N-Acetylcysteine in Biliary Atresia After Kasai Portoenterostomy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for N-Acetylcysteine in Biliary Atresia After Kasai Portoenterostomy (NCT03499249), a na phase 2 study. The primary outcome is Number of Patients With Biliary Atresia (BA) Achieving Total Serum Bile Acids Less Than or Equal to 10 *U*Mol/L Within 24 Weeks of Kasai Portoenterostomy (KP).

2. Clinical Question

3. Trial Design

This was a completed Phase 2, single-group trial of N-acetylcysteine after Kasai portoenterostomy for biliary atresia. Baylor College of Medicine was the sponsor. The registry lists enrollment as 13 and describes the intervention group as receiving intravenous N-acetylcysteine. Allocation was listed as not applicable, and masking was listed as none. Thus, the registered design does not include a randomized comparison or a concurrent control group.

Treatment was intended to begin within 24 hours of completion of the procedure and continue for a total of 7 days. The registered dose was 6.25 mg/kg/hour of a 10 mg/ml solution, corresponding to 0.625 ml/kg/hour and 150 mg/kg/day. These details describe the intervention in the record; treatment adherence and the amount actually received by each participant are not reported.

The registry gives the trial start date as 2018-05-18, primary completion date as 2022-10-31, and status as completed. It calls the study a minimax Phase 2 clinical trial. The detailed protocol, including any design thresholds or decision rules associated with that description, is not reported in the registry record.

The primary objective was to assess whether total serum bile acid concentrations reached the stated threshold within 24 weeks after the procedure. Secondary objectives included changes in liver-related laboratory measures during treatment, sentinel events in the first 2 years of life, and adverse events possibly related to N-acetylcysteine. The record contains outcome definitions and some safety figures, but it does not report the observed primary endpoint result or a statistical analysis of that endpoint.

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:

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 Patients With Biliary Atresia (BA) Achieving Total Serum Bile Acids Less Than or Equal to 10 *U*Mol/L Within 24 Weeks of Kasai Portoenterostomy (KP), measured over Within 24 weeks after KP.

The primary endpoint is the number of participants with biliary atresia whose total serum bile acid concentration was 10 µmol/L or lower within 24 weeks after Kasai portoenterostomy. This is a binary outcome at the participant level: each participant either meets the recorded threshold within the specified period or does not. The registry expresses the result as a count of participants, rather than as a continuous measurement or a time-to-event summary.

The threshold is used to operationalize the study’s question about normalization of bile acids after the procedure. According to the registry description, achieving a normal total serum bile acid concentration is uncommon under current standard care and is predicted to be associated with better long-term outcomes. The record states an expected value of approximately 5% based on historical controls and describes a higher number achieving the threshold as a better outcome. That historical expectation is contextual information, not a concurrent comparator result.

The endpoint’s specified time window makes the assessment about whether the threshold was achieved within 24 weeks, not about long-term persistence or outcomes beyond that period. The registry does not report the observed number meeting the threshold, how measurements over time were handled, or what approach was used for participants without an available measurement. Therefore, the endpoint definition is available, but its observed result and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial is described as a single-group Phase 2 study. In general, a single-group design observes outcomes among people receiving the intervention without a concurrent control group. Such a design can describe the outcome frequency and characterize events in the treated group. It cannot, by itself, separate the effect of treatment from changes that might have occurred over time or from other factors related to participants’ care. The registry lists allocation as not applicable and masking as none; it does not describe a randomized allocation process or masked assessment.

What does the binary endpoint represent?

The primary outcome is a count of participants who met a threshold for total serum bile acids within a specified period. A binary outcome classifies each participant according to whether the criterion was met. Summarizing a binary outcome as a count is straightforward, but interpretation also depends on the number of participants assessed and on whether outcome information is available for all participants. The registry defines the endpoint and lists enrollment as 13, but it does not report the primary outcome count, an analyzed denominator, or an analysis population. No outcome proportion should be inferred from the record.

A confidence interval is a statistical range used to communicate uncertainty around an estimate. For a binary outcome, it can indicate how compatible the observed data are with a range of possible underlying event frequencies. Wider intervals generally indicate less precision, while narrower intervals indicate greater precision under the method’s assumptions. No confidence interval for the primary outcome is reported in the registry record, so its precision cannot be evaluated.

Why does the lack of a control group matter?

A concurrent control group provides a comparison observed during the same trial period under a different assigned treatment or control condition. Here, the registry describes one treatment group and does not report a concurrent comparator. The historical expectation of approximately 5% appears in the primary outcome description, but a historical reference is not equivalent to participants enrolled and followed as a control group in this study. Differences in population, procedures, follow-up, or measurement can affect comparisons across studies. The registry record does not provide enough detail to assess comparability with the historical controls mentioned.

