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 Sitaxsentan Efficacy And Safety Trial With A Randomized Prospective Assessment Of Adding Sildenafil (SR-PAAS) (NCT00795639), a randomized phase 3 study. The primary outcome is Change From Baseline in Total Distance Walked During 6 Minute Walk Distance (6MWD) at Week 12.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00795639 |
| Phase | Phase 3 |
| Condition | Pulmonary Arterial Hypertension, Pulmonary Hypertension |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 183 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned subjects with pulmonary arterial hypertension. Its registry description also lists pulmonary hypertension as a condition. The primary endpoint population is the intent-to-treat population, defined as all participants who were randomized. The registry reports enrollment of 183 participants. It does not report further participant characteristics in the record, such as age, disease severity, prior treatment, or eligibility details. Those details therefore cannot be used to characterize who the findings would apply to beyond the stated study population.
Intervention
The intervention was sitaxsentan, described as monotherapy. The registry identifies it as a drug, but does not report the dose, schedule, or other administration details in this record. The study was described as a phase 3 investigation and as the first of 3 studies in the Sitaxsentan Efficacy and Safety Trial with Randomized Prospective Assessment of Adding Sildenafil program. That program description does not mean this study tested adding sildenafil: the listed intervention arms are sitaxsentan and sitaxsentan placebo, both described as monotherapy.
Comparator
The comparator was placebo, with the placebo arm also described as monotherapy. The registry identifies randomized allocation and double masking, but the randomization ratio and the details of masking are not reported in the registry record. The record describes a parallel-group design. It does not report whether participants could receive other concurrent treatments or how such treatments were handled in the analysis. The trial’s listed intervention comparison is sitaxsentan versus placebo.
Primary question
The primary question concerned change from baseline in total distance walked during the 6-minute walk distance test at Week 12. The registry defines change as the Week 12 result minus the baseline result, with distance measured in meters. Participants walked at a comfortable pace and could take as many breaks as needed; continuous pulse oximetry was used during the test for safety. The registry identifies the median and full range as the endpoint summary. It does not report a numerical treatment contrast, confidence interval, or p-value for this endpoint in the record. Thus, the research question can be described, but the magnitude and precision of the posted primary endpoint result cannot be assessed from the registry record.
3. Trial Design
This was a phase 3, multicenter, randomized, double-blind, placebo-controlled study with a parallel-group design. Its official title describes a safety and efficacy study of sitaxsentan sodium in subjects with pulmonary arterial hypertension. The listed arms were sitaxsentan monotherapy and sitaxsentan placebo monotherapy. The registry reports enrollment of 183 participants. It does not state the randomization ratio, the allocation concealment procedure, or the operational details used to maintain masking.
The registry lists the study status as terminated. The start is recorded as 2008-12 and primary completion as 2011-03. The reason for termination is not reported in the registry record, so the status alone does not establish whether termination was related to safety, efficacy, recruitment, funding, or another consideration. The sponsor is Pfizer.
The primary outcome was change from baseline in total distance walked during a 6-minute walk test at Week 12. Secondary outcomes listed were change from baseline in World Health Organization Functional Classification at Weeks 4, 8 and 12, and time to clinical worsening. The registry lists 3 outcome measures and 2 analyses, but the details and results of all analyses are not reported in the registry record. The posted primary endpoint summary is specified as a median with full range, but a numerical estimate is not present in the registry record.
