Confirming The Sitaxsentan Dose In Patients Undergoing Heart Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Confirming The Sitaxsentan Dose In Patients Undergoing Heart Surgery (NCT00838383), a randomized phase 2 study. The primary outcome is Percent Change From 0 Hour in Pulmonary Vascular Resistance (PVR) at 0.5 Hour Post-separation From Cardiopulmonary Bypass (CPB).

2. Clinical Question

The question concerns a short-term physiological measurement following cardiac surgery, rather than a long-term clinical outcome. PVR was derived from mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output. The primary outcome used the change from the zero-hour reference to the measurement at 0.5 hour after separation from CPB.

The posted arm summaries describe mean percentage changes and their standard deviations. The registry also reports sponsor analyses comparing each sitaxsentan dose with placebo. Those comparisons are estimates from an analysis of covariance (ANCOVA), with confidence intervals and p-values. The record does not report the covariates used in that analysis, so the extent and nature of its adjustment cannot be assessed from the registry record.

This is a dose-confirmation study in a specific perioperative setting. Its findings address the recorded physiological outcome and other outcomes listed in the registry; they should not be read as evidence about every potential benefit or harm, or about people having other types of surgery.

3. Trial Design

The registry describes NCT00838383 as a completed phase 2, randomized, parallel-group study with no masking. It lists an enrollment of 29 and identifies the sponsor as Pfizer. The study is described as multicenter and included participants undergoing elective CABG, cardiac valve replacement, or combined CABG and valve replacement procedures requiring CPB.

Participants were assigned to sitaxsentan at 1 mg/kg, sitaxsentan at 2 mg/kg, or placebo. The primary outcome population is described as the safety analysis set: participants who received one of the study treatments. For this outcome, the recorded number analyzed means the number evaluable for the measure. The primary outcome summaries include 9 participants in the 1 mg/kg group, 9 in the 2 mg/kg group, and 10 in the placebo group. These are outcome-specific counts and should not be treated as a substitute for the overall enrollment figure.

The registry lists the study start as 2006-08-10 and primary completion as 2008-03-31, with status recorded as completed. The brief summary describes intravenous administration around elective surgery requiring CPB. The registry lists 22 outcome measures, 8 analyses, and 16 secondary results posted.

Although the record gives the three intervention groups and their dose labels, detailed arm descriptions are empty. Specific dosing timing, duration, treatment adherence, and other implementation details are not reported in the registry record. The registry record also does not report a masking procedure, and its design field explicitly records no masking.

The randomized parallel-group structure makes the intended comparisons between each dose group and placebo. However, the record does not give enough detail to assess the randomization sequence, allocation concealment, or any stratification. Those design details are not reported in the registry record and should not be inferred from the fact that the study was randomized.

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

Analysis population for the primary outcome, as defined in the registry: Safety analysis set included all participants who received either sitaxsentan 1 mg/kg, sitaxsentan 2 mg/kg, or placebo during the study. Here, "number of participants analyzed" signifies participants who were evaluable for this outcome measure.

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: Safety analysis set included all participants who received either sitaxsentan 1 mg/kg, sitaxsentan 2 mg/kg, or placebo during the study.

6. Primary Endpoint

The registry lists the primary outcome as Percent Change From 0 Hour in Pulmonary Vascular Resistance (PVR) at 0.5 Hour Post-separation From Cardiopulmonary Bypass (CPB), measured over 0 hour, 0.5 hour post-separation from CPB.

The primary endpoint is percentage change from zero hour in PVR at 0.5 hour after separation from CPB. In the registry, zero hour is the reference point, and separation from CPB is defined as the time immediately following cross-clamp release. PVR is calculated using mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output. The stated formula is (mean PAP minus PCWP) divided by CO, multiplied by 80; cardiac output is described as stroke volume multiplied by heart rate.

PVR is a derived continuous physiological measure: it combines pressure measurements with cardiac output rather than representing a direct count of clinical events. In general, a change measure can describe how a participant’s measurement differs from a specified reference time. A percentage-change endpoint expresses that change relative to the reference value, but the registry does not report the individual-level reference values or the details of how missing measurements were handled.

The measure is used in this study because the investigators were examining endothelin type A receptor inhibition in the immediate period after cardiac surgery with CPB. That rationale follows the trial title and the specified perioperative physiological outcomes; the record does not provide a more detailed mechanistic justification. A short-term PVR measurement can characterize physiology at the stated time point, but it is not by itself a measure of recovery, survival, or longer-term clinical benefit.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a continuous primary endpoint summarized as a mean and standard deviation, along with sponsor-reported ANCOVA comparisons. The following explanations describe general statistical concepts and how they relate to the analyses recorded for this study.

What do the arm summaries describe?

A mean is a measure of the center of a set of numerical observations. Here, each arm mean summarizes percentage change in PVR at the specified postoperative time. The standard deviation describes how dispersed individual observations are around the mean. It is not the same as a confidence interval: standard deviation describes variation among observations, while a confidence interval describes uncertainty in an estimated quantity.

The standard deviations are large, especially in the placebo group. In general, substantial dispersion makes it harder to estimate a group mean or a between-group contrast precisely, particularly when the number of observations is limited. It also means the group mean may not describe the experience of an individual participant. The registry does not provide the individual observations or a distributional plot in the registry record for this interpretation, so the shape of the data and the influence of extreme observations cannot be assessed.

