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 An Open-Label Uncontrolled Study of the Safety and Efficacy of Ambrisentan in Participants With Exercise-Induced Pulmonary Arterial Hypertension (PAH) (NCT01338636), a na phase 4 study. The primary outcome is Changes From Baseline in Peak Exercise Mean Pulmonary Artery Pressure (mPAP), Transpulmonary Pressure Gradient (TPG), and Pulmonary Capillary Wedge Pressure (PCWP).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01338636 |
| Phase | Phase 4 |
| Condition | Exercise-induced Pulmonary Arterial Hypertension |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 30 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Brigham and Women's Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Participants with exercise-induced pulmonary arterial hypertension (EIPAH). The registry lists enrollment as 30; the primary analysis population is described as evaluable participants who completed the 24-week treatment period.
Intervention
Open-label ambrisentan. The record describes the study as evaluating its safety and efficacy in participants with EIPAH.
Comparator
There was no concurrent control group. The study is recorded as single-group, with allocation and masking listed as not applicable and none, respectively. It therefore does not compare ambrisentan with placebo or another treatment.
Primary question
How did peak-exercise mean pulmonary artery pressure (mPAP), transpulmonary pressure gradient (TPG), and pulmonary capillary wedge pressure (PCWP) change from baseline to Week 24 among evaluable participants who completed treatment?
The research question is about change over time within the treated group, rather than a difference between treatment groups. The registry lists the primary outcomes as changes in three pressure measures. The posted record does not give the resulting means, standard deviations, confidence intervals, or tests of those changes. As a result, the direction, magnitude, and precision of the observed changes cannot be assessed from the record.
The study also lists change in 6-minute walk distance, Borg Dyspnea Scale score, and World Health Organization Functional Class as secondary outcomes. The registry describes the overall purpose as assessing safety and whether ambrisentan could help people with EIPAH. That statement describes the study's aim; it is not a result. Without reported outcome estimates and a comparison group, the record does not establish whether any change was attributable to treatment.
3. Trial Design
The registry describes NCT01338636 as a Phase 4, open-label, uncontrolled study of ambrisentan in participants with exercise-induced pulmonary arterial hypertension. Its design is classified as single-group. Allocation is listed as not applicable, and masking is listed as none. Participants received open-label ambrisentan; the record does not describe a placebo or active comparator arm.
The registry lists enrollment as 30. It records the study as completed, with a start date of 2008-09 and primary completion in 2016-02. The sponsor is Brigham and Women's Hospital. These administrative details describe the registered trial, but do not supply outcome results or explain how participants were selected for analysis beyond the primary population description.
The primary outcomes are changes from baseline to Week 24 in peak-exercise mPAP, TPG, and PCWP. The listed primary analysis population consists of evaluable participants who completed the 24-week treatment period. The registry does not report how many participants met that definition or how the analysis handled participants who did not complete treatment.
An uncontrolled, open-label design can describe measurements made during treatment, but it cannot by itself separate treatment-related change from changes that might have occurred over time for other reasons. The lack of masking can also affect outcomes that involve subjective assessment or participant reporting. These design features do not make the measurements unusable; they define what conclusions the study can support. In particular, the design does not provide a like-for-like comparison with an untreated or differently treated group.
The registry lists 8 outcome measures and no posted analyses. Details of randomization, a statistical analysis plan, interim analyses, and a sample-size justification are not reported in the registry record. They should not be inferred from the study's Phase 4 designation or from its listed enrollment.
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 | Exercise-induced PAH |
|---|---|
| STARTED | 30 |
| COMPLETED | 22 |
| NOT COMPLETED | 8 |
Reasons for not completing this period:
| Reason | Exercise-induced PAH |
|---|---|
| Withdrawn due to lack of improvement | 8 |
Analysis population for the primary outcome, as defined in the registry: The analysis population included evaluable participants who completed the 24-week treatment period.
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.