As a result, a treated-group outcome could be described, but a treatment-versus-control contrast cannot be estimated from the registered design alone. General causal interpretation requires caution when treatment exposure and the passage of time occur together without a concurrent comparison. This does not invalidate descriptive observations; it limits what those observations can establish.

What can be learned from the safety summaries?

The registry lists counts of participants with serious and other adverse events in the treatment group, along with selected serious-event terms and percentages. These are descriptive safety summaries. A serious adverse event is a classification of an event according to seriousness criteria; it is not the same as a judgment that the treatment caused the event. The registry also lists adverse events possibly related to N-acetylcysteine as a secondary outcome, but the summary does not provide a complete event-level account of relatedness assessments.

General safety interpretation considers the number of participants at risk, event definitions, follow-up duration, repeated events, and how events were collected. Participant counts and event counts are not interchangeable: one participant may experience more than one event. The record lists participant-level figures for the treatment group but does not report full event-level details, exposure-adjusted rates, or a comparative safety estimate. No such quantities can be reconstructed from the posted summaries without additional data.

What is the status of the analysis information?

The registry lists no analysis entries. It therefore does not report the statistical method used for the primary endpoint, the approach to uncertainty estimation, or whether any adjusted analysis was performed. A statistical method should be interpreted in light of the endpoint, design, and assumptions; without an analysis description or posted primary result, those features cannot be evaluated for this outcome.

The record describes a minimax Phase 2 design. In general, a minimax design is a type of phase 2 design that uses decision criteria to guide whether further study is warranted under specified assumptions. The record does not report the detailed design assumptions, decision boundaries, or sample-size justification, so those elements should not be inferred from the design label alone.

The posted sample-size material is described as a planning illustration computed from the observed effect, with two-sided significance level 0.05, equal allocation, and a normal approximation. Such calculations are prospective illustrations of the sample size that might be needed under their assumptions; they are not observed power, and they do not replace the trial’s own analysis. The registry record does not report the underlying observed primary effect or the calculated values needed to assess those illustrations. Any planning interpretation should therefore remain separate from conclusions about the trial’s observed outcome.

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("N-Acetylcysteine Treatment")
n      <- c(12)
events <- c(0)
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  N-Acetylcysteine Treatment  12  0  0.0  0.0  26.5  0.0  24.2  0.2  24.7

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and several secondary outcomes. The secondary outcomes include changes in AST, ALT, GGT, and conjugated bilirubin at 3 days and 7 days after Kasai portoenterostomy during treatment; sentinel events in the first 2 years of life; and adverse events possibly related to N-acetylcysteine. Multiple outcomes create the general possibility that some findings may appear notable by chance, particularly when many comparisons are made. The registry record does not report a multiplicity strategy, a hierarchy for interpreting secondary outcomes, or a prespecified adjustment method.

The record lists no analysis entries and does not describe how missing primary or secondary outcome data were handled. It does not report whether every enrolled participant had measurements at the scheduled assessment times, how incomplete follow-up was treated, or whether any sensitivity analyses were conducted. These details matter because the interpretation of a count or change depends on which participants contributed data and how missing measurements were addressed. No assumptions about those procedures can be made from the endpoint definitions alone.

The analysis population is also not reported in the registry record. The record does not state whether the primary endpoint was assessed among all enrolled participants, among those who received treatment, or under another population definition. Although enrollment is listed as 13, the analysis denominator for the primary outcome is not given. The completed status does not resolve these reporting gaps. Consequently, the scope of the analysis, handling of missingness, and control of multiplicity remain unclear.

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: febrile illness (15.4%), alt 700 iu/l >pre-kp value (7.7%), inr >2.0 (7.7%), tachycardia (7.7%).

The registry lists 5 participants with serious adverse events and 11 with other adverse events in the N-acetylcysteine treatment group; 0 deaths are listed. The listed percentages for selected serious-event terms are febrile illness, 15.4%; ALT 700 IU/L >pre-KP value, 7.7%; INR >2.0, 7.7%; and tachycardia, 7.7%. These are the safety summaries recorded for this group.

These figures should be read as descriptive reports, not as proof that N-acetylcysteine caused the events. The registry does not provide a concurrent control group for comparing event frequencies. It also does not report detailed event timing, duration, recurrence, or the full basis for judgments about whether events were possibly related to treatment. Seriousness and treatment-relatedness are distinct classifications: an event may be serious without being attributed to the intervention.

The percentages are reported as listed; they should not be treated as comparative risks or as a complete account of safety. The registry lists participant counts for serious and other adverse events, but does not provide all event-level information needed to determine whether participants experienced multiple events. The listed 0 deaths is a descriptive entry for this study, not a guarantee about risk outside the trial.

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

The registry record establishes that a Phase 2, single-group trial evaluated intravenous N-acetylcysteine after Kasai portoenterostomy and defined a primary outcome based on reaching a total serum bile acid threshold within 24 weeks. It also records treatment details, secondary outcome topics, and selected adverse-event summaries. Those details describe what the study set out to assess and what safety information was registered.

