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 Efficacy of Treprostinil to Facilitate Liver Transplantation in Patients With Portopulmonary Hypertension (NCT01028651), a registered phase not stated study. The primary outcome is Number of Subjects Who Achieved Hemodynamic Parameters Appropriate for Orthotopic Liver Transplantation Candidacy at Week 24..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01028651 |
| Phase | Phase not stated |
| Condition | Portopulmonary Hypertension, Pulmonary Arterial Hypertension, Pulmonary Hypertension |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 13 |
| Arms in the primary outcome | n/a |
| Lead sponsor | United Therapeutics |
| Results posted | Yes |
2. Clinical Question
Population
Patients with portopulmonary hypertension were enrolled. The primary endpoint description focuses on patients with severe portopulmonary hypertension. The registry record states that the primary population was the total number of subjects enrolled and analyzed.
Intervention
Treprostinil was the drug intervention. Treatment was administered as recommended by treating physicians, and patients were followed according to standard of care.
Comparator
No like-for-like control comparison is reported. The study is described as observational and open-label, and allocation is not stated.
Primary question
At Week 24, how many patients with severe portopulmonary hypertension achieved both a mean pulmonary arterial pressure (mPAP) < 35 mmHg and a pulmonary vascular resistance (PVR) < 3 Wood units (WU)?
The question concerns whether patients reached a pair of hemodynamic thresholds described as appropriate for orthotopic liver transplantation candidacy. Both thresholds are part of the endpoint: reaching only one would not meet the stated definition. The registry record describes collection of clinical data and biologic specimens while patients received treatment in clinical care. It does not report a control group against which to compare the endpoint, nor does it report the number of patients who met the thresholds. The study therefore addresses an observed outcome among treated patients, rather than a randomized comparison of treatment strategies.
3. Trial Design
The registry record describes a multicenter, prospective, observational, open-label study of treprostinil in patients treated for portopulmonary hypertension. Patients who met the study’s inclusion and exclusion criteria received treatment as recommended by their treating physicians and were followed according to standard of care. The study collected clinical data and biologic specimens. Enrollment was 13. The record lists United Therapeutics as sponsor and gives the status as completed, with a start in 2011-01 and primary completion in 2013-04.
The study’s stated goal was to achieve hemodynamic parameters appropriate for orthotopic liver transplantation candidacy. For the primary endpoint in patients with severe portopulmonary hypertension, those parameters were mPAP < 35 mmHg and PVR < 3 WU at Week 24. The intervention listing names treprostinil. The record does not describe a like-for-like control arm, and allocation is not stated. Consequently, the design does not provide a randomized treatment-versus-control estimate.
Other planned outcome areas include changes in hemodynamic measures assessed by right heart catheterization, resting heart rate, cardiac output, arterial and venous oxygen saturation, PVR, six-minute walk distance, and echocardiographic measures of right atrial and right ventricular size. The listed follow-up times for these outcomes include Weeks 12 and 24, with some measures specified at Week 24. The registry lists 13 outcome measures, but it does not report analysis entries. The specific analysis methods, handling of missing measurements, and details of the study’s statistical plan 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 | Treprostinil Injection |
|---|---|
| STARTED | 13 |
| COMPLETED | 10 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Treprostinil Injection |
|---|---|
| Death | 2 |
| Adverse Event | 1 |
Analysis population for the primary outcome, as defined in the registry: The total number of subjects enrolled and analyzed.
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 | Treprostinil Injection |
|---|---|---|
| Participants analysed | 13 | |
| Age, Continuous | Years | 55.8 (SD 8.00) |
| Gender: Female | Participants | 8 |
| Gender: Male | Participants | 5 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 5 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 8 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 13 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | Participants | 13 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Subjects Who Achieved Hemodynamic Parameters Appropriate for Orthotopic Liver Transplantation Candidacy at Week 24., measured over 24 Weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of subjects who achieved the hemodynamic parameters specified for orthotopic liver transplantation candidacy at Week 24. The definition requires both mPAP < 35 mmHg and PVR < 3 WU, among patients with severe portopulmonary hypertension. It is a count endpoint: it records how many patients met the joint threshold definition, rather than the average value of either measurement.
