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 Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study (NCT03154476), a randomized phase 3 study. The primary outcome is Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03154476 |
| Phase | Phase 3 |
| Condition | Cirrhosis, Congenital Heart Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Mayo Clinic |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns patients with liver disease after a Fontan operation. The registry lists cirrhosis and congenital heart disease as conditions. It does not report the detailed eligibility criteria, participant characteristics, or the number of participants with each condition.
Intervention
The intervention was sildenafil. The registry describes a titration schedule: 5 mg 3 times per day for the first week, 10 mg 3 times per day for the second week, then 20 mg 3 times per day from the third week through the 12-month study period.
Comparator
The comparator was placebo, with treatment planned for 12 months. The registry's placebo description says “placebo times per day” but does not state the frequency. Further details of placebo administration are not reported in the registry record.
Primary question
The study was intended to assess whether sildenafil could slow or stop liver-disease progression after a Fontan operation. The listed primary outcome was mean liver stiffness measured by magnetic resonance elastography, in kPa, at baseline, 12 months (52 weeks), and 24 months (104 weeks). The registry record does not report the outcome values or a between-group analysis, so it does not establish what the comparison found.
3. Trial Design
The registry classifies the SiFALD Study as a phase 3, randomized, parallel-group trial with quadruple masking. Random allocation is intended to reduce systematic differences between treatment groups at the start of a trial. A parallel design assigns participants to a group and compares those groups over the study, rather than having each participant receive both interventions. The registry does not report the randomization procedure, allocation concealment, or which roles were included in quadruple masking.
The listed enrollment is 20. The record names sildenafil and placebo as the interventions, and describes the intended sildenafil dose escalation over the first weeks followed by 20 mg 3 times per day through 12 months. The placebo description gives a 12-month duration but leaves its frequency incomplete; the frequency is not reported in the registry record. Detailed adherence information and any changes to assigned treatment are not reported in the registry record.
Mayo Clinic is listed as the sponsor. The study start date is 2017-07-05, the primary completion date is 2019-06-30, and the registry status is completed. Completion status indicates that the study is recorded as completed; it does not itself establish that results were analyzed or establish the direction or size of any treatment difference.
The primary outcome is described at baseline, 12 months (52 weeks), and 24 months (104 weeks). The intervention description refers to a 12-month study period, while outcome follow-up includes a 24-month time point. The record does not explain the follow-up procedures or how measurements at those times were incorporated into an analysis. It also does not report a protocol-level analysis plan or the number of participants completing each assessment.
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 | Sildenafil | Placebo |
|---|---|---|
| STARTED | 10 | 10 |
| COMPLETED | 6 | 6 |
| NOT COMPLETED | 4 | 4 |
Reasons for not completing this period:
| Reason | Sildenafil | Placebo |
|---|---|---|
| Lost to Follow-up | 4 | 4 |
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 | Sildenafil | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 10 | 20 | |
| Age, Continuous | years | 28 (SD 6) | 29 (SD 5) | 29 (SD 5) |
| Sex: Female, Male: Female | Participants | 3 | 3 | 6 |
| Sex: Female, Male: Male | Participants | 7 | 7 | 14 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: United States | participants | 10 | 10 | 20 |
6. Primary Endpoint
The registry lists the primary outcome as Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE), measured over Baseline, 12 months (52 weeks), 24 months (104 weeks).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | kPa |
| Endpoint classification | Continuous Endpoint |
The listed primary endpoint is mean liver stiffness measured by magnetic resonance elastography (MRE), reported in kilopascals (kPa). MRE uses magnetic resonance imaging to derive a measure of liver stiffness. The registry describes the outcome as MRE-derived liver stiffness and identifies the mean as its summary measure, with standard deviation as the dispersion measure.
Stiffness is used as a measurable characteristic of liver tissue that can be followed over time. In a study concerned with progression, repeated measurements can describe whether the recorded measure changes during follow-up and whether its pattern differs between assigned groups. This is a general explanation of how a continuous measurement can be used in a longitudinal trial; the registry does not provide additional evidence about how MRE was validated or interpreted for these participants.
The stated measurement times are baseline, 12 months (52 weeks), and 24 months (104 weeks). Baseline can provide a starting measurement, while later measurements can describe status during follow-up. The registry record does not report any means, standard deviations, changes from baseline, or comparisons between groups at these times. It therefore does not show the magnitude, direction, or precision of any observed difference in liver stiffness.
