Compassionate Use of Omegaven to Reverse Parenteral Nutrition Induced Cholestasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Compassionate Use of Omegaven to Reverse Parenteral Nutrition Induced Cholestasis (NCT01173159), a na na study. The primary outcome is Number of Participants With a Change in Conjugated/Direct Bilirubin.

2. Clinical Question

The study title frames Omegaven as compassionate use to reverse parenteral nutrition-induced cholestasis. The summary describes the research purpose as assessing whether replacing the usual soy-derived lipid emulsion with a fish oil-containing emulsion may be better tolerated and may reduce or reverse liver effects associated with prolonged intravenous nutrition. These are stated aims, not reported findings.

The primary endpoint is a threshold-based participant count, rather than a reported average change in bilirubin. It asks whether a participant's conjugated/direct bilirubin reached below 1 mg/dl. The registry does not provide a baseline value, a participant-level trajectory, or a count of participants reaching the threshold. The clinical question therefore cannot be answered from the outcome results recorded in this entry.

3. Trial Design

This is a completed, single-group intervention study listed under the title Compassionate Use of Omegaven to Reverse Parenteral Nutrition Induced Cholestasis. The intervention is Omegaven, categorized as a drug. The registry lists enrollment of 10 and identifies cholestasis as the condition. The listed phase and allocation are NA, and masking is NONE. No randomized allocation or masking procedure is reported.

The arm description says participants received Omegaven at a dose of up to 1 g/kg body weight/day. Treatment was to continue until participants no longer required Total Parenteral Nutrition, or until conjugated/direct bilirubin had normalized and enteral lipid intake was sufficient to discontinue intravenous lipids. The primary endpoint timeframe is completion of therapy, described as 1-14 weeks. The entry does not report how long each participant was treated or which stopping condition applied to each participant.

The study start is recorded as 2010-07, primary completion as 2018-12, and status as COMPLETED. These registry dates describe the study record and do not supply participant-level follow-up information. The sponsor is Children's Hospital Medical Center, Cincinnati.

Because this is a single-group study, the registry describes no concurrent control arm for comparison. Observations during treatment cannot, by themselves, separate a treatment-associated change from the natural course of illness, concurrent care, or other influences. The registry record does not report a protocol-level statistical plan, a sample-size justification, or details about how treatment and outcome assessments were implemented beyond the arm and endpoint descriptions.

The registry lists a primary outcome and secondary outcomes concerning bilirubin, liver enzymes, and triglycerides. It does not provide the actual primary outcome count or results for those secondary outcomes. Completion status indicates that the study is recorded as completed; it does not establish that all planned data were collected or that every outcome was analyzed.

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 Number of Participants With a Change in Conjugated/Direct Bilirubin, measured over Completion of Therapy (time frame from 1-14 weeks).

The primary endpoint is the number of participants with a change in conjugated/direct bilirubin to below 1 mg/dl. Its timeframe is completion of therapy, specified as 1-14 weeks. It is a threshold endpoint: participants are counted according to whether their bilirubin reached the stated level, rather than the endpoint expressing the size of an average change.

Conjugated/direct bilirubin is used in this record as the marker for the primary question about parenteral nutrition-induced cholestasis. In general, a prespecified threshold can make an outcome clinically interpretable as a defined state, but it does not describe how far a participant's value changed, when the threshold was reached, or whether the change persisted. Those details would require additional outcome data.

The endpoint title and description are not fully interchangeable in emphasis: the title refers to participants with a change, while the description defines the change as a level below 1 mg/dl. The registry does not report a baseline threshold status, the number who reached the endpoint, the timing of individual changes, or a statistical estimate with uncertainty. It also does not report whether the endpoint was assessed consistently for every participant.

As a result, the endpoint can be described from the registry, but its observed result cannot. A count, proportion, confidence interval, or test of the primary endpoint is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a count of participants meeting a binary condition: conjugated/direct bilirubin changed to below 1 mg/dl by completion of therapy. In general, binary outcomes classify each participant into a defined category, such as meeting or not meeting an endpoint. A count can be accompanied by a proportion and a confidence interval. A confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the method; it does not remove limitations caused by study design, missing information, or lack of a comparison group.