Using a threshold-based endpoint can make the clinical target explicit. A count can describe how many patients crossed the stated criteria, while continuous measurements such as mPAP and PVR retain information about the size and direction of changes. Those are different summaries: a patient’s measurement may change without crossing a threshold, and the count does not show how close patients were to either threshold. These are general properties of threshold and continuous outcomes.
The registry record states the endpoint definition and its Week 24 timeframe, but does not report the observed count or the number assessed at that time. It therefore does not show how many patients met the joint criteria, nor does it provide a numerical estimate of uncertainty around that count. A result for this endpoint is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record defines a clinically oriented, binary endpoint: patients either meet both stated hemodynamic thresholds at Week 24 or do not. However, it does not report the number who achieved the endpoint. Without that result, the endpoint cannot be quantified from the registry record, and no estimate of its precision can be described. The absence of a reported result is not evidence that no patients met the criteria; it means the outcome is not reported in the registry record.
Enrollment was 13, and the primary population is described as the total number of subjects enrolled and analyzed. The record does not provide the number with Week 24 measurements, the number included in the endpoint calculation, or the number missing an assessment. Those details matter because an endpoint count depends on who was observed and how unavailable measurements were handled. The analysis population and missing-data approach are not reported in the registry record.
The observational, open-label design also shapes what the data could establish. Treatment was recommended by treating physicians, and follow-up was according to standard of care. With no reported like-for-like control comparison, a result among treated patients would describe their observed outcomes, not isolate the effect of treprostinil from other influences. General statistical reasoning: changes over time in an observational study can reflect the treatment context, patient characteristics, concurrent care, measurement variation, or other factors. The design does not by itself distinguish among these explanations.
The endpoint combines two measurements. Meeting the definition requires both mPAP and PVR to be below their respective thresholds; a summary of the count alone would not show the distribution of either measure or how close participants were to the cutoffs. The registry also lists secondary outcome areas, including hemodynamic measures, walking distance, and echocardiographic parameters, but it does not report their results in the record.
Serious adverse-event information is reported separately: 8 of 13 participants were affected by serious events, and 13 of 13 were affected by other adverse events. These figures describe safety reporting in the treated group. They do not provide a control-group comparison or establish that an event was caused by treprostinil. The registry record gives serious-event terms and percentages, but does not report a numerical primary efficacy result or an inferential analysis. Accordingly, the available record supports a description of the study design and reported safety counts, but not a numerical conclusion about the primary endpoint.
9. Statistical Methods Explained
The primary endpoint is a count of participants who meet a joint threshold definition. In general, a binary endpoint reduces each participant’s outcome to whether the specified condition was met. That can be straightforward to interpret, but it discards detail about the underlying measurements. For this study, the criteria combine mPAP and PVR at Week 24. Both conditions must be satisfied for a participant to count as having achieved the endpoint.
The registry record does not report the endpoint count, the number assessed at Week 24, or an analysis of the endpoint. It also does not report a confidence interval or a hypothesis test for the primary outcome. A confidence interval is a statistical range intended to express uncertainty around an estimate, under specified assumptions. General explanation: with a small study population, estimates can be imprecise, and uncertainty depends on the observed data and the method used. No interval can be described for this endpoint without a reported result and analysis population.
For a count endpoint, the analysis plan could specify a proportion or another summary, along with a method for estimating uncertainty. That is a general description, not a claim about this study’s analysis. The registry record does not state whether the primary endpoint was analyzed as a count, a proportion, or another measure beyond its stated outcome unit of participants. It does not state a statistical test, confidence-interval method, covariate adjustment, or criterion for statistical significance. These analysis details are not reported in the registry record.
