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 Study to Assess Safety and Efficacy of Ifetroban for Treatment of Portal Hypertension in Cirrhotic Patients (NCT02802228), a randomized phase 2 study. The primary outcome is Safety (Incidence and Severity of Adverse Events).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02802228 |
| Phase | Phase 2 |
| Condition | Portal Hypertension, Liver Cirrhosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 30 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Cumberland Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Cirrhotic patients with portal hypertension. The registry record does not report further eligibility details or a specific description of the analysis population.
Intervention
A 90-day course of oral ifetroban following an intravenous loading dose.
Comparator
A 90-day course of placebo following an intravenous dose of 5% dextrose in water (D5W).
Primary question
What number of adverse events, and what incidence and severity of adverse events, were reported in each treatment group through 97 days, comprising 90 days of treatment and 7 days of follow-up?
The study also posted outcome measures relating to hepatic venous pressure gradient (HVPG), liver enzymes, the aspartate aminotransferase/platelet ratio (APRI), and occurrence of variceal bleeds. The main registry endpoint, however, concerns safety: it counts adverse events during treatment and follow-up. That is distinct from asking whether the intervention changed portal pressure or another measure of liver-related status.
The registry describes this as a randomized, double-blind, placebo-controlled pilot study. Its stated purpose was to assess safety and efficacy. The posted record gives group-level results for the primary safety measure and three secondary outcomes. It does not report analysis results for every listed secondary outcome, nor does it provide a reported statistical analysis of the primary count as a two-arm comparison. The clinical question can therefore be framed from the recorded design and outcomes, while the strength and scope of any comparative conclusion remain limited by what the record reports.
3. Trial Design
This was a phase 2, randomized, double-blind, parallel-group, placebo-controlled pilot study. The registry reports 30 participants enrolled: 20 in the ifetroban group and 10 in the placebo group. The study is marked completed. Its recorded start date is 2017-03-06, and its primary completion date is 2018-07-17. The registry identifies Cumberland Pharmaceuticals as the sponsor.
The ifetroban group received a 90-day course of oral ifetroban after an intravenous loading dose. The placebo group received a 90-day course of placebo after an intravenous dose of 5% dextrose in water (D5W). Double masking means that the study record describes the trial as blinded to two parties, but it does not specify in the registry record which individuals were masked or how masking was maintained.
The primary outcome is the number of adverse events, assessed through 97 days, covering the treatment period and a 7-day follow-up. Secondary outcomes listed in the record include change in HVPG, change in AST, ALT, APRI, and occurrence of variceal bleeds. Posted numerical summaries are available for HVPG, AST, and ALT. Numerical results for APRI and variceal bleeds are not reported in the registry record.
The registry calls the study a pilot but does not report a sample-size justification, the intended allocation ratio, or a detailed statistical analysis plan. The posted group sizes should therefore be treated as the enrolled group sizes, not as evidence of the rationale for choosing them. The trial’s small overall enrollment and pilot designation are important context for interpreting estimates, uncertainty, and the scope of the conclusions that can be drawn from the posted results.