What does the ANCOVA comparison estimate?

ANCOVA is a general method for comparing group outcomes while accounting for one or more covariates. The registry reports the result as a mean difference (net) for each sitaxsentan dose versus placebo. The reported estimate is -70.0 for 1 mg/kg versus placebo and -73.2 for 2 mg/kg versus placebo. The record does not identify the covariates, the model specification, or the handling of assumptions; those details are not reported in the registry record.

Because the registry labels these estimates as ANCOVA results, they should be understood as the sponsor’s reported analysis, not as a simple subtraction of the displayed arm means. Adjusted and unadjusted estimates can differ because adjustment can account for measured covariates. Without the model details and covariate values, the specific contribution of adjustment cannot be evaluated.

How should the confidence intervals be read?

A confidence interval expresses statistical uncertainty around an estimate under the assumptions of the analysis. The 95% intervals for both reported comparisons include zero and are broad. In general, zero represents no mean difference on the scale of a difference. These intervals therefore leave considerable uncertainty about both the magnitude and direction of the underlying contrast. They do not prove that the groups are identical, nor do they by themselves establish a clinically important effect.

A p-value measures how incompatible the observed data are with a specified statistical null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The record reports p-values for the two ANCOVA comparisons. Their interpretation should remain connected to the corresponding estimates, wide confidence intervals, and the trial’s broader analysis context rather than being treated as a stand-alone verdict.

Why does over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a model would expect under its assumed distribution. The reported standard deviations point to substantial variability in the continuous endpoint, although the registry record does not formally label this as over-dispersion or report a diagnostic assessment. When variability is high, uncertainty can increase and model assumptions become more consequential. A careful assessment would usually consider the outcome distribution, influential values, and whether the chosen model adequately represents the data; the relevant diagnostics are not reported in the registry record.

The endpoint is calculated from several physiological measurements. In general, derived measures can inherit measurement variability from their component quantities. The registry provides the formula but does not report measurement reliability, timing deviations, or how component measurements were processed when unavailable. Those details cannot be assumed.

What do the planning illustrations mean?

Any sample-size outputs associated with this record are planning illustrations based on the observed effect, not observed power. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such calculations illustrate the sample size a future study might require under those assumptions. They do not show the probability that this completed trial detected an effect, and they are not evidence that the original design was adequately powered.

The registry record does not report the trial’s own sample-size justification, target effect, or formal power calculation. It also does not report whether an interim analysis was planned or conducted. No assumptions about those features should be inferred from planning illustrations based on the observed outcome.

What can be inferred from the analysis record?

The registry lists 8 analyses and identifies ANCOVA for the two primary comparisons. It does not give a complete statistical analysis plan, explain whether covariates were prespecified, or describe model diagnostics. General statistical interpretation therefore has to distinguish the quantities that are posted from the methods details that are not. The posted estimates and confidence intervals describe the reported analysis; they do not supply the missing information about model selection, departures from assumptions, or robustness checks.

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("Sitaxsentan (1 mg/kg)", "Sitaxsentan (2 mg/kg)", "Placebo")
n   <- c(9, 9, 10)
m   <- c(-7.75, -10.94, 62.22)
sp  <- c(55.277, 37.967, 260.172)
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  Sitaxsentan (1 mg/kg)  9  -7.750  55.277  -50.240  34.740
CARM  Sitaxsentan (2 mg/kg)  9  -10.940  37.967  -40.124  18.244
CARM  Placebo  10  62.220  260.172  -123.896  248.336

11. Analyses Reported by the Sponsor

The sponsor’s reported primary analyses are ANCOVA comparisons of each sitaxsentan dose with placebo. The registry gives a mean difference (net) of -70.0, with a 95% confidence interval from -291.3 to 151.4, for 1 mg/kg versus placebo. For 2 mg/kg versus placebo, it gives -73.2, with a 95% confidence interval from -294.5 to 148.2. The record also reports the corresponding p-values.

The displayed arm means are descriptive summaries, whereas the ANCOVA estimates are results from the sponsor’s model. They are not necessarily numerically identical to an unadjusted difference between the arm means. The covariates and model details are not reported in the registry record, so the adjustment cannot be reconstructed from the record.

No separate recalculated comparison estimate is reported in the registry record, so a numerical comparison between an unadjusted recalculation and the sponsor’s ANCOVA result cannot be made from the recorded details. The discrepancy indicator is false. The sponsor’s analysis remains the reported inferential analysis, and the wide confidence intervals convey substantial uncertainty in both dose-versus-placebo contrasts.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists 22 outcome measures, 8 analyses, and 16 secondary results posted. Multiple outcomes and comparisons raise a general multiplicity concern: as the number of statistical tests increases, the chance of obtaining at least one seemingly unusual result by chance can increase. The appropriate response depends on which outcomes were prespecified as primary, how comparisons were prioritized, and whether an adjustment or hierarchical testing strategy was planned.

The registry identifies a primary PVR endpoint and reports two dose-versus-placebo ANCOVA comparisons. It does not report a multiplicity adjustment, testing hierarchy, or a complete statistical analysis plan. It is therefore not possible to determine from the registry record whether the two primary contrasts or the secondary outcomes were treated as confirmatory, or how the family of tests was defined. Unