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 Safety, Tolerability, and Pharmacokinetics of Oral Treprostinil in Pediatric PAH Patients Aged 7 to 17 Years (NCT02276872), a non-randomized phase 2 study. The primary outcome is Number of Participants With Successful Transition From IV/SC Remodulin to Oral Treprostinil (Cohort 1), From Inhaled Prostacyclin to Oral Treprostinil (Cohort 2), or as an add-on to Current PAH Therapy in de Novo Prostacyclin Subjects (Cohort 3)..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02276872 |
| Phase | Phase 2 |
| Condition | PAH |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 32 |
| Arms in the primary outcome | n/a |
| Lead sponsor | United Therapeutics |
| Results posted | Yes |
2. Clinical Question
Population
Children and adolescents aged 7 to 17 years with pulmonary arterial hypertension (PAH). The study description identifies participants with stable PAH and includes three treatment pathways: transition from parenteral Remodulin, transition from inhaled prostacyclin, or initiation of oral treprostinil as an add-on to current PAH therapy for participants not currently receiving prostacyclin therapy.
Intervention
Oral treprostinil extended-release tablets. Participants either transitioned to oral treprostinil from a prior prostacyclin treatment or began oral treprostinil as a de novo add-on to current PAH therapy.
Comparator
There was no randomized control group. The study was non-randomized, open-label, and uncontrolled. The three cohorts represent different treatment pathways, not like-for-like comparator arms.
Primary question
How many participants met the registry’s definition of successful transition from IV/SC Remodulin or inhaled prostacyclin, or successful initiation as an add-on, through Week 24? The registry record defines these outcomes but does not report the number of participants who met them.
The question is therefore about successful use of oral treprostinil within each pathway, rather than a comparative estimate of treatment effect. For Cohorts 1 and 2, success required receiving oral treprostinil and no longer receiving the respective prior prostacyclin treatment at Week 4, followed by clinical maintenance on oral treprostinil through Week 24. Cohort 3 had a different definition: participants had to be clinically maintained on oral treprostinil through Week 24.
These definitions distinguish the pathways but do not make their outcomes directly interchangeable. The transition cohorts had a specified change from prior therapy at Week 4, while the add-on cohort was assessed on maintenance through Week 24. Because allocation was not randomized and there was no control group, the study cannot by itself estimate what would have happened to comparable participants under a different treatment strategy. The registry record also does not report a primary outcome count, so the observed extent of successful transition or initiation cannot be described from this record.
3. Trial Design
This was a phase 2, multicenter, open-label, uncontrolled study of oral treprostinil in pediatric participants with PAH. The registry record reports non-randomized allocation, no masking, and a parallel model. Enrollment was 32. The study started on 2014-12-18, reached primary completion on 2017-07-20, and is listed as completed.
Participants entered one of three treatment pathways. Cohort 1 transitioned from IV or SC Remodulin to oral treprostinil. Cohort 2 transitioned from inhaled prostacyclin to oral treprostinil. Cohort 3 received oral treprostinil as a de novo add-on to current PAH therapy. These pathways describe distinct clinical circumstances, not randomized treatment arms with a shared comparator. The adverse-event record lists 10 participants at risk in Cohort 1, 10 in Cohort 2, and 12 in Cohort 3.
The study was open-label, so masking was not used. The registry record does not report a blinding procedure, a control intervention, or a randomized allocation process; it explicitly identifies the study as uncontrolled and non-randomized. That design is suited to describing treatment experience in the enrolled cohorts, but it does not support a randomized comparison between oral treprostinil and another treatment.
The primary outcome timeframe was up to 24 weeks. For the two transition cohorts, the outcome definition included both a treatment-status condition at Week 4 and clinical maintenance through Week 24. For the add-on cohort, the definition concerned clinical maintenance through Week 24. Secondary outcomes included cardiopulmonary exercise measures, symptoms, functional class, six-minute walk distance, and Borg dyspnea score, each described as a change from baseline or over the study period. The registry lists 25 outcome measures overall, but does not report analysis results for those outcomes in the registry record for this account.
The registry record does not report the planned sample-size justification, the statistical analysis plan, interim analyses, or a detailed schedule of assessments. Those details should not be inferred from the phase, enrollment, or study duration.
