This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study of Ambrisentan With Antifibrotic Agent Combination Therapy in Diffuse Systemic Sclerosis (NCT01093885), a na na study. The primary outcome is The Benefit That an Antifibrotic Agent and Ambrisentan Combination Have on the Cutaneous Involvement of Patients With Early Diffuse Systemic Sclerosis by Utilizing the MRSS.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01093885 |
| Phase | NA |
| Condition | Systemic Sclerosis, Scleroderma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 15 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Pennsylvania |
| Results posted | Yes |
2. Clinical Question
Population
People with early diffuse systemic sclerosis are the population named in the primary outcome description. The condition list also includes systemic sclerosis and scleroderma. The registry record does not provide further eligibility details or a fuller description of the outcome population.
Intervention
The listed intervention is open-label ambrisentan. The study title and primary outcome description refer to combination therapy with an antifibrotic agent, but the registry intervention list does not identify a second agent.
Comparator
There is no separate comparator group in the recorded design. Allocation is listed as NA, and the model is single-group. The registry record therefore does not describe a randomized or concurrent control comparison.
Primary question
The stated primary question is whether combination therapy is associated with change in cutaneous involvement, measured by the modified Rodnan skin score (MRSS) at baseline and 12 months. The registry record does not report the measured score values or an estimate of change.
The study rationale describes systemic sclerosis as a condition with varied manifestations, including interstitial lung disease, pulmonary arterial hypertension and skin involvement. Its stated hypothesis is that an endothelin receptor antagonist and an antifibrotic agent may have complementary effects. That is a rationale and hypothesis, not evidence that the proposed effects occurred in this study.
The registered primary endpoint focuses specifically on skin involvement. It does not, by itself, answer whether the intervention affected other manifestations, quality of life, survival or the course of systemic sclerosis as a whole. A secondary outcome is listed as systemic sclerosis quality of life assessed by the SF-36, but no secondary outcome results are reported.
Because the design is single-group and open-label, the question is not a direct comparison of ambrisentan-based therapy with placebo or another treatment. In the absence of a reported analysis, even the amount and direction of change in MRSS cannot be determined from this registry record.
3. Trial Design
The registry describes a completed, open-label, single-group study sponsored by the University of Pennsylvania. The listed enrollment is 15. The phase is recorded as NA, allocation is NA, and masking is listed as none. These entries describe a study without a recorded randomized allocation or masking scheme; they do not define a control-group comparison.
The study start is recorded as 2010-02 and primary completion as 2016-07. Its status is completed. Those dates describe the registry record's study timeline, but they do not establish how long each participant was followed or whether every participant completed the planned assessments. Participant-level follow-up and completion details are not reported in the registry record.
Ambrisentan is the only intervention named in the intervention list. The arm is described as open-label medication ambrisentan. The arm description states that dosing begins at 5mg daily for the first month; it says half the patients remain at 5mg daily and the remaining patients increase to 10mg daily on the fourth week. The remainder of the description is truncated, so the full dose and schedule details are not reported in the registry record. The title and primary outcome wording refer to an antifibrotic agent in combination, but the intervention list does not name that agent.
A single-group design can describe outcomes over time among participants receiving the registered intervention, but it cannot by itself separate a treatment-associated change from changes that might occur for other reasons. Open-label status also means the record describes no masking. No comparator arm or concurrent control is recorded, and the registry does not report a statistical analysis that addresses these limitations.
The registry record includes an outcome count of 2 and lists the primary MRSS outcome and a secondary SF-36 quality-of-life outcome. It lists 0 analyses. The record does not provide a detailed statistical plan, eligibility criteria, analysis population, participant flow or outcome results. Further design details beyond the entries 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.
Before assignment: None of the patients were able to increase the dosage of ambrisentan from the initial dose of 5 mg to 10 mg.
