Use of Methacetin Breath Test to Predict Liver Failure in Patients With Cirrhosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Use of Methacetin Breath Test to Predict Liver Failure in Patients With Cirrhosis (NCT01157845), a non-randomized phase 3 study. The primary outcome is Mortality From Liver Failure.

2. Clinical Question

The question is prognostic: whether a breath-test measurement might help identify declining liver function in a population awaiting transplantation. That is distinct from a treatment-effect question. The test is the study intervention, while mortality from liver failure is the primary outcome; the endpoint is not a direct measure of breath-test performance, such as a reported accuracy measure or a comparison of predictions with outcomes.

Liver transplantation was listed as a secondary outcome. The registry record does not report its observed result, nor does it give a numerical result for the primary outcome. Consequently, the record supports describing the clinical question and the planned outcome, but not judging how well the test predicted either outcome or whether test-guided decisions changed care.

3. Trial Design

The registry records this as a Phase 3 study of the BreathID methacetin breath test in patients with cirrhosis awaiting liver transplantation. The study was non-randomized, unmasked, and single-group, with enrollment of 165. The sponsor was Virginia Commonwealth University. The record labels the group Laboratory Assay; it does not describe a parallel control group.

The study began in 2010-03, reached primary completion in 2012-07, and is marked completed. These dates describe the study’s recorded timeline; they do not establish when each participant entered the study or how long each participant was followed. The primary outcome timeframe is stated as 1 year from study entry.

In a randomized comparison, random allocation can help make treatment groups comparable on average, supporting an estimate of a treatment contrast. That framework does not apply to this single-group, non-randomized study. There is no like-for-like control comparison in the registry record, so differences between people with different test results, if reported, could reflect differences in their underlying health or other factors rather than a causal effect of the test.

The record describes the breath test as a device intervention and gives the hypothesis that it might allow earlier detection of declining liver function. It does not report the detailed testing schedule, eligibility criteria, enrollment methods, or how test measurements were used in clinical decisions. The record also does not state whether participants received other care according to a common protocol. Those details should not be inferred from the study title or its Phase 3 designation.

Completion status does not mean that outcome results are available. The record lists two outcome measures, including the primary mortality outcome and secondary liver transplantation, but reports no numerical result for the primary endpoint. It lists no analysis results. The study design and intended question can therefore be described, while the clinical findings remain unquantified in the registry record.

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.

Population: All chronic liver disease patients with clinically proven cirrhosis and candidates for liver transplant.

6. Primary Endpoint

The registry lists the primary outcome as Mortality From Liver Failure, measured over 1 year.

The primary endpoint was Mortality From Liver Failure, defined as a participant dying from liver-related causes within 1 year of study entry. It is a binary outcome for each participant: the event either occurred within the specified timeframe or it did not. The registry describes the endpoint unit as participants and the measure as a number, rather than a rate or a time-to-event estimate.

Mortality is a direct, consequential outcome, and in this study it addresses whether a measure of hepatic metabolic reserve might help identify patients at risk of deterioration. The registry’s stated rationale is that the methacetin breath test could allow earlier detection of declining liver function among patients with cirrhosis awaiting transplantation. The endpoint therefore concerns an outcome that could follow such decline, rather than simply recording a breath-test value.

The outcome definition leaves important analytic details unstated. The registry record does not report how liver-related cause of death was adjudicated, how deaths from other causes were treated, or what happened to participants whose outcome status was unavailable at the end of follow-up. It does not provide the observed number of primary events or a comparison of event risk by test result.

Liver transplantation was listed as a secondary outcome. Transplantation may occur before the full follow-up period has elapsed, but the registry record does not say how this event was handled in the primary mortality analysis. Without those details and the observed results, the endpoint definition identifies what was intended to be counted but does not establish how completely it was measured or what the study found.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is binary at the participant level: death from liver-related causes within 1 year of study entry. For a binary endpoint, a basic description would report the number of participants with the event and the number whose status was assessed, with an event proportion if appropriate. The registry record reports the intended outcome definition and enrollment, but not the number of primary events or a primary-outcome estimate. No such estimate can be reconstructed from the record.

What a single-group design can estimate

A single-group study can describe outcomes observed among its participants. If test measurements and subsequent outcomes are both collected and analyzed, it may also describe an association between the measurement and outcome. Such an association is not automatically a treatment effect or proof that acting on the measurement improves outcomes. Because this study is non-randomized and has no like-for-like control comparison, differences among participants may reflect their condition or other characteristics.

The registry does not report how the breath-test result was summarized, whether a threshold was specified, or how an association with mortality was modeled. It does not report a sensitivity, specificity, predictive value, discrimination measure, calibration assessment, or adjusted effect estimate. These are examples of distinct ways a prognostic test can be evaluated; they should not be assumed to have been used in this study.