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 | Cohort 1 (Transitioning From Parental) | Cohort 2 (Transitioning From Inhaled) | Cohort 3 (Add-on to Current PAH Therapy) |
|---|---|---|---|
| STARTED | 10 | 10 | 12 |
| COMPLETED | 9 | 10 | 12 |
| NOT COMPLETED | 1 | 0 | 0 |
Reasons for not completing this period:
| Reason | Cohort 1 (Transitioning From Parental) | Cohort 2 (Transitioning From Inhaled) | Cohort 3 (Add-on to Current PAH Therapy) |
|---|---|---|---|
| Adverse Event | 1 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety Population
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 | Cohort 1 (Transitioning From Parental) | Cohort 2 (Transitioning From Inhaled) | Cohort 3 (Add-on to Current PAH Therapy) | Total |
|---|---|---|---|---|---|
| Participants analysed | 10 | 10 | 12 | 32 | |
| Age, Categorical: <=18 years | Participants | 10 | 10 | 12 | 32 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 |
| Age, Continuous | years | 10.0 (7 to 17) | 13.5 (8 to 17) | 13.5 (8 to 17) | 12 (7 to 17) |
| Sex: Female, Male: Female | Participants | 9 | 7 | 7 | 23 |
| Sex: Female, Male: Male | Participants | 1 | 3 | 5 | 9 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 4 | 2 | 1 | 7 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 6 | 8 | 11 | 25 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 | 0 | 0 | 1 |
| Race (NIH/OMB): Asian | Participants | 1 | 1 | 2 | 4 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 7 | 9 | 10 | 26 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 0 | 0 | 1 |
| Region of Enrollment: United States | Participants | 10 | 10 | 12 | 32 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Successful Transition From IV/SC Remodulin to Oral Treprostinil (Cohort 1), From Inhaled Prostacyclin to Oral Treprostinil (Cohort 2), or as an add-on to Current PAH Therapy in de Novo Prostacyclin Subjects (Cohort 3)., measured over Up to 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is a count: the number of participants who met a pathway-specific definition of successful transition or initiation of oral treprostinil. The registry identifies the safety population as the outcome population and gives the timeframe as up to 24 weeks. It does not report the observed count.
For Cohort 1, success meant that a participant had transitioned from IV/SC Remodulin, was receiving oral treprostinil and no longer receiving IV/SC Remodulin at Week 4, and was clinically maintained on oral treprostinil through Week 24. Cohort 2 used the same structure for transition from inhaled prostacyclin: oral treprostinil without inhaled prostacyclin at Week 4, followed by clinical maintenance through Week 24. For Cohort 3, success meant clinical maintenance on oral treprostinil through Week 24.
As a general statistical matter, a count endpoint can describe how many participants satisfy a prespecified outcome definition. It is useful when the study question concerns whether participants can complete a treatment transition or remain on an initiated treatment over a defined period. The clinical meaning depends on the precise criteria used and on the completeness of outcome ascertainment. Here, the definitions specify treatment status and clinical maintenance, but the registry record does not report the primary outcome counts, the handling of participants with incomplete follow-up, or the criteria used to judge clinical maintenance. Consequently, the endpoint can be described, but its observed result and precision cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study context and the primary outcome definition, but it does not report the primary outcome result. In particular, it gives no number of participants who met the successful transition definition in Cohort 1 or Cohort 2, or the successful initiation definition in Cohort 3. It also reports no confidence interval or other uncertainty measure for that endpoint. The central endpoint therefore cannot be quantified from the record.
The enrolled population was divided among three different pathways: transition from IV/SC Remodulin, transition from inhaled prostacyclin, and add-on treatment for participants not currently receiving prostacyclin therapy. The adverse-event record lists 10 participants at risk in Cohort 1, 10 in Cohort 2, and 12 in Cohort 3. These cohort counts do not supply the missing primary endpoint counts. Nor should the cohorts be treated as randomized comparators: the study was non-randomized and uncontrolled, and participants entered pathways based on their treatment circumstances.
The endpoint definitions also differ in a way that matters for interpretation. Cohorts 1 and 2 had to be off their prior prostacyclin therapy and receiving oral treprostinil at Week 4, then remain clinically maintained through Week 24. Cohort 3 was assessed on clinical maintenance through Week 24, without the same prior-treatment discontinuation condition. A comparison of raw counts across these cohorts would therefore combine distinct outcome requirements and different clinical pathways.