The primary outcome result itself is not reported in the registry record. There is no posted count of participants who reached the threshold, no estimate of the uncertainty around that outcome, and no analysis entry describing how it was assessed. The trial’s outcome therefore cannot be characterized as meeting or not meeting its objective on the basis of this record.

The design also has no concurrent comparator group. Even if a primary outcome count were available, a single-group result would describe observed outcomes among participants in the treatment group; it would not, on its own, demonstrate that treatment caused those outcomes or establish how they compare with outcomes under another approach. The historical expectation noted in the endpoint description is not a randomized or concurrent control result.

The safety figures are similarly descriptive. They document serious and other adverse events and selected serious-event terms, but do not establish causation or provide a controlled comparison. The absence of a reported analysis plan, analysis population, and missing-data approach further limits interpretation of the endpoint and secondary results.

Accordingly, the record supports a description of the trial’s design, intervention, endpoint definitions, and reported safety counts. It does not provide enough information to determine the primary efficacy result, quantify its precision, or draw a comparative conclusion. Those limits should remain explicit when considering what this study contributes.

14. Why This Trial Matters Statistically

This trial is statistically notable as a Phase 2, single-group study with a defined binary endpoint and an explicit follow-up window. The endpoint asks whether total serum bile acid concentrations reached a stated threshold within 24 weeks after Kasai portoenterostomy. Clear endpoint definitions help readers understand what a study intends to count, while a clearly described analysis is needed to understand how the count was estimated and how uncertain it is.

The registry’s single-group design makes the distinction between description and comparison especially important. A treated-group outcome can characterize what was observed in that group. Without a concurrent control group, however, the design does not provide a direct randomized estimate of the difference between treatment strategies. The historical expectation cited in the endpoint description offers context but does not have the same role as a control group observed within the trial.

The registry also calls the study a minimax Phase 2 trial. This design label signals that decision-making was part of the intended phase 2 framework, but the record does not report the detailed assumptions or decision rules. Those details would be needed to assess how the design was intended to guide interpretation or subsequent research.

Finally, the gap between a defined endpoint and an unreported endpoint result illustrates why registration details and results reporting serve different purposes. The record specifies the question and intervention, and it contains selected safety summaries. It does not report the primary outcome analysis, its precision, or the handling of missing data. For statistical interpretation, those omissions are material: a clear question is necessary, but an interpretable answer also requires the observed result and enough analysis detail to assess its reliability.

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 most important limitation for interpreting this trial from the registry record is that the primary endpoint result is not reported. The record defines the threshold and time window but gives no observed count, estimate, or uncertainty interval. The completed status does not supply the missing result.

The study is registered as single-group, with no concurrent comparator and no masking. This design can describe outcomes among treated participants but cannot provide a randomized comparison with another group. The historical expectation in the outcome description is not a substitute for a concurrent control, and the registry does not provide details needed to judge comparability with those historical controls.

The record lists enrollment as 13, but does not report the primary analysis denominator, analysis population, treatment adherence, or how missing measurements were handled. It also does not describe the statistical method for the primary endpoint. No analysis entries are listed, so the analysis strategy and any assessment of precision cannot be reviewed.

Several secondary outcomes are registered, but the record does not report a multiplicity approach or a prespecified hierarchy for interpreting multiple outcomes. The detailed protocol and the assumptions or decision rules behind the minimax design are not reported in the registry record. These omissions prevent a fuller assessment of the trial’s planned decision framework.

Safety interpretation is limited by the lack of a control group and by the absence of detailed event-level reporting, including timing and relatedness assessment. The listed counts and percentages should be treated as descriptive, not causal or comparative. Taken together, these limitations mean that the registry supports an account of the study design and selected safety information, but not a complete evaluation of the primary outcome or treatment effect.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: N-Acetylcysteine in Biliary Atresia After Kasai Portoenterostomy — NCT03499249.
• Registry record last updated 2024-03-26; status last verified 2024-03.
• Results first posted 2024-01-10.
• 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

The registry describes a completed Phase 2, single-group trial of intravenous N-acetylcysteine after Kasai portoenterostomy for biliary atresia. Enrollment is listed as 13. Treatment was to begin within 24 hours of the procedure and continue for 7 days. The primary endpoint was the number of participants reaching total serum bile acid concentrations of 10 µmol/L or lower within 24 weeks.

The record also lists secondary laboratory and safety outcomes. It reports 5 participants with serious adverse events, 11 with other adverse events, and 0 deaths in the treatment group, with selected serious-event terms and percentages. The primary endpoint result, its statistical analysis, the analysis population, and the handling of missing data are not reported in the registry record. Because the study has no concurrent comparator, its registered design does not support a randomized treatment comparison.