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 A Study to Assess the Safety and Effects of Intravenous (IV) Conivaptan on the Hepatic Hemodynamic Response in Cirrhotic Patients (NCT00592475), a randomized phase 2 study. The primary outcome is Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00592475 |
| Phase | Phase 2 |
| Condition | Liver Cirrhosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Cumberland Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Stable euvolemic or hypervolemic patients with cirrhosis. The condition listed in the registry record is liver cirrhosis. Enrollment was 20, but the number analyzed for the primary outcome by treatment group is not reported in the registry record.
Intervention
Intravenous conivaptan was studied in two regimens. Regimen 1 was a 10 mg loading dose plus 2.5 mg continuous infusion over 6.5 hours. Regimen 2 was a 20 mg loading dose plus 5 mg continuous infusion over 6.5 hours.
Comparator
The comparator was placebo, administered as a continuous intravenous infusion over 6.5 hours. The registry record describes a randomized, double-blind, placebo-controlled, parallel study.
Primary question
The primary endpoint was change from baseline in hepatic venous pressure gradient (HVPG) at 0.5, 1, and 1.5 hours after dosing. The study also aimed to evaluate safety. Numerical results for the primary endpoint are not reported in the registry record.
In statistical terms, the study asked whether hepatic hemodynamic measurements changed after dosing and how those changes were distributed across the conivaptan regimens and placebo. The registry record defines change as the value at a time point minus the baseline value. Baseline procedures were performed before study drug administration.
The question is limited to the studied population, regimens, and assessment period. It does not establish what happens beyond the recorded follow-up or in other patient populations. Serum sodium was listed as a secondary outcome, with assessments at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 hours and on Day 8 post dose. Numerical results for that outcome are not reported in the registry record.
3. Trial Design
This was a Phase 2, randomized, double-blind, placebo-controlled study with a parallel-group design. The registry record describes dose escalation and identifies three regimens: conivaptan 12.5 mg, conivaptan 25 mg, and placebo. The two active regimens differed in their loading dose and continuous infusion amount. Each infusion was described over 6.5 hours.
The study population was stable euvolemic or hypervolemic patients with cirrhosis. The registry record lists enrollment of 20. It does not report the number randomized to each regimen, nor does the enrollment figure alone establish how many participants contributed endpoint data in each group. For the primary outcome, the analysis population is described as the Full Analysis Set: all randomized patients who received at least one dose of study drug and had HVPG data at baseline. The record says that the number of participants per arm is consistent across all categories of the data table, but the group-specific counts are not reported.
Randomization is intended to allocate participants to treatment groups by chance, helping create groups that are comparable on average at the start of a study. Double blinding is intended to limit the influence of treatment knowledge on participant experience, clinical management, and outcome assessment. These design features can reduce some sources of bias, but they do not remove uncertainty arising from a small enrollment or incomplete reporting.
The registry record lists the study as completed and gives a start of 2007-12 and primary completion of 2008-11. It does not report the randomization method, allocation concealment details, the specific blinding procedures, or a rationale for the enrollment target. Those details are not reported 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
| Stage | Regimen 1 Conivaptan 12.5 mg | Regimen 2 Conivaptan 25 mg | Regimen 3 Placebo |
|---|---|---|---|
| STARTED | 6 | 9 | 5 |
| COMPLETED | 6 | 9 | 5 |
| NOT COMPLETED | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Participants Analyzed represents Full Analysis Set (FAS): All randomized patients who had at least 1 dose of study drug \& who had hepatic venous pressure gradient data at baseline. The number of participants per arm is consistent for all categories of the data table.