No primary outcome count, proportion, confidence interval, or inferential test is reported in the registry record. The record lists n analyses as zero, so there are no posted analyses to interpret. This prevents assessment of the observed endpoint frequency and its precision. It also means that any recalculation from outcome summary statistics is unavailable: no outcome summary statistics for the primary endpoint are recorded.

For a single-group binary endpoint, an analysis could describe the number meeting the endpoint relative to the number assessed. The number assessed need not always equal enrollment if outcome data are unavailable, but the registry does not report the analyzed population or missing endpoint counts. Therefore, the appropriate denominator for an endpoint estimate cannot be established from this record. In general, reporting both the enrolled and assessed populations helps readers understand whether incomplete follow-up may affect interpretation.

The endpoint uses a threshold rather than a continuous change score. Thresholds can aid interpretation, but categorizing a continuous measurement discards information about the magnitude of change and about values near the threshold. The registry does not report individual bilirubin measurements, a group summary of change, or a threshold sensitivity analysis. No such analysis should be inferred.

The registry also names secondary outcomes concerning unconjugated/total bilirubin, AST, ALT, alkaline phosphatase, GGT, and triglycerides. These are listed as participant counts with a change. It does not give the operational definitions, assessment schedules, observed counts, or statistical summaries for these outcomes. The number of outcome measures is listed as 7 overall. The record does not explain how the primary and secondary outcomes were selected or prioritized beyond labeling the primary outcome.

Multiplicity refers, in general, to the interpretive problem that can arise when many outcomes or statistical tests are examined: the chance of at least one apparently notable result can increase as more tests are considered. A prespecified approach may address this through outcome hierarchy, adjusted significance thresholds, or a focus on estimation rather than multiple significance claims. The registry record does not report a multiplicity strategy, a testing hierarchy, or whether any adjustment was planned. Since no analyses are posted, there are no p-values or multiple-testing adjustments to evaluate.

Over-dispersion is a general feature of count data in which variability exceeds what a simple statistical model expects. It can affect standard errors and confidence intervals when counts are analyzed with a model that assumes less variability. It is not possible to assess over-dispersion for this study from the registry information: the primary outcome is a participant count with no reported distribution or model-based analysis. This concept should not be confused with the ordinary uncertainty in a small sample.

A confidence interval is generally more informative than a point estimate alone because it communicates a range of values compatible with the data and method. Its width depends on the amount and distribution of information, among other assumptions. No interval is reported for the primary endpoint or secondary outcomes. Any interval calculated without the missing outcome counts would require inventing data and is not warranted.

The registry includes text describing sample-size assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detection of a stated fraction of an observed effect. Such illustrations are planning tools, not observed power and not evidence of the study's design rationale. This study is recorded as single-group, so the two-arm assumptions do not describe its observed design. The record does not report the calculations' resulting participant numbers, a trial-specific sample-size justification, or a planned effect size. No sample-size adequacy conclusion can be drawn from the available entry.

In general, interim analyses are planned examinations of accumulating data before final study completion, often accompanied by rules governing decisions or statistical interpretation. Interim analyses and stopping boundaries are not reported in the registry record. The treatment stopping conditions in the arm description concern individual therapy and should not be mistaken for trial-level interim analysis rules.

Likewise, an analysis population describes which participants are included in an analysis, such as all enrolled participants or only those with evaluable outcomes. The registry does not report an analysis population, exclusions, missing-data methods, or a participant flow. No imputation or sensitivity analysis is described. These omissions matter because a complete-case count can be difficult to interpret if outcome availability differs across participants.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Omegaven")
n      <- c(10)
events <- c(4)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Omegaven  10  4  40.0  12.2  73.8  16.8  68.7  16.7  69.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures overall: the primary endpoint of participants with a change in conjugated/direct bilirubin, and secondary outcomes addressing changes in unconjugated/total bilirubin, AST, ALT, alkaline phosphatase, GGT, and triglycerides. It does not report a statistical testing hierarchy or any method for addressing multiplicity. The entry also lists no analyses, so no test results or adjustments are available to assess.

