Methacetin Breath Test in Patients With Liver Disease Secondary to Heart Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Methacetin Breath Test in Patients With Liver Disease Secondary to Heart Disease (NCT04176458), a na na study. The primary outcome is Methacetin Breath Test Results in Patients Undergoing Heart and Liver Transplant Evaluation..

2. Clinical Question

The central research question was whether MBT measurements could characterize liver metabolic function in people with heart disease or a Fontan circulation, where liver function may be affected by the underlying circulation and liver disease. The registry description identifies cumulative percent dose recovery at 20 minutes (CPDR20) as the MBT measure of interest, noting that it was selected because it correlated with liver-disease severity. The broader project aimed to explore whether MBT measures were associated with existing clinical information, including cardiac assessments, liver imaging or stiffness measures, laboratory investigations, and clinical characteristics. These aims describe questions the investigators intended to study; they are not evidence that the proposed associations were tested or established. The registry states that the required second MBT test could not be completed because of COVID-19 restrictions and that data analysis could not be performed. Consequently, the record does not report an estimate of MBT results for the study population, a comparison with normal controls, or an association between MBT and clinical measures.

3. Trial Design

The registry classifies this as a single-group study with no allocation and no masking. The intervention was the Methacetin Breath Test. The record reports enrollment of 4 and lists the study as terminated. Its stated purpose was to assess a non-invasive liver-function test in people undergoing heart and liver transplant evaluation, with particular interest in patients with a Fontan circulation and patients with congestive (dilated) cardiomyopathy.

The planned primary assessment involved measuring MBT results in the clinical groups and comparing them with published normal controls. Those published controls were not a parallel group enrolled and followed under the same study design. The record does not describe a randomized or concurrent control group, and the planned comparison should not be interpreted as a randomized treatment comparison. The study was not designed to compare assigned treatments: the intervention was a measurement procedure, and there was no treatment allocation.

The record describes a requirement for 2 MBT tests. It states that, because of COVID-19 restrictions, subjects could not return for the second test, so data analysis could not be performed. The study is listed as terminated, but the reason for termination is not separately stated in the registry record. The start date is 2019-04-21, and the primary completion date is 2021-03-19. The record does not report a statistical analysis plan, a sample-size justification, interim analyses, or completed outcome analyses. As a result, the design and aims can be described, but the intended analyses cannot be treated as completed findings.

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:

Analysis population for the primary outcome, as defined in the registry: Per the protocol, 2 MBT tests are required. Due to covid 19 restrictions, subjects could not return for the 2nd test and therefore data analysis could not be performed.

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: However, with the 4 subjects that we did get baseline data on we have listed results for Breath test (added baseline measure), age, sex, race and region of enrollment.

6. Primary Endpoint

The registry lists the primary outcome as Methacetin Breath Test Results in Patients Undergoing Heart and Liver Transplant Evaluation., measured over 90 minutes MBT measurement is taken.

The primary outcome is titled “Methacetin Breath Test Results in Patients Undergoing Heart and Liver Transplant Evaluation.” The registry describes the ¹³C-Methacetin Breath Test as a non-invasive assessment of liver metabolic function. After administration of ¹³C-methacetin, the test measures the ratio of ¹³CO₂ to ¹²CO₂ in exhaled breath. The description identifies cumulative percent dose recovery at 20 minutes, or CPDR20, as the measure of interest and states that it was selected because it correlated with the degree of liver-disease severity.

The listed timeframe is a 90-minute MBT measurement. This describes the stated measurement period; CPDR20 refers specifically to the cumulative percent dose recovery at 20 minutes. The intended purpose was to measure MBT parameters in the clinical groups and compare the results with published normal controls. This is a measurement outcome, not a treatment outcome.

The record does not report numerical MBT results, a group summary, or a comparison with normal controls. It states that the required second MBT test could not be completed and that data analysis could not be performed. Therefore, the endpoint’s measurement rationale and intended use are documented, but its observed distribution and any relationship with clinical status are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group study mean?

In a single-group study, participants receive or undergo the same study procedure rather than being assigned across randomized treatment groups. Here, the procedure was the Methacetin Breath Test. The design can describe measurements collected from participants, but it does not by itself provide a randomized comparison between treatments. The registry’s plan to compare results with published normal controls is distinct from enrolling a concurrent control group. Such a comparison can be informative as context, but it cannot remove differences between the study participants and people described in other sources.

What does the breath test measure?

As described in the registry, the MBT uses ¹³C-methacetin and measures the ratio of ¹³CO₂ to ¹²CO₂ in exhaled breath. The primary outcome description focuses on CPDR20, cumulative percent dose recovery at 20 minutes. The record identifies this measure as relevant because it correlated with liver-disease severity. That rationale explains the choice of measure; it does not demonstrate that the measure predicts outcomes or performs well in this study population. The stated 90-minute measurement timeframe and the CPDR20 time point refer to different aspects of the test description: the former is the listed outcome timeframe, while the latter names the particular cumulative recovery measure.