Population: The analysis population included all participants.
| Characteristic | Unit | Exercise-induced PAH |
|---|---|---|
| Participants analysed | 30 | |
| Age, Continuous | years | 60.12 (SD 9.17) |
| Sex: Female, Male: Female | Participants | 19 |
| Sex: Female, Male: Male | Participants | 11 |
6. Primary Endpoint
The registry lists the primary outcome as Changes From Baseline in Peak Exercise Mean Pulmonary Artery Pressure (mPAP), Transpulmonary Pressure Gradient (TPG), and Pulmonary Capillary Wedge Pressure (PCWP), measured over Baseline to Week 24.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | mmHg |
| Endpoint classification | Continuous Endpoint |
The primary endpoint listing concerns change from baseline to Week 24 in peak-exercise mean pulmonary artery pressure (mPAP), transpulmonary pressure gradient (TPG), and pulmonary capillary wedge pressure (PCWP). The record describes mPAP as blood pressure in the main artery of the lung. It defines TPG as the difference between mean pulmonary arterial pressure and left atrial pressure, and PCWP as pressure measured by wedging a pulmonary catheter, with an inflated balloon, into a small pulmonary arterial branch. All three are expressed in mmHg.
These measures describe pressures assessed during peak exercise. In general, measuring change from baseline asks whether the recorded value at follow-up differs from the participant's starting value. Reporting several related pressure measures can provide different views of the hemodynamic response being assessed; the registry does not explain how the three measures were prioritized relative to one another.
The listed timeframe is Baseline to Week 24, and the analysis population is evaluable participants who completed the 24-week treatment period. The registry does not give the observed baseline or follow-up means, the mean changes, or their standard deviations. It therefore does not permit assessment of the size or precision of change in any of the three measures. The endpoint description identifies what was to be measured, not what the measurements showed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary outcomes and their measurement period, but does not report numerical results for mPAP, TPG, or PCWP. There are no posted mean changes, standard deviations, confidence intervals, or p-values for these outcomes in the record. Consequently, it is not possible to describe whether the measures increased or decreased, how large any change was, or how compatible the results are with a range of possible effects.
That absence matters for interpretation. A mean change would describe the average within-participant difference over the stated period in the analyzed population. Its standard deviation would describe variation in individual changes around that average. A confidence interval, if reported, would convey the statistical uncertainty around the estimated mean change. Without these quantities, neither the size of the observed change nor its precision can be evaluated. A statement of the study's purpose cannot substitute for outcome estimates.
The analysis population is limited in the registry description to evaluable participants who completed the 24-week treatment period. The record does not report the number included in that analysis or the handling of missing measurements. Therefore, the results cannot be assumed to represent every participant listed under enrollment. The extent and possible consequences of missing follow-up measurements are also unclear.
Even if within-group changes were reported, this design would not estimate a treatment-versus-control contrast. Participants were not assigned to a control group, and the study was open-label. Change from baseline can reflect treatment exposure as well as time-related influences, measurement variability, or other factors. Without a concurrent comparison, those explanations cannot be distinguished by the design alone.
The registry lists three secondary outcomes: change from baseline in 6-minute walk distance, Borg Dyspnea Scale score, and World Health Organization Functional Class. Numerical findings for those outcomes are not reported in the registry record. It also lists 8 outcome measures overall and no analyses. No conclusions about the direction, magnitude, or statistical uncertainty of these secondary outcomes can be drawn from the listed outcome names alone.
The adverse-event record reports 0 participants affected by serious adverse events among 30 at risk, and 25 affected by other adverse events among 30 at risk. This is a descriptive safety count, not a comparison with another group. The record does not list serious adverse-event terms or a death count. These entries should be read as the recorded counts, not as a complete account of event timing, attribution, or risk relative to another treatment.
Overall, the available registry information describes the study's question, design, and selected counts, but not its primary efficacy results. It supports a description of what was planned and the recorded adverse-event counts; it does not support a numerical estimate of change in the primary pressure outcomes or a causal estimate of treatment effect.