Safety information is reported separately. The record lists serious adverse events affecting 5 participants in Cohort 1, 0 in Cohort 2, and 4 in Cohort 3. It lists other adverse events affecting 10, 10, and 12 participants in those respective cohorts, and deaths of 0 in each cohort. The record also lists serious-event terms with associated percentages. These figures describe reported safety events in the enrolled groups; they do not establish comparative risk or explain whether a particular event was related to treatment.
As a general statistical matter, an estimate is more informative when accompanied by a measure of uncertainty, such as a confidence interval. A confidence interval describes the range of values reasonably compatible with the observed data under the specified statistical method; it does not resolve design limitations or create a treatment comparison where none was randomized. Since the primary result and its uncertainty are not reported in the registry record, no conclusion about the frequency or precision of successful transition or initiation can be drawn from this record alone.
The study can be read as a descriptive investigation of oral treprostinil across three pediatric PAH treatment pathways. It cannot, on the information reported, answer a comparative-effectiveness question or show how the primary outcome varied by pathway. The registry record does not report the analysis details needed to assess missing outcome data, adjustment, or other sources of uncertainty.
9. Statistical Methods Explained
The design and outcome structure determine what statistical claims can be made from this study. The registry record describes a phase 2, non-randomized, open-label, uncontrolled, parallel study. The primary outcome is a participant count, not a continuous measurement or time-to-event measure. No primary outcome result or inferential analysis is reported in the registry record.
What does non-randomized mean for interpretation?
In general, random allocation aims to make treatment groups comparable with respect to both measured and unmeasured characteristics, on average. Without randomization, group membership may reflect prior treatment, clinical circumstances, or other factors. In this study, the three cohorts were defined by treatment pathway: transition from IV/SC Remodulin, transition from inhaled prostacyclin, or add-on treatment. Those pathways are not interchangeable control conditions. Differences between their outcomes, if reported, could reflect differences in the participants or pathways as well as any treatment-related factors.
The study is also uncontrolled. In general, a control group offers a concurrent reference for interpreting outcomes under the study conditions. Without one, a descriptive outcome can characterize what was recorded among participants receiving the study intervention, but it cannot isolate the effect of the intervention from other explanations. The registry record does not provide a randomized or untreated comparison.
What does the primary count represent?
The primary outcome counts participants meeting the registry’s defined success criteria. A count is straightforward to describe, but it needs a clear denominator and outcome ascertainment for interpretation. The record identifies the safety population and defines success separately for each pathway. It does not report the numbers meeting those criteria, the number with evaluable outcome data, or the approach to participants whose outcome status was unknown.
As a general statistical matter, a proportion can be used to express the count relative to the number assessed, and a confidence interval can communicate the uncertainty around that estimate. No such primary result or interval is reported in the registry record. No proportion should be inferred from cohort enrollment or from adverse-event counts, because those figures do not give the primary outcome numerators.
How does the time requirement affect the endpoint?
The primary endpoint includes conditions at different times. For Cohorts 1 and 2, it requires an oral-treatment and prior-treatment status at Week 4, followed by clinical maintenance through Week 24. For Cohort 3, it requires clinical maintenance through Week 24. In general, a multistep endpoint can be informative about completing a treatment pathway over time, but its interpretation depends on the exact definitions and how each condition is assessed. The registry record does not report further operational criteria for clinical maintenance or the handling of incomplete follow-up.
The endpoint is not described as time to an event. It is a participant count within a timeframe of up to 24 weeks. A time-to-event analysis would require information about event timing and censoring; no such primary analysis is reported. The registry record lists zero analyses for the reported outcomes in the registry record for this account.
What do the posted planning assumptions mean?
The registry record includes assumptions for sample-size planning illustrations: 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 record notes that these illustrations are planning exercises based on an observed effect, rather than the trial’s own design. They are not observed power and do not establish that the study was designed around those assumptions.