Because multiple time points are listed, interpretation would depend on the prespecified comparison and the way repeated measurements were analyzed. Those details are not reported in the registry record. A measure of stiffness alone is not a complete account of liver disease, and the registry does not report other clinical outcomes that could provide additional context.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the clinical question and the planned outcome, but it does not include the outcome results needed to answer that question statistically. Although liver stiffness is listed at baseline, 12 months (52 weeks), and 24 months (104 weeks), no group means, standard deviations, changes, confidence intervals, or statistical tests are reported. The record also lists no outcome analyses. As a result, the treatment contrast, its uncertainty, and the compatibility of the observations with different possible effects cannot be assessed from the posted results.
This absence of results is not evidence that the groups had the same outcome. A conclusion of similarity would require an estimate and uncertainty assessment, and neither is reported in the registry record. It is also not possible to conclude that one group had greater improvement or worsening. The study's completed status and its listed enrollment do not substitute for outcome data.
The outcome is continuous, and the registry specifies a mean and standard deviation. In general, a mean describes the central value of measurements in a group, while a standard deviation describes their spread. A between-group estimate would describe the contrast under a chosen analysis, and a confidence interval would convey the precision of that estimate. None of those numerical results is reported, so no effect size or precision statement can be made.
Measurements are planned at more than one time point. Different statistical questions could be asked about the endpoint: a comparison at a particular follow-up time, a change from baseline, or a pattern across follow-up. The registry record does not specify which contrast was the primary estimand, how repeated measurements were handled, or which time point was used for a treatment-effect test. Without these details and the corresponding results, the listed outcome cannot be translated into a single estimate of treatment effect.
The record lists 20 participants enrolled, but does not report how many contributed outcome measurements at each time point or were included in an analysis. The safety groups list 10 participants at risk in each arm, but those entries do not supply an outcome analysis population. The record also does not report the degree of missing outcome data or the methods used to handle it. These gaps limit assessment of both precision and potential bias.
A planning illustration based on an observed effect, when available, is not observed power and is not evidence that a trial did or did not detect an effect. The registry does not report an observed outcome contrast from which to assess an effect-based planning illustration. Its own sample-size justification is not reported in the registry record. The responsible reading is therefore descriptive: the record documents a randomized comparison and a planned MRE endpoint, but does not provide results from which the clinical question can be answered.
9. Statistical Methods Explained
What does randomization contribute?
Randomization assigns participants to treatment groups by chance. In general, this helps limit systematic differences between groups at the outset, including differences that investigators may not have measured. It does not guarantee that groups will be identical, particularly in a small study, and it does not by itself prevent bias after assignment. The registry classifies this study as randomized but does not report the sequence-generation method or allocation concealment. Those operational details are not reported in the registry record.
What does masking mean?
The record classifies masking as quadruple. Masking is intended to reduce the influence of knowledge about assigned treatment on participant behavior, clinical care, outcome assessment, or analysis. The registry does not identify which participant or study roles were masked, how masking was maintained, or whether it was assessed. Those specifics are not reported in the registry record, so the classification should not be expanded into assumptions about who knew assignments.
How should a continuous endpoint be summarized?
Liver stiffness is a continuous measurement recorded in kPa. In general, a mean gives a group’s average measurement, and a standard deviation describes how dispersed individual measurements are around that average. A comparison of means can summarize the difference between groups, but its interpretation depends on the selected time point or change measure, the analysis population, and the statistical model. The registry names the mean and standard deviation but does not report the numerical summaries or the comparison method.
A confidence interval is a range of values compatible with the data and the statistical model at a stated confidence level. It is useful because an estimate alone does not show how precisely the effect has been estimated. A narrow interval generally reflects greater precision than a wide interval, while an interval that includes values of different practical importance can leave substantial uncertainty. No confidence interval is reported in the registry record, so precision cannot be evaluated.
Why does the time structure matter?
The endpoint is listed at baseline, 12 months (52 weeks), and 24 months (104 weeks). Measurements from the same participant over time are related rather than independent. In general, an analysis of repeated measurements should account for that within-participant relationship and should clarify whether the target is a follow-up value, a change from baseline, or a trajectory across time. These choices can lead to different estimates and interpretations. The registry does not report the model, the primary contrast, or the handling of repeated measurements.
