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 Efficacy and Safety Study of Ammonul® in Patients With Grade 3 or 4 Hepatic Encephalopathy (NCT00597909), a randomized phase 2 study. The primary outcome is Efficacy, as Assessed by Time to Grade 2 or Less in the West Haven Criteria Sustaining for 4 Hours or Longer.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00597909 |
| Phase | Phase 2 |
| Condition | Hepatic Encephalopathy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Amgen |
| Results posted | Yes |
2. Clinical Question
Population
Hospitalized patients with Grade 3 or 4 hepatic encephalopathy were the intended population. The primary-outcome population description says that one participant enrolled but did not receive drug or was randomized; the wording is ambiguous and does not establish whether that participant was randomized, received treatment, or both.
Intervention
The study was designed to evaluate two doses of AMMONUL®: sodium phenylacetate and sodium benzoate injection 10% / 10%. The registry lists the drug twice, but the arm descriptions are blank, so it does not connect a particular dose with a particular arm or state the dose amounts.
Comparator
The registered comparator was placebo solution (10% dextrose). The registry does not provide an arm description or additional details about how treatment was administered.
Primary question
The primary endpoint asked how long it took to reach Grade 2 or less on the West Haven Criteria and sustain that state for 4 hours or longer. The record contains no estimate of this time, no comparison between treatment groups, and no primary-outcome analysis.
In statistical terms, the intended question was whether the time to a sustained improvement differed across the registered treatment groups. That question requires observed endpoint information and a defined comparison. Neither is available in the registry record. The record therefore describes the question the trial set out to assess, but does not provide evidence with which to estimate a treatment contrast.
The trial title and summary identify the setting as hospitalized patients with severe hepatic encephalopathy, specifically Grade 3 or 4. The endpoint uses a threshold on the West Haven Criteria and requires that the threshold state persist for a specified period. This combines a clinical state with a duration condition: a momentary assessment at Grade 2 or less would not, by itself, meet the stated endpoint.
3. Trial Design
The registry identifies this as a Phase 2, randomized, parallel-group, placebo-controlled study. The official title describes a double-blind study of two doses of AMMONUL®, and the registry’s masking classification is quadruple. Those descriptions indicate that masking was part of the registered design, but the record does not identify the roles covered by the quadruple-masking classification or explain how masking was implemented.
The planned comparison involved two AMMONUL® doses and placebo solution (10% dextrose). The two active-treatment entries use the same intervention name. Arm descriptions are blank, so the record does not show which arm corresponded to each dose, how groups were allocated, or what dose amounts were intended. The design is labeled randomized, but the primary-outcome population description raises uncertainty about whether the enrolled participant was randomized. The record does not resolve that uncertainty.
Enrollment is reported as 1. The study status is TERMINATED. The start is listed as 2007-12 and primary completion as 2008-09. The reason for termination is not reported in the registry record. The record also does not give a recruitment history, a protocol deviation account, or details explaining the relationship between the planned parallel-group design and the enrollment information.
These design features describe the registered plan, not a completed comparison. Randomization and masking can help limit bias when implemented, while a parallel-group structure assigns participants to a treatment group for comparison. Those general design strengths do not yield an estimate in the absence of outcome data and confirmed treatment assignments. In this record, the enrollment and population statements do not establish that an analyzable randomized comparison took place.
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: One participant was enrolled but did not receive drug or was randomized.
Overall Study
| Stage | Arm 1 | Arm 2 | Arm 3 |
|---|---|---|---|
| STARTED | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: One participant enrolled but did not receive drug or was randomized.
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 | Arm 1 | Arm 2 | Arm 3 | Total |
|---|---|---|---|---|---|
| Participants analysed | 0 | 0 | 0 | 0 | |
| Age, Categorical: <=18 years | — | — | — | — | |
| Age, Categorical: Between 18 and 65 years | — | — | — | — | |
| Age, Categorical: >=65 years | — | — | — | — |
6. Primary Endpoint
The registry lists the primary outcome as Efficacy, as Assessed by Time to Grade 2 or Less in the West Haven Criteria Sustaining for 4 Hours or Longer, measured over Time to Grade 2 or less sustaining for 4 hours or longer.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was time to reach Grade 2 or less on the West Haven Criteria and sustain that level for 4 hours or longer. It is a time-to-event measure: the event is the first qualifying improvement that also meets the duration condition. The timeframe field repeats the sustained Grade 2-or-less definition but does not specify a time unit for reporting the result.