Overall Study
| Stage | Open Label: Medication Ambrisentan |
|---|---|
| STARTED | 15 |
| COMPLETED | 10 |
| NOT COMPLETED | 5 |
Reasons for not completing this period:
| Reason | Open Label: Medication Ambrisentan |
|---|---|
| Adverse Event | 4 |
| Lost to Follow-up | 1 |
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: Participant number as per power calculation, less is worse
| Characteristic | Unit | Open Label: Medication Ambrisentan |
|---|---|---|
| Participants analysed | 15 | |
| Age, Continuous | years | 47.6 (SD 10.7) |
| Sex: Female, Male: Female | Participants | 10 |
| Sex: Female, Male: Male | Participants | 5 |
| Region of Enrollment: United States | Participants | 15 |
| Extent of skin sclerosis | units on a scale | 21 (SD 7.4) |
6. Primary Endpoint
The registry lists the primary outcome as The Benefit That an Antifibrotic Agent and Ambrisentan Combination Have on the Cutaneous Involvement of Patients With Early Diffuse Systemic Sclerosis by Utilizing the MRSS, measured over Baseline and 12 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary outcome concerns cutaneous involvement in people described as having early diffuse systemic sclerosis. It uses the modified Rodnan skin score (MRSS), a clinical measure of skin involvement. The record states that the scale ranges from 0-51 and that higher numbers indicate worse skin involvement. The endpoint is specified at baseline and 12 months, making the intended assessment one of skin score over time.
A skin score is relevant to this study because the stated objective focuses on cutaneous manifestations rather than every possible feature of systemic sclerosis. A standardized clinical measure can make assessments more consistent than an informal description, although the registry record does not report how assessors were trained, whether assessments were blinded, or how measurement consistency was monitored.
The outcome is recorded as a continuous measure summarized by a mean and standard deviation. In general, a mean describes the average score in a group, while a standard deviation describes the spread of individual scores around that average. Neither quantity establishes how much participants changed unless the values at the relevant assessments, or a change estimate, are reported.
The record gives the assessment time points but no baseline mean, 12-month mean, mean change, standard deviation, confidence interval or test result. It therefore does not show the direction, size or precision of any observed change. Although the endpoint title refers to combination therapy, the registered intervention list names ambrisentan alone; the second agent is not identified in the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record provides a stated endpoint and study design, but it does not provide the primary outcome results. There are no reported MRSS means at baseline or 12 months, no reported mean change, and no reported confidence interval or significance test. As a result, the posted information cannot establish whether scores rose, fell or stayed similar during follow-up, nor how precisely an estimated change was measured.
The distinction between an intended outcome and an observed result is important. The primary outcome description says that MRSS would be used to assess cutaneous involvement at baseline and 12 months. That description explains what the investigators planned to measure. It is not itself a finding. Likewise, the study hypothesis about an endothelin receptor antagonist and an antifibrotic agent is a proposed biological rationale, not a result of an analysis.
The design is open-label and single-group. In general, repeated measurements in one group can describe the course of an outcome over time, but a before-and-after pattern cannot by itself identify why that pattern occurred. Changes could reflect treatment, the natural course of disease, other care, changes in measurement, or who remained available for follow-up. A concurrent comparison group can help distinguish these possibilities; none is recorded for this study.
Even if a numerical change were available, its interpretation would depend on the size and uncertainty of the estimate, the completeness of follow-up, the reliability of the measurements and the clinical context. A confidence interval, in general, expresses the range of values reasonably compatible with the data and analysis assumptions. No interval is reported for the primary endpoint, so the precision of any effect cannot be assessed from this record.
The registry lists a secondary quality-of-life outcome assessed by the SF-36, but it does not report its results either. The record also lists 0 analyses. There is consequently no posted statistical result on which to base a conclusion about either the primary skin score or the secondary quality-of-life measure. A completed status indicates that the study is marked completed in the record; it does not substitute for outcome reporting.
The record's adverse-event entries describe reported safety events, not the primary efficacy endpoint. They do not resolve the missing MRSS analysis. Nor can they establish comparative safety, because the study has no recorded control arm and the registry does not give event-level context or a comparative analysis. The available information supports a description of the registered design, endpoints and adverse-event counts, but not an estimate of treatment effect.
9. Statistical Methods Explained
The record identifies MRSS as a continuous primary outcome, summarized using a mean and standard deviation. It lists baseline and 12 months as the assessment times. These entries describe the planned measurement and summary scale, but not the statistical method used to compare assessments. The analysis method is not reported in the registry record.
What does a mean describe?