In general, examining multiple outcomes can increase the chance that one result appears noteworthy by chance. A prespecified strategy may distinguish a primary endpoint from secondary or exploratory outcomes and state how claims will be interpreted. The record labels a primary outcome and secondary outcomes, but does not report further rules for interpreting them together. No conclusion about multiplicity control can be made.

Missing-data status is not reported in the registry record. It does not state whether all enrolled participants had primary endpoint data, whether any outcomes were unavailable, or how incomplete observations were handled. It also does not describe an analysis population, exclusions, imputation, or sensitivity analyses. Therefore, the denominator and representativeness of any outcome analysis cannot be verified from this entry.

The record's enrollment is 10, but enrollment alone does not establish the number evaluated for each endpoint. An observed result, if available elsewhere, would need to be read alongside the number assessed and any missingness details. Here, the primary endpoint result and secondary outcome results are not reported in the registry record.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sepsis (10.0%), acute kidney injury (10.0%), compartment syndrome following surgery (10.0%), thrombocytopenia (10.0%), sinus bradycardia (10.0%).

For the Omegaven group, the registry records 10 participants at risk for serious adverse events and 4 participants affected in the serious adverse event count. It records 10 participants at risk for other adverse events and 6 participants affected in that count. Deaths are recorded as 0. These are descriptive figures for the study group, not comparisons against an untreated or alternative-treatment group.

The listed serious adverse event terms are Sepsis, Acute Kidney Injury, Compartment Syndrome Following Surgery, Thrombocytopenia, Sinus Bradycardia, and Hyperkalemia Causing Cardiac Dysrhythmia. Each term is reported at 10.0%. The record does not provide event-level descriptions, timing, duration, severity details beyond the serious classification, or whether the same participant experienced more than one listed term. The figures should not be added together to infer a count of distinct participants.

In general, an adverse event recorded during a study is not necessarily caused by the intervention. A single-group record cannot compare event frequency with a concurrent control, and the listed counts do not establish attribution. The registry does not report an assessment of relatedness or a comparative safety analysis. Zero recorded deaths is a descriptive count for this group and should not be interpreted as proof that there was no risk.

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

The registry entry establishes that a completed single-group study of Omegaven was registered for children with cholestasis associated with parenteral nutrition. It specifies a primary endpoint based on conjugated/direct bilirubin falling below 1 mg/dl by completion of therapy, with a timeframe of 1-14 weeks. It also records enrollment of 10 and provides a limited set of adverse event counts.

The entry does not report how many participants met the primary endpoint. It also does not report the secondary outcome findings or statistical analyses. Consequently, readers cannot estimate the proportion with the defined bilirubin outcome, evaluate the precision of an estimate, or determine the pattern of change across the listed liver and lipid measures from this record alone.

Even if a before-and-after result were available, a single-group design would not show what would have happened to the same population under a different lipid emulsion or without the intervention. Differences over time could reflect multiple influences. The registry does not report a randomized comparison that could support a direct treatment contrast. The study's stated purpose and endpoint should therefore be distinguished from evidence of a comparative treatment effect.

The safety counts are also descriptive. The recorded serious and other adverse event counts, the listed serious terms, and the death count do not identify whether events were caused by Omegaven. They do not provide a comparative risk estimate, and the record lacks details needed to interpret overlap or timing.

These limitations do not establish that Omegaven did or did not change bilirubin, liver enzymes, triglycerides, or adverse event risk. They mean that the registry information is insufficient to answer those questions. A completed registry status and a stated study objective are not substitutes for reported outcomes and an analysis that matches the question being asked.