Requiring a sustained state distinguishes the endpoint from an improvement observed at a single assessment. In general, this can make an endpoint more reflective of persistent change rather than a brief fluctuation. The endpoint also turns an ordered clinical assessment into a threshold event: reaching the specified category and maintaining it for the required period count toward the event definition.
Time-to-event measures are often used when both whether an event occurs and how long it takes are relevant. General analysis of such outcomes may account for participants who have not reached the event by the end of observation, but the registry record does not report whether anyone was followed, how follow-up was handled, or what analysis method was planned. It supplies no event times, group summaries, hazard estimate, confidence interval, or test result.
The population description states that one participant enrolled but did not receive drug or was randomized. Because this wording does not establish treatment receipt or assignment, it does not support an endpoint comparison. The endpoint is defined in the registry, but its observed value and the comparison needed to answer the trial question are not reported.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record permits a description of the intended trial question and design, but not an interpretation of treatment effects. Enrollment is reported as 1, the status is TERMINATED, and the primary-outcome record describes one participant as enrolled but not receiving drug or being randomized in ambiguous wording. No analyzed primary-outcome result is reported. There is consequently no posted estimate of time to the sustained endpoint for any group and no statistical comparison between the registered groups.
The record lists nine outcome measures and zero analyses. The primary endpoint is time to Grade 2 or less sustained for 4 hours or longer; the secondary outcomes include assessments using the West Haven Criteria, the Glasgow Coma Scale, safety measures, blood ammonia levels, amino acids and carnitine, and pharmacokinetic characteristics. Listing outcome measures does not mean that values were collected or analyzed. No results for these secondary outcomes are included in the record information.
The adverse-event entries list zero participants at risk and zero affected participants in each of the three groups. These entries do not establish that no adverse events occurred among treated participants: the at-risk counts are also zero, and the record does not establish treatment exposure. The death fields are null, which is not the same as a reported count of zero. Thus, these entries do not support a safety comparison.
No p-value, confidence interval, effect estimate, or group-level outcome summary is available. A confidence interval, in general, describes the precision of an estimated quantity under an analysis model; it cannot be interpreted when the estimate itself is absent. Likewise, a significance test cannot establish evidence for or against a difference without an analyzable comparison. The absence of a result in the registry is not a finding that the groups were equivalent, nor is it evidence of benefit or harm.
The registered design called for randomization and masking, but the population description leaves the participant’s assignment and drug exposure unresolved. Even if a planned statistical approach were available, these record details would not establish that the planned comparison was carried out. The statistical plan, including any adjustment or handling of incomplete observations, is not reported in the registry record.
Any sample-size planning illustration should be kept separate from observed evidence. Planning figures describe hypothetical requirements under assumptions; they are not observed power and do not substitute for trial results. Since the registry information contains no observed effect estimate or analyzable treatment comparison, it cannot show how precisely the intended effect was estimated.
9. Statistical Methods Explained
The registered design combines random allocation, masking, a parallel-group structure, and a placebo comparator. These features describe ways a trial may organize a comparison; they do not themselves provide outcome evidence. The registry does not report the allocation procedure, the intended dose amounts, or enough arm information to map each active intervention to its group. It also does not confirm that randomization occurred for the enrolled participant.
What does randomization contribute?
In general, randomization assigns participants to groups by chance. It is intended to reduce systematic differences between groups at the point of assignment, so that a later outcome contrast can be interpreted more fairly. Randomization does not guarantee identical groups, especially in small studies, and it cannot correct for absent outcome measurements or unknown treatment exposure. Here, the record labels the design randomized but does not establish a completed allocation or an analyzable randomized comparison.
What does masking contribute?
Masking is intended to limit the influence of expectations or knowledge of assignment on participant care, outcome assessment, or reporting. The official title says double-blind, while the registry classification says quadruple masking. The record does not explain these labels or identify who was masked. Therefore, the masking status can be described as part of the registered design, but its implementation and success cannot be assessed from the record.
How should the endpoint be understood?