9. Statistical Methods Explained
The primary outcomes are continuous measurements, and the registry identifies the summary as a mean with standard deviation. In general, a mean summarizes the average value in the analyzed group, while a standard deviation describes how dispersed individual values are around that average. For an outcome defined as change from baseline, the mean change summarizes the average within-participant change. It does not imply that every participant changed by that amount or in the same direction.
What would a change estimate describe?
For each pressure measure, an estimate of mean change would describe the average difference between the baseline measurement and the measurement at Week 24 in the analysis population. The registry names peak-exercise mPAP, TPG, and PCWP and identifies mmHg as the unit. It does not report the numerical changes or their standard deviations. No recalculated estimate can be made from the record because the necessary summary values are absent.
In general, a confidence interval is a way to express statistical uncertainty around an estimated quantity. A narrower interval indicates greater precision under the assumptions of the analysis; a wider interval indicates greater uncertainty. The registry record does not report confidence intervals for the primary outcomes, so precision cannot be judged from an interval. A p-value, if reported, would address compatibility with a specified statistical null model; it would not by itself describe the size or clinical importance of a change. No primary-outcome p-values are reported in the registry record.
Why does the uncontrolled design matter?
The primary outcomes are changes within a treated group. In general, a within-group change and a between-group treatment contrast answer different questions. A within-group estimate describes how measurements changed over time among those analyzed. A comparison with a concurrent control group would help distinguish treatment-associated change from influences that may affect measurements over time in either group. This study is classified as uncontrolled and single-group, so it does not provide that comparison.
The study is also open-label, with masking listed as none. In general, knowledge of treatment assignment can influence expectations, reporting, and assessment, especially for outcomes involving judgment or subjective experience. The pressure measures are defined as measured quantities, but open-label status remains part of the study context. The record does not report procedures intended to limit measurement or assessment bias.
How should planning calculations be understood?
The planning framework described for sample-size illustrations uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It treats the effect to detect as a stated fraction of the observed effect. These are planning assumptions, not a description of this trial's single-group design. Any sample-size values based on that framework are planning illustrations, not observed power and not evidence about the results of this study. The registry record does not report a sample-size justification for the actual trial.
In general, a planning calculation estimates the number of participants that a hypothetical design might require under specified assumptions. Its output depends on the assumed effect and variability, the target power, the significance level, and the allocation structure. It does not reveal the probability that a completed study has demonstrated an effect, and it cannot replace the reported estimates and uncertainty from the actual analysis. No trial-specific statistical plan or sample-size justification is reported in the registry record.
What role can over-dispersion play?
In general, over-dispersion occurs when the variability in data is greater than a statistical model assumes. If ignored in a setting where it applies, uncertainty estimates may be too small and tests may appear more informative than they are. The primary outcomes in this study are continuous pressure measures summarized as means and standard deviations; the registry does not identify a count model or report an over-dispersion assessment. This general concept should not be taken to imply that over-dispersion was present or relevant to the primary analysis.
The record lists no analyses. It does not describe the statistical test, model, covariate adjustment, confidence-interval method, or handling of multiple primary measures. Those details cannot be reconstructed from the outcome titles or the fact that the outcomes are continuous. The absence of a reported analysis is a limit on interpretation, rather than a reason to infer which method was used.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome listing includes changes in mPAP, TPG, and PCWP. Considering more than one outcome raises a general multiplicity question: when several hypotheses are tested, the chance of at least one apparently noteworthy result can increase if each is assessed without an adjustment or a prespecified hierarchy. The registry record does not report whether the three primary measures were tested separately, whether one was designated as most important, or whether any multiplicity procedure was used. The record therefore does not support a claim that multiplicity was controlled.
The registry also lists 8 outcome measures overall, including secondary outcomes for 6-minute walk distance, Borg Dyspnea Scale score, and World Health Organization Functional Class. It does not report outcome-specific analyses or a testing strategy for these measures. Their listing alone does not show whether they were analyzed, how results were interpreted, or whether their analyses were prespecified.