How should estimates and uncertainty be understood?

In general, a point estimate summarizes the observed data, while a confidence interval communicates the range of values reasonably compatible with the data under the statistical model. A narrow interval indicates greater precision than a wide interval, but neither an estimate nor an interval establishes causation by itself. This registry record reports no outcome estimate or confidence interval, so the precision of any MBT result cannot be assessed. It also reports no completed statistical analyses. A missing estimate should not be interpreted as an estimate of zero.

In general, tests of statistical significance address how compatible observed data are with a specified null model under assumptions. A p-value is not the probability that a hypothesis is true, nor does it measure the clinical importance of an effect. No p-values or other inferential results are reported in the registry record. With no reported analysis, there is no basis to make a significance claim about MBT values or their relationship to other clinical measures.

Why can over-dispersion matter?

In general, over-dispersion occurs when outcome variability is greater than a statistical model expects. If it is ignored, standard errors may be too small and confidence intervals may be too narrow, making results appear more precise than they are. The appropriate response depends on the outcome and model; it can involve accounting for extra variability or choosing a different model. The registry record does not describe an analysis model, distributional assumptions, or a check for over-dispersion. No claim can therefore be made about whether this issue was assessed or relevant to an analysis.

How should the planning illustrations be read?

The stated sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is expressed as a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations are expressed as participants per arm for 80% power or another stated power level; time-to-event illustrations use a total event count. These calculations are planning aids, not observed power. They do not indicate that the study enrolled those numbers, achieved a particular power, or completed a comparison.

In this case, the record states that data analysis could not be performed after the required second test was not completed. It does not report an observed effect estimate or completed inferential result. Planning calculations based on an effect should therefore be understood as hypothetical design scenarios rather than evidence about the clinical groups. They cannot remedy the absence of analyzed study results.

What can the design establish?

A measurement study can characterize the measurements it actually obtains and, if data and an analysis are available, examine whether those measurements are associated with other recorded variables. Association does not establish that one variable caused another. In this study, the registry describes planned exploration of relationships between MBT parameters and cardiac hemodynamics, imaging, liver stiffness, laboratory tests, and clinical characteristics. The record does not report completed analyses of those relationships. It also does not report the number of participants in each clinical subgroup or the results for individual measures. The study’s aims should therefore be distinguished from its evidentiary contribution in the registry: the former are documented, while the latter is limited by the absence of analyzed outcome data.

10. Multiplicity, Missing Data and Analysis Populations

The registry describes several aims: measurement of MBT parameters and comparison with published normal controls, followed by exploration of relationships with multiple clinical, cardiac, and liver assessments. When several outcomes or associations are examined, multiplicity can increase the chance of finding at least one apparently noteworthy result by chance. Statistical plans sometimes address this through a prespecified primary analysis, adjustment procedures, or a clearly labeled exploratory strategy. The statistical plan and any multiplicity approach are not reported in the registry record. Because data analysis could not be performed, the record gives no results from which to assess whether multiplicity affected interpretation.

The record states that the protocol required 2 MBT tests and that subjects could not return for the second test because of COVID-19 restrictions. It also states that data analysis could not be performed. This identifies a barrier to completing the planned assessment, but the registry does not describe the availability or completeness of other measurements, participant-level missingness, or any method for handling missing data. It does not report imputation, a complete-case analysis, or sensitivity analyses.

The analysis population is not described beyond the reported enrollment of 4 and the explanation that the required second test was not completed. The registry does not report how many participants contributed to any outcome analysis, and it does not report an analyzed population. The reasons and timing of missing measurements beyond the stated return-visit restriction are not reported in the registry record. Without outcome data and a stated analysis population, the magnitude of possible bias from incomplete measurement cannot be assessed.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The adverse-event record lists the MBT in Liver Disease group, with 4 participants at risk. It reports 0 participants with a serious adverse event, 0 with another adverse event, and 0 deaths. These are recorded counts, not estimates of a rate or proof that no risk exists. The record does not provide further event descriptions, severity details, or an analysis of safety by subgroup.

Safety counts are most informative when considered alongside how many people were assessed, how events were defined, how long participants were followed, and how completely events were collected. The registry record provides limited information on those details. It reports that the study was terminated and that analysis could not be performed because participants could not return for a required second test, but it does not describe the safety follow-up period or its completeness. The zero counts should therefore be read as the events recorded in this study, not as evidence that adverse events are impossible or that safety has been established.

The study assessed a breath-test procedure rather than comparing treatment assignments. The reported safety counts do not answer the study’s planned question about MBT measurements or their associations with liver and cardiac assessments.

