This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study of Lactulose in Children With Chronic Liver Disease (NCT00811434), a randomized phase 2 study. The primary outcome is Incidence of Minimal Hepatic Encephalopathy (MHE) in Children With Cirrhosis.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00811434 |
| Phase | Phase 2 |
| Condition | Minimal Hepatic Encephalopathy |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 16 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Indiana University |
| Results posted | Yes |
2. Clinical Question
Population
Children with chronic liver disease were the population of interest. The study focused on minimal hepatic encephalopathy (MHE) in children with cirrhosis. The registry summary describes cognitive and developmental testing to identify children with MHE before the treatment periods.
Intervention
Lactulose was the active treatment. Its arm description specifies therapy for 3 months based on patient weight. The registry summary describes a blinded treatment period, but does not report a specific lactulose dose.
Comparator
The comparator was placebo, described as sugar water given orally at 1.5 ml/kg day for three months. The intended design also included a washout period with no treatment before participants switched to the opposite treatment.
Primary question
The registered primary outcome was the incidence of MHE at baseline, defined by failure of one cognitive function test. That measure characterizes MHE at study entry; it is not a direct comparison of cognitive outcomes during lactulose and placebo treatment.
The study’s stated broader aim was to assess whether lactulose treatment affected MHE, cognitive function, and healthcare-related quality of life. Its listed secondary outcomes include health-related quality of life and effects of lactulose treatment on MHE as measured by cognitive function. Those aims make the crossover sequence relevant: each participant was intended to receive both treatments, separated by a washout period, so cognitive and developmental testing could be repeated during the study.
However, the registry record does not report results for those treatment-period outcomes or a statistical comparison between lactulose and placebo. It records enrollment of 16 and a terminated status, but does not report why the trial was terminated or how many participants contributed outcome data. Consequently, the record supports a description of the question and planned sequence, but not a conclusion about the observed effect of lactulose relative to placebo.
3. Trial Design
The registry classifies this as a Phase 2, randomized, triple-masked crossover trial of lactulose and placebo. It records enrollment of 16 and lists Indiana University as the sponsor. The study start is recorded as 2009-01, primary completion as 2010-11, and status as terminated. The reason for termination is not reported in the registry record.
The registry summary describes a sequence beginning with cognitive and developmental testing to determine whether a child had MHE. Children identified as having MHE would then receive a blinded 3-month period of placebo or lactulose, followed by a washout period without treatment. The summary describes retesting and then a second 3-month treatment period in which the treatment was switched. This describes the intended crossover sequence; the record does not establish how many participants completed each period or whether the sequence was carried out as planned.
The lactulose arm is described as 3 months of therapy based on patient weight. The placebo arm is described as sugar water, given orally at 1.5 ml/kg day for three months. The registry identifies random allocation and triple masking, but does not report the randomization procedure, allocation sequence, or which parties were masked. It also does not report how the treatment order was assigned or whether the treatment sequence was balanced.
A crossover design can allow treatment comparisons within the same participant, which may reduce the influence of stable differences between participants. This is a general feature of crossover designs, not evidence about how this trial’s analysis was conducted. Such a design also makes the washout and period-specific measurements important: effects may carry over, and outcomes may change over time for reasons unrelated to treatment. The registry record does not report analyses addressing period effects, carryover, or the adequacy of the washout.
The record lists three outcome measures, including the primary baseline MHE measure and secondary outcomes concerning health-related quality of life and cognitive function. It reports no analyses. The number of participants enrolled should therefore not be read as the number analyzed, the number completing both treatment periods, or the number contributing to any outcome.
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: Two subjects were withdrawn prior to randomization.Two did not meet entry criteria.
