Tolvaptan for Ascites in Cirrhotic Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Tolvaptan for Ascites in Cirrhotic Patients (NCT01292304), a na phase 4 study. The primary outcome is Number of Participants With Worsening Ascites (Increase in Number of Paracentesis Procedures to Remove 2 Liters of Ascites Fluid).

2. Clinical Question

The clinical question is therefore about the observed course of ascites among participants receiving tolvaptan with their current management, not about a treatment effect estimated against a concurrent control group. A change in paracentesis frequency can describe how often participants required this procedure during the specified periods. However, without an untreated or alternative-treatment group, any observed change cannot by itself separate the course associated with study participation from other influences, including ongoing ascites management or changes over time.

The registry record names additional outcomes concerning reduction of ascites, low sodium levels, and time to worsening ascites. These outcomes address other aspects of the clinical course, but their results are not reported in the registry record. The primary endpoint result is also not reported, so the clinical question is specified but cannot be answered from the posted outcome results.

3. Trial Design

This is a Phase 4, single-center, open-label pilot study sponsored by the University of Florida. The record lists a single group receiving tolvaptan and current ascites management, with no separate control arm. Allocation is recorded as not applicable, and masking is listed as none. Consequently, the design does not support a randomized comparison between treatment groups.

The recorded enrollment is 10. The study is marked completed. Its recorded start is 2012-03 and its primary completion is 2014-12. The listed regimen is tolvaptan 15 mg once daily for 7 days, followed by 30 mg once daily according to efficacy and tolerability. The brief description states that tolvaptan is administered in combination with current ascites management.

The primary endpoint is a participant count for worsening ascites by Week 12. Worsening is defined by an increase in the number of therapeutic paracentesis procedures to remove 2 liters of ascites fluid, comparing the 12 weeks during study-drug dosing with the 12 weeks before dosing. The record also lists secondary outcomes addressing reduction of ascites, sodium levels between 130 mmol/L and 135 mmol/L, and time from baseline to worsening ascites requiring therapeutic paracentesis.

The registry record does not report a detailed statistical analysis plan, a sample-size justification, or interim analyses. It lists no analyses for the outcomes. The primary endpoint result and the results for the listed secondary outcomes are not reported in the registry record. Thus the study design and outcome definitions can be described, but the posted record does not provide the outcome estimates needed to assess the observed course of ascites.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Worsening Ascites (Increase in Number of Paracentesis Procedures to Remove 2 Liters of Ascites Fluid), measured over Week 12.

The primary endpoint counts participants with worsening ascites by Week 12. Worsening is defined as an increase in the number of therapeutic paracentesis procedures to remove 2 liters of ascites fluid during the 12 weeks of study-drug dosing, compared with the 12 weeks before study-drug dosing. The outcome is therefore a participant count based on a change in procedure frequency across two periods.

In general, a clinical endpoint is useful when it translates a clinical question into an observable measure. A count of participants meeting a defined worsening criterion can communicate how many participants experienced that event, while the specified time period makes clear when the event is being assessed. The before-and-during comparison also gives the endpoint a within-participant reference period, rather than relying on a separate concurrent control group.

That structure has important limits. A participant’s experience before dosing is not a randomized control condition, and differences between periods cannot establish that the study drug caused any change. Other changes over time or in current ascites management may also matter. In addition, a binary participant count does not show the amount of change in paracentesis frequency for each person. The registry record does not report the number of participants meeting the primary definition, so the endpoint is defined but its observed result cannot be interpreted from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary outcome count?

The primary outcome is a binary participant-level measure: participants are classified according to whether they meet the worsening-ascites definition. The definition uses an increase in the number of therapeutic paracentesis procedures to remove 2 liters of ascites fluid during the 12 weeks of study-drug dosing compared with the 12 weeks before dosing. In general, a binary outcome simplifies a clinical event into whether it occurred or did not occur. This can make a result easier to communicate, but it does not preserve every detail of the event. For example, the count alone would not describe how many procedures each participant had or the magnitude of any change.

What can a single-group study estimate?

A single-group study can describe outcomes observed in the participants who received the study intervention. Here, the registry record describes an open-label group receiving tolvaptan with current ascites management. Because there is no concurrent control group, a change over time is not the same as a randomized treatment contrast. In general, a randomized comparison aims to make treatment groups comparable on average, so differences in their outcomes can be more credibly associated with assigned treatment. A before-and-during comparison within one group does not offer that protection: time trends, other care, and changes in participant status may influence the observed outcome. The registry record does not report an adjusted causal analysis.

How should counts and uncertainty be read?

