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 13C-Methacetin Breath Test for the Prediction of Outcome in in ALI or ALF (NCT02786836), a na phase 2, phase 3 study. The primary outcome is Peak Percent Dose Recovery (PDR) Value.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02786836 |
| Phase | Phase 2, Phase 3 |
| Condition | Acute Liver Failure |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 76 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Texas Southwestern Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
Eligible patients with severe acute liver injury or acute liver failure were enrolled. The registry summary describes illness duration under 26 weeks. Severe acute liver injury was described as an INR of at least 2.0 without hepatic encephalopathy and not related to acetaminophen overdose; acute liver failure was described as an INR of at least 1.5. Further eligibility details are not reported in the registry record.
Intervention
Patients received 13C-Methacetin Breath Testing. The test measures metabolism of the 13C-Methacetin substrate through changes in the ratio of exhaled 13CO2 to 12CO2. Testing could be repeated during the study, subject to contraindications and whether the patient remained eligible for further tests.
Comparator
There was no randomized control group or separate treatment comparator. For the primary endpoint, mean peak PDR values were compared between patients with transplant-free survival and those with death or transplantation by Day 21. This is an outcome-group comparison, not a randomized comparison of treatments.
Primary question
Among eligible patients with Day 1 breath-test results and a 21-day outcome, how did mean peak percent dose recovery differ between those with transplant-free survival and those who died or received a transplant? The registry record describes this question but does not report the comparison's numerical results.
3. Trial Design
This was a completed, open-label, non-randomized, single-group study of 13C-Methacetin Breath Testing in patients with severe acute liver injury or acute liver failure. The registry lists Phase 2 and Phase 3, an enrollment of 76, and the University of Texas Southwestern Medical Center as sponsor. The study dates are 2016-06-10 to 2019-09-18 for start and primary completion, respectively. The registry status is completed.
The brief summary describes a multicenter study in patients with severe acute liver injury not related to acetaminophen overdose or acute liver failure who met eligibility criteria. It describes an intended enrollment of up to 200 evaluable patients, defining an evaluable patient as someone who completed one or more breath tests for at least 30 minutes after receiving the substrate. The registry enrollment is 76; the record does not explain the difference between that enrollment and the intended number.
The first breath test was planned at study admission on Day 1, with repeat tests on Days 2, 3, 5 and 7 if no contraindication was present. Further tests were not to be performed after transplantation, discharge or transfer, or death before Day 7. Patients were to be contacted on Day 21 to establish spontaneous survival, transplantation and serious adverse events. The registry does not report how many patients completed each planned test or follow-up.
The primary endpoint was peak PDR, a continuous measure, with mean values compared between transplant-free survival and death or transplantation at Day 21. The registry also names cumulative PDR20 as a secondary outcome. Because assignment was not randomized and there was no control arm, the design does not estimate a causal treatment contrast.
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
| Stage | 13C-Methacetin Breath Test (MBT) |
|---|---|
| STARTED | 76 |
| Eligible Patients Enrolled Into the Stud | 76 |
| COMPLETED | 62 |
| NOT COMPLETED | 14 |
Reasons for not completing this period:
| Reason | 13C-Methacetin Breath Test (MBT) |
|---|---|
| Death | 1 |
| Lack of Efficacy | 2 |
| Protocol Violation | 3 |
| Withdrawal by Subject | 3 |
| Liver Transplantation | 2 |
| Device or Pharmacy Issues | 3 |
Analysis population for the primary outcome, as defined in the registry: Eligible patients enrolled into the study with available Day 1 13C-MBT results and 21-day outcome.
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.