The endpoint also depends on the measurement process. mPAP and PVR are specified as hemodynamic parameters, and the study lists right heart catheterization among the methods for assessing hemodynamic outcomes. The primary endpoint description does not state how measurements were summarized, whether any repeated measurements were used, or what rules applied when one component was unavailable. General explanation: when a composite definition requires multiple measurements, missing information for any required component can affect whether the participant can be classified. The handling rule should be explicit to understand the resulting count; it is not reported in the registry record.
The study is described as prospective and observational, not as a randomized comparison. An observational analysis can describe outcomes in the patients who received treatment, but it cannot on its own attribute those outcomes to treatment. Randomization, when used, aims to balance measured and unmeasured factors between groups; that design feature is not described. General explanation: without a comparable control group, before-and-after observations can be influenced by factors other than the intervention, including differences in patient condition, concurrent care, and natural variation. No adjusted treatment-effect estimate is reported in the registry record.
The registry lists secondary outcome measures involving hemodynamics, heart rate, cardiac output, oxygen saturation, PVR, six-minute walk distance, and echocardiographic parameters. Multiple outcomes can raise multiplicity concerns when many statistical tests are conducted, because the chance of at least one apparently notable result can increase. General explanation: a statistical plan may address this through a prespecified outcome hierarchy or another adjustment method. The registry record does not report whether any multiplicity procedure was planned or used. It lists 13 outcome measures and 0 analysis entries.
Sample-size planning is distinct from analysis of observed trial data. The stated planning illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. The assumptions describe an illustration, not the study’s own design. The record does not provide numerical planning outputs in the information reported, and no trial-specific sample-size justification is reported. Such planning quantities, when presented, are not observed power and do not show what the study found.
The equal-allocation, two-arm assumptions do not match the described observational design with no reported like-for-like control comparison. They therefore should not be read as evidence that the trial enrolled randomized arms or used those assumptions in its protocol. General explanation: sample-size calculations depend on the design, endpoint, target effect, variability or event rate, and analysis method. If those assumptions differ from the actual study, the resulting illustration may not characterize the study’s ability to estimate its outcome. The study’s protocol assumptions and any planned interim analyses are not reported in the registry record.
Finally, the count of participants with serious adverse events is descriptive safety information. It is not an efficacy test and does not supply a comparative risk estimate. General explanation: safety summaries can describe how many participants were affected and which event terms were recorded, but interpretation also depends on event definitions, follow-up, attribution, and the completeness of reporting. The registry record provides participant counts at risk and affected, along with selected serious-event terms and percentages, but does not report a causal analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 13 outcome measures, including the primary endpoint and secondary measures covering hemodynamics, functional capacity, and echocardiographic parameters. When investigators assess multiple outcomes, multiplicity can arise if several tests are used to draw inferential conclusions. General explanation: the more tests conducted, the greater the possibility of at least one apparently notable result by chance, depending on the testing strategy. A prespecified hierarchy or adjustment can address that issue, but no multiplicity approach is reported in the registry record.
The record lists 0 analysis entries. It does not report which outcomes were tested, whether tests were prespecified, whether any adjustment was applied, or how the primary endpoint was prioritized in statistical inference. Those details are not reported in the registry record and should not be inferred from the list of outcomes alone.
Missing-data handling is also not reported. The record does not give the number of participants assessed at Week 24, the number with unavailable measurements, reasons for missing assessments, or rules for classifying participants whose mPAP or PVR data were incomplete. General explanation: missing outcomes can affect both the analysis population and the interpretation of an endpoint, especially when the endpoint requires all components to determine success.