Missing-data information is also limited. The primary analysis population is described as evaluable participants who completed the 24-week treatment period, but the number in that population is not reported. The record does not state how participants who did not complete treatment were handled, whether all outcomes were measured at follow-up, or whether any missing measurements were imputed. It does not report sensitivity analyses examining the effect of missing data.
These omissions affect both precision and interpretation. A completer-based population may differ from the enrolled population, but the registry does not provide information to assess that possibility. Without the analysis population size, missingness details, and analysis methods, readers cannot determine the extent to which incomplete follow-up influenced the reported findings. Because numerical primary results are also not reported, the practical impact of multiplicity or missing data cannot be evaluated from this 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 |
|---|---|---|---|
| Exercise-induced PAH | 0 | 30 | 0.0% |
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 |
|---|---|
| Exercise-induced PAH | 25 of 30 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Exercise-induced PAH |
|---|---|---|
| Worsening dyspnea on exertion | Cardiac disorders | 8 of 30 |
| Peripheral edema | Metabolism and nutrition disorders | 7 of 30 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 7 of 30 |
| Headache | Nervous system disorders | 5 of 30 |
| Flushing | Vascular disorders | 4 of 30 |
| Increased cough | Respiratory, thoracic and mediastinal disorders | 4 of 30 |
| Joint and body pain | Musculoskeletal and connective tissue disorders | 3 of 30 |
| Rash | Skin and subcutaneous tissue disorders | 2 of 30 |
| Upper respiratory infection | Respiratory, thoracic and mediastinal disorders | 2 of 30 |
| Gastrointestinal infection | Gastrointestinal disorders | 2 of 30 |
The registry records 0 participants affected by serious adverse events among 30 at risk in the exercise-induced PAH group. It records 25 participants affected by other adverse events among 30 at risk. These are counts as entered in the registry, and the record does not list any serious adverse-event terms. The death count is not reported in the registry record.
In general, serious and other adverse events are distinct reporting categories; the count for other adverse events should not be read as a count of serious events. These figures do not establish whether an event was caused by ambrisentan. The registry entry does not give event timing, duration, severity details for the other events, or a breakdown by event type. It also does not provide a control group, so the counts cannot be used to compare safety with another treatment or with no treatment.
The counts describe recorded participants affected, not the full distribution of events or their clinical context. The record does not report how adverse events were collected or the period over which the risk counts apply. Accordingly, the figures should be interpreted narrowly as the adverse-event counts recorded for this study, not as a complete estimate of treatment-related risk.
12. What the Result Does, and Does Not, Mean
The study addresses a clinically specific question: how selected pulmonary pressure measures changed from baseline to Week 24 during open-label ambrisentan treatment in people with exercise-induced pulmonary arterial hypertension. The registry defines the primary measures and describes the analysis population as evaluable participants who completed the treatment period. It does not report the numerical results for those measures, so the magnitude, direction, and precision of any change are unknown from this record.
The design also limits what a within-group result could mean. There is no concurrent control group, and participants and assessors were not masked. In general, a change observed during treatment does not by itself establish that treatment caused the change. The design cannot separate treatment effects from other influences on measurements over time. It also cannot estimate a comparative effect against placebo or another therapy.
The adverse-event entries report 0 affected by serious adverse events and 25 affected by other adverse events, with 30 at risk for each category. These are descriptive registry counts. They do not establish whether events were treatment-related, and they cannot support comparative safety conclusions without a control group and additional context about event types and timing.
The record's stated purpose and endpoint definitions should not be mistaken for findings. The registry lists secondary outcomes and 8 outcome measures overall, but does not report numerical results for them. It also does not report analyses. Consequently, the record does not establish whether the primary or secondary measures changed, whether any change was statistically distinguishable from no change, or how precisely an effect was estimated.