In general, sample-size planning estimates how much information a future study might need to detect a specified effect under stated assumptions. A planning result depends on the assumed effect, variability or event frequency, allocation, significance level, and analysis method. The registry record does not report the specific planning illustration values or the original sample-size justification, so no participant requirement can be stated from the record. These calculations should not be interpreted as a measure of the study’s achieved power.
Why does over-dispersion matter in general?
Over-dispersion is a general issue for count data: observed variability can exceed what a simple count model assumes. When it is present and not accounted for, standard errors and uncertainty intervals may be too small. That concept is relevant to count outcomes in general, but the primary endpoint is a count of participants meeting a binary success definition, and the registry record does not report a model, dispersion estimate, or analysis addressing over-dispersion. It would be inappropriate to assume that such a method was used.
What information is missing for statistical assessment?
The registry record does not report the primary endpoint result, a confidence interval, a detailed statistical analysis plan, handling of missing data, or interim analyses. It lists 25 outcome measures but no analyses in the registry record for this account. In general, these details help readers understand which outcomes were analyzed, how uncertainty was quantified, and whether incomplete data could affect interpretation. Their absence means the design and definitions can be described, but the primary statistical result cannot be evaluated.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 25 outcome measures and identifies a primary endpoint alongside multiple secondary outcomes. The listed secondary outcomes include changes in peak oxygen uptake, minute ventilation to carbon dioxide output slope, peak watts, PAH symptoms, Panama and WHO functional class, six-minute walk distance, and Borg dyspnea score. The record does not report analyses for these outcomes in the registry record for this account.
In general, testing many outcomes can increase the chance of at least one apparently unusual finding when each is assessed separately. Multiplicity procedures, such as a prespecified testing hierarchy or adjustment to significance thresholds, can address that concern. The statistical plan for handling multiplicity is not reported in the registry record, so it is not possible to determine whether any adjustment or prioritization was planned or performed. The presence of a designated primary endpoint does not, by itself, establish how secondary outcomes were handled.
Missing-data handling is also not reported. The registry record does not state how participants without an assessable Week 24 outcome were treated, whether any outcomes were imputed, or how the analysis population was defined beyond identifying the safety population for the primary endpoint. In general, incomplete follow-up can affect both the number counted as meeting an endpoint and the interpretation of an estimate. The direction and extent of that effect depend on why data are missing and on the analysis approach; neither can be inferred.
The record lists 25 outcome measures and zero analyses in the registry record for this account. It does not explain whether analyses were planned but not posted, or whether other reporting circumstances account for this. The analysis population definitions, multiplicity strategy, and missing-data methods 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 |
|---|---|---|---|
| Cohort 1 (Transitioning From Parental) | 5 | 10 | 50.0% |
| Cohort 2 (Transitioning From Inhaled) | 0 | 10 | 0.0% |
| Cohort 3 (Add-on to Current PAH Therapy) | 4 | 12 | 33.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort 1 (Transitioning From Parental) | 0 of 10 |
| Cohort 2 (Transitioning From Inhaled) | 0 of 10 |
| Cohort 3 (Add-on to Current PAH Therapy) | 0 of 12 |
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 |
|---|---|
| Cohort 1 (Transitioning From Parental) | 10 of 10 |
| Cohort 2 (Transitioning From Inhaled) | 10 of 10 |
| Cohort 3 (Add-on to Current PAH Therapy) | 12 of 12 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 1 (Transitioning From Parental) | Cohort 2 (Transitioning From Inhaled) | Cohort 3 (Add-on to Current PAH Therapy) |
|---|---|---|---|---|
| Chest pain | General disorders | 0 of 10 | 0 of 10 | 2 of 12 |
| Seizure | Nervous system disorders | 2 of 10 | 0 of 10 | 0 of 12 |
| Tachycardia | Cardiac disorders | 0 of 10 | 0 of 10 | 1 of 12 |
| Device related infection | Infections and infestations | 1 of 10 | 0 of 10 | 0 of 12 |
