assumptions. This is not observed power.

The trial's own original sample-size justification, assumptions, and planned target effect are not reported in the registry record. The planning figures should therefore not be used to infer why enrollment was set at 36 or to judge the investigators' original design process.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -300.600; pooled standard deviation σ = 742.182.
2. n = 2 × (1.96 + 0.842)² × 742.182² / -300.600² = 95.7, rounded up to 96 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -300.6                      # observed difference in means
sigma <- 742.181702819465                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(858390)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 96 (80% power), 129 (90% power)
 75% of observed effect: n per arm = 171 (80% power), 228 (90% power)
 50% of observed effect: n per arm = 383 (80% power), 513 (90% power)
power.t.test: 96.7 
Simulated power at n = 96 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record posts one outcome measure, the primary IL-6 measure, and reports no secondary outcomes. It gives an unadjusted p-value of 0.224 for the primary comparison. No multiplicity procedure or prespecified hierarchy of outcomes is reported in the registry record. Without that information, it is not possible to determine whether the posted result was one of several analyses considered or how any multiple-testing issue was addressed.

Missing-data handling is not reported in the registry record. The posted arm summaries give 18 participants per group, but the record does not say whether those counts represent everyone randomized, everyone with an available IL-6 measurement, or a defined analysis population. It does not report the number of missing measurements, reasons for missingness, exclusions, or any imputation method. This prevents assessment of whether the outcome summaries may be affected by incomplete measurement.

The analysis population is not defined. The registry record does not say whether the comparison followed an intention-to-treat approach, included only participants who received the assigned feeding, or used another population definition. No per-protocol or sensitivity analysis is posted. These are not merely technical details: population definitions and missingness can influence the estimate when inclusion in the analysis is related to treatment or outcome.

The record also does not report a detailed statistical analysis plan, the exact test used, or covariate adjustment. The reported p-value is explicitly unadjusted, and the posted comparison does not identify an adjusted estimate. No interim analyses are reported in the registry record. Absence of reporting is not evidence that a particular procedure was or was not used; it means those details cannot be evaluated from the registry record.

14. 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 record lists 18 participants at risk for serious adverse events in standard care and 18 in enteral feeding. It records 0 participants affected by a serious adverse event in each group. The other adverse-event fields also list 18 at risk and 0 affected in each group. No serious adverse-event terms are listed.

These entries describe what was recorded in the registry. A zero count should not be read as proof that an event was impossible, or as evidence that there was no risk. The record does not provide event definitions, collection procedures, follow-up details for adverse events, or information about whether reporting was complete. It also does not describe how adverse events were compared statistically.

Deaths are not reported in the registry record. The absence of listed serious-event terms and the zero affected counts do not supply additional detail about event types or severity beyond the posted fields. These safety entries should be interpreted narrowly as registry-reported counts, not as a comprehensive assessment of safety.

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

The posted primary results describe IL-6 concentrations measured at 12+/-2 hours before organ explantation. The mean was 565.5 pg/ml in standard care and 264.9 pg/ml in enteral feeding. The estimated mean difference, defined as enteral feeding relative to standard care, was -300.6 pg/ml. The 95% confidence interval, -785.5 to 184.3 pg/ml, includes zero, and the unadjusted p-value is 0.224. Taken together, these results show a lower observed group mean in the enteral-feeding arm, but considerable uncertainty around the estimated difference.

The findings do not establish that enteral feeding caused a change in IL-6. Random allocation is a design feature that can support causal comparisons, but the record does not report enough detail about implementation, missing data, or the analysis population to assess all sources of bias. The absence of masking is recorded, and the registry does not state whether outcome measurement or analysis was blinded.

The posted primary outcome is not a direct measure of nutrient absorption or overall nutritional status. Although the brief summary mentions prealbumin, resting energy expenditure, breath tests, and TNFalpha, results for those measures are not reported in the registry record. No secondary outcomes are posted. The IL-6 result therefore cannot be used to infer what happened to those other measures or to make a broad conclusion about nutritional recovery.