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 | Regimen 1 Conivaptan 12.5 mg | Regimen 2 Conivaptan 25 mg | Regimen 3 Placebo | Total |
|---|---|---|---|---|---|
| Participants analysed | 6 | 9 | 5 | 20 | |
| Age, Continuous | years | 63.7 (SD 8.52) | 60.0 (SD 9.72) | 55.2 (SD 7.19) | 59.9 (SD 8.95) |
| Sex: Female, Male: Female | Participants | 3 | 2 | 0 | 5 |
| Sex: Female, Male: Male | Participants | 3 | 7 | 5 | 15 |
| Race/Ethnicity, Customized: White | Participants | 6 | 9 | 5 | 20 |
| Underlying Cause of Hyponatremia: Euvolemic - Cirrhosis | Participants | 1 | 1 | 1 | 3 |
| Underlying Cause of Hyponatremia: Euvolemic - Not Hyponatremia | Participants | 2 | 1 | 1 | 4 |
| Underlying Cause of Hyponatremia: Euvolemic - Other | Participants | 1 | 0 | 0 | 1 |
| Underlying Cause of Hyponatremia: Hypervolemic - Cirrhosis | Participants | 2 | 3 | 3 | 8 |
| Underlying Cause of Hyponatremia: Hypervolemic - Not Hyponatremia | Participants | 0 | 3 | 0 | 3 |
| Underlying Cause of Hyponatremia: Hypervolemic - Other | Participants | 0 | 1 | 0 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose, measured over Baseline and 0.5, 1, and 1.5 hours post dose.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | mmHg |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in hepatic venous pressure gradient (HVPG), measured in mmHg at 0.5, 1, and 1.5 hours post dose. The registry record defines the change as the post-dose time-point value minus the baseline value, with baseline procedures performed before study drug administration. The endpoint is described as a mean with standard deviation as the measure of dispersion.
HVPG is a pressure measurement used to characterize hepatic hemodynamics. In general, assessing change from baseline can help describe how a measurement shifts after an intervention while accounting for the participant’s starting value. A negative change under the registry’s stated calculation would indicate a lower measured value than baseline, and a positive change would indicate a higher measured value; this is a general interpretation of subtraction, not a claim about the trial’s results.
Assessing the endpoint at multiple early post-dose time points can describe the timing and pattern of change during the period following administration. However, the registry record does not identify one of those time points as the sole primary comparison, nor does it report a prespecified summary across them. Numerical means, standard deviations, group differences, confidence intervals, and p-values for the primary outcome are not reported in the registry record. Therefore, the endpoint definition can be described, but the magnitude and precision of any observed change cannot be evaluated from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary endpoint and its measurement schedule, but it does not report numerical primary-outcome results. No group-specific mean changes or standard deviations, treatment contrasts, confidence intervals, or p-values are reported in the registry record. The statistical interpretation is therefore necessarily about what the endpoint and design allow one to assess, rather than about the direction or size of an observed effect.
For each participant, the endpoint is a post-dose HVPG value minus the baseline value. A group mean change would describe the average shift from baseline among participants included in that group’s analysis. A standard deviation would describe how dispersed individual changes were around that group mean. Neither quantity, by itself, gives the uncertainty around a comparison between treatment groups. A treatment contrast and its uncertainty would be needed to assess how clearly the observed group changes differed.
A confidence interval, in general, represents a range of values compatible with the observed data under the analysis assumptions. Its width reflects precision: a wider interval indicates less precision than a narrower one. Since confidence intervals are not reported in the registry record, the precision of any treatment comparison cannot be assessed. A p-value, if reported, would address how compatible the data are with a specified null hypothesis under the chosen statistical model; it would not measure clinical importance or establish that a treatment is beneficial. No p-values or statistical tests are reported in the registry record.
The three regimens and the repeated assessment times create several possible comparisons. The registry record does not specify which contrasts were intended to support the primary conclusion, whether a particular time point had priority, or how results across time points were to be interpreted together. The listing of a primary endpoint does not by itself provide those details. The numerical outcome results and the analysis plan are not reported in the registry record.
The enrollment was 20, and the primary analysis population required randomization, at least one dose, and baseline HVPG data. The group-specific analysis counts are not reported in the registry record. Without those counts and the outcome distributions, it is not possible to judge how much information contributed to each regimen’s estimate or how sensitive the results might be to individual observations.
The record also describes safety outcomes, but the available adverse-event figures do not supply the missing HVPG results. They answer a different descriptive question. Taken together, the registry record establishes the study’s design, population, intervention schedules, and endpoint definition, but it does not provide enough numerical information to estimate the primary treatment effects or their precision.
9. Statistical Methods Explained
The statistical methods that can be described from the registry record are limited. The record identifies a randomized, double-blind, parallel-group Phase 2 design, a continuous primary endpoint expressed as a mean with standard deviation, and a Full Analysis Set definition. It does not report the statistical test or model used for the primary outcome, a treatment-effect estimate, or an inferential result. The explanations below describe general statistical concepts, not methods confirmed as having been used in this study.
What does a mean change describe?