The primary population is described as the total number of subjects enrolled and analyzed, but the record does not give the number analyzed for the primary endpoint or state whether all enrolled participants contributed to that endpoint. It also does not describe any imputation, sensitivity analysis, or other missing-data method. The analysis population and missing-data procedures are therefore not reported in 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 |
|---|---|---|---|
| Treprostinil Injection | 8 | 13 | 61.5% |
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 |
|---|---|
| Treprostinil Injection | 13 of 13 |
Most frequent serious adverse event terms
| Event term | Organ system | Treprostinil Injection |
|---|---|---|
| Chronic hepatic failure | Hepatobiliary disorders | 2 of 13 |
| Pneumonia | Infections and infestations | 2 of 13 |
| Renal failure acute | Renal and urinary disorders | 2 of 13 |
| Anaemia macrocytic | Blood and lymphatic system disorders | 1 of 13 |
| Death | General disorders | 1 of 13 |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 1 of 13 |
| Hepatic encephalopathy | Nervous system disorders | 1 of 13 |
| Hepatorenal syndrome | Hepatobiliary disorders | 1 of 13 |
| Hip fracture | Injury, poisoning and procedural complications | 1 of 13 |
| Hypotension | Vascular disorders | 1 of 13 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treprostinil Injection |
|---|---|---|
| Nausea | Gastrointestinal disorders | 10 of 13 |
| Headache | Nervous system disorders | 8 of 13 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 7 of 13 |
| Vomiting | Gastrointestinal disorders | 7 of 13 |
| Pain in jaw | Musculoskeletal and connective tissue disorders | 6 of 13 |
| Infusion site pain | General disorders | 5 of 13 |
| Decreased appetite | Metabolism and nutrition disorders | 4 of 13 |
| Diarrhoea | Gastrointestinal disorders | 4 of 13 |
| Urinary tract infection | Infections and infestations | 3 of 13 |
| Infusion site infection | Infections and infestations | 3 of 13 |
Serious events with the highest arm-level rate: chronic hepatic failure (15.4%), pneumonia (15.4%), renal failure acute (15.4%), anaemia macrocytic (7.7%), death (7.7%).
The safety summary lists 13 participants at risk for serious adverse events and 8 affected. For other adverse events, it lists 13 at risk and 13 affected. These are counts of participants, not counts of individual event episodes. A participant may have experienced more than one event, so participant counts should not be interpreted as the total number of events.
The registry lists selected serious-event terms with percentages: chronic hepatic failure, pneumonia, and acute renal failure are each reported as 15.4%; macrocytic anaemia, death, and gastrointestinal haemorrhage are each reported as 7.7%. These are the terms and percentages recorded; the registry information does not give event counts for each term. The death count is not reported in the registry record.
General explanation: an adverse event recorded during a study is not necessarily caused by the intervention. The listed safety figures describe events observed among participants receiving treprostinil in an open-label observational study. There is no reported like-for-like control group for comparing event frequencies, and the registry record does not provide a causal attribution analysis. The figures should therefore be read as descriptive safety reporting, not as an estimate of treatment-attributable risk.
12. What the Result Does, and Does Not, Mean
The registry record describes an observational study of treprostinil in patients with portopulmonary hypertension and defines a Week 24 endpoint based on two hemodynamic thresholds. It also reports enrollment and selected safety counts. These registry entries describe the study’s purpose and some aspects of its conduct, but the record does not report the number of patients who achieved the primary endpoint.
That missing endpoint result limits what can be concluded about the stated transplant-candidacy target. The record does not show how many patients met both thresholds, how many had measurements available, or how precise an estimate would be. The endpoint result is not reported in the registry record; that should not be interpreted as either success or failure.
The observational design is important when interpreting any treated-group outcome. Treatment followed treating physicians’ recommendations, and follow-up was according to standard of care. No like-for-like control comparison is reported. General explanation: outcomes observed in a treated group do not, by themselves, identify what would have happened to those same patients under a different treatment or without treatment. Differences over time may have multiple explanations, and an observational description cannot separate them without appropriate design and analysis.
