Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan (NCT01051960), a na phase 4 study. The primary outcome is Change in Exercise Pulmonary Hemodynamics From Baseline to Week 24.

2. Clinical Question

3. Trial Design

The registry describes a phase 4, prospective, single-center, open-label pilot study. It lists the study as completed, with a start date of 2009-03 and primary completion in 2010-06. Enrollment is listed as 12. The brief summary describes a purpose involving 15 patients, and the record does not explain the difference between that figure and the enrollment field.

The design is single-group, with ambrisentan as the intervention. The listed dosing was either 5mg or 10mg orally once per day. Allocation is recorded as NA, and masking as none. No randomized control arm or like-for-like comparison is described. Results from a single group can describe changes over time in that group, but by themselves cannot isolate the effect of treatment from other explanations for change.

The primary outcome concerns change in exercise pulmonary hemodynamics from baseline to week 24. The record also lists secondary outcomes concerning distance walked in six minutes from baseline to 24 Week, quality of life based on SF36 and HAQ-DI, HAQ-DI, and St. George's Respiratory Questionnaire. The registry lists 5 outcome measures and 2 analyses, but does not report the analysis methods or numerical findings for these outcomes.

The brief summary describes both characterization of exercise-induced pulmonary hypertension and an assessment of ambrisentan. These are related but distinct aims: describing profiles is not the same as estimating a treatment effect. The single-group, open-label design supports a descriptive account of the enrolled group, while a controlled comparison would be needed to separate treatment-associated changes from time trends and other influences. Details of the enrollment process, eligibility criteria, treatment duration, and protocol deviations 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

Reasons for not completing this 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.

6. Primary Endpoint

The registry lists the primary outcome as Change in Exercise Pulmonary Hemodynamics From Baseline to Week 24, measured over 24 weeks.

The primary endpoint is change in exercise pulmonary hemodynamics from baseline to week 24. It is described as a continuous measure, summarized as a mean with standard deviation and expressed in mmHg. Hemodynamic measurements characterize pressures and gradients during exercise; their change can describe how the recorded physiology differs between the two assessment times. The registry’s outcome description identifies mPAP, PCWP, and transpulmonary gradient (TPG), with TPG defined as mPAP minus PCWP.

The record defines ePH, ePVH, and eoPH using stated thresholds for mPAP, PCWP, and TPG. The definitions appear in the outcome description, which also states a hypothesis about differences in pathophysiology among participants with normal exercise physiology, ePVH, ePH, and eoPH. These definitions provide context for the study’s physiological focus, but the record does not report how many participants met any category or provide category-specific results.

Using change from baseline makes each participant’s later measurement interpretable relative to that participant’s starting measurement. In general, a mean describes the average change in a group, while a standard deviation describes the spread of individual values around that mean. Neither the numerical mean change nor its standard deviation is reported in the registry record. The record also does not state whether the primary analysis combined the listed hemodynamic components or reported them separately, or how measurements were collected.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry labels the primary outcome continuous and specifies a mean and standard deviation. In general, a continuous outcome can take values across a measurement scale, and a mean gives its arithmetic average. For a change endpoint, the quantity of interest is the difference between a later measurement and a baseline measurement for each participant, followed by a summary across the group. The record does not state the sign convention used for change, so the direction that would correspond to an increase or decrease is not specified.

What does the mean describe?

In general, the mean change describes the average change for the participants included in the analysis. It does not say that every participant changed by that amount. A mean can also be influenced by unusually large or small individual changes, particularly in a small pilot study. The registry record gives no individual measurements or numerical mean change, so the magnitude and distribution of changes cannot be assessed.

What does the standard deviation describe?

In general, the standard deviation describes how spread out observed measurements are around their mean. A smaller standard deviation indicates less observed spread, while a larger one indicates more. It describes variation among measurements, not the precision of the estimated mean. Precision depends on factors including the amount of information available and the variability of the measurements. The standard deviation for this endpoint is not reported in the registry record.

How should uncertainty be interpreted?

In general, a confidence interval gives a range of values compatible with the data and the assumptions of a particular analysis. A narrow interval indicates more precision than a wide interval, while an interval’s position relative to a null value may be relevant to a hypothesis test. Those interpretations depend on the endpoint, analysis, and design. The registry record does not report a confidence interval, a p-value, a test statistic, or the primary analysis method, so statistical significance and precision cannot be evaluated from the record.

What does the single-group structure imply?