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 | Ifetroban | Placebo |
|---|---|---|
| STARTED | 20 | 10 |
| COMPLETED | 15 | 10 |
| NOT COMPLETED | 5 | 0 |
Reasons for not completing this period:
| Reason | Ifetroban | Placebo |
|---|---|---|
| Withdrawal by Subject | 2 | 0 |
| Lost to Follow-up | 1 | 0 |
| Adverse Event | 1 | 0 |
| Physician Decision | 1 | 0 |
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 | Ifetroban | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 20 | 10 | 30 | |
| Age, Continuous | years | 53.8 (SD 8.1) | 58.2 (SD 9.1) | 55.2 (SD 8.6) |
| Sex: Female, Male: Female | Participants | 15 | 8 | 23 |
| Sex: Female, Male: Male | Participants | 5 | 2 | 7 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 | 1 | 3 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 18 | 9 | 27 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 20 | 10 | 30 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Primary Cirrhosis Etiology: Hepatitis B only | Participants | 0 | 0 | 0 |
| Primary Cirrhosis Etiology: Hepatitis C only | Participants | 2 | 3 | 5 |
| Primary Cirrhosis Etiology: Hepatitis B and C | Participants | 1 | 0 | 1 |
| Primary Cirrhosis Etiology: Non-alcoholic Steatohepatitis | Participants | 8 | 3 | 11 |
| Primary Cirrhosis Etiology: Alcoholic | Participants | 4 | 4 | 8 |
| Primary Cirrhosis Etiology: Auto-immune | Participants | 3 | 0 | 3 |
| Primary Cirrhosis Etiology: Cryptogenic | Participants | 2 | 0 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Safety (Incidence and Severity of Adverse Events), measured over Through 97 days (90 days treatment and 7 days follow-up).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Number of adverse events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the total number of adverse events reported in each treatment group through 97 days: 90 days of treatment and 7 days of follow-up. The record describes incidence as measured by the total number of adverse events reported for each group. This is a count of events, not necessarily a count of participants who experienced at least one event. One participant could contribute more than one event, so event totals should not be read as participant totals.
Adverse-event monitoring is used to describe the safety experience observed during a study. Recording both incidence and severity can help characterize the types and frequency of events in the groups over the stated observation period. Here, however, the posted primary outcome is expressed as a total count, and the registry does not post a two-arm comparative analysis for that count. The counts alone do not establish how events were distributed across individuals, their timing, or their relationship to treatment.
The primary endpoint is safety-focused; it is not a direct measure of portal pressure or clinical benefit. HVPG and the other listed outcomes address different aspects of the study question. Keeping these endpoints distinct matters: a count of adverse events answers a different statistical and clinical question from a comparison of changes in a continuous measure such as HVPG.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports 23 adverse events in the ifetroban group of 20 participants and 2 in the placebo group of 10 participants. These are total event counts. They do not tell how many participants experienced any event, how many events occurred in each person, or whether events were judged related to study treatment. The record also reports serious adverse events affecting 2 of 20 participants in the ifetroban group and 1 of 10 in the placebo group. Deaths were reported as 0 in each group.
The primary outcome is not accompanied by a reported two-arm statistical comparison. The record indicates that a comparison was not estimable or was unavailable for this count endpoint. Consequently, the event totals should be read descriptively rather than as a quantified treatment-group effect. No confidence interval or inferential p-value for the primary count comparison is reported in the registry record.
For the secondary outcomes with numerical results, the mean change in HVPG was 1.6 mmHg in the ifetroban group and -0.1 mmHg in the placebo group. The posted unadjusted mean difference was 1.7 mmHg, with a confidence interval that includes zero; the unadjusted p-value was 0.185. For AST, mean changes were -1.2 U/L and 4.2 U/L, respectively. The posted unadjusted mean difference was -5.4 U/L, with a confidence interval that includes zero; the unadjusted p-value was 0.244. For ALT, mean changes were -4.8 U/L and 2.2 U/L. The posted unadjusted mean difference was -7.0 U/L, and its confidence interval does not include zero; the unadjusted p-value was 0.039.
These secondary estimates are based on outcome-specific groups of 15 and 10 for HVPG, and 17 and 10 for AST and ALT. They are not reported analyses in the registry record. The confidence intervals and p-values are unadjusted, and the record does not report a multiplicity procedure. The ALT result should therefore be understood as one unadjusted finding among several listed outcomes, not as a stand-alone confirmatory conclusion. None of these secondary summaries changes the fact that the primary outcome is a safety-event count without a posted inferential comparison.
9. Statistical Methods Explained
What does a group mean describe?
For the continuous secondary outcomes, the registry reports mean changes from baseline to 90 days and a standard deviation for each group. A mean is a summary of the observed changes across participants with a reported value. It can describe the group’s average direction and size of change, but it does not show the full distribution of individual results. The standard deviation describes how dispersed the observed values are around the group mean. A larger standard deviation indicates more variation among participants; it is not the same as the uncertainty in the estimated mean.