| Pneumonia | Infections and infestations | 0 of 10 | 0 of 10 | 1 of 12 |
| Stoma site infection | Infections and infestations | 1 of 10 | 0 of 10 | 0 of 12 |
| Syncope | Nervous system disorders | 1 of 10 | 0 of 10 | 0 of 12 |
| Bronchial hyperreactivity | Respiratory, thoracic and mediastinal disorders | 0 of 10 | 0 of 10 | 1 of 12 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 0 of 10 | 0 of 10 | 1 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1 (Transitioning From Parental) | Cohort 2 (Transitioning From Inhaled) | Cohort 3 (Add-on to Current PAH Therapy) |
|---|---|---|---|---|
| Headache | Nervous system disorders | 6 of 10 | 8 of 10 | 12 of 12 |
| Diarrhoea | Gastrointestinal disorders | 6 of 10 | 7 of 10 | 9 of 12 |
| Nausea | Gastrointestinal disorders | 7 of 10 | 5 of 10 | 9 of 12 |
| Vomiting | Gastrointestinal disorders | 9 of 10 | 5 of 10 | 7 of 12 |
| Flushing | Vascular disorders | 6 of 10 | 4 of 10 | 8 of 12 |
| Abdominal pain upper | Gastrointestinal disorders | 4 of 10 | 4 of 10 | 5 of 12 |
| Viral upper respiratory tract infection | Infections and infestations | 2 of 10 | 4 of 10 | 2 of 12 |
| Pain in jaw | Musculoskeletal and connective tissue disorders | 1 of 10 | 1 of 10 | 6 of 12 |
| Dizziness | Nervous system disorders | 3 of 10 | 1 of 10 | 4 of 12 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 10 | 5 of 10 | 2 of 12 |
Serious events with the highest arm-level rate: seizure (20.0%), chest pain (16.7%), device related infection (10.0%), stoma site infection (10.0%), syncope (10.0%).
The registry record reports serious adverse events by cohort as the number of participants at risk and the number affected. Cohort 1 lists 10 participants at risk and 5 affected; Cohort 2 lists 10 at risk and 0 affected; Cohort 3 lists 12 at risk and 4 affected. The record lists other adverse events affecting 10 participants in Cohort 1, 10 in Cohort 2, and 12 in Cohort 3. Deaths are listed as 0 in each cohort.
The listed serious-event terms and percentages are Seizure, 20.0%; Chest pain, 16.7%; Device related infection, 10.0%; Stoma site infection, 10.0%; Syncope, 10.0%; and Tachycardia, 8.3%. These are registry-reported terms and percentages. The record does not provide further details in the registry record for this account about event timing, severity grading, relationship to treatment, or how the term percentages map to individual cohorts.
In general, a participant count affected is not the same as a count of distinct events: one participant may experience more than one event. The figures should therefore be read as reported participant counts rather than as a full account of event frequency or duration. Because the study was non-randomized and uncontrolled, the cohort figures do not provide a like-for-like estimate of comparative safety. The registry record reports the counts, but does not establish causation or comparative risk.
12. What the Result Does, and Does Not, Mean
The registry record describes an open-label study of oral treprostinil across three treatment pathways in pediatric participants with PAH. Its primary endpoint was designed to count participants who completed a pathway-specific transition or initiation definition through Week 24. That focus makes the outcome relevant to describing treatment experience in the enrolled cohorts, but the record does not report the number who met the primary definition.
Accordingly, the record does not establish the observed frequency of successful transition or initiation, nor the precision of such an estimate. It reports no confidence interval for the primary endpoint and no analysis result from which one could assess uncertainty. The listed cohort sizes in the safety record cannot substitute for the missing primary outcome counts.
The study also cannot answer whether oral treprostinil performed better or worse than another treatment strategy. It was non-randomized and uncontrolled, and the cohorts correspond to different treatment circumstances. A direct comparison across them would be difficult to interpret because the success criteria differ: the transition cohorts had a Week 4 status requirement involving discontinuation of prior prostacyclin therapy, while the add-on cohort was assessed on maintenance through Week 24.
The safety information shows reported serious adverse-event counts of 5 participants in Cohort 1, 0 in Cohort 2, and 4 in Cohort 3, other adverse events affecting all listed participants, and no deaths listed. These are descriptive registry figures. They do not establish that oral treprostinil caused an event, nor do they quantify comparative safety against a control group. The listed serious-event terms provide additional descriptions, but do not replace a complete analysis of event timing, attribution, or severity.