The primary endpoint compares measurements over time within a single group. In general, when the same participants are assessed at baseline and follow-up, analyses may account for the relationship between those measurements. This is a general methodological point, not a description of the method used in this trial: the registry does not state whether the analysis used paired changes, a repeated-measures model, or another approach. Regardless of method, without a control group a before-and-after change cannot by itself identify what would have happened without treatment.

The outcome description refers to mPAP, PCWP, and TPG, and defines TPG as mPAP minus PCWP. The record does not clarify whether each measure was analyzed as a separate continuous endpoint, whether any measures were combined, or how the stated ePH, ePVH, and eoPH definitions were used in the analysis. The thresholds are part of the outcome description; no category counts or category-specific estimates are reported.

What do the planning assumptions mean?

The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect, and distinguishes participant-per-arm planning from total-event planning for time-to-event outcomes. These are planning assumptions, not a description of this study’s actual design. This trial is recorded as single-group, so equal allocation between two arms does not describe its enrollment structure. The numerical planning results are not reported in the registry record.

In general, a sample-size illustration estimates how much information a future design might need under stated assumptions. It is not an observed result and does not show the probability that the completed study detected an effect. Such calculations depend on the effect size, variability, analysis, allocation, and other assumptions. The record does not report the trial’s own sample-size justification, and the planning illustrations should not be read as observed power.

Why might over-dispersion matter?

Over-dispersion is a general concern for count data when observed variability exceeds what a simple count model assumes. It is not a direct description of this continuous primary endpoint, which is expressed as a mean and standard deviation. The registry record does not identify a count-based primary analysis. For the continuous endpoint, the more relevant reported summaries would include the mean change and its variability, neither of which is available in this record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Ambrisentan")
n   <- c(11)
m   <- c(37.4)
sp  <- c(8.3)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Ambrisentan  11  37.400  8.300  31.824  42.976

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures and 2 analyses. The named secondary outcomes include change in distance walked in six minutes from baseline to 24 Week, quality of life based on SF36 and HAQ-DI, HAQ-DI, and St. George's Respiratory Questionnaire. The record does not specify how the 5 measures relate to the listed analyses, or which outcomes were included in each analysis.

Multiplicity is a general issue when several outcomes or statistical tests are considered: the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and relationship of tests. The registry record does not report a multiplicity adjustment, a hierarchy of outcomes, or a prespecified testing strategy. It also does not report p-values or numerical outcome estimates from which the impact of multiplicity could be assessed.

Missing-data methods and analysis populations are not reported in the registry record. There is no account of how many participants contributed data at baseline or week 24 for the primary endpoint, how incomplete measurements were handled, or whether analyses followed an intention-to-treat, per-protocol, or other population definition. These omissions matter because the interpretation of a change estimate depends on who was analyzed and how missing follow-up information was addressed.

The record does not report interim analyses or the trial’s statistical analysis plan. Its planning assumptions concern an illustration and are not evidence of the completed trial’s analysis choices. Without these details, the registry record cannot establish whether outcome selection, missingness, or analysis decisions could have influenced the reported findings.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: edema (8.3%).

The adverse-event record lists an ambrisentan group with 12 participants at risk for serious adverse events and 1 affected. It lists 12 at risk for other adverse events and 12 affected, and reports 0 deaths. These are counts in the registry record; they are not comparative estimates because no control group is listed.

Edema is named as the top serious adverse-event term, with 8.3% reported. The record does not provide the full event-term listing or explain whether the percentage refers to participants affected, event occurrences, or another denominator. It should therefore be read as the registry’s reported term and percentage, not as a rate recalculated from the participant counts.

In general, safety counts describe what was recorded under the study’s collection and reporting procedures. They do not, by themselves, establish that an event was caused by the intervention, and counts from a small, single-group study cannot support a controlled safety comparison. The registry record does not report event timing, severity beyond the serious-event classification, duration, resolution, or participant-level details. The counts also do not describe the safety profile beyond the participants and observations recorded in this study.

13. What the Result Does, and Does Not, Mean

The record establishes that a completed, open-label, single-group pilot study evaluated ambrisentan in a systemic-sclerosis context and designated change in exercise pulmonary hemodynamics from baseline to week 24 as its primary endpoint. It also records secondary outcomes related to walking distance, quality of life, disability, and respiratory health. These details clarify the study question and measurement focus.

The record does not report numerical primary-endpoint results. Therefore, it does not show the observed average change, the spread of individual changes, or the precision of an estimate. It cannot establish whether the hemodynamic measures changed, how large any change was, or whether any change was statistically distinguishable from no change under a specified analysis.