What the record can support is a description of the study design, registered outcomes, analysis population definition, and selected adverse-event counts. It cannot support a conclusion that ambrisentan did or did not produce a particular clinical effect. That distinction is especially important for an uncontrolled study: the absence of a comparative estimate is a design limitation, while the absence of posted outcome estimates means even the observed within-group changes cannot be assessed.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the difference between an outcome being defined and an outcome being reported. The registry specifies three primary pressure measures, their unit, the baseline-to-Week-24 timeframe, and a completer-based analysis population. Those details clarify what the study aimed to measure. But the record contains no numerical primary outcome results, so the central statistical questions about effect magnitude and precision remain unanswered.
The uncontrolled single-group design also illustrates the difference between change over time and a treatment contrast. A within-group estimate, if available, would describe change among participants analyzed. It would not by itself establish what would have happened without treatment. A concurrent comparator is needed to estimate a between-group difference under the design's assumptions. This study's allocation is listed as not applicable, and it has no like-for-like control comparison.
The registry's adverse-event counts offer another useful interpretive distinction. Counts of participants affected are descriptive; without event details, attribution information, timing, and a comparator, they are not a comparative safety estimate. The record reports 0 affected by serious adverse events and 25 affected by other adverse events, but does not report a death count.
Finally, the record identifies a population of evaluable participants who completed the 24-week treatment period without reporting its size or missing-data methods. That makes it difficult to assess who contributed to the primary analysis and how incomplete follow-up may affect interpretation. The trial matters statistically because these features show why endpoint definitions, analysis populations, numerical estimates, uncertainty measures, and design context all need to be considered together. Here, several design details are recorded, while key outcome and analysis information is not reported in the registry 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 principal limitation for interpreting the trial's results is that numerical findings for the primary outcomes are not reported in the registry record. Mean changes, standard deviations, confidence intervals, and p-values are absent for mPAP, TPG, and PCWP. The direction and size of change, and the precision of any estimate, therefore cannot be assessed. Numerical findings for the listed secondary outcomes are also not reported.
The study has no concurrent control group and is open-label. Any within-group change would not by itself distinguish a treatment-associated effect from other changes over time. The record also does not describe procedures for blinded measurement or assessment. These design features limit causal interpretation even if outcome estimates were available.
The primary analysis population is restricted to evaluable participants who completed the 24-week treatment period, but the size of that population is not reported. The registry does not describe missing-data handling, imputation, or sensitivity analyses. It is therefore not possible to assess whether incomplete follow-up could have influenced the analysis.
The record lists multiple primary measures and 8 outcome measures overall, but does not report a statistical analysis plan, a multiplicity strategy, or analyses. The sample-size justification is not reported in the registry record. The adverse-event entry lacks event terms for serious events, a reported death count, and information about event timing or attribution. These omissions limit assessment of both outcome evidence and safety context.
These limitations are specific to what the registry record documents. They do not establish that analyses or additional information do not exist elsewhere; they mean that those details are not reported in the registry record and cannot be used in interpreting the posted information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Open-Label Uncontrolled Study of the Safety and Efficacy of Ambrisentan in Participants With Exercise-Induced Pulmonary Arterial Hypertension (PAH) — NCT01338636.
- Registry record last updated 2022-01-18; status last verified 2022-01.
- Results first posted 2017-05-22.
- 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
NCT01338636 is recorded as a completed Phase 4, open-label, uncontrolled, single-group study of ambrisentan in exercise-induced pulmonary arterial hypertension, sponsored by Brigham and Women's Hospital. The registry lists enrollment as 30, a start date of 2008-09, and primary completion in 2016-02.
The primary outcomes are changes from baseline to Week 24 in peak-exercise mPAP, TPG, and PCWP, analyzed in evaluable participants who completed the 24-week treatment period. The registry lists 8 outcome measures and no analyses. Numerical primary and secondary outcome results, missing-data methods, and a multiplicity strategy are not reported in the registry record.
The adverse-event record lists 0 participants affected by serious adverse events and 25 affected by other adverse events, with 30 at risk in each category. Serious-event terms are not listed, and the death count is not reported in the registry record. The uncontrolled design does not provide a treatment comparison, and the posted record does not support a numerical estimate of the primary outcome changes.