The number of participants contributing to a result is relevant to interpreting its precision. The posted sample sizes differ across outcomes: HVPG uses 15 participants in the ifetroban group and 10 in placebo, while AST and ALT use 17 and 10. These outcome-specific counts are smaller than the total enrollment in at least one group. The registry record does not report why the available numbers differ, so the reason for the missing measurements cannot be inferred.
How should a mean difference and confidence interval be read?
A mean difference compares the group averages, with the direction depending on which group is subtracted from which. The posted comparisons are framed as ifetroban relative to placebo. A confidence interval gives a range of values compatible with the data under the analysis assumptions; it communicates uncertainty around the estimated difference. An interval that includes zero is compatible with no mean difference, as well as with differences in either direction. An interval that does not include zero indicates that zero is outside that interval, but it does not by itself establish clinical importance or resolve concerns about multiple comparisons, study size, or analysis choices.
The registry’s unadjusted p-value measures how unusual the observed data, or more extreme data, would be under a specified null model. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of a difference. The listed p-values are unadjusted. The registry record does not report whether any adjustment or prespecified hierarchy was used for the secondary outcomes, so they should not be treated as multiplicity-adjusted evidence.
Why does the event-count endpoint need different treatment?
The primary endpoint is a count of adverse events, whereas the posted secondary comparisons concern continuous measurements summarized by means and standard deviations. Event counts can be unevenly distributed, and a participant may contribute multiple events. A comparison based only on group totals does not account for how those events are clustered among participants. Statistical methods for count outcomes may also need to account for over-dispersion: in general, over-dispersion occurs when variability is greater than a chosen count model expects, which can make standard errors and inferences unreliable if ignored. The registry record does not report a count-model analysis or sufficient event-level information to assess these features.
The primary count totals are not accompanied by a reported inferential comparison. The registry indicates that values were missing or not estimable for a two-arm comparison. Therefore, no comparative confidence interval or p-value for the primary endpoint should be inferred from the group counts alone.
What do the planning illustrations mean?
The planning illustrations are based on the observed effects and are not the trial’s original design justification. They give participants per arm for stated power levels under assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect. For HVPG and AST, planning for 100% of the observed effect gives 61 participants per arm for 80% power and 82 for 90% power; planning for 75% gives 109 and 145; planning for 50% gives 244 and 326. For ALT, the corresponding figures are 21 and 28, 37 and 50, and 84 and 112.
These are planning illustrations, not observed power, and they are not proof that the study was designed around those effects. They depend on the assumptions stated in the registry record and on effects estimated from this small study. Because observed effects are uncertain, the illustrations should not be treated as precise sample-size recommendations or as a retrospective measure of the probability that the trial detected a true effect.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several secondary outcomes in addition to the primary safety endpoint. It posts numerical comparisons for HVPG, AST, and ALT, but does not report numerical results for APRI or variceal bleeds. The record does not report a multiplicity adjustment, a testing hierarchy, or which outcomes, if any, were designated as confirmatory. Without that information, the unadjusted secondary p-values should be interpreted cautiously. In general, testing multiple outcomes without adjustment can make an isolated low p-value less persuasive than a result from a single prespecified analysis.
The registry does not report a detailed missing-data method, an imputation approach, or reasons why outcome-specific participant counts vary. For example, the reported numbers contributing to HVPG, AST, and ALT are not identical. This difference may reflect incomplete measurements or other analysis-population decisions, but the record does not say which. It is not possible to determine from the posted summaries whether missingness could have affected the group comparisons.
The record also does not report a detailed definition of the analysis population used for each outcome, such as whether analyses followed all randomized participants or another specified group. Although enrollment and group sizes are reported, those details alone do not establish the analysis population. The registry does not report methods for handling protocol deviations or withdrawals.