For this endpoint, each change is defined as the value at a post-dose time point minus the baseline value. The mean of those changes describes the average within-participant shift for the participants included in an analysis group. It is not the same as the mean post-dose value, because it uses each participant’s baseline as the reference. A mean can summarize the group while obscuring variation between participants, so it is normally read alongside a measure of dispersion and the number of observations.
The standard deviation describes the spread of observed changes around their mean. It reflects variability among participants, not the precision of the estimated mean itself. Precision also depends on how many observations contribute and on the analysis. The group-specific counts are not reported in the registry record, and the primary outcome’s numerical means and standard deviations are not reported there either. Consequently, neither the extent of participant-to-participant variation nor the precision of a group mean can be assessed from the registry record.
How would a treatment comparison differ from a within-group change?
A within-group change answers whether the group’s measured values shifted from baseline on average. A comparison between groups asks whether the shifts differ between assigned regimens. Those are distinct questions: observing a change in one group alone does not establish that the change differs from what would have occurred under another regimen. A comparative estimate, together with its uncertainty, is generally needed to interpret the randomized contrast.
The registry record does not report a comparative estimate, the statistical method used to obtain one, or confidence intervals. It therefore does not establish whether the primary analysis compared changes directly, adjusted for baseline values, or used another approach. Those analysis details are not reported in the registry record.
Why do repeated assessment times matter?
HVPG was assessed at 0.5, 1, and 1.5 hours post dose. Repeated measurements can describe whether a response appears to change over time, but they also create more than one possible time-specific comparison. A statistical plan may specify a primary time point, a summary across time, or a model that accounts for the relationship among repeated observations. The registry record does not report such a plan or identify a single time point as the primary comparison.
Measurements collected from the same participant are generally related rather than independent. In general, a repeated-measures analysis can account for that relationship and use the data across time points. This is a general statistical explanation; the registry record does not say whether such a model was used. Without the analysis specification and numerical results, the shape and consistency of any time pattern cannot be evaluated.
What does the analysis population mean?
The Full Analysis Set is defined in the registry record as all randomized patients who had at least one dose of study drug and baseline HVPG data. This definition specifies eligibility for the primary endpoint analysis as recorded, but it is not equivalent to knowing how many participants were analyzed in each regimen. The record says the number per arm is consistent across the data categories, but does not report the arm-specific counts in the information available for interpretation.
Analysis populations matter because excluding participants after randomization can affect comparability between groups, depending on who is excluded and why. The registry record does not provide participant-level flow, reasons for exclusion, or details about participants without baseline or follow-up measurements. It also does not report the handling of missing endpoint measurements. These details are not reported in the registry record.
What can be concluded from the statistical reporting?
The endpoint type, summary measure, time points, and Full Analysis Set definition are described. The statistical test or model, effect estimates, measures of uncertainty, and p-values are not reported in the registry record. The record lists 0 analyses. That absence of reported analyses should not be read as evidence of no change or no difference; it means that the posted registry information does not permit a numerical assessment of the primary endpoint.
General statistical interpretation also distinguishes statistical evidence from clinical importance. A small p-value, if available, would not by itself establish that a difference is meaningful, and a non-significant result would not prove that groups are equivalent. Estimates and confidence intervals help show both the plausible size of an effect and how precisely it is estimated. Since these results are not reported in the registry record, neither statistical evidence nor the precision of the primary comparison can be evaluated.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome was assessed at 0.5, 1, and 1.5 hours post dose. Considering several assessment times can raise a multiplicity issue: when many comparisons are made, the chance of at least one apparently unusual result can increase. Statistical plans commonly address this by defining a primary time point, adjusting for multiple comparisons, or treating the set of results as descriptive. Which approach was used in this study is not reported in the registry record.
The study also included three regimens and listed serum sodium as a secondary outcome with several assessment times. The registry record does not report a multiplicity strategy covering the primary and secondary outcomes, the treatment contrasts, or the time points. It also does not report a hierarchy of hypotheses or which comparisons were prespecified. Without those details, any isolated result would need cautious interpretation; numerical outcome results are not reported in the registry record.
For the primary outcome, the Full Analysis Set includes randomized patients who received at least one dose and had baseline HVPG data. The record does not report how many randomized participants lacked those data, how many lacked post-dose measurements, or the reasons for any missing values. It does not state whether missing observations were excluded, imputed, or handled using a model that can use incomplete repeated measurements. These missing-data methods are not reported in the registry record.