For a binary outcome, a count of affected participants describes the observed frequency in the group. In general, uncertainty intervals around such a count or proportion can show how imprecise an estimate may be, particularly when the study is small. A confidence interval is a range produced by a statistical procedure that, under its assumptions, reflects uncertainty about an underlying quantity. It is not a guarantee that the true value falls within that particular interval, and it does not address design limitations such as the lack of a control group. The primary outcome count and any interval are not reported in the registry record, so neither the observed frequency nor its precision can be assessed.

What does the record say about statistical planning?

The registry record does not report the study’s sample-size justification, a detailed statistical analysis plan, or interim analyses. It lists no analyses for the outcomes. Those omissions mean that readers cannot determine from the registry record how the investigators planned to handle the primary comparison, which statistical model they intended to use, or how they intended to express uncertainty. A planning illustration based on an observed effect, when available, is not the same as the trial’s original design justification and is not observed power. In general, planning calculations depend on explicit assumptions about the effect of interest, variability, significance level, and allocation. They describe a hypothetical design, not evidence that a study did or did not have adequate power after its data were collected.

Why does the endpoint’s time structure matter?

The primary definition compares two periods for each participant: the 12 weeks before study-drug dosing and the 12 weeks during dosing. In general, paired or within-participant comparisons account for the fact that measurements from the same person are related. However, the periods occur at different times rather than representing randomized conditions. A statistical method can describe or model the paired data, but it cannot by itself remove time-related influences that were not measured or controlled. The registry record does not report the individual measurements, the analysis method, or an estimate of change.

What can be said about secondary outcomes?

The registry record names secondary measures for reduction of ascites, low sodium levels, and time from baseline to worsening ascites requiring one or more therapeutic paracentesis procedures. These represent different outcome types: a participant count, a threshold-based laboratory classification, and a time-to-event measure. In general, time-to-event analyses can use information about when an event occurs and may account for participants who have not had the event by the end of observation. Interpretation depends on how follow-up and censoring are handled. Those details, the corresponding estimates, and the analysis methods are not reported in the registry record. No conclusions about these secondary outcomes can therefore be drawn from the posted results.

Overall, statistical methods can quantify observed patterns and uncertainty, but their interpretation depends on the design, definitions, data completeness, and analysis plan. The record supplies outcome definitions but does not report outcome analyses for the primary or listed secondary endpoints. Statistical significance, effect size, and precision for those outcomes cannot be assessed.

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("Tolvaptan")
n      <- c(10)
events <- c(0)
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  Tolvaptan  10  0  0.0  0.0  30.8  0.0  27.8  0.2  28.5

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and several secondary outcomes, but it does not report a multiplicity strategy. In general, testing multiple outcomes can increase the chance of obtaining at least one apparently unusual result when all underlying effects are absent. A prespecified approach may control that risk or clarify which outcomes are confirmatory and which are exploratory. Without a reported plan, readers cannot determine how the investigators intended to interpret multiple statistical tests. The record lists no analyses, and outcome results are not reported in the registry record.

Missing-data methods are not reported in the registry record. The record does not state how incomplete outcome measurements, withdrawals, or participants without a Week 12 assessment were handled. In general, missingness can affect an estimate if the participants with observed data differ systematically from those without observed data. The direction and extent of that effect depend on why data are missing and on the analysis method, so neither can be inferred from this record.

The analysis population is also not described in detail. The record does not report whether the primary analysis included all enrolled participants, only participants who completed treatment, or another defined group. The listed enrollment is 10, but the number contributing data to each outcome is not reported. Without analysis-population definitions and outcome-specific denominators, readers cannot assess whether all enrolled participants were represented in each analysis.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pleural effusion (10.0%).

The adverse-event record lists 10 participants at risk for serious adverse events and 1 affected. It also lists 10 at risk for other adverse events and 9 affected. Pleural effusion is named among the top serious adverse-event terms at 10.0%. The record does not state in the listed information whether these events were judged related to tolvaptan.

These counts describe events recorded in the Tolvaptan group; they do not estimate a difference in risk versus another treatment because there is no separate control group. In general, an adverse event occurring during a study is not by itself proof that the study treatment caused it. Interpretation also depends on how events were defined, collected, attributed, and followed, details not reported in the registry record.

The death count is not reported in the registry record. It should not be interpreted as a reported count of zero. The adverse-event figures are descriptive of this small study group and do not establish how frequently such events would occur in a broader population.

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

The registry record documents a completed, open-label, single-group pilot study of tolvaptan administered alongside current ascites management. It defines worsening ascites by a change in therapeutic paracentesis frequency and specifies an assessment at Week 12. Those details clarify what the primary question was intended to measure. The record also includes adverse-event counts for the treated group.