The safety summary indicates that serious adverse events affected 8 of 13 participants, while other adverse events affected 13 of 13. The registry also lists serious-event terms and percentages. These observations do not establish causation, and they cannot be compared with a control group from the information reported. The record does not include the death count.
More generally, the study has a small enrollment and no reported analysis entries. The registry record does not report inferential methods, missing-data procedures, multiplicity handling, or a statistical analysis plan. Thus, the available information supports a description of the planned endpoint and recorded safety experience, but it does not support a numerical efficacy estimate or a comparative claim about treatment.
13. Why This Trial Matters Statistically
This study is statistically notable because its primary question is framed around a defined clinical target rather than a treatment-versus-control contrast. It asks how many patients reached both specified hemodynamic thresholds at Week 24. That framing makes the target explicit, while also requiring care in interpreting a count: the endpoint alone would not show the size of changes in mPAP or PVR, or how close participants were to either threshold.
The study also illustrates the distinction between prospective data collection and randomized treatment assignment. A prospective observational design can collect clinical measurements over time while care proceeds under treating physicians’ recommendations. It does not, by itself, create a control group that can support a like-for-like treatment comparison. General explanation: causal interpretation depends on design and assumptions as well as on the numerical result, so an observed outcome in treated patients is not automatically a treatment effect.
Enrollment was 13, making transparency about who was assessed and how uncertainty was handled especially relevant. Yet the registry record does not report the primary endpoint count, the number assessed at Week 24, or the statistical analysis details. It also lists multiple outcome areas without reporting an analysis plan or multiplicity approach. Those gaps make it difficult to assess precision or the role of secondary findings.
The safety information provides another useful statistical distinction: participant counts affected are not the same as counts of individual events, and observed adverse events are not necessarily attributable to treatment. The record reports serious-event and other-event participant counts, along with selected serious-event terms, but no control comparison. Overall, the study highlights how endpoint definition, design, precision, and transparent reporting jointly determine what a clinical trial record can establish.
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 registry record does not report the primary endpoint result, even though it defines the endpoint and its timeframe. It also does not report the number of participants assessed at Week 24 or the number contributing to the endpoint calculation. This prevents a direct description of the observed transplant-candidacy threshold count and its precision.
Enrollment was 13. The study is described as observational and open-label, with treatment recommended by treating physicians and follow-up according to standard of care. Allocation is not stated, and no like-for-like control comparison is reported. These design features limit comparative interpretation: outcomes among treated patients cannot, on their own, establish what difference treatment made relative to another strategy.
The record does not report the statistical analysis plan, endpoint analysis method, confidence interval, hypothesis test, missing-data handling, multiplicity procedure, or analysis population details beyond the statement that the primary population was the total number enrolled and analyzed. It also does not report protocol-specific sample-size justification or interim analyses. The planning assumptions described are illustrative and do not document the study’s own design.
The record lists secondary outcomes but does not report their results or analysis entries. The safety summary reports participant counts and selected serious-event terms, but does not report a death count or a causal attribution analysis. These limitations are specific to what the registry record reports; they do not establish that additional information was not collected outside the record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Assess the Safety and Efficacy of Treprostinil to Facilitate Liver Transplantation in Patients With Portopulmonary Hypertension — NCT01028651.
- Registry record last updated 2017-02-24; status last verified 2017-01.
- Results first posted 2017-02-24.
- 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
NCT01028651 is a completed, multicenter, prospective, observational, open-label study sponsored by United Therapeutics. Enrollment was 13. The record gives a start date of 2011-01 and primary completion in 2013-04. Patients with portopulmonary hypertension received treprostinil as recommended by treating physicians and were followed according to standard of care.
The primary endpoint was the number of patients with severe portopulmonary hypertension who achieved mPAP < 35 mmHg and PVR < 3 WU at Week 24. The result is not reported in the registry record. The record lists 13 outcome measures and 0 analysis entries. Serious adverse events affected 8 of 13 participants; other adverse events affected 13 of 13. No like-for-like control comparison is reported.