The record does not provide an interim-analysis plan, a sample-size justification, or a detailed statistical analysis plan. Those details are not reported in the registry record. As a result, the extent to which the endpoint testing, missing data, and multiple comparisons were addressed in advance cannot be assessed from the registry record.
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 |
|---|---|---|---|
| Regimen 1 Conivaptan 12.5 mg | 0 | 6 | 0.0% |
| Regimen 2 Conivaptan 25 mg | 2 | 9 | 22.2% |
| Regimen 3 Placebo | 0 | 5 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Regimen 1 Conivaptan 12.5 mg | 1 of 6 |
| Regimen 2 Conivaptan 25 mg | 6 of 9 |
| Regimen 3 Placebo | 0 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | Regimen 1 Conivaptan 12.5 mg | Regimen 2 Conivaptan 25 mg | Regimen 3 Placebo |
|---|---|---|---|---|
| Atrial tachycardia | Cardiac disorders | 0 of 6 | 1 of 9 | 0 of 5 |
| Urinary tract infection | Infections and infestations | 0 of 6 | 1 of 9 | 0 of 5 |
| Hepatic encephalopathy | Nervous system disorders | 0 of 6 | 1 of 9 | 0 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Regimen 1 Conivaptan 12.5 mg | Regimen 2 Conivaptan 25 mg | Regimen 3 Placebo |
|---|---|---|---|---|
| Phlebitis | Vascular disorders | 0 of 6 | 2 of 9 | 0 of 5 |
| Atrial flutter | Cardiac disorders | 0 of 6 | 1 of 9 | 0 of 5 |
| Nausea | Gastrointestinal disorders | 0 of 6 | 1 of 9 | 0 of 5 |
| Vomiting | Gastrointestinal disorders | 0 of 6 | 1 of 9 | 0 of 5 |
| Polydipsia | Metabolism and nutrition disorders | 0 of 6 | 1 of 9 | 0 of 5 |
| Back Pain | Musculoskeletal and connective tissue disorders | 0 of 6 | 1 of 9 | 0 of 5 |
| Dizziness | Nervous system disorders | 1 of 6 | 0 of 9 | 0 of 5 |
| Productive cough | Respiratory, thoracic and mediastinal disorders | 0 of 6 | 1 of 9 | 0 of 5 |
| Dry skin | Skin and subcutaneous tissue disorders | 0 of 6 | 1 of 9 | 0 of 5 |
Serious events with the highest arm-level rate: atrial tachycardia (11.1%), urinary tract infection (11.1%), hepatic encephalopathy (11.1%).
The registry record reports serious adverse events by regimen as numbers of participants at risk and numbers affected. For Regimen 1 Conivaptan 12.5 mg, 6 participants were at risk and 0 were affected. For Regimen 2 Conivaptan 25 mg, 9 were at risk and 2 were affected. For Regimen 3 Placebo, 5 were at risk and 0 were affected. These are descriptive counts; they do not by themselves establish that a regimen caused or prevented an event.
The record lists atrial tachycardia, urinary tract infection, and hepatic encephalopathy among the top serious terms, each at 11.1%. The registry information does not provide enough detail to connect those terms to particular treatment groups or explain their timing, severity, or relationship to study drug. Death counts are not reported in the registry record.
Other adverse events are reported as 1 affected participant among 6 at risk for Regimen 1, 6 among 9 for Regimen 2, and 0 among 5 for placebo. These counts should be read separately from the serious adverse-event counts. The registry record does not provide event-level context, exposure-adjusted rates, or a detailed account of how adverse events were collected. Small group counts also make descriptive differences difficult to interpret, and no causal conclusion should be drawn from these figures alone.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, double-blind Phase 2 study was designed to assess safety and the hepatic hemodynamic response to intravenous conivaptan in stable euvolemic or hypervolemic patients with cirrhosis. It identifies two conivaptan regimens, a placebo comparator, and change from baseline in HVPG at 0.5, 1, and 1.5 hours post dose as the primary endpoint. It also defines the primary analysis population.
Those details explain what the investigators intended to measure, but they do not show the observed primary outcome. Numerical HVPG results, estimates comparing regimens, confidence intervals, and p-values are not reported in the registry record. The record therefore does not support a conclusion about the direction, magnitude, or precision of any primary-outcome difference. Missing numerical results should not be interpreted as evidence that there was no effect.