First Intervention
| Stage | Lactulose First, Then Placebo | Placebo First, Then Lactulose |
|---|---|---|
| STARTED | 7 | 5 |
| COMPLETED | 4 | 5 |
| NOT COMPLETED | 3 | 0 |
Washout (1 Month)
| Stage | Lactulose First, Then Placebo | Placebo First, Then Lactulose |
|---|---|---|
| STARTED | 4 | 5 |
| COMPLETED | 4 | 5 |
| NOT COMPLETED | 0 | 0 |
Second Intervention
| Stage | Lactulose First, Then Placebo | Placebo First, Then Lactulose |
|---|---|---|
| STARTED | 4 | 5 |
| COMPLETED | 4 | 5 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | All Participants |
|---|---|---|
| Participants analysed | 12 | |
| Age, Categorical: <=18 years | Participants | 12 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 8 |
| Sex: Female, Male: Male | Participants | 4 |
| Region of Enrollment: United States | participants | 12 |
6. Primary Endpoint
The registry lists the primary outcome as Incidence of Minimal Hepatic Encephalopathy (MHE) in Children With Cirrhosis, measured over baseline.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participant |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is the incidence of minimal hepatic encephalopathy in children with cirrhosis, measured at baseline. The registry defines MHE for this outcome as failure of one cognitive function test. In this context, the endpoint is a count of participants meeting that test-based definition, rather than a score describing the degree of impairment.
Cognitive testing is relevant to the study’s stated focus because MHE may involve changes in behavior, intelligence, and neurological function. A test-based definition gives the registry a way to identify the condition at study entry and to describe how frequently it is present in the target population. The record does not identify the specific cognitive test, its scoring rules, or how multiple test results were combined beyond the stated criterion that failure of one test indicates MHE.
The baseline timeframe is important for interpretation. A baseline incidence measure describes the condition before the planned treatment comparison; by itself, it cannot establish whether lactulose changes cognitive function or MHE. The registry lists treatment-related cognitive function and health-related quality of life among the secondary outcomes, but does not report their values or analyses. Nor does it report a treatment-effect estimate for the primary outcome. Thus, the registered primary measure can be understood as a characterization of MHE at study entry, not as evidence of a treatment benefit or harm.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a clinical question about lactulose and cognitive outcomes in children with chronic liver disease, but its posted results do not provide a treatment comparison. The registered primary outcome is MHE incidence at baseline. Its definition is failure of one cognitive function test, and its timeframe is baseline. This is a measure of condition status before the intended treatment periods, not a measure of change attributable to lactulose.
No primary outcome value is reported in the record presented, and no treatment-period cognitive or health-related quality-of-life results are reported. The record lists three outcome measures and reports zero analyses. There is therefore no reported treatment-effect estimate, confidence interval, or hypothesis test to interpret for lactulose versus placebo. The absence of an estimate is different from an estimate showing no effect: the available record does not quantify the treatment contrast.
The study’s crossover design is relevant to what a treatment comparison could have meant. In general, a crossover comparison may use outcomes from both treatment periods within the same participant. Interpretation then depends on the treatment sequence, washout, period effects, and whether participants contributed data in both periods. The registry describes a washout and switching treatments, but does not report completion, period-specific data, or an analysis accounting for these design features. The planned design alone cannot substitute for results.
The status is terminated. That status indicates the registered trial did not remain active as recorded, but the reason for termination and its timing relative to enrollment or follow-up are not reported in the registry record. The record also does not state how many participants completed the planned sequence or contributed outcome data. Enrollment of 16 is not an analysis denominator and should not be treated as proof that all enrolled participants had complete outcome information.
The safety record lists zero serious adverse events for the lactulose group among 12 at risk and for the placebo group among 9 at risk. The corresponding other-adverse-event counts are also zero, with the same group-specific at-risk figures. These are descriptive registry counts. They do not show that no adverse events occurred outside the categories or recording period represented, and the record does not explain how these at-risk counts map to exposure periods in the crossover design. Deaths are not reported in the registry record.
Overall, the posted information allows a careful account of the registered population, interventions, baseline endpoint, and recorded safety counts. It does not permit an estimate of the effect of lactulose on MHE, cognition, or quality of life. No clinical conclusion about treatment effectiveness can be drawn from the missing treatment-comparison results.