In general, the mean is the arithmetic average of the observations included in an analysis. For a continuous score, it provides a summary of the group's central level. A mean at baseline and a mean at follow-up can describe the group at each time point, but comparing those two summaries is not necessarily the same as analyzing each participant's change. The registry record does not say whether the primary analysis was planned around follow-up scores, individual changes, or another model.
In general, a standard deviation describes how dispersed observations are around a mean. It is not the same as a standard error: the standard deviation concerns variation among observed scores, while a standard error concerns uncertainty in an estimated quantity. A confidence interval for a mean or mean change would help communicate precision. No such interval, standard error or primary outcome estimate is reported.
What would a repeated-measures analysis address?
In general, when the same participants are measured more than once, the observations are related. An analysis of within-participant change can account for that relationship and may differ from a comparison of group means treated as independent. The appropriate approach depends on the measurement schedule, the analysis question, the assumptions and the available data. The record identifies two assessment times but does not report the model or test used, the handling of within-person correlation, or whether the analysis used all available measurements.
MRSS ranges from 0-51, with higher scores indicating worse skin involvement. This direction helps interpret a reported change if one is available. A lower follow-up score relative to baseline would describe less measured skin involvement on the scale; a higher score would describe more. The record does not report a change estimate, so no direction can be assigned to this study's results.
Why does the single-group design matter?
In general, an uncontrolled before-and-after analysis estimates change over time among observed participants, not the contrast between what happened under treatment and what would have happened under a comparison condition. Time trends, other treatments, participant selection, measurement variability and missing follow-up can all affect a within-group pattern. Random allocation to a concurrent comparator can help balance factors between groups, but allocation is NA and the model is single-group in this record. No causal effect estimate can be recovered from a design description alone.
Open-label status means the record lists no masking. In general, knowledge of treatment may influence subjective reports, clinical assessments or decisions about continued participation. MRSS is a clinical measure, and the registry record does not say whether assessors were masked or how assessment procedures were standardized. These details are not reported in the registry record.
How should uncertainty and significance be read?
In general, a confidence interval communicates the uncertainty around an estimate under the chosen statistical model. A narrow interval indicates greater precision than a wide interval, while an interval's location helps show which effect sizes are compatible with the data. A p-value, when reported, measures how unusual data at least as incompatible with a null hypothesis would be under specified assumptions; it does not measure the probability that a treatment works or the size of an effect. Neither a p-value nor a confidence interval for MRSS is reported in this record. The registry does not report whether any statistical test was performed.
The primary outcome is one of 2 listed outcome measures, with SF-36 quality of life listed as secondary. In general, testing multiple outcomes or time points can increase the chance of at least one apparently notable result if no multiplicity strategy is used. A prespecified hierarchy or adjustment can address that concern, but the analysis plan and any multiplicity procedure are not reported in the registry record. The presence of an outcome listing does not reveal whether it was analyzed or how the results were selected for reporting.
What do the sample-size assumptions mean?
In general, a sample-size calculation is a planning exercise based on an assumed effect, variability, significance level, power and design. It is not a result observed in the trial and cannot establish the precision of the analysis that was actually conducted. The record describes planning illustrations using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation and fractions of an observed effect. It also notes that time-to-event illustrations use total events, while other illustrations use participants per arm. Those assumptions describe a planning framework, not the registered single-group design; the record does not report the trial's own sample-size justification. Such illustrations are not observed power.
In general, the observed effect used in a planning illustration should be treated cautiously, particularly when it comes from a small study: it may be imprecise and can overstate or understate an effect that would be seen elsewhere. Since no primary MRSS result or associated uncertainty is reported, this record does not offer a basis for judging the observed effect or its precision. The registry lists 0 analyses, and the statistical method for the primary endpoint is not reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 2 outcome measures: the MRSS primary outcome and a secondary systemic sclerosis quality-of-life outcome assessed by the SF-36. It does not report a plan for controlling multiplicity across outcomes, time points or analyses. In general, when several hypotheses are tested, the chance of at least one nominally notable result can increase unless the analysis plan accounts for the number and structure of tests. The record does not say whether an adjustment, hierarchy or other strategy was used.