Counts, risks, and follow-up

A count of participants with an event answers how many people experienced it in the group assessed. An event proportion relates that count to the number whose outcome status is known. A time-to-event analysis instead uses when events occurred and accounts for participants whose event time is not observed during follow-up. These approaches answer different questions. Although the primary endpoint has a 1-year timeframe, the registry record does not report event times, censoring, follow-up completeness, or a time-to-event analysis.

In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. It helps distinguish a precise estimate from one compatible with a broad range of values. The registry record reports no primary estimate or confidence interval, so neither the magnitude nor precision of an association can be evaluated from the posted outcome information.

Planning calculations are not trial findings

The record describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It specifies that the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration is described in terms of total events; for other outcomes, it is described in participants per arm. These are planning conventions, not observed results or evidence that the study achieved a particular level of power.

Those assumptions do not map directly onto the recorded design: this study is single-group and non-randomized, while the planning description assumes two arms with equal allocation. The record does not report the numerical planning outputs, and it does not report a numerical observed effect for the primary endpoint. Thus no specific planning count or effect size can be interpreted from this record. A planning illustration, even when available, is not observed power and does not replace reporting the actual endpoint results.

Over-dispersion and model choice

For count outcomes, a statistical model may need to account for variation greater than the model’s simplest assumptions allow; this is called over-dispersion. It can affect standard errors and uncertainty estimates. This study’s primary endpoint is described as a number of participants with a binary event, rather than as a repeated count per person. The registry record does not report a count model, a dispersion estimate, or any assessment of over-dispersion. General considerations about count models therefore should not be mistaken for a description of the analysis used.

The record lists no analysis results and does not describe the statistical model for the primary outcome. It does not report covariate adjustment, the handling of competing events, missing outcome data, or a prespecified approach for evaluating predictive performance. These omissions prevent a detailed appraisal of model assumptions and of how the analysis, if performed, relates to the study’s prognostic question.

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("Laboratory Assay")
n      <- c(165)
events <- c(11)
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  Laboratory Assay  165  11  6.7  3.4  11.6  3.8  11.5  3.8  11.5

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures: mortality from liver failure as the primary outcome and liver transplantation as a secondary outcome. It does not report a multiplicity strategy for interpreting more than one outcome, or any adjustment for multiple statistical tests. Without a reported analysis, it is not possible to determine how many outcome comparisons were made or how results across outcomes were interpreted.

The record does not report interim analyses, stopping rules, or a statistical analysis plan. Those details should not be inferred from the study’s phase or completion status. It also does not describe whether any outcome definitions or analyses changed after study initiation.

Missing-data handling is not reported in the registry record. In particular, the record does not state how participants with incomplete follow-up, unknown vital status, or missing breath-test measurements were handled. It does not give the number of participants with complete primary-outcome information or describe an imputation or sensitivity-analysis method. For a 1-year outcome, incomplete observation can affect interpretation if event status is not known for every participant; the available record does not establish whether this occurred.

The analysis population is also not described. Enrollment is recorded as 165, but the record does not say whether all enrolled participants were included in each outcome analysis or whether exclusions occurred. Enrollment alone cannot establish the number analyzed. These reporting gaps mean that the completeness and robustness of the planned outcome assessment cannot be evaluated from the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: transplantation (20.6%), death (6.7%), abdominal pain (4.8%), sbp (spontaneous bacterial peritonitis) (4.8%), sepsis (4.2%).

The registry lists 165 participants at risk in the Laboratory Assay group for serious adverse events and 165 at risk for other adverse events. It records 107 participants affected by serious adverse events and 92 affected by other adverse events. These are separate categories in the record; a participant may potentially appear in both, so the counts should not be added together. The record does not explain event duration, severity grading beyond the serious/non-serious classification, or whether each event was judged related to the device.

The listed serious-event terms and percentages are Transplantation, 20.6%; Death, 6.7%; Abdominal pain, 4.8%; SBP (spontaneous bacterial peritonitis), 4.8%; Sepsis, 4.2%; and Hepatic Encephelopathy, 3.6%. The registry record does not describe the event-term coding or explain whether participants could contribute more than one event term. These percentages should therefore be read as the record’s listed figures, not as mutually exclusive categories to be summed.

These safety entries describe events recorded during the study; they do not establish that the test caused them. The population had cirrhosis and was awaiting liver transplantation, but the registry does not provide a comparator that would support a like-for-like assessment of excess risk. The safety listings should be interpreted alongside that design limitation and the absence of reported attribution details.

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

The registry establishes that a study of the BreathID methacetin breath test was conducted in patients with cirrhosis awaiting liver transplantation, with the aim of assessing whether the test could support earlier detection of declining liver function. It identifies death from liver-related causes within 1 year of study entry as the primary outcome and liver transplantation as a secondary outcome. Those details clarify the intended clinical question.