Nor does the record establish a causal treatment effect. In general, a single-group before-and-after study lacks a concurrent control that could help distinguish changes associated with treatment from other changes over time. The open-label design also means masking is listed as none. These design features limit comparative interpretation, but do not negate the descriptive value of the study’s stated physiological question.

The safety fields report serious and other adverse-event counts and a top serious adverse-event term. Those counts do not supply an efficacy result, nor do they permit a comparison against a control group. The record does not provide enough detail to interpret event timing or attribution.

The enrollment field and brief summary differ, listing 12 and 15 patients respectively. The record does not resolve this inconsistency. Overall, the registry describes aims, design, outcomes, and limited safety information, but it does not contain the numerical outcome results needed to assess what was observed. Planning illustrations, where used, are hypothetical calculations rather than evidence of an observed effect or observed power.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between its stated treatment aim and its single-group design. The brief summary aims to determine ambrisentan effectiveness, while the recorded structure has no randomized comparator. A before-and-after endpoint can describe within-group change, but a treatment-effect claim requires a comparison that addresses what would have happened over the same period without the intervention.

The primary outcome focuses on exercise pulmonary hemodynamics, summarized as a mean and standard deviation over a 24-week timeframe. This gives the study a physiological focus distinct from its secondary measures of walking distance, quality of life, disability, and respiratory health. The registry record does not provide numerical findings for these measures, so their observed behavior cannot be evaluated.

The enrollment discrepancy also matters for statistical reading: the enrollment field lists 12, while the brief summary refers to 15 patients. Because the record does not explain the difference, readers cannot resolve it from the registry entry. This reinforces the importance of clearly distinguishing planned descriptions, enrollment, analysis populations, and outcome reporting.

Finally, the record’s planning assumptions describe an illustration with two-arm allocation, whereas the study itself is recorded as single-group. Separating hypothetical planning scenarios from the actual design prevents a sample-size calculation from being mistaken for observed power or evidence of an outcome. Together, these features make the study useful for understanding the limits of interpreting uncontrolled clinical measurements, while leaving its numerical primary result unreported in the registry record.

15. 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 its numerical results are not reported in the registry record. There is no mean change, standard deviation, confidence interval, or p-value. As a result, readers cannot assess the size or precision of observed hemodynamic change from this entry.

The single-group, open-label design has no randomized control comparison. Any within-group change, if available elsewhere, would not by itself separate an intervention-associated change from time-related or other explanations. The record lists allocation as NA and masking as none, and the study is explicitly described as single-group. It should not be interpreted as a like-for-like controlled comparison.

The enrollment field lists 12, while the brief summary refers to 15 patients. This discrepancy is not explained. The record also does not report the analysis population or how many participants contributed primary outcome data at week 24. Missing-data procedures, eligibility criteria, recruitment details, treatment duration, and protocol deviations are not reported in the registry record.

Statistical methods for the primary endpoint are not specified. The record does not identify the model or test used, the handling of multiple outcomes, or whether any interim analyses occurred. The listed planning assumptions are not the trial’s own design description, and no numerical planning results are included in the record. These limitations make the registry entry insufficient for reconstructing the analysis or evaluating its statistical precision.

The safety information is also limited: the record gives participant counts and a top serious adverse-event term but does not describe timing, duration, attribution, or the full event listing. These omissions restrict both efficacy and safety interpretation to the limited descriptive information recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan — NCT01051960.
• Registry record last updated 2020-11-02; status last verified 2020-10.
• Results first posted 2020-11-02.
• 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.

19. Record Summary

The registry identifies a completed phase 4, prospective, single-center, open-label, single-group pilot study of ambrisentan in systemic sclerosis. Enrollment is listed as 12, although the brief summary refers to 15 patients. The recorded dose was either 5mg or 10mg orally once per day; allocation is NA and masking is none.

The primary outcome is change in exercise pulmonary hemodynamics from baseline to week 24, summarized as a mean with standard deviation in mmHg. The registry lists secondary outcomes concerning walking distance, quality of life, disability, and respiratory health, along with 5 outcome measures and 2 analyses. Numerical primary-endpoint results and analysis details are not reported in the registry record.

The adverse-event entry reports 1 affected among 12 at risk for serious events, 12 affected among 12 at risk for other events, and 0 deaths. Edema is the top serious adverse-event term, reported as 8.3%. The single-group design does not provide a controlled comparison, and the record does not resolve the enrollment discrepancy.