The trial’s stated intent-to-treat population included all randomized participants. For missing Week 12 values, the registry says the last non-missing value was carried forward, including a non-missing value collected at early termination. Other design details, including recruitment targets, sample-size justification, interim monitoring, and a prespecified analysis plan, are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Sitaxsentan | Placebo |
|---|---|---|
| STARTED | 91 | 92 |
| Randomized and Not Treated | 0 | 1 |
| COMPLETED | 70 | 66 |
| NOT COMPLETED | 21 | 26 |
Reasons for not completing this period:
| Reason | Sitaxsentan | Placebo |
|---|---|---|
| Death | 1 | 6 |
| Withdrawal by Subject | 1 | 3 |
| Pregnancy | 1 | 0 |
| Adverse Event | 5 | 2 |
| Other | 0 | 2 |
| Terminated by sponsor | 13 | 12 |
| Randomized and not treated | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Intent to treat population (ITT): all participants who were randomized; missing value at Week 12 imputed with last non-missing value, including the non-missing value obtained at early termination based on last observation carried forward (LOCF)
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 | Sitaxsentan | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 91 | 91 | 182 | |
| Age, Customized: less than 18 years | participants | 0 | 3 | 3 |
| Age, Customized: 18 to 44 years | participants | 53 | 53 | 106 |
| Age, Customized: 45 to 64 years | participants | 30 | 26 | 56 |
| Age, Customized: greater than or equal to 65 years | participants | 8 | 9 | 17 |
| Sex: Female, Male: Female | Participants | 71 | 68 | 139 |
| Sex: Female, Male: Male | Participants | 20 | 23 | 43 |
| World Health Organization (WHO) Functional Class: Functional Class I | Participants | 0 | 0 | 0 |
| World Health Organization (WHO) Functional Class: Functional Class II | Participants | 2 | 0 | 2 |
| World Health Organization (WHO) Functional Class: Functional Class III | Participants | 88 | 87 | 175 |
| World Health Organization (WHO) Functional Class: Functional Class IV | Participants | 0 | 0 | 0 |
| World Health Organization (WHO) Functional Class: Functional Class Unknown | Participants | 1 | 4 | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Total Distance Walked During 6 Minute Walk Distance (6MWD) at Week 12, measured over Baseline/Day 1 and Week 12.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | Meters (m) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was change from baseline in total distance walked during the 6-minute walk distance test at Week 12. Distance is measured in meters, and the registry defines change as the Week 12 result minus the baseline result. A positive change under that definition would indicate a greater distance at Week 12 than at baseline, while a negative change would indicate a shorter distance; this describes the direction of the measure, not a finding from this trial.
In general, a timed walking test can summarize functional exercise capacity using a task that is observable and quantifiable. The registry’s instructions allowed participants to walk at a comfortable pace and take as many breaks as needed. Continuous pulse oximetry was conducted during the test for safety. These procedures describe how the outcome was collected; the registry does not report additional details on test standardization or assessor training.
The endpoint was summarized using the median and full range. In general, the median describes the middle of the observed distribution and is less influenced by extreme values than the mean. The full range displays the minimum and maximum observed values, but can be sensitive to extremes and does not convey the distribution of values between them. The numerical median, range, and between-arm contrast are not reported in the registry record. Consequently, the size and precision of any difference in walking distance cannot be judged from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a randomized, double-blind comparison of sitaxsentan monotherapy with placebo monotherapy in subjects with pulmonary arterial hypertension. It specifies a Week 12 primary endpoint based on change from baseline in 6-minute walk distance, summarized as a median and full range. However, the registry record does not report the numerical primary endpoint results. Without arm-specific estimates or a treatment contrast, it is not possible to describe the direction or magnitude of the observed primary outcome difference.
The record also does not report a confidence interval or p-value for the primary outcome. A confidence interval, in general, indicates the precision of an estimated effect and the range of values compatible with the data under the analysis assumptions. A p-value, in general, measures how unusual the data would be under a specified null hypothesis and statistical model. Neither can be interpreted for the primary endpoint from the information in the registry record. The absence of these values should not be treated as evidence of no difference, evidence of a difference, or evidence that an effect is precisely estimated.
Secondary outcomes included change in World Health Organization Functional Classification at Weeks 4, 8 and 12, and time to clinical worsening. The registry record does not report their results or the corresponding uncertainty measures. The record lists 3 outcome measures and 2 analyses, but does not provide enough detail to reconstruct the analysis set, model, or all reported comparisons. The registry also does not report subgroup results or an account of how the listed secondary outcomes relate to any confirmatory claims.
The trial is marked terminated, but the reason is not reported in the registry record. Termination is a study-status description, not an explanation of the results. It cannot by itself show whether the trial stopped because of a treatment effect, safety concern, recruitment difficulty, or an administrative decision.
The registry reports safety counts by arm, including participants with serious and other adverse events, as well as a list of serious adverse event terms and percentages. These are descriptive safety data. The listed terms are not assigned to a particular arm in the record, and the death counts are not reported. Such limitations prevent a complete comparison of safety outcomes. Overall, the posted record documents the question, design, endpoint definition, missing-value rule, and some safety counts, but does not provide the primary efficacy estimate or the details needed for a full statistical interpretation.
9. Statistical Methods Explained
The primary outcome is a continuous distance measure, defined as the Week 12 6-minute walk distance minus the baseline distance. The registry identifies the median and full range as the summary statistics. In general, a median is the central observation after values are ordered. It can be useful when a distribution is skewed or contains extreme values, because an extreme observation has less influence on the median than on the mean. The full range reports the lowest and highest observations, but it does not show how densely values cluster between those endpoints. No numerical median or range is reported for the primary outcome in the registry record.