The record does not report the primary endpoint result or results for the listed secondary outcomes. As a result, it does not show how many participants experienced worsening ascites, whether ascites reduction was observed, or how the other named outcomes developed. It also does not provide an estimate of effect or a confidence interval for the primary question. The clinical outcome findings and their statistical precision therefore cannot be judged from the posted results.

Even if a before-and-during change had been reported, a single-group study would not establish that tolvaptan caused that change. The preceding period is a reference period, not a randomized control group. In general, outcome changes may reflect the intervention, other care, the passage of time, or a combination of influences. A randomized comparator is needed to support a stronger estimate of a treatment difference.

The safety counts describe recorded events among participants in the Tolvaptan group, but there is no concurrent group for comparison, and the record does not report attribution to treatment. These figures should be read as descriptive observations, not as proof of causation or a complete characterization of safety. Overall, the registry record identifies the study question and design but does not report the primary efficacy result needed to answer that question.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between describing an outcome and estimating a treatment effect. Its primary outcome is concrete: it classifies participants according to an increase in paracentesis procedures over a specified period. Such a definition can make an endpoint interpretable, but the endpoint definition alone is not a result. The registry record does not report the number of participants meeting it.

The study also illustrates why design matters to interpretation. A single-group, open-label pilot can record outcomes and adverse events in participants receiving an intervention, but it does not create a randomized comparison. Comparing participants with their own earlier period may be clinically descriptive, yet it cannot isolate the intervention’s effect from time-related changes or other management. Statistical sophistication cannot substitute for a missing comparison group.

Small pilot studies can be useful for documenting feasibility and collecting early descriptive information. In general, however, small samples tend to leave estimates uncertain, and the absence of reported outcome analyses prevents readers from evaluating even that uncertainty. The record does not report its sample-size justification, analysis plan, or interim analyses. Nor does it report results for the primary and listed secondary endpoints.

The adverse-event counts show another important distinction: event occurrence in a study group is not the same as evidence that the intervention caused the event. Comparative data and clear attribution methods help contextualize safety findings. The record offers a limited descriptive account but no comparator. Taken together, the study’s value for statistical interpretation lies in its clearly specified primary question and in showing the limits that follow from a single-group design and unreported outcome results.

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 primary limitation for interpreting efficacy is that the registry record does not report the primary outcome result. The same is true for the listed secondary outcomes. Without outcome counts, estimates, or uncertainty measures, the observed clinical course cannot be evaluated from the posted results.

The single-group design provides no concurrent control for comparison. The primary endpoint uses the 12 weeks before dosing as a reference, but a prior period is not equivalent to a randomized comparator. Differences between periods may reflect changes over time or in current ascites management as well as any association with study-drug dosing. The open-label design also means masking is listed as none; the record does not describe procedures to limit the influence of knowledge of treatment assignment.

The recorded enrollment is 10, and the record does not state the outcome-specific numbers of participants with available data. It does not report missing-data methods, the analysis population, or how participants who did not complete follow-up were handled. These gaps prevent assessment of whether missing observations could have affected the results.

The registry record does not report a sample-size justification, detailed statistical analysis plan, or interim analyses. It lists no analyses for the outcomes. Consequently, readers cannot assess the planned statistical approach, multiplicity handling, or the precision intended for the primary estimate. Safety information is also limited: event counts are descriptive, treatment attribution is not stated in the listed information, and deaths are not reported. These limitations are specific to the design and information recorded for this study and constrain both efficacy and safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Tolvaptan for Ascites in Cirrhotic Patients — NCT01292304.
• Registry record last updated 2015-07-27; status last verified 2015-06.
• Results first posted 2015-07-27.
• 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 describes NCT01292304, a completed Phase 4, single-center, open-label pilot study sponsored by the University of Florida. It enrolled 10 participants with cirrhotic ascites and evaluated tolvaptan alongside current ascites management. The listed regimen was 15 mg once daily for 7 days, followed by 30 mg once daily according to efficacy and tolerability.

The primary endpoint was the number of participants with worsening ascites by Week 12, defined by an increase in therapeutic paracentesis procedures compared with the preceding 12 weeks. Secondary outcomes addressed ascites reduction, low sodium levels, and time to worsening ascites. The primary and secondary outcome results are not reported in the registry record.

Adverse-event entries list 1 of 10 participants with a serious adverse event and 9 of 10 with other adverse events; pleural effusion is listed at 10.0% among serious-event terms. The study has no separate control group, and the record does not report its detailed statistical plan, missing-data methods, or analysis populations.