The primary endpoint is a time-to-event outcome. The event is reaching Grade 2 or less on the West Haven Criteria and sustaining that state for at least 4 hours. In general, a time-to-event analysis needs a clearly defined event, a time origin, and information about observation through the event or the end of follow-up. A participant who has not reached the event by the end of observation may contribute incomplete event-time information, often described as censoring. The registry record does not report the time origin, follow-up details, event observations, censoring rules, or analysis method.
The duration condition matters because the endpoint is not merely an assessment of clinical category at one instant. It requires both a threshold and persistence. The record states that definition but does not provide the schedule of assessments or explain how continuity across assessments was established. Those details are relevant in general to the reproducibility of a sustained-state endpoint.
Why are estimates and uncertainty needed?
A treatment comparison usually reports an effect estimate and a measure of uncertainty. A confidence interval is a general way to express the range of values compatible with the data and an analysis model, while a test result addresses a specified statistical hypothesis. Neither can be reconstructed from the record because it contains no primary-outcome values, group assignment information, or analysis results. There is also no stated unit for the time endpoint in the timeframe or unit fields.
Over-dispersion is a general issue for some count outcomes: it occurs when observed variability exceeds what a simple model assumes, and can make standard errors too small if the model fails to allow for that extra variation. It is not possible to assess whether over-dispersion is relevant to the primary endpoint in this record. No outcome distribution or fitted model is reported, and the primary endpoint is described as time to an event rather than as a count outcome.
Recalculated estimates based on posted summary statistics would be unadjusted reconstructions, not the sponsor’s analysis. No such summary statistics or sponsor analysis are reported in the registry information, so no recalculated treatment effect or comparison can be described. The analysis plan, model, covariates, significance threshold, and handling of protocol deviations are not reported in the registry record.
What can planning calculations say?
In general, sample-size calculations depend on assumptions about the effect to detect, variability or event patterns, significance level, power, and allocation. A planning illustration is a hypothetical design aid, not an observed result and not observed power. The registry’s stated planning assumptions refer to an effect based on an observed effect, but no observed primary effect is available in the record information. Without an effect estimate and a specified comparison, such an illustration cannot be used to characterize the evidence from this trial.
The record also does not report whether an interim analysis was planned or conducted, whether any stopping boundary applied, or how the terminated status affected analysis. These are not details that can be inferred from the phase, masking, or allocation labels. They remain unreported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The record lists nine outcome measures, including the primary time-to-event endpoint and secondary measures of clinical status, safety, laboratory values, and pharmacokinetics. It also describes two AMMONUL® doses and a placebo comparator, but does not map the active arms to doses or specify which contrasts were intended for formal testing. When a study considers several outcomes or comparisons, multiplicity can increase the chance of at least one apparently unusual result by chance. General approaches include prespecifying a primary comparison, adjusting inference, or treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy.
The record reports zero analyses. It does not provide primary or secondary outcome estimates, a statistical analysis plan, or a description of which outcomes were collected. Therefore, there is no basis to determine whether the outcomes were analyzed, whether a correction for multiple comparisons was used, or how any analysis was prioritized.
Missing-data handling is also not reported in the registry record. The enrollment and primary-outcome population descriptions indicate uncertainty about whether the participant received study drug or was randomized. They do not explain whether endpoint observations were obtained, why the study was terminated, or whether any data were excluded from analysis. No analysis population definitions—such as randomized, treated, or evaluable participants—are reported.
These gaps matter because an analysis population and missing-data approach can affect both the estimate and its interpretation. The record does not support an assumption that an unobserved outcome was a failure, a success, or equivalent to an observed result. It also does not support treating the zero at-risk adverse-event counts as evidence of no events. The available information identifies important uncertainties but does not resolve them.
11. What the Result Does, and Does Not, Mean
The record establishes that a Phase 2 study was registered to assess two doses of AMMONUL® against placebo for hospitalized patients with Grade 3 or 4 hepatic encephalopathy. It specifies a primary endpoint based on time to a sustained Grade 2-or-less state on the West Haven Criteria. It also shows that the study status is TERMINATED and enrollment is reported as 1.
It does not establish a treatment effect. There is no reported time-to-event estimate, no group comparison, no uncertainty interval, and no test result. The primary-outcome population statement leaves the participant’s randomization and treatment receipt unclear. Without an observed comparison, the record cannot show whether the groups differed or how precisely any difference was estimated.