There is also a distinction between the intervention period and outcome follow-up. The sildenafil description specifies treatment through 12 months, while the primary outcome lists a 24-month measurement. The registry does not explain whether treatment continued after the 12-month period, how follow-up was organized, or what comparison was intended at 24 months. Those details are not reported in the registry record.
What does a planning illustration represent?
A sample-size planning illustration is a hypothetical calculation: it describes the number of participants that might be needed under specified assumptions to detect a chosen effect with a chosen statistical procedure. It is not a result observed in the trial, and it is not observed power. The planning assumptions stated for this record use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is described as a stated fraction of an observed effect. These assumptions define an illustrative calculation, not the trial's documented design rationale.
Such an illustration depends on the effect used as its starting point and on the assumptions about variability and analysis. Since the registry record does not report the MRE group summaries or observed effect, the outcome evidence needed to interpret an effect-based illustration is absent. The trial's own sample-size justification is not reported in the registry record. No planning calculation can replace a treatment-effect estimate with uncertainty from the actual observations.
What can be inferred from the absence of an analysis?
The registry lists no analyses and provides no primary outcome results. That means the posted record does not support a numerical assessment of the treatment contrast, its uncertainty, or its statistical significance. It does not establish that no analysis was ever performed; it means that an analysis is not reported in the registry record. Likewise, it does not permit a conclusion that the groups were equivalent, that a difference was absent, or that a difference was present.
For sound interpretation, a statistical result would ordinarily be read alongside its analysis population, endpoint definition, missing-data approach, and prespecified contrast. These elements determine what participants and measurements the estimate represents and how robust it may be to incomplete observations. The registry does not report these methods. The appropriate statistical reading is therefore limited to the trial structure and endpoint that are recorded, not an unsupported reconstruction of an analysis.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome is listed at baseline, 12 months (52 weeks), and 24 months (104 weeks). Multiple time points can create more than one possible comparison. If several comparisons are tested, the chance of at least one chance-positive finding can increase unless the analysis plan accounts for multiplicity. This is a general statistical concern, not a claim about what happened in this study. The registry record does not report a multiplicity strategy, hierarchy of time points, or a single prespecified treatment contrast.
The record lists one outcome measure but no analyses. It does not report whether baseline was used only as a starting measurement or included in a repeated-measures model, nor does it identify a primary follow-up time for the treatment comparison. The statistical plan and any interim analyses are not reported in the registry record. No interim analysis should be assumed.
Missing-data methods and analysis populations are also not reported in the registry record. The listed enrollment is 20, but outcome availability at each measurement time is not stated. The record does not say whether analyses were based on all randomized participants, participants who completed treatment, or another defined population. It also does not report how withdrawals, missed assessments, or other incomplete measurements were handled. In general, missingness can affect both precision and validity, depending on why measurements are absent and how the analysis addresses them. Without the relevant details, the impact cannot be assessed.
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 |
|---|---|---|---|
| Sildenafil | 0 | 10 | 0.0% |
| Placebo | 0 | 10 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Sildenafil | 0 of 10 |
| Placebo | 0 of 10 |
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 |
|---|---|
| Sildenafil | 0 of 10 |
| Placebo | 0 of 10 |
The registry lists 10 participants at risk in the sildenafil group and 10 in the placebo group for the serious-adverse-event reporting, with 0 affected in each group. It also lists 10 at risk in each group for other adverse events, with 0 affected in each group. Deaths are recorded as 0 in both groups. These are the safety figures in the registry record; they are not estimates of comparative risk with a reported uncertainty interval.
A zero count means that no affected participants are recorded in these entries. It does not establish that the underlying risk is zero, and it does not show that the groups have identical safety profiles. With limited numbers of participants, uncommon events may not be observed. The record does not provide event definitions, observation time by participant, detailed adverse-event terms, or methods for collecting and adjudicating events. The list of serious-event terms is empty. These limitations matter when interpreting the scope of the reported counts.
The safety entries should be read separately from the unreported primary MRE outcome. They do not provide evidence about liver-stiffness changes or answer the study's primary question. They also do not support medical advice or a broad conclusion about safety beyond the counts recorded for this study.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, quadruple-masked, parallel-group study was conducted to compare sildenafil with placebo in people with liver disease after a Fontan operation. It identifies MRE-derived liver stiffness as the primary outcome and lists measurements at baseline, 12 months (52 weeks), and 24 months (104 weeks). It also records an enrollment of 20 and a completed status. These registry entries describe the trial's design and intended measurement, not its treatment effect.