9. Statistical Methods Explained
Statistical methods describe how outcomes are defined, compared, and interpreted. For this trial, the registry record provides the design classification and baseline endpoint definition, but does not report an analysis plan or treatment-effect analyses. The concepts below explain how such methods generally relate to the registered design; they do not describe analyses confirmed to have been performed.
What does randomization contribute?
In general, randomization assigns treatment order by a chance process, helping to balance measured and unmeasured participant characteristics across treatment assignments. In a crossover trial, participants receive both treatments, so randomization may concern the order in which treatments are received. The registry identifies the study as randomized, but does not report the allocation method, the sequence assignments, or how randomization was implemented. It is not possible to assess those details from the registry record.
What does masking mean?
The record classifies the study as triple-masked. Masking is intended to reduce the influence of expectations or knowledge of treatment assignment on study conduct, outcome assessment, or reporting. The registry does not identify which participants or study personnel were masked, how masking was maintained, or whether it was successful. The fact that masking is registered does not establish that treatment assignments remained unknown throughout the trial.
How does a crossover comparison work?
Generally, a crossover design compares outcomes under different treatments within the same participant. This can account for stable characteristics that might otherwise make comparisons between separate groups less precise. The registry summary describes an initial treatment period, a washout without treatment, and a second period in which treatment is switched. It does not report treatment sequence assignments, the number completing both periods, or the statistical model used to compare outcomes.
Time and sequence matter in crossover analyses. A participant’s outcome may change between periods for reasons other than treatment, and an effect of the first treatment may persist into the next period. These are commonly described as period and carryover concerns. The registry record does not report whether these possibilities were assessed, whether the washout was considered adequate, or whether the analysis included period or sequence terms. No conclusion about these design issues can be drawn from the registration description alone.
What does the primary endpoint measure?
The primary endpoint is a baseline count of participants meeting the MHE definition. The registry states that failure of one cognitive function test indicates MHE. A count endpoint records how many people meet a defined condition; it does not convey the size of a treatment-related change unless measurements and comparisons across relevant timepoints are also reported. Here, the specified timeframe is baseline, and no primary outcome value is reported.
The specific cognitive test and its measurement properties are not reported in the registry record. The record also does not explain how testing was standardized, how assessors handled incomplete tests, or whether a participant could be classified as having MHE using other clinical information. Such details can affect the reproducibility and interpretation of a test-based endpoint.
Why do estimates and confidence intervals matter?
In general, an effect estimate describes the observed contrast between treatment conditions, using a scale appropriate to the outcome. A confidence interval expresses the statistical uncertainty around an estimate and indicates which values remain compatible with the data under the method’s assumptions. A narrow interval conveys greater precision than a wide interval, while neither precision nor statistical significance alone establishes clinical importance.
The registry record reports no treatment-effect estimate or confidence interval for cognitive function, MHE, or health-related quality of life. There is consequently no precision to characterize and no basis for discussing whether a treatment contrast is compatible with benefit, no meaningful difference, or harm. A missing estimate must not be interpreted as a zero estimate.
What can a p-value establish?
Generally, a p-value summarizes how unusual the data would be under a specified statistical model and null hypothesis. It does not measure the probability that a treatment works, nor does it indicate the size or clinical importance of an effect. Its interpretation depends on a prespecified analysis and on the assumptions behind that analysis.
No p-value or statistical test for a treatment comparison is reported in the registry record. The record reports zero analyses, so there is no posted inferential result to interpret. The statistical plan, including any prespecified contrasts or decision criteria, is not reported in the registry record.
Why can outcome distributions affect analysis?
General statistical considerations depend on the outcome type. A binary outcome, such as meeting or not meeting a test-based MHE definition, is often analyzed with methods suited to event probabilities. A continuous cognitive or quality-of-life score may require a model that reflects its scale and distribution. Repeated measurements in a crossover design also require attention to the relationship between measurements from the same participant.