The registry record does not report the numerical primary-outcome result, a result for transplantation, or an analysis of how test measurements related to either outcome. It therefore does not establish how many participants experienced liver-related death, how precisely any association was estimated, or how well the test predicted an outcome. The record also does not report a measure of prediction accuracy or a comparison of outcomes by test result.

The design matters when interpreting any claimed relationship. This was a non-randomized, single-group study, not a randomized comparison of a test-guided strategy with an alternative. A prognostic association, if one were reported, would not by itself show that the test changed decisions or improved outcomes. The record does not describe whether clinicians used test results to guide care.

The safety listings document adverse events but do not establish that the device caused them. Without a control comparison or reported attribution information, the counts cannot isolate the test’s contribution to events occurring in this clinical population.

In short, the registry record describes a completed study and its intended outcomes, but does not provide the outcome analyses needed to judge the test’s predictive performance or clinical consequences. It neither demonstrates nor rules out a relationship between breath-test measurements and subsequent liver-related death. A conclusion about those questions would require results and methods not reported in the registry record.

14. Why This Trial Matters Statistically

This study raises a statistical question that is different from comparing two treatments: can a measurement help forecast a future outcome in a clinically vulnerable group? Answering that requires more than recording a test and a subsequent event. The analysis needs to connect measurements to outcomes, describe how prediction was evaluated, and quantify uncertainty. The registry identifies the intended primary outcome and the rationale for measuring hepatic metabolic reserve, but it does not report those analyses.

The design is important to that question. A single-group, non-randomized study can be useful for describing observed outcomes and exploring prognostic associations, but it does not create a randomized control comparison. Baseline differences and disease severity can influence both test measurements and outcomes. Statistical adjustment may sometimes address measured differences, but the registry record does not report an adjusted analysis, and adjustment cannot be presumed.

Outcome definition and follow-up also matter. The primary measure concerns liver-related death within 1 year, while transplantation is listed separately as a secondary outcome. How transplantation, other causes of death, and incomplete follow-up are handled can affect the interpretation of a mortality analysis. The record does not report those analytic details.

Finally, precision and prediction are not interchangeable. A result can be estimated with varying degrees of uncertainty, and an association does not automatically demonstrate accurate prediction or clinical usefulness. Because the registry record contains no numerical primary-outcome result, uncertainty interval, or prediction assessment, it supports a discussion of the study’s design and statistical needs rather than a quantitative judgment of performance. This distinction is central to reading prognostic studies responsibly.

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 main limitation for interpreting this particular record is that it reports the study’s design and outcome definitions but not numerical results for the primary or secondary outcome. Without those results, there is no basis in the registry record to quantify the rate of liver-related death or transplantation, assess precision, or evaluate the relation between breath-test measurements and subsequent outcomes.

The single-group, non-randomized design has no like-for-like control group. It cannot by itself distinguish an association with test measurements from differences related to participants’ underlying condition or other characteristics. The registry record does not report an adjusted analysis, so the extent to which measured differences were addressed is unknown.

Key operational and analytic details are also not reported in the registry record. These include eligibility criteria, the testing schedule, the use of test results in care, the handling of transplantation in the mortality analysis, cause-of-death adjudication, completeness of follow-up, missing-data methods, and the analysis population. The record does not provide a statistical analysis plan or interim-analysis details. Their absence from the registry record does not establish that no such procedures existed; it means their use cannot be assessed from this record.

Safety information has its own limitations. The record lists affected-participant counts and serious-event terms, but does not report attribution to the device or a control-group comparison. Events occurring in the study therefore cannot be interpreted as caused by the test on the basis of these listings alone. Together, these limitations constrain both clinical interpretation and statistical appraisal.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Use of Methacetin Breath Test to Predict Liver Failure in Patients With Cirrhosis — NCT01157845.
• Registry record last updated 2014-05-16; status last verified 2014-04.
• Results first posted 2014-03-04.
• 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 record identifies NCT01157845, titled Use of Methacetin Breath Test to Predict Liver Failure in Patients With Cirrhosis. The official title describes the use of the BreathID Methacetin Breath Test to assess hepatic metabolic reserve and predict hepatic decompensation in patients awaiting liver transplantation.

The study is recorded as Phase 3, non-randomized, unmasked, and single-group, with enrollment of 165. The sponsor is Virginia Commonwealth University. The recorded start was 2010-03, primary completion was 2012-07, and status is completed.

The primary outcome was the number of participants dying from liver-related causes within 1 year of study entry. Liver transplantation was listed as a secondary outcome. Numerical outcome results and analysis results are not reported in the registry record. Safety listings include serious and other adverse-event counts, along with listed serious-event terms.