For the primary safety outcome, the registry posts event totals but no two-arm inferential comparison. The record does not report a statistical model, uncertainty estimate, or analysis population definition for that count comparison. These omissions limit the ability to assess comparative precision or to determine how repeated events within participants were handled. The missing information should not be filled in by assuming a conventional approach.
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 |
|---|---|---|---|
| Ifetroban | 2 | 20 | 10.0% |
| Placebo | 1 | 10 | 10.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Ifetroban | 0 of 20 |
| 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 |
|---|---|
| Ifetroban | 10 of 20 |
| Placebo | 1 of 10 |
Most frequent serious adverse event terms
| Event term | Organ system | Ifetroban | Placebo |
|---|---|---|---|
| Ascites | Hepatobiliary disorders | 1 of 20 | 0 of 10 |
| oesophageal varices haemorrhage | Hepatobiliary disorders | 0 of 20 | 1 of 10 |
| Non-cardiac chest pain | Respiratory, thoracic and mediastinal disorders | 1 of 20 | 0 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ifetroban | Placebo |
|---|---|---|---|
| Eccymosis | Blood and lymphatic system disorders | 1 of 20 | 1 of 10 |
| Petechiae | Blood and lymphatic system disorders | 1 of 20 | 1 of 10 |
| Anaemia | Blood and lymphatic system disorders | 1 of 20 | 0 of 10 |
| Dental discomfort | Gastrointestinal disorders | 1 of 20 | 0 of 10 |
| Diarrhoea | Gastrointestinal disorders | 1 of 20 | 0 of 10 |
| Nausea | Gastrointestinal disorders | 1 of 20 | 0 of 10 |
| Peripheral swelling | General disorders | 1 of 20 | 0 of 10 |
| Subacute cutaneous lupus erythematosus | Immune system disorders | 1 of 20 | 0 of 10 |
| Procedural pain | Injury, poisoning and procedural complications | 1 of 20 | 0 of 10 |
| Thromboelastogram | Investigations | 1 of 20 | 0 of 10 |
Serious events with the highest arm-level rate: oesophageal varices haemorrhage (10.0%), ascites (5.0%), non-cardiac chest pain (5.0%).
The registry reports serious adverse events affecting 2 of 20 participants in the ifetroban group and 1 of 10 in the placebo group. It reports no deaths in either group. These are participant counts for serious adverse events, distinct from the primary endpoint’s total number of adverse events. The record also reports other adverse events affecting 10 of 20 participants in the ifetroban group and 1 of 10 in the placebo group.
The listed serious-event terms are oesophageal varices haemorrhage (10.0%), ascites (5.0%), and non-cardiac chest pain (5.0%). These terms and percentages do not provide a complete account of event timing, recurrence, severity grading, or relatedness to treatment. The registry record does not provide those details in the stated results.
Group counts in a small pilot study are descriptive and can be imprecise. The serious-event figures do not come with a reported comparative statistical analysis, and event counts can differ from counts of affected participants because individuals may have more than one event. They should be read as the safety experience recorded during the study, not as a definitive estimate of comparative risk.
12. What the Result Does, and Does Not, Mean
The posted results describe a completed pilot study with 30 enrolled participants and group-level summaries for a safety endpoint and several secondary measures. They show the numbers of adverse events recorded in each group, the number of participants with serious and other adverse events, and the mean changes for three secondary outcomes. They also show uncertainty around the posted continuous-outcome comparisons, with differing interval results across those measures.
These data do not establish a definitive comparative safety effect. The primary endpoint is a total event count, and the registry record does not report an inferential two-arm comparison for it. The counts do not show the full distribution of events across participants or their relationship to treatment. Likewise, the serious-event counts are descriptive and are not accompanied by a comparative estimate or uncertainty interval.
The secondary outcome results are also limited in what they can establish. The registry reports unadjusted comparisons for three outcomes, while two other listed outcomes lack numerical results. The record does not report a multiplicity strategy or a detailed missing-data and analysis-population plan. In that context, an individual secondary p-value should not be interpreted as a definitive finding, and a lack of a result for an outcome should not be taken as evidence that no change occurred.