Some count outcomes vary more widely than a simple model expects; this is called over-dispersion. When present, over-dispersion can make standard errors too small if a model assumes less variability than the data contain. Whether it applies depends on the actual outcome distribution and model. The registry does not report enough analysis detail to determine the methods used or whether over-dispersion was relevant.
In short, the record supplies a design description and endpoint definition but not the inferential machinery or results needed to evaluate a treatment contrast. The general statistical concepts above clarify what would ordinarily matter; they should not be mistaken for the trial’s unreported statistical plan.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when several outcomes, timepoints, treatment contrasts, or subgroup questions are tested. Repeated testing can increase the chance of finding an apparently notable result by chance. General approaches include identifying a primary comparison in advance, adjusting for a family of tests, or interpreting secondary analyses as exploratory. The registry lists a primary outcome and secondary outcomes concerning health-related quality of life and cognitive function, but does not report a multiplicity strategy or a prespecified hierarchy for the analyses.
The registry reports three outcome measures and zero analyses. It does not report treatment-comparison estimates for the primary or secondary outcomes, so there are no posted tests to assess for multiplicity. The statistical analysis plan, including any rules for selecting outcomes or timepoints, is not reported in the registry record. The outcome list alone does not establish which comparisons were planned or performed.
Missing-data methods are also not reported in the registry record. The record does not explain how incomplete cognitive tests, missed visits, withdrawal, or failure to complete the crossover sequence would be handled. It does not report an analysis population, such as whether participants would be analyzed according to assigned sequence or only if they completed both treatment periods.
These omissions matter because a crossover analysis depends on what measurements are available from each period and how incomplete participation is addressed. Enrollment of 16 does not indicate how much outcome information was collected or included in an analysis. Without stated analysis populations and missing-data procedures, the risk of bias from incomplete observations cannot be evaluated from the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Lactulose | 0 | 12 | 0.0% |
| Placebo | 0 | 9 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Lactulose | 0 of 12 |
| Placebo | 0 of 9 |
The registry’s serious adverse event figures are recorded separately by group. For lactulose, the record lists zero serious adverse events among 12 at risk; for placebo, it lists zero among 9 at risk. The record also lists zero other adverse events in each group, with the same group-specific at-risk counts. These are counts as entered in the registry and should be read as descriptive safety information, not as a comparative statistical analysis.
The crossover design makes the meaning of group-specific at-risk counts important. The record does not explain whether these counts refer to participants, treatment-period exposure, or another registry reporting unit, and it does not describe the observation period for the safety figures. Because participants were intended to switch treatments, the counts should not be used to infer the number completing the study or the amount of exposure to each treatment.
Zero reported events do not establish that a treatment is free of risk. They describe only the events recorded in these categories for the stated at-risk groups; the registry does not provide event definitions, event-collection details, or a fuller account of follow-up. Deaths are not reported in the registry record. The figures therefore provide limited descriptive information and do not support a precise comparison of safety between lactulose and placebo.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, triple-masked crossover trial was registered to study lactulose and placebo in children with chronic liver disease. It identifies a baseline MHE outcome defined by failure of one cognitive function test, and describes intended treatment periods with a washout and a switch. It also lists health-related quality of life and cognitive function among the secondary outcomes.
What the record does not establish is whether lactulose changed MHE, cognitive function, or quality of life. It reports no treatment-period outcome values, treatment-effect estimates, confidence intervals, or treatment-comparison tests. The baseline outcome is not a before-and-after treatment contrast. Likewise, zero reported adverse events in the listed groups is not proof that either treatment has no risks, particularly when event collection and exposure details are not reported.
In general, a treatment result is most informative when it reports the outcome in each relevant condition, an effect estimate, and its uncertainty, alongside details of the analysis population and missing data. Those elements are not reported for the treatment comparison in this registry record. A sample-size planning illustration, if available elsewhere in the statistical presentation, would be a planning calculation rather than observed treatment evidence; it cannot replace trial results or establish observed power.