The reported adverse-event counts offer a limited descriptive account of safety events in the groups. They are not a substitute for a complete safety analysis, and they do not establish that an event was caused by study drug. The listed serious-event terms are accompanied by percentages, but the registry record does not provide enough context to interpret those terms by regimen or assess their clinical course.
The study’s scope is also bounded by its recorded population, regimens, endpoint, and short post-dose HVPG assessment schedule. The registry record does not report findings beyond those specified assessment times or establish how results apply to populations outside the study description. In general, a treatment effect estimate is most informative when accompanied by uncertainty and complete analysis details; those elements are not reported in the registry record.
13. Why This Trial Matters Statistically
This study raises useful statistical questions because it combines randomization, multiple active regimens, a placebo group, and repeated measurements of a continuous hemodynamic endpoint. Its design illustrates the difference between specifying a clinically relevant measurement and reporting enough information to evaluate the resulting treatment comparisons. The registry record defines the endpoint and its timing, but does not report the numerical estimates or uncertainty needed to interpret the primary outcome.
The Full Analysis Set definition is another important detail. It makes explicit that primary endpoint inclusion depended on randomization, receipt of at least one dose, and baseline HVPG data. To understand the consequences of that definition, readers would also need participant counts and explanations for missing data or exclusions. Those details are not reported in the registry record.
Repeated measurements can offer a view of how an outcome changes over time, but they require clear planning about the comparisons of interest and how to handle correlated observations and multiple testing. This study’s primary endpoint has multiple post-dose time points, while serum sodium is also listed as a secondary outcome at several times. The registry record does not report the analysis strategy for these repeated outcomes or how multiplicity was addressed.
For clinical researchers and statisticians, the record therefore serves as a reminder that design labels alone do not determine the strength of evidence. Randomization and masking are useful safeguards, but interpretation also depends on transparent outcome reporting, analysis methods, participant flow, and precision. These elements are not fully reported in the registry record, so the available information supports a description of the study design and endpoint rather than a quantitative conclusion about the primary treatment effect.
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.
Primary-outcome reporting is the central limitation for interpreting this study. The registry record names the endpoint and measurement schedule but does not report group-specific HVPG means, standard deviations, treatment contrasts, confidence intervals, or p-values. Without those results, neither the observed effect nor its precision can be assessed.
Enrollment was 20, and the registry record does not report the number randomized to each regimen or the group-specific counts included in the Full Analysis Set. It also does not report participant flow, the number with missing measurements, reasons for missingness, or the methods used to handle missing data. These omissions limit assessment of how much information contributed to each group’s endpoint estimate.
The record does not describe the primary statistical test or model, the prespecified comparison of interest, a multiplicity strategy, or an interim-analysis plan. It does not report a sample-size justification. These analysis and design details are not reported in the registry record, so it is not possible to assess whether the chosen approach was aligned with the repeated time points and multiple regimens.
The endpoint follow-up described for HVPG covers 0.5, 1, and 1.5 hours post dose. The record does not report later HVPG measurements or provide evidence about outcomes outside this assessment schedule. Safety reporting is also limited: event-level context and death counts are not reported in the registry record. These limitations constrain both the statistical and clinical interpretation of the posted information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Assess the Safety and Effects of Intravenous (IV) Conivaptan on the Hepatic Hemodynamic Response in Cirrhotic Patients — NCT00592475.
- Registry record last updated 2014-05-15; status last verified 2014-04.
- Results first posted 2010-09-28.
- 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 registry record describes NCT00592475, a completed Phase 2 randomized, double-blind, placebo-controlled, parallel study sponsored by Cumberland Pharmaceuticals. It enrolled 20 patients with cirrhosis and compared two intravenous conivaptan regimens with placebo. The study aimed to evaluate safety and characterize hepatic hemodynamic response in stable euvolemic or hypervolemic patients.
The primary endpoint was change from baseline in HVPG at 0.5, 1, and 1.5 hours post dose, summarized as a mean with standard deviation. The primary analysis population was defined as randomized participants who received at least one dose and had baseline HVPG data. Serum sodium was listed as a secondary outcome.
Numerical primary-outcome results and the statistical analysis methods are not reported in the registry record. The record includes descriptive adverse-event counts by regimen, but does not provide enough context for causal interpretation.