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

The registry record contributes information about a planned study of a non-invasive liver-function measurement in patients undergoing heart and liver transplant evaluation. It identifies MBT and CPDR20 as the measurement of interest, explains the planned comparison with published normal controls, and lists clinical factors the investigators intended to explore. It also states why the planned data analysis could not be performed: participants could not return for the required second test because of COVID-19 restrictions.

The record does not report analyzed MBT results, a comparison with normal controls, or estimates of associations with cardiac or liver measures. It therefore does not establish whether MBT values were higher or lower than any reference values, whether they varied by clinical characteristics, or how precisely any such differences could be estimated. The registry does not report a statistical analysis plan or results of inferential tests. A lack of reported findings is not evidence that the planned associations were absent.

The study is listed as terminated, and enrollment is reported as 4. Those details describe the record, but they do not provide an estimate of the performance of MBT or its prognostic value. The stated hypothesis and aims are research questions rather than results. Likewise, the rationale that CPDR20 correlated with liver-disease severity does not show that this study demonstrated such a relationship in its intended population.

The adverse-event record lists no serious adverse events, other adverse events, or deaths among the participants recorded at risk. Those counts should be interpreted within the limited study record and should not be generalized as proof of safety. Any planning illustrations are also not clinical findings: they describe assumptions for hypothetical future comparisons and are not observed power or evidence of an effect. The main conclusion is that the registry documents an intended assessment but supplies no completed statistical answer to its primary question.

13. Why This Trial Matters Statistically

This study is statistically notable because the registry distinguishes a planned measurement project from a completed analysis. The question was potentially important to researchers evaluating non-invasive measures of liver function in people with complex cardiac conditions. The record describes a biological rationale for MBT and an intended comparison with published normal controls, along with plans to examine relationships with existing clinical assessments. But a research rationale and a list of planned comparisons do not constitute evidence that the measurement was informative in the enrolled participants.

The stated inability to complete a required second test illustrates how incomplete measurement can interrupt the analysis itself, not merely reduce precision. The registry says that data analysis could not be performed. Accordingly, there are no reported outcome estimates to interpret, no confidence intervals with which to judge precision, and no reported association results. This prevents readers from distinguishing a potentially meaningful estimate from a highly uncertain one or from no measurable pattern.

The single-group design also matters. Comparing study measurements with published controls is not the same as comparing concurrently enrolled, randomized groups. In general, external comparisons may be affected by differences in participant characteristics or measurement conditions. The record does not report enough detail to assess such differences or to characterize an adjusted comparison.

Finally, the stated sample-size assumptions concern planning illustrations, not observed power. That distinction matters because power calculations do not supply missing outcome information and cannot establish whether the planned measurement would have produced a precise or clinically useful result. The record’s statistical value is therefore chiefly descriptive: it identifies the study aims, design, and obstacle to analysis, while leaving the intended empirical questions unanswered.

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 main trial-specific limitation is that the registry states data analysis could not be performed. Participants could not return for the protocol-required second MBT test because of COVID-19 restrictions. No primary outcome values, comparisons, or association analyses are reported, so the planned research questions cannot be answered from the registry record.

Enrollment was 4, and the record does not provide a breakdown of participants by the planned clinical groups. It is therefore not possible to assess subgroup representation or to understand whether the intended groups were both represented in the analyzed data. The record also does not describe an analyzed population, the completeness of other study measurements, or methods for handling missing data.

The design was single-group, with no allocation and no masking. The planned comparator was published normal controls rather than a concurrent randomized group. The registry does not report details that would allow assessment of comparability between the study participants and those external controls. It also does not report a statistical analysis plan, sample-size justification for the trial, interim analyses, or a multiplicity strategy for the several planned measures and associations.

The study is listed as terminated, but the reason for termination is not separately reported. The registry does not give a completed analysis from which to assess precision, bias, or generalizability. The adverse-event counts are recorded, but further details about event definitions and safety follow-up are not reported. These limitations mean that the study’s stated aims and measurement rationale should not be mistaken for evidence about MBT performance or prognostic value.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Methacetin Breath Test in Patients With Liver Disease Secondary to Heart Disease — NCT04176458.
• Registry record last updated 2023-04-05; status last verified 2023-03.
• Results first posted 2023-04-05.
• 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.

18. Record Summary

The registry record describes a terminated, single-group study of the Methacetin Breath Test in patients undergoing heart and liver transplant evaluation. It reports enrollment of 4, no allocation, and no masking. The primary outcome concerned MBT results, with CPDR20 identified as the measure of interest and a 90-minute measurement timeframe listed. Planned comparisons were to published normal controls, with additional exploration of clinical associations.

The record states that 2 MBT tests were required, but participants could not return for the second test because of COVID-19 restrictions; data analysis could not be performed. No outcome estimates or completed statistical analyses are reported. The adverse-event record lists 0 serious adverse events, 0 other adverse events, and 0 deaths. The record does not report the statistical analysis plan, a trial sample-size justification, or an analysis population.