More generally, an observed difference is not automatically clinically important, and a statistical result does not by itself establish causation or benefit. The study’s pilot designation, modest enrollment, and outcome-specific participant counts are relevant when considering precision and generalizability. The record is informative about what was observed and posted, but it does not answer every question about analysis methods, missing data, or the clinical significance of the results.
13. Why This Trial Matters Statistically
This trial is statistically instructive because its primary endpoint is a count of events, while several secondary outcomes are continuous measures. These require different summaries and potentially different analysis methods. A mean difference and its confidence interval can describe changes in continuous outcomes, but they cannot simply be substituted for an analysis of event counts. The primary event totals, without a reported comparative estimate, illustrate why a group-level count alone may be insufficient for judging the precision of a treatment contrast.
The study also shows why outcome-specific sample sizes matter. The posted numbers contributing to the continuous outcomes vary, which affects precision and raises questions about missing measurements and analysis populations. The registry does not explain these differences. Transparent reporting of participant flow and missing-data methods would help readers assess how representative the available observations may be.
Another statistical lesson concerns multiple outcomes. Several measures are listed, but the record does not describe a hierarchy or multiplicity adjustment. An isolated unadjusted secondary result therefore needs to be interpreted in relation to the broader outcome set and the uncertainty around the estimates, rather than treated as conclusive on its own.
Finally, the planning illustrations are explicitly based on observed effects and stated assumptions, not on the study’s original design. They can help illustrate how required sample sizes depend on the effect one aims to detect, but they are not observed power and do not recover the trial’s design rationale. The registry record does not report that rationale. Keeping these distinctions clear helps separate descriptive results, exploratory comparisons, and prospective planning.
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.
Several limitations are specific to the posted record. The primary safety outcome is reported as total adverse-event counts, but the registry does not provide a comparative estimate, confidence interval, or p-value. Counts alone do not reveal how events were distributed among participants, whether the same participant had recurrent events, or how events were related to treatment.
For the secondary outcomes, numerical comparisons are available only for HVPG, AST, and ALT. APRI and variceal-bleed results are not reported in the registry record. The contributing sample sizes also vary by outcome, and the registry does not explain the differences or specify how missing observations were handled. This makes it difficult to judge whether the posted groups are comparable for every outcome.
The record does not report a detailed analysis plan, analysis-population definitions, a multiplicity strategy, or a sample-size justification. It also does not provide detailed information on event timing, repeated adverse events, or the attribution of events to treatment. These gaps limit interpretation of both the safety counts and unadjusted secondary comparisons.
Enrollment was 30 in a study identified as a pilot, so estimates may be imprecise and may not represent results in broader populations. The registry record identifies the participants as cirrhotic patients with portal hypertension but does not report further eligibility characteristics in the registry entries. Generalizability beyond the recorded study population therefore cannot be assessed in detail.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Assess Safety and Efficacy of Ifetroban for Treatment of Portal Hypertension in Cirrhotic Patients — NCT02802228.
- Registry record last updated 2022-01-19; status last verified 2021-01.
- Results first posted 2022-01-19.
- 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
NCT02802228 is a completed phase 2, randomized, double-blind, parallel-group, placebo-controlled pilot study sponsored by Cumberland Pharmaceuticals. It enrolled 30 participants, with 20 assigned to ifetroban and 10 to placebo. The recorded study dates are 2017-03-06 for start and 2018-07-17 for primary completion.
The primary outcome was the number of adverse events through 97 days. The registry reports 23 events in the ifetroban group and 2 in placebo, but no inferential two-arm comparison for this count. It also reports serious adverse events affecting 2 of 20 and 1 of 10 participants, respectively, and no deaths in either group.
Numerical secondary summaries are posted for HVPG, AST, and ALT; results for APRI and variceal bleeds are not reported in the registry record. The posted continuous-outcome comparisons are unadjusted, and the registry does not report a detailed multiplicity, missing-data, or analysis-population plan.