Population: Eligible patients enrolled into the study with at least one 13C-MBT measured for a minimum of 30 minutes after ingestion of the 13C-Methacetin solution.
| Characteristic | Unit | 13C-Methacetin Breath Test (MBT) |
|---|---|---|
| Participants analysed | 62 | |
| Age, Continuous | years | 43 (28 to 58) |
| Sex: Female, Male: Female | Participants | 24 |
| Sex: Female, Male: Male | Participants | 38 |
| Race/Ethnicity, Customized: White | Participants | 49 |
| Race/Ethnicity, Customized: Black | Participants | 11 |
| Race/Ethnicity, Customized: Asian | Participants | 2 |
| Race/Ethnicity, Customized: Hispanic | Participants | 4 |
| Day 1 MBT measured for a minimum of 30 minutes after ingestion of the 13C-Methacetin solution | Participants | 56 |
6. Primary Endpoint
The registry lists the primary outcome as Peak Percent Dose Recovery (PDR) Value, measured over Days 1 and 21.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | percentage per hour |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was peak percent dose recovery, or peak PDR, measured in percentage per hour. It is defined as the maximal PDR rate and reflects the maximum rate of 13C-Methacetin metabolism. The measure is based on the change in the 13CO2-to-12CO2 ratio after ingestion of the substrate and is normalized using the patient's height and weight.
The endpoint was assessed at Days 1 and 21. The registry describes a comparison of mean peak PDR values between patients with transplant-free survival and patients with death or transplantation by Day 21. The primary analysis population was eligible patients with available Day 1 breath-test results and a 21-day outcome. These restrictions matter: the stated endpoint comparison concerns that defined group, not necessarily every enrolled patient.
As a general statistical point, a continuous physiological measure can preserve information about variation across patients rather than reducing the measure to a yes-or-no category. A mean describes the group's central value, while a standard deviation describes the spread of individual values around that mean. The registry names the mean and standard deviation as the endpoint's summary format, but does not report the group values. It also does not report the numerical difference, uncertainty interval or test result for the comparison.
The clinical rationale in the study description is prediction of outcome through assessment of liver metabolic function. The registry's stated comparison can show whether the measured values differed across outcome groups, but without reported numerical findings it cannot establish the direction or magnitude of any difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record sets out a prognostic question: whether peak PDR values differed between patients with transplant-free survival and patients who died or underwent transplantation by Day 21. It does not report the mean PDR values for either group, the difference between groups, a confidence interval, a p-value or another numerical estimate of the primary comparison. The direction and precision of the observed relationship therefore cannot be assessed from the registry record.
The record identifies the population for the primary endpoint as eligible patients with Day 1 breath-test results and a 21-day outcome. This definition is important because enrollment alone does not establish that every participant contributed to the endpoint. Counts with the required test result and outcome, or reasons those data were unavailable, are not reported in the registry record.
The comparison groups are defined by what happened to patients after enrollment. Transplant-free survival is contrasted with the combined outcome of death or transplantation. This grouping is not randomized. Differences between groups could reflect differences in illness or other patient characteristics, as well as any relationship between metabolism and outcome. The registry record does not report an adjusted analysis or details of covariates used to account for such differences.
Peak PDR is a continuous measure, and the planned summary uses means and standard deviations. In general, a mean difference describes the separation between group averages, while a confidence interval describes the range of values reasonably compatible with the observed data under the analysis assumptions. A p-value, if reported, would address compatibility with a specified null hypothesis; it would not measure the size or clinical importance of a difference. None of these inferential results is reported in the registry record.
The registry names cumulative PDR20 as a secondary outcome, but no numerical result for it is reported. The record lists 3 outcome measures and 0 analyses. That information does not supply an estimate of predictive performance, such as discrimination or calibration, nor does it establish whether any threshold was selected or evaluated. Details of those methods are not reported in the registry record.
Accordingly, the available record describes how the primary comparison was framed, not what it found. No conclusion about whether peak PDR values were higher or lower in either outcome group, or how well the test predicted outcome, can be drawn from the posted results.
9. Statistical Methods Explained
The study is described as open label, non-randomized and single group. In general, open-label means that masking of treatment or study procedures was absent; the registry lists masking as none. A single-group design means there was no parallel control arm assigned to a different intervention. The registry lists allocation as not applicable. These design features fit a study of a test used to measure physiology, but they also mean that the primary outcome-group comparison is observational rather than a randomized treatment comparison.
What does a mean and standard deviation describe?
The primary endpoint is continuous, and the registry specifies a mean with standard deviation. In general, the mean is the arithmetic average of measured values in a group. The standard deviation describes how dispersed individual observations are around that group average. It is not the same as a confidence interval: a standard deviation describes variability among observations, while a confidence interval expresses uncertainty about an estimated quantity such as a mean or a difference in means.