14. Why This Trial Matters Statistically

This study raises statistical issues common to small, single-group clinical investigations. The primary endpoint is clearly expressed as a participant count tied to a bilirubin threshold, but the result is not reported. Defining an endpoint and reporting its observed count are both necessary for readers to assess what happened. Without the count and the number assessed, neither an outcome frequency nor its precision can be understood.

The single-group design also highlights the distinction between documenting change and estimating a comparative effect. A measurement changing during treatment would be a within-group observation. It would not identify how outcomes would differ under another treatment, because no concurrent comparator is reported. That distinction is central when interpreting clinical records that describe an intervention with an intended benefit.

The modest enrollment of 10 makes transparent outcome reporting especially important: each participant's status can meaningfully affect a group summary. Confidence intervals and clear denominators would help communicate uncertainty if results were available. The registry record does not report those estimates, the analysis population, or missing-data handling.

The record names several secondary measures in addition to the primary endpoint. This creates a need for a clear plan about which outcomes carry confirmatory weight and how multiple findings are interpreted. No such plan is reported, and no analyses are posted. The study therefore illustrates why registration of outcome names alone is not enough to evaluate results or their statistical strength.

Finally, the safety figures demonstrate the importance of separating descriptive surveillance from causal inference. Counts in a treated group can identify events recorded during follow-up, but without a comparator and attribution details they do not quantify excess risk. The registry is useful for understanding the intended question, design, treatment conditions, and reported safety counts, while leaving the principal efficacy result unresolved.

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 principal limitation for interpreting this particular record is that the primary endpoint result is absent. The number of participants with conjugated/direct bilirubin below 1 mg/dl is not reported, and the registry lists no analyses. As a result, the central outcome cannot be quantified or assessed for precision.

The study is single-group, with allocation listed as NA and masking as NONE. No concurrent comparison is reported, so the entry cannot provide a randomized contrast or isolate changes associated with Omegaven from other influences. The record's enrollment of 10 also means that any available group summary would need to be interpreted with its uncertainty and denominator in view; those details are not reported.

Participant characteristics, eligibility criteria, baseline bilirubin values, individual treatment duration, endpoint assessment details, and participant flow are not reported in the registry record. Although the primary timeframe is described as 1-14 weeks and the arm description specifies treatment stopping conditions, the record does not say how those features applied to each participant. Missing data and the analysis population are likewise not described.

The registry lists secondary outcomes, but does not report their results or sufficient analysis detail to assess them. It does not report a statistical plan, sample-size justification, multiplicity approach, interim analyses, or missing-data methods. The sample-size assumptions described for planning illustrations use two-arm planning conditions and do not establish the rationale for this single-group study.

The adverse event information is limited to group counts and listed terms. The record does not report timing, participant overlap across terms, relatedness assessments, or a concurrent comparator. These limitations restrict both efficacy and safety interpretation; they do not show that an outcome was absent or that an event was caused by the intervention.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Compassionate Use of Omegaven to Reverse Parenteral Nutrition Induced Cholestasis — NCT01173159.
• Registry record last updated 2020-06-17; status last verified 2020-06.
• Results first posted 2020-05-08.
• 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

NCT01173159 is a completed, single-group compassionate-use study of Omegaven for cholestasis associated with parenteral nutrition. The registry records enrollment of 10, masking as NONE, allocation as NA, and phase as NA. Study dates are 2010-07 for start and 2018-12 for primary completion.

The intervention was Omegaven at up to 1 g/kg body weight/day, with therapy continuing until a stated clinical stopping condition. The primary endpoint was the number of participants with conjugated/direct bilirubin change to below 1 mg/dl by completion of therapy, described as 1-14 weeks. The endpoint result and secondary outcome results are not reported in the registry record, and no analyses are listed.

Safety entries record 4 participants affected in the serious adverse event count, 6 in the other adverse event count, and 0 deaths. Six serious adverse event terms are listed, each at 10.0%. The single-group design and absence of posted outcome analyses prevent estimation of a comparative treatment effect from this entry.