In general, an uncontrolled study can characterize observations during treatment, while causal conclusions require careful consideration of the design and alternative explanations. The information reported for this study supports description of its population, treatment pathways, outcome definitions, and safety counts. It does not support a claim about comparative efficacy, a causal treatment effect, or the primary endpoint result. Those conclusions would require outcome and analysis information not reported in the registry record.
13. Why This Trial Matters Statistically
This study is statistically notable for examining three distinct pathways within one pediatric PAH study: transition from IV/SC Remodulin, transition from inhaled prostacyclin, and add-on treatment for participants not currently receiving prostacyclin therapy. The pathways make the study question clinically specific, while also making a single pooled interpretation less straightforward. The primary endpoint definitions reflect those differences rather than applying an identical transition requirement to every participant.
The design illustrates the role of descriptive evidence. In general, non-randomized, uncontrolled studies can document treatment experience in a defined population and provide information about outcomes observed during follow-up. They do not, by themselves, separate treatment effects from differences in patient characteristics, treatment history, or other factors. Recognizing that distinction is essential when interpreting cohort counts and safety observations.
The record also highlights why outcome definitions and outcome results must be considered separately. The registry gives a detailed primary definition involving Week 4 treatment status and maintenance through Week 24 for the transition cohorts, with a maintenance definition for the add-on cohort. However, the primary counts and uncertainty estimates are not reported. A well-specified endpoint does not allow readers to infer its result.
Finally, the study’s multiple secondary measures cover exercise testing, symptoms, functional class, walking distance, and dyspnea. Such breadth can describe different aspects of participant status, but makes transparent analysis and multiplicity handling important. The statistical plan and analyses are not reported in the registry record. The study therefore offers a useful example of how design, endpoint structure, and reporting completeness shape what can be concluded from a clinical trial record.
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 most direct limitation for interpreting the primary endpoint is that the registry record does not report its observed result. The number of participants meeting the success definition in each cohort, along with any confidence interval or other uncertainty estimate, is not reported in the registry record. This prevents assessment of the endpoint’s observed frequency and precision.
The study was non-randomized, open-label, and uncontrolled. It therefore lacks a randomized comparator for estimating outcomes under an alternative treatment strategy. Cohort membership also reflects different prior-treatment situations, and the primary success definitions are not identical across all three pathways. These features limit direct comparisons between cohorts and prevent a causal interpretation of any difference in outcomes.
The record identifies the safety population for the primary endpoint, but further analysis-population details are not reported. The handling of missing or incomplete outcome data, the criteria used to judge clinical maintenance, and the approach to participants without Week 24 assessments are not reported in the registry record. These omissions limit assessment of how reliably the primary endpoint could be determined for every participant.
The registry lists 25 outcome measures but the registry entries available for this account report zero analyses. The statistical analysis plan, multiplicity strategy, interim analyses, and sample-size justification are not reported in the registry record. The planning assumptions described for sample-size illustrations do not establish the original design rationale or the study’s achieved power.
Safety counts are descriptive and do not, on their own, establish treatment attribution or comparative risk. The record does not provide additional details about event timing, severity, or relationship to treatment. The enrolled population was pediatric participants aged 7 to 17 years with PAH, so the record does not describe outcomes outside that population.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety, Tolerability, and Pharmacokinetics of Oral Treprostinil in Pediatric PAH Patients Aged 7 to 17 Years — NCT02276872.
- Registry record last updated 2025-03-30; status last verified 2025-03.
- Results first posted 2019-01-04.
- 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
This completed phase 2 study evaluated oral treprostinil in pediatric participants aged 7 to 17 years with PAH. It was multicenter, open-label, non-randomized, parallel, and uncontrolled, with enrollment of 32. The study started on 2014-12-18 and reached primary completion on 2017-07-20.
Participants followed one of three pathways: transition from IV/SC Remodulin, transition from inhaled prostacyclin, or add-on treatment to current PAH therapy. The primary endpoint counted participants meeting a pathway-specific definition of successful transition or initiation through Week 24. The primary outcome result is not reported in the registry record.
The safety record lists serious adverse events affecting 5 participants in Cohort 1, 0 in Cohort 2, and 4 in Cohort 3; other adverse events affected 10, 10, and 12 participants, respectively. Deaths are listed as 0 in each cohort. These are descriptive counts from an uncontrolled study and do not provide a randomized comparison.