The registry record does not report the means or standard deviations for the outcome groups. It also does not report a standard error, confidence interval, or inferential test for the primary comparison. Therefore, the size of the difference and its statistical precision cannot be evaluated from the posted results.
How should the outcome-group comparison be understood?
The planned comparison separates patients by their Day 21 outcome: transplant-free survival versus death or transplantation. In general, comparing group means can describe whether the measured endpoint varies with the outcome category. Because patients were not randomly assigned to these outcome groups, the comparison alone cannot show that a change in breath-test measurement caused a difference in outcome. Patient characteristics and illness severity may be related both to the measured value and to the subsequent outcome. Whether an analysis adjusted for such factors is not reported in the registry record.
The target population for this endpoint is also restricted to eligible patients with an available Day 1 result and 21-day outcome. If data availability differs across patients or outcome groups, the analyzed subset may not represent all enrolled participants. The record does not report the number contributing to the primary comparison, the amount of missing endpoint data, or methods used to address missingness.
What does repeated testing add?
The protocol summary describes tests on Day 1 and repeat testing on Days 2, 3, 5 and 7 when no contraindication was present. Repeated measurements can describe change over time as well as a single measurement, but they also require an analysis that accounts for multiple observations from the same person. In general, observations within a person are correlated rather than independent. The primary endpoint described in the registry, however, is a comparison of mean peak PDR values at Days 1 and 21; the specific handling of repeated measures is not reported in the registry record.
The schedule also allows testing to stop after transplantation, discharge or transfer, or death before Day 7. This means availability of later tests may depend on events related to a patient's clinical course. The record does not report how this affected the repeated-measure data or how any resulting missing values were handled.
What can be inferred from a predictive study?
In general, a predictive marker is evaluated by how well its measurements relate to future outcomes in a defined population. A difference in group averages, if reported, would be one aspect of that relationship. It would not by itself show how accurately individual patients can be classified or how well predicted risks match observed outcomes. Measures of discrimination, calibration, decision thresholds, validation, and uncertainty would be needed to assess those additional properties. Such results and methods are not reported in the registry record.
The registry lists a secondary outcome, cumulative PDR20, but does not report its numerical result or analysis. No multiplicity procedure or prespecified hierarchy among outcomes is reported. In general, testing multiple outcomes or time points can increase the chance of a nominally positive finding unless the analysis plan addresses multiplicity. Whether that issue was addressed in this study is not reported in the registry record.
Finally, the registry lists 3 outcome measures and 0 analyses. This is not a substitute for a statistical analysis plan, and the record does not describe a sample-size justification, interim analyses, or the precise statistical test used for the primary endpoint. Those details are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 3 outcome measures. The primary outcome is peak PDR; the named secondary outcomes are peak PDR and cumulative PDR20 as recorded in the outcome listings. No numerical results for the secondary outcomes are reported. The record lists 0 analyses, and does not describe a hierarchy for testing outcomes, a multiplicity adjustment, or a prespecified approach to repeated time points. Whether such procedures were used is not reported in the registry record.
Multiplicity is a general concern when several outcomes, time points or analyses are examined. Each additional statistical test creates another opportunity for a result that appears unusual under a null hypothesis. A prespecified testing plan or adjustment can help control the interpretation of a collection of tests. Without a reported plan and results, the degree to which multiplicity was considered cannot be assessed.
The primary endpoint population required both available Day 1 13C-MBT results and a 21-day outcome. The record does not report the number of patients meeting that definition, the extent or reasons for missing data, or how missing observations were handled. It also does not report whether the primary comparison used all eligible patients with those data or a further restricted group.
Repeated testing was planned on Days 1, 2, 3, 5 and 7 when possible, and testing could stop following transplantation, discharge or transfer, or death before Day 7. In general, data missing because of such events may be related to outcome, so the pattern and handling of missing observations can affect interpretation. The statistical methods for repeated measurements and missing data are not reported in the registry record.
The registry's sample-size justification, interim-analysis plan and detailed analysis plan are also not reported in the registry record. Without them, the planned precision and inferential framework cannot be evaluated.