The primary endpoint has two stated assessment times, baseline and 12 months. The record does not explain how those measurements were to be compared, whether other time points were collected, or how multiple measurements would enter an analysis. It does not report an analysis plan or results for either listed outcome. The record lists 0 analyses.
Missing-data handling is not reported in the registry record. It does not state how many participants had an MRSS measurement at each time, whether any observations were missing, why they were missing, or whether the analysis used complete cases, imputation or another approach. These omissions matter because an analysis limited to participants with available follow-up can be affected if follow-up availability is related to health status or outcome.
The analysis population is also not reported. The record does not specify whether the intended analysis included everyone enrolled, those who began medication, or participants with paired measurements. Without an analysis population and participant flow, it is not possible to assess how the results correspond to the enrolled group. No assumptions about missingness, exclusions or adherence can be inferred from the completed status or the enrollment entry.
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 |
|---|---|---|---|
| Open Label: Medication Ambrisentan | 4 | 15 | 26.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Open Label: Medication Ambrisentan | 0 of 15 |
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 |
|---|---|
| Open Label: Medication Ambrisentan | 15 of 15 |
Most frequent serious adverse event terms
| Event term | Organ system | Open Label: Medication Ambrisentan |
|---|---|---|
| Anemia | Blood and lymphatic system disorders | 1 of 15 |
| Lower Extremity Swelling | Product Issues | 1 of 15 |
| Pruritis | Skin and subcutaneous tissue disorders | 1 of 15 |
| Adynamic ileus | Gastrointestinal disorders | 1 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Open Label: Medication Ambrisentan |
|---|---|---|
| Ankle Swelling | Cardiac disorders | 4 of 15 |
| Gastrointestinal illness | Gastrointestinal disorders | 3 of 15 |
| Nasal congestion | Infections and infestations | 3 of 15 |
| Rash | Skin and subcutaneous tissue disorders | 2 of 15 |
| Dizziness | General disorders | 2 of 15 |
| Hypertension | Cardiac disorders | 1 of 15 |
| Flu | Immune system disorders | 1 of 15 |
| Sore throat | Infections and infestations | 1 of 15 |
| Urinary Tract Infection | Infections and infestations | 1 of 15 |
| Headache | Nervous system disorders | 1 of 15 |
Serious events with the highest arm-level rate: anemia (6.7%), lower extremity swelling (6.7%), pruritis (6.7%), adynamic ileus (6.7%).
The registry records 4 participants affected by serious adverse events among 15 at risk in the open-label ambrisentan group. It separately records 15 affected by other adverse events among 15 at risk. These are registry counts for the categories as entered; they do not supply event-level detail, timing, severity distribution or an analysis comparing treatment groups. The record lists 0 deaths.
The serious adverse-event terms with percentages listed are anemia, lower extremity swelling, pruritis and adynamic ileus, each at 6.7%. The record does not state in this listing whether these terms occurred in separate participants or whether any participant had more than one event. The percentages should therefore be read as the registry's reported figures, not converted into additional counts or summed.
Serious adverse events and other adverse events are separate registry categories. The count for other adverse events is not an estimate of serious events, and the listed serious terms do not describe the full safety profile. The record does not report a control group, comparative risk estimate, event attribution method or detailed follow-up period for safety. These entries describe reported events in the study group; they do not establish whether an event was caused by the medication or how the event frequency compares with another treatment.
12. What the Result Does, and Does Not, Mean
The record establishes that an open-label, single-group study of ambrisentan was registered with a primary outcome focused on MRSS at baseline and 12 months. It also establishes that the study is marked completed, with enrollment listed as 15, and that a secondary SF-36 outcome was listed. These registry entries describe the study's registration and intended assessments.
The record does not establish the primary outcome result. It contains no reported MRSS scores, change estimate, confidence interval or statistical test. Therefore, it cannot show whether skin involvement changed during follow-up, how large any change was, or how precise an estimate might be. The same absence of results applies to the listed quality-of-life outcome.
Even with a reported within-group change, a single-group study would not by itself provide the treatment-versus-control contrast needed to distinguish an intervention effect from other changes over time. Open-label assessment and unreported missing-data handling would also be relevant to interpretation. This is a limitation of what can be concluded from the registered design, not a claim about what happened to any participant.