The record also does not establish that AMMONUL® was safe or unsafe in this study. Adverse-event groups have zero participants at risk and zero affected participants listed; those entries cannot be interpreted as zero events among exposed participants. Death fields are null, not reported counts. No conclusion about adverse-event frequency can be drawn from these entries.
In general, a study with little or no analyzable outcome information may be uninformative about the treatment contrast even when its design is clearly registered. That limitation is not evidence that the treatments are the same, and it is not evidence that either treatment has a particular effect. It means the registered question remains unanswered by the outcome information in this record.
The registry information should therefore be read as a description of the planned study and its limited reported status, rather than as a completed efficacy or safety comparison. The reason for termination and any outcome data beyond the registry entries are not reported in the registry record.
12. Why This Trial Matters Statistically
This trial is statistically notable because the registered design and the available evidence are sharply different kinds of information. The record gives a defined clinical question, a primary endpoint, a randomized parallel-group design, masking classifications, and three listed treatment groups. At the same time, enrollment is reported as 1, the study is marked TERMINATED, and there are zero analyses. Design detail cannot substitute for observed endpoint data.
The primary endpoint also illustrates why a precise definition matters. It requires reaching a specified West Haven Criteria threshold and sustaining it for 4 hours or longer. A time-to-event endpoint of this kind needs information about when the threshold was reached and whether the duration condition was met. The registry supplies the definition, but not those observations, the time unit, or the analysis method.
The record highlights the distinction between no reported evidence and evidence of no effect. Without a treatment contrast and its uncertainty, there is no statistical basis for judging whether the intended groups differed. Similarly, zero at-risk counts do not describe an observed safety experience. Correct interpretation depends on recognizing the limits of the reported denominators and analyses.
Finally, the participant description makes treatment assignment and exposure uncertain despite the randomized-design label. This does not resolve what happened operationally; it identifies why readers should separate the registered plan from the evidence the record actually documents. The termination reason, analysis population, and statistical plan are not reported in the registry record.
13. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The principal limitation is the absence of a usable outcome analysis. The record reports enrollment of 1 and zero analyses, with no estimate for the primary endpoint and no secondary-outcome results. Accordingly, it cannot support a treatment-effect estimate or an assessment of precision.
The primary-outcome population description is ambiguous: it says that one participant enrolled but did not receive drug or was randomized. This does not clearly state whether randomization occurred, whether treatment was received, or whether both were absent. The record does not clarify the discrepancy between that description and the registered randomized design.
Arm-level information is limited. The two AMMONUL® entries are not distinguished by dose amount, the three arm descriptions are blank, and the mapping between interventions and arms is not reported. The official title says double-blind, while the masking classification says quadruple; the roles masked and implementation details are not reported.
The endpoint definition is available, but the record does not specify its time unit, time origin, assessment schedule, follow-up, or method for handling participants who did not reach the endpoint. It does not report a statistical analysis plan, analysis populations, missing-data methods, multiplicity handling, interim analyses, or the reason for termination.
Safety information is also limited. The at-risk counts are zero for the listed groups, and the death entries are null. These fields do not establish the safety experience among participants exposed to study treatment. The record therefore leaves both efficacy and safety questions unresolved.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Efficacy and Safety Study of Ammonul® in Patients With Grade 3 or 4 Hepatic Encephalopathy — NCT00597909.
- Registry record last updated 2024-12-17; status last verified 2024-11.
- Results first posted 2016-03-31.
- 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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17. Record Summary
The registry describes a Phase 2, randomized, parallel-group, placebo-controlled study of two doses of AMMONUL® in hospitalized patients with Grade 3 or 4 hepatic encephalopathy. The official title describes a double-blind study; the registry masking classification is quadruple. The listed comparator is placebo solution (10% dextrose), but arm descriptions are blank and dose amounts are not reported.
The primary endpoint is time to Grade 2 or less on the West Haven Criteria, sustained for 4 hours or longer. Enrollment is reported as 1 and the status is TERMINATED. The primary-outcome population wording leaves treatment receipt and randomization unclear. The record lists nine outcome measures and zero analyses, with no reported primary-outcome estimate or group comparison.
The reason for termination, statistical analysis plan, and treatment assignments are not reported in the registry record. The posted information describes the intended trial question but does not provide an efficacy or safety result.