What does change from baseline represent?
A change score expresses each participant’s follow-up value relative to that participant’s baseline value. Here, the stated calculation is Week 12 results minus baseline results. In general, change scores can account for differences in starting values when describing within-participant movement. A comparison of change between randomized arms is still needed to estimate how the arms differed over the study period. The registry does not report an arm-level contrast or a confidence interval for that contrast, so the change definition alone does not establish a treatment effect.
The stated endpoint time was Week 12, with baseline measured at Baseline/Day 1. The walking test allowed a comfortable pace and breaks as needed, and continuous pulse oximetry was conducted for safety. In general, consistent administration matters because variation in instructions or test conditions can contribute to measurement variability. Further detail about test oversight, repeat testing, or assessor procedures is not reported in the registry record.
How should uncertainty be assessed?
In general, an effect estimate describes the observed contrast, while a confidence interval communicates its statistical precision. A narrow interval usually indicates greater precision than a wide interval, although interpretation depends on the design and model. A p-value addresses compatibility with a specified null hypothesis, not the size or practical importance of an effect. The registry record does not report the primary endpoint’s estimate, confidence interval, or p-value. There is therefore no basis in the posted primary outcome information to evaluate either the direction or precision of the contrast.
The registry’s sample-size assumptions describe a planning illustration based on the observed effect, a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For time-to-event outcomes, the illustration is defined in total events; for other outcomes, it is defined in participants per arm. These are planning assumptions, not a report of the trial’s original design justification. The numerical planning values and the fractions used are not reported in the registry record. Such calculations should not be interpreted as observed power. In general, power is a design-stage probability under specified assumptions; a post hoc calculation based on an observed effect does not establish how persuasive or precise the trial’s result is.
The registry indicates that the primary outcome has several categories or time points and is not reduced to one comparison. This limits the usefulness of a single simplified comparison for interpreting the posted outcome. In general, when outcomes or time points create multiple opportunities for testing, the chance of at least one apparently notable result can increase unless multiplicity is addressed. The registry record does not report a multiplicity adjustment or a hierarchy of hypotheses, so it is not possible to determine how multiple outcomes or comparisons were handled.
What does the analysis population mean?
The primary endpoint population is described as intent to treat and includes all participants who were randomized. In general, an intent-to-treat analysis preserves the randomized group assignment and aims to retain participants regardless of whether they completed the assigned treatment. This can help preserve the comparability created by randomization. The registry does not report further details about exclusions, analysis denominators at each time point, or sensitivity analyses.
For missing Week 12 values, the record specifies last observation carried forward. A last non-missing value was carried forward, including a non-missing value from early termination. In general, this approach substitutes an earlier measurement for a missing later measurement. It assumes, for the purpose of that substitution, that the earlier value can stand in for the unobserved Week 12 value. If participant outcomes continue to change after the last observed measurement, the carried-forward value may not represent the outcome that would have been measured at Week 12. The direction and size of any resulting bias depend on the missingness and outcome patterns; those patterns are not reported in the registry record. No alternative missing-data analyses are reported.
The record does not report the statistical test or model used for the primary outcome, whether adjustment for baseline values was applied, or how the full range was calculated across arms. It also does not report an interim analysis plan or a sample-size justification. These details are necessary for a fuller assessment of model assumptions and analysis choices, but they cannot be inferred from the outcome label or study design.
10. Multiplicity, Missing Data and Analysis Populations
The listed secondary outcomes were change from baseline in World Health Organization Functional Classification at Weeks 4, 8 and 12, and time to clinical worsening. The primary outcome also concerns a follow-up time point. When several outcomes, time points, or analyses are examined, multiple testing can increase the chance of obtaining at least one apparently notable result by chance. In general, multiplicity procedures can control this risk or a prespecified hierarchy can clarify which comparisons are confirmatory. The registry record does not report whether such a procedure or hierarchy was used. It also does not report the analysis plan in enough detail to identify how outcomes and time points were prioritized.
The primary analysis population is described as all randomized participants. This is an intent-to-treat definition, but the record does not report the number analyzed for each outcome or details of any exclusions after randomization. Missing Week 12 values were handled using last observation carried forward, including a non-missing value obtained at early termination. This rule is explicit, but its impact cannot be assessed without information about how many values were missing, when observations ended, and how missingness differed between arms. Those details are not reported in the registry record.