The title and outcome wording refer to combination therapy with an antifibrotic agent, while the intervention list names ambrisentan and does not identify a second agent. The record therefore does not fully specify the combination it describes. That gap limits what can be inferred about the intervention from the registry entry.
The adverse-event entries provide descriptive counts and named serious-event terms, but no control comparison or causal attribution. The number of events recorded should not be treated as proof of safety or harm relative to another option. Taken together, the posted information supports a cautious account of the study's design, stated aims and recorded safety entries, but it does not support a conclusion about efficacy or comparative safety.
13. Why This Trial Matters Statistically
This study is statistically notable as a single-group, open-label investigation of a condition and treatment rationale that the registry describes in terms of challenges for long-term controlled trials. The record's rationale cites rarity, recruitment difficulty, cost and ethical concerns about placebo use in diffuse systemic sclerosis. Those considerations explain why investigators may explore other study designs, but they do not remove the inferential limits of an uncontrolled design.
The primary endpoint also illustrates the difference between selecting a clinically relevant measure and reporting evidence from that measure. MRSS is specified as a continuous skin-involvement score, with higher values indicating worse involvement, and the assessment times are named. Yet without the values, an effect estimate and its uncertainty, readers cannot assess the observed pattern or its precision. Endpoint definition is not a substitute for outcome reporting.
The record also highlights the importance of internal consistency in registry descriptions. The title and endpoint wording describe combination therapy, whereas the intervention list identifies ambrisentan alone and does not name an antifibrotic agent. Clear identification of all study interventions is necessary for readers to know what regimen the outcome is intended to represent.
Finally, the registry lists 0 analyses despite listing primary and secondary outcomes. Without analysis methods, missing-data information, an analysis population or results, statistical interpretation remains limited. The study's completed status and its safety counts are useful descriptive entries, but neither can stand in for a transparent outcome analysis. These features make the record a clear example of why design, measurement, analysis and reporting must all be considered when evaluating clinical evidence.
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 primary endpoint is that results are not reported in the registry record. No MRSS means, changes, dispersion estimates, confidence intervals or test results are available. This prevents assessment of the direction, magnitude and precision of the outcome.
The single-group, open-label design has no recorded comparator. Accordingly, an observed change over time, if one were reported, could not be attributed to the intervention on the basis of this design alone. Allocation is NA and masking is none. The record does not state whether outcome assessors were masked, whether assessments were standardized beyond use of the MRSS, or how other care was handled.
The registry's intervention description is incomplete for a study titled and described as combination therapy. Ambrisentan is named, but no antifibrotic agent is identified in the intervention list. The arm description is also truncated after the dosing information. These gaps limit a precise account of the registered regimen.
Participant flow, eligibility criteria, follow-up completeness, adherence, withdrawals and the analysis population are not reported in the registry record. Missing-data methods and the statistical analysis plan are also absent. The record lists a secondary SF-36 outcome but does not report its results or a multiplicity approach. It lists 0 analyses, leaving no analysis details with which to evaluate these issues.
Safety reporting is limited to event counts, listed serious-event terms and their percentages. The record does not provide comparative data, event timing, attribution or detailed participant-level context. These limitations mean the safety entries should be interpreted descriptively rather than as estimates of comparative risk.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Ambrisentan With Antifibrotic Agent Combination Therapy in Diffuse Systemic Sclerosis — NCT01093885.
- Registry record last updated 2018-11-29; status last verified 2018-11.
- Results first posted 2018-11-29.
- 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
NCT01093885 is recorded as a completed, open-label, single-group study sponsored by the University of Pennsylvania, with enrollment of 15. The study start is listed as 2010-02 and primary completion as 2016-07. Phase and allocation are recorded as NA, and masking is listed as none.
The intervention list names ambrisentan. The primary outcome concerns MRSS at baseline and 12 months; the scale ranges from 0-51, with higher values indicating worse skin involvement. A secondary outcome is systemic sclerosis quality of life assessed by the SF-36. The registry lists 2 outcome measures and 0 analyses.
Primary and secondary outcome results, analysis methods, missing-data handling and analysis populations are not reported in the registry record. Safety entries include serious and other adverse-event counts and 0 deaths. The title and outcome description refer to an antifibrotic combination, but the registry intervention list does not name an antifibrotic agent.