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 |
|---|---|---|---|
| 13C-Methacetin Breath Test (MBT) | 28 | 62 | 45.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 13C-Methacetin Breath Test (MBT) | 11 of 62 |
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 |
|---|---|
| 13C-Methacetin Breath Test (MBT) | 40 of 62 |
Most frequent serious adverse event terms
| Event term | Organ system | 13C-Methacetin Breath Test (MBT) |
|---|---|---|
| Acute hepatic failure | Hepatobiliary disorders | 14 of 62 |
| Multiple organ dysfunction syndrome | General disorders | 7 of 62 |
| Brain injury | Nervous system disorders | 2 of 62 |
| Acute coronary syndrome | Cardiac disorders | 1 of 62 |
| Hepatic encephalopathy | Nervous system disorders | 1 of 62 |
| Liver injury | Hepatobiliary disorders | 1 of 62 |
| Presyncope | Nervous system disorders | 1 of 62 |
| Transplant | Surgical and medical procedures | 1 of 62 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 13C-Methacetin Breath Test (MBT) |
|---|---|---|
| Vomiting | Gastrointestinal disorders | 5 of 62 |
| Nausea | Gastrointestinal disorders | 3 of 62 |
| Constipation | Gastrointestinal disorders | 2 of 62 |
| Diarrhoea | Gastrointestinal disorders | 2 of 62 |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 2 of 62 |
| Leukocytosis | Blood and lymphatic system disorders | 2 of 62 |
| Tachycardia | Cardiac disorders | 2 of 62 |
| Abdominal distension | Gastrointestinal disorders | 1 of 62 |
| Abdominal pain | Gastrointestinal disorders | 1 of 62 |
| Acute kidney injury | Renal and urinary disorders | 1 of 62 |
Serious events with the highest arm-level rate: acute hepatic failure (22.6%), multiple organ dysfunction syndrome (11.3%), brain injury (3.2%), acute coronary syndrome (1.6%), hepatic encephalopathy (1.6%).
The registry reports a 13C-Methacetin Breath Test group with 62 participants at risk for serious adverse events and 28 affected. It also reports 62 at risk for other adverse events and 40 affected, with 11 deaths. These are separate adverse-event summaries; the record does not explain whether the affected groups overlap. The listed counts should not be treated as mutually exclusive categories.
The serious adverse-event terms reported most often include acute hepatic failure at 22.6%, multiple organ dysfunction syndrome at 11.3%, brain injury at 3.2%, acute coronary syndrome at 1.6%, hepatic encephalopathy at 1.6%, and liver injury at 1.6%. The registry does not specify the denominator for these term percentages in the information, so the percentages should be read as listed rather than converted into patient counts.
These safety figures describe events recorded in the study group; they do not establish that the breath test caused those events. Patients were enrolled because of severe acute liver injury or acute liver failure, and the registry does not report event attribution, timing, severity breakdown beyond the serious-event category, or a comparison group. A single-group safety summary cannot separate events associated with the underlying illness from those related to study procedures or other causes. Further details about causality and event-level reporting are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The study was designed to examine whether 13C-Methacetin breath-test measurements were associated with 21-day outcome in eligible patients with severe acute liver injury or acute liver failure. Its primary endpoint was peak PDR, with mean values compared between transplant-free survival and death or transplantation. The record also names cumulative PDR20 as a secondary outcome.
The registry record does not report the numerical primary endpoint findings. It therefore does not establish the size, direction, or precision of any difference between the outcome groups. It also does not report numerical secondary-outcome findings or measures of predictive performance. The posted information cannot show how accurately an individual patient's outcome could be predicted from a breath-test result.
Even if a group difference were available, a non-randomized comparison between outcome groups would describe an association, not prove that the test result caused the outcome. The groups may differ in illness characteristics or other factors. The record does not report an adjusted analysis that would clarify whether such factors were considered.
In general, assessing a test as a predictor requires more than comparing group averages. Researchers may examine how well the test distinguishes outcome groups, whether predicted risks agree with observed outcomes, and whether the findings are reproducible in another population. The registry record does not report these evaluations. It also does not report the number of participants included in the primary comparison, missing-data handling, or the detailed statistical plan.