In general, carrying forward an earlier measurement is a simple imputation approach that treats that observation as a substitute for the missing follow-up value. It does not directly represent uncertainty about the unobserved value. Sensitivity analyses can explore whether conclusions change under alternative assumptions, but such analyses are not reported in the registry record. The record also does not report interim analyses, stopping rules, a missing-data sensitivity plan, or a multiplicity adjustment. No conclusion about these methods should be inferred from the terminated status or the number of listed analyses.
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 |
|---|---|---|---|
| Sitaxsentan | 9 | 91 | 9.9% |
| Placebo | 12 | 91 | 13.2% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 3% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sitaxsentan | 23 of 91 |
| Placebo | 24 of 91 |
Most frequent serious adverse event terms
| Event term | Organ system | Sitaxsentan | Placebo |
|---|---|---|---|
| Cardiac failure | Cardiac disorders | 1 of 91 | 2 of 91 |
| Right ventricular failure | Cardiac disorders | 1 of 91 | 1 of 91 |
| Sudden cardiac death | General disorders | 2 of 91 | 0 of 91 |
| Alanine aminotransferase increased | Investigations | 2 of 91 | 0 of 91 |
| Aspartate aminotransferase increased | Investigations | 2 of 91 | 0 of 91 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 1 of 91 | 1 of 91 |
| Anaemia | Blood and lymphatic system disorders | 1 of 91 | 0 of 91 |
| Acute myocardial infarction | Cardiac disorders | 0 of 91 | 1 of 91 |
| Acute right ventricular failure | Cardiac disorders | 0 of 91 | 1 of 91 |
| Arrhythmia | Cardiac disorders | 0 of 91 | 1 of 91 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sitaxsentan | Placebo |
|---|---|---|---|
| Oedema peripheral | General disorders | 5 of 91 | 8 of 91 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 3 of 91 | 7 of 91 |
| Vomiting | Gastrointestinal disorders | 2 of 91 | 5 of 91 |
| Aspartate aminotransferase increased | Investigations | 5 of 91 | 2 of 91 |
| Dizziness | Nervous system disorders | 5 of 91 | 2 of 91 |
| Chest pain | General disorders | 2 of 91 | 3 of 91 |
| Fatigue | General disorders | 1 of 91 | 4 of 91 |
| Oedema | General disorders | 3 of 91 | 2 of 91 |
| Alanine aminotransferase increased | Investigations | 4 of 91 | 1 of 91 |
| Decreased appetite | Metabolism and nutrition disorders | 1 of 91 | 4 of 91 |
Serious events with the highest arm-level rate: cardiac failure (2.2%), sudden cardiac death (2.2%), alanine aminotransferase increased (2.2%), aspartate aminotransferase increased (2.2%), anaemia (1.1%).
The registry reports 91 participants at risk in each arm for the serious adverse event summary. Serious adverse events affected 9 participants in the sitaxsentan group and 12 in the placebo group. For other adverse events, 23 participants in the sitaxsentan group and 24 in the placebo group were affected, with 91 participants at risk in each arm. These are participant counts, not event rates calculated for comparison. The record does not report a statistical comparison or uncertainty interval for these counts.
The listed serious adverse event terms and percentages are cardiac failure, 2.2%; sudden cardiac death, 2.2%; alanine aminotransferase increased, 2.2%; aspartate aminotransferase increased, 2.2%; anaemia, 1.1%; and acute myocardial infarction, 1.1%. The registry record does not assign these listed terms to a particular arm in the information. The death counts are not reported in the registry record.
In general, adverse event counts are descriptive and do not by themselves establish that an event was caused by the study intervention. Interpretation also depends on event definitions, follow-up duration, ascertainment, and the number of participants exposed over time. Those details are not reported in the registry record. The listed counts should therefore be read as the safety information recorded, not as a complete comparative assessment.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, double-blind, placebo-controlled, parallel-group phase 3 study was conducted in pulmonary arterial hypertension, with sitaxsentan and placebo monotherapy arms. It specifies a primary endpoint based on change in 6-minute walk distance at Week 12, and it defines the intent-to-treat population and a last-observation-carried-forward rule for missing Week 12 measurements. These details clarify the study question and some aspects of how the primary outcome was to be handled.
The record does not report the numerical primary outcome result, a treatment contrast, a confidence interval, or a p-value. It therefore does not allow a reader to determine the observed direction, magnitude, or precision of the primary endpoint comparison. This lack of reported result should not be interpreted as proof of benefit, lack of benefit, equivalence, or no difference. The listed secondary outcomes likewise have no numerical results reported in the registry record.