The terminated status is part of the record but does not explain why the trial stopped. The registry does not report whether termination followed recruitment challenges, operational decisions, safety concerns, or another cause. No such explanation should be inferred. Similarly, the enrollment entry does not demonstrate completion or an analyzed sample.
The appropriate interpretation is therefore limited: the registry documents the research question, planned crossover framework, baseline endpoint, and a small set of safety counts, but it does not provide the results needed to estimate treatment effects. This is an absence of reported evidence in the registry record, not evidence that the treatments were equivalent or that no effect occurred.
13. Why This Trial Matters Statistically
This trial is statistically notable because its registered primary endpoint and its broader treatment aim address different questions. The primary endpoint measures baseline MHE incidence using a cognitive-test failure definition. The study summary, by contrast, describes assessing effects of lactulose on MHE and cognitive function after treatment periods. A baseline count can characterize the enrolled population, but it cannot by itself quantify a treatment effect. Keeping those questions separate prevents a descriptive measure from being mistaken for an efficacy comparison.
The crossover design also highlights the importance of analysis details. In general, within-participant comparisons can account for stable differences between participants, but period effects, carryover, sequence, and incomplete follow-up require consideration. The registry describes a washout and switching treatments, yet does not report the analysis methods or completion information needed to evaluate those features. Design labels alone do not establish that a comparison is unbiased or precise.
Finally, the registry record illustrates why enrollment and outcome reporting must be interpreted separately. The enrollment entry is not an analyzed sample size, and the terminated status does not explain what data were collected. Without outcome estimates and uncertainty, readers cannot distinguish a small effect from a large but imprecise effect, or assess whether the data are compatible with different possibilities. Statistical interpretation depends not just on a trial’s question and design, but also on transparent reporting of outcomes, analysis populations, and uncertainty.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
Several limitations specific to this record constrain interpretation. The primary endpoint is defined at baseline, whereas the study’s stated broader aim concerns treatment effects on cognitive function and MHE. No baseline outcome value is reported, and no post-treatment values or treatment comparisons are reported. The registry does not identify the cognitive test, its scoring procedure, or how test completion and classification were handled beyond the criterion that failure of one cognitive function test indicates MHE.
The record describes a crossover sequence but does not report whether participants completed both periods, how treatment order was assigned, or whether the washout and possible carryover were addressed in analysis. It reports no analysis methods, statistical plan, estimates, confidence intervals, or tests. The analysis population and handling of missing observations are not reported in the registry record.
Although enrollment is recorded as 16, the record does not state how many participants contributed to each outcome or completed follow-up. The status is terminated, but the reason for termination is not reported. It is therefore not possible to determine from the registry record whether the missing results reflect incomplete data collection, unreported analyses, or another circumstance.
The safety entries list group-specific at-risk figures and zero reported serious and other adverse events, but the record does not explain the exposure unit or event-collection period. Deaths are not reported in the registry record. These limitations mean the posted information is insufficient for estimating treatment effects or making a complete safety comparison.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Lactulose in Children With Chronic Liver Disease — NCT00811434.
- Registry record last updated 2014-02-10; status last verified 2014-02.
- Results first posted 2014-02-10.
- 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.
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18. Record Summary
The registry record describes a Phase 2, randomized, triple-masked crossover study of lactulose and placebo in children with chronic liver disease, with a focus on minimal hepatic encephalopathy. It records enrollment of 16, sponsor Indiana University, a study start of 2009-01, primary completion of 2010-11, and terminated status.
The registered primary outcome is baseline MHE incidence, defined as failure of one cognitive function test. The study summary describes two 3-month treatment periods separated by a washout, with treatment switched between periods. Secondary outcomes include health-related quality of life and cognitive function. The record reports three outcome measures and zero analyses, and provides no treatment-effect results. Serious and other adverse event counts are recorded as zero for both listed groups; deaths are not reported in the registry record.