The safety listings describe adverse events among study participants, including serious events and deaths. They do not establish that the breath test caused those events, and the single-group design offers no randomized safety comparison. Taken together, the registry record documents the study's question, endpoint definitions, design and some safety counts, but it does not provide enough outcome results to judge the breath test's predictive performance.
13. Why This Trial Matters Statistically
This study addresses a statistical question about measurement and prognosis in severe acute liver injury or acute liver failure. Rather than comparing two assigned treatments, it examines whether a physiological measurement, peak PDR, differed across groups defined by a later clinical outcome. That distinction is important: prognostic association and treatment effect are different kinds of evidence, and the study's non-randomized single-group design targets the former.
The registry's endpoint definition makes the timing and analysis population explicit. The primary comparison focuses on eligible patients with Day 1 test results and 21-day outcome, and groups them according to transplant-free survival or death or transplantation. This framing highlights practical issues that matter in prognostic research, including whether measurements are available for the intended population and whether outcome ascertainment is complete.
The repeated testing schedule also raises a general methodological issue. Measurements collected several times from the same patient are related, and availability of later measurements can depend on clinical events. Appropriate analysis and transparent reporting are important to distinguish change over time from differences caused by who remains available for measurement. The analysis details are not reported in the registry record.
Most importantly, a stated prognostic aim is not itself evidence of predictive accuracy. Numerical endpoint estimates, uncertainty measures, missing-data information and validation results are needed to assess the strength and reliability of a proposed predictor. Those results are not reported in the registry record. The study remains statistically relevant as an example of a design where the endpoint's definition and data availability are central to interpretation, while the posted outcome information is insufficient to assess performance.
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.
The registry record has limited outcome reporting. It defines the primary endpoint and the groups being compared, but does not report the group means, standard deviations, difference, confidence interval, p-value or other numerical primary analysis result. Numerical findings for cumulative PDR20 are also not reported. As a result, neither the magnitude nor precision of the primary comparison can be evaluated.
The design is non-randomized and single group, with outcome groups defined after enrollment. It can describe an association between peak PDR and outcome but cannot establish a causal effect of testing or rule out confounding. The registry does not report an adjusted comparison, the covariates considered, or a detailed analysis method.
The number included in the primary endpoint population is not reported. The registry specifies that participants needed available Day 1 results and a 21-day outcome, but does not give the counts with each component, reasons for missing data, or the approach used to handle missingness. The planned repeat testing could stop after clinical events, and the record does not describe the impact of that on later measurements.
The brief summary describes an intended enrollment of up to 200 evaluable patients, while the registry lists enrollment of 76. Reasons for the difference are not reported in the registry record. The record also does not report a sample-size justification, interim analyses, a detailed statistical plan, multiplicity procedures, or evaluation of predictive performance such as discrimination, calibration or external validation.
Finally, safety events are reported for a single study group without a randomized comparator or attribution details. The reported event counts and percentages therefore do not establish whether events were caused by the breath test or distinguish study-related risk from the underlying illness.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: 13C-Methacetin Breath Test for the Prediction of Outcome in in ALI or ALF — NCT02786836.
- Registry record last updated 2020-12-22; status last verified 2020-11.
- Results first posted 2020-12-22.
- 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
NCT02786836 is a completed, open-label, non-randomized, single-group study sponsored by the University of Texas Southwestern Medical Center. The registry lists Phase 2 and Phase 3 and enrollment of 76. It evaluates 13C-Methacetin Breath Testing in severe acute liver injury or acute liver failure.
The primary endpoint is mean peak PDR, comparing transplant-free survival with death or transplantation by Day 21 among eligible patients with available Day 1 results and 21-day outcome. Testing was planned on Day 1 and could be repeated on Days 2, 3, 5 and 7. Cumulative PDR20 is listed as a secondary outcome.
The registry record does not report numerical primary or secondary outcome results, the detailed statistical plan, or missing-data methods. It reports serious and other adverse-event counts and selected serious-event terms, but no randomized safety comparator or event-attribution details.