The registry does not report the primary outcome values, a comparison between groups, or an analysis. Consequently, the result cannot be characterized as favoring sildenafil, favoring placebo, or showing no difference. The size and direction of any observed contrast are unknown from the registry record, as is its statistical precision. A missing result must not be interpreted as a null result.
The safety entries record 0 serious adverse events and 0 other adverse events in each group, and 0 deaths in each group, with 10 participants at risk in each arm for the event categories listed. Those counts describe the reported entries only. They do not establish the absence of possible risks outside the recorded counts or provide a precise comparative safety estimate.
In general, trial conclusions depend on both the estimate and its uncertainty, as well as on the population analyzed, endpoint definition, follow-up, and missing-data handling. Those analysis details are not reported in the registry record. The study's completed status cannot fill those gaps. The most defensible conclusion is that the registry documents a trial designed to examine MRE liver stiffness but does not contain enough outcome information to determine what the comparison found.
13. Why This Trial Matters Statistically
This study illustrates why a registered trial design and a trial result are different kinds of evidence. The registry describes a randomized comparison, masking classification, treatment arms, and a continuous primary endpoint. Those details help identify the intended question and measurement. Without the resulting group summaries and analysis, however, neither the direction nor the precision of the treatment contrast can be evaluated.
The endpoint also makes the analysis question important. Measurements are listed at baseline and at two later time points, so interpretation depends on how the longitudinal data were reduced to a comparison. A follow-up value, a baseline change, and a pattern across time answer related but distinct questions. If multiple contrasts are considered, the statistical plan should clarify which one is primary and how multiplicity is handled. The registry does not report these choices.
The listed enrollment of 20 highlights the importance of reporting uncertainty rather than relying on a point estimate alone. In general, smaller datasets can yield estimates with substantial imprecision, but no precision estimate is available in this record. The listed safety counts likewise need context about event definitions and observation, which is not reported.
Finally, a planning illustration is not a substitute for outcome evidence. Calculations based on an observed effect and specified assumptions can help illustrate design requirements, but they do not reveal whether this trial's groups differed or whether any estimate is precise. The registry's missing analysis details limit reproducibility and prevent readers from evaluating how the primary question was addressed.
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 central limitation for interpretation is that the registry record does not report numerical results for the primary MRE outcome or any analysis comparing sildenafil with placebo. Group means, standard deviations, treatment-effect estimates, confidence intervals, and statistical tests are not reported. The clinical question therefore cannot be answered from the recorded results.
The outcome is listed across baseline, 12 months (52 weeks), and 24 months (104 weeks), but the intended contrast and repeated-measures method are not reported. The relationship between the stated 12-month treatment period and the 24-month outcome time point is also not explained. The record does not report whether participants continued follow-up after treatment or how measurements at that later time were analyzed.
The listed enrollment is 20, but the registry does not report the number with available outcome data at each time point, the analysis population, adherence, withdrawals, or missing-data methods. Eligibility details and participant characteristics are not reported, limiting assessment of how well the studied group represents the intended population. The placebo frequency is incomplete in the arm description, and detailed administration information is not reported in the registry record.
Although the trial is classified as quadruple-masked and randomized, operational details about allocation and masking are not reported. The protocol-level statistical plan, multiplicity approach, interim analyses, and sample-size justification are also not reported in the registry record. These gaps do not show that the procedures were absent; they limit what can be verified from the record. Safety counts are sparse descriptions without event definitions or a detailed event listing, so they cannot support broad claims beyond the recorded entries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study — NCT03154476.
- Registry record last updated 2021-08-23; status last verified 2021-07.
- Results first posted 2021-07-28.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The SiFALD Study is listed as a completed phase 3 randomized, quadruple-masked, parallel-group trial sponsored by Mayo Clinic. The registry lists enrollment of 20 and a study start date of 2017-07-05, with primary completion on 2019-06-30. The groups were sildenafil and placebo. The sildenafil schedule escalated from 5 mg 3 times per day to 10 mg 3 times per day, then to 20 mg 3 times per day through the 12-month study period.
The primary outcome was mean liver stiffness measured by MRE in kPa, with assessments listed at baseline, 12 months (52 weeks), and 24 months (104 weeks). The registry record does not report outcome values, a treatment comparison, analysis methods, or missing-data handling. Safety entries list 0 serious adverse events, 0 other adverse events, and 0 deaths in each group. These counts do not replace the unreported primary outcome analysis.