The registry reports zero affected participants for the recorded serious and other adverse-event fields in both groups, but those counts do not demonstrate that no harm was possible. The available safety information is limited by the details not reported in the registry record.

Overall, the record supports a restrained description of the observed IL-6 summaries and their uncertainty. It does not support a definitive claim about the effect of feeding on IL-6, other biological outcomes, or clinical outcomes.

16. Why This Trial Matters Statistically

This trial illustrates why the estimated effect, its precision, and the study design need to be read together. The observed difference in group means is substantial in pg/ml, but the confidence interval spans both negative and positive values. The p-value alone cannot convey that range of uncertainty, and the point estimate alone cannot show how variable the measurements were.

The standard deviations differ considerably between groups, with particularly wide spread in standard care. This is a reminder that group means can conceal heterogeneity among participants. In clinical research, an average contrast is useful, but it does not describe how consistently individual measurements are distributed or whether a few extreme values influence the average. The registry record does not provide the distributions needed to investigate those questions.

The record also separates the investigators' stated interests from the results actually posted. Its brief summary describes several aspects of nutritional status and absorption, while the posted primary result is IL-6 and no secondary outcomes are reported. For statistical interpretation, conclusions must follow the outcome data available rather than extend from the study rationale to unreported measures.

Finally, planning illustrations based on an observed effect can show how smaller effects generally require more participants under stated assumptions. They are not evidence of the completed trial's power, and they do not reveal the original design rationale. This distinction is important when using registry results to plan future studies or assess what a modest trial can estimate. Here, the interval and variability make precision central to interpreting the comparison.

17. 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 available registry record leaves several trial-specific details unclear. It describes randomized allocation but does not explain sequence generation, allocation concealment, or the practical conduct of randomization. Masking is listed as none, but it is not stated whether laboratory staff or analysts were masked. These details matter when considering possible sources of bias.

The intervention is described as enteral feeding with Oxepa® and RESOURCE® GLUTASOLVE®, while the brief summary discusses continuing or initiating enteral feeding and nutritional supplementation. The record does not specify which participants were already receiving feeding, the dose or duration of supplementation, adherence, or how standard care was defined. It also does not explain whether care besides the feeding intervention was otherwise comparable.

Only the primary IL-6 outcome is posted. Results for prealbumin, resting energy expenditure, breath tests, and TNFalpha are not reported in the registry record, and no secondary outcome results are posted. Thus, the proposed broader assessment of nutritional status and absorption cannot be evaluated from the results presented.

The record does not report a detailed statistical plan, original sample-size justification, analysis population, missing-data handling, or participant-level distributions. The group standard deviations indicate substantial variation, but the summaries cannot show skewness or the influence of extreme values. These limitations do not invalidate the reported numbers; they constrain the conclusions that can be drawn from them.

Safety reporting is also limited to the recorded affected counts and risk-set counts. Event definitions, follow-up details, and death data are not reported in the registry record. The status is completed, but completion alone does not resolve these reporting gaps.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Nutritional Status and Enteral Absorption Capability After Brain Death — NCT00858390.
• Registry record last updated 2014-06-26; status last verified 2014-06.
• Results first posted 2014-06-16.
• 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.

21. Record Summary

The registry describes a completed randomized, parallel-group trial of enteral feeding versus standard care among organ donors after brain death. Enrollment is listed as 36, with 18 participants in each primary-outcome group. Masking is listed as none. The recorded start is 2009-02, and primary completion is 2012-08.

The posted primary outcome is plasma IL-6 in pg/ml, measured by ELISA at 12+/-2 hours before organ explantation. Mean levels were 565.5 in standard care and 264.9 in enteral feeding. The posted mean difference was -300.6, with a 95% confidence interval from -785.5 to 184.3 and an unadjusted p-value of 0.224.

The registry record posts no secondary outcomes or analysis entries. It does not report the original sample-size justification, missing-data handling, or analysis-population definition. The adverse-event fields record 0 affected participants in each group; deaths are not reported in the registry record.