The safety record gives counts of participants affected by serious and other adverse events and lists several serious adverse event terms with percentages. It does not provide the arm attribution for each listed term, death counts, or a comparative statistical analysis. The counts can describe what was recorded, but they are not enough to establish causation or a comprehensive between-arm safety difference.
The terminated status is also limited information: the reason for termination is not reported in the registry record. It should not be used as a substitute for efficacy or safety results. More broadly, the record does not report the original sample-size justification, interim analysis plan, full statistical analysis plan, or sensitivity analyses for missing data. Those omissions constrain interpretation of the study’s statistical evidence, but do not establish what those methods or results would have been.
13. Why This Trial Matters Statistically
This trial raises several statistical issues that matter when reading registry results. First, the primary endpoint is a change score summarized by the median and full range. Those summaries describe the center and extremes of the observed data, but they do not by themselves quantify the between-arm effect or its precision. Without arm-level estimates and an uncertainty measure, the endpoint’s statistical evidence cannot be assessed from the registry record.
Second, missing follow-up values were handled with last observation carried forward. This makes the missing-data rule visible, which is important for interpretation, but it does not show how much missing data occurred or whether the rule affected the findings. The inclusion of measurements obtained at early termination is specifically stated. Alternative analyses that examine sensitivity to missing-data assumptions are not reported in the registry record.
Third, multiple outcomes and time points are listed. In general, examining multiple comparisons requires attention to the risk of chance findings and to which results were prespecified as primary or confirmatory. A multiplicity strategy or detailed outcome hierarchy is not reported in the registry record. The primary endpoint is also described as having several categories or time points and is not reduced to a single comparison, so a simplified one-comparison reading would omit that complexity.
Finally, the registry contains a planning illustration based on the observed effect and specified assumptions. Such a calculation is not the same as the trial’s original sample-size justification and is not observed power. The record does not report the original justification. Together, these features show why the endpoint definition, analysis population, missing-data rule, and multiplicity context should be considered alongside any numerical result. In this record, the central efficacy estimate itself is not reported, limiting what can be concluded statistically.
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 interpretation is that the registry record does not report numerical results for the primary endpoint. It gives the endpoint definition, time point, summary measure, and population, but not the arm-specific changes or the contrast between arms. The corresponding confidence interval and p-value are also not reported. This prevents assessment of effect magnitude, direction, and precision.
The record lists secondary outcomes, but does not report their numerical findings or inferential results. It also does not provide a detailed statistical analysis plan, test or model for the primary endpoint, baseline adjustment details, or a multiplicity strategy. Consequently, the planned relationship among outcomes and analyses cannot be established from the registry record.
Although the missing-data rule is stated, the amount and pattern of missing Week 12 data are not reported. No sensitivity analyses are reported to assess whether the last-observation-carried-forward assumption affected results. The registry also does not report the original sample-size justification, interim analyses, or stopping rules. The reason the study was terminated is not reported in the registry record.
The safety information is limited to participant counts and listed serious adverse event terms with percentages. The listed terms are not assigned to arms in the record, death counts are not reported, and no comparative analysis is provided. Details such as event follow-up duration and ascertainment procedures are not reported. These omissions limit comparisons and causal interpretation; they do not establish that unreported outcomes or analyses had any particular result.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Sitaxsentan Efficacy And Safety Trial With A Randomized Prospective Assessment Of Adding Sildenafil (SR-PAAS) — NCT00795639.
- Registry record last updated 2015-03-24; status last verified 2015-03.
- Results first posted 2012-03-01.
- 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
The registry describes NCT00795639 as a phase 3, randomized, double-blind, parallel-group, placebo-controlled study of sitaxsentan monotherapy in subjects with pulmonary arterial hypertension. Enrollment was 183, and the status is terminated. The start is recorded as 2008-12 and primary completion as 2011-03; the sponsor is Pfizer.
The primary endpoint was change from baseline in 6-minute walk distance at Week 12, summarized as a median and full range. The intent-to-treat population included all randomized participants, and missing Week 12 values were handled by carrying forward the last non-missing value, including a value from early termination. Secondary outcomes included change in World Health Organization Functional Classification and time to clinical worsening.
The numerical primary endpoint findings, confidence interval, p-value, reason for termination, and detailed analysis plan are not reported in the registry record. Safety counts are reported, but the listed serious adverse event terms are not assigned to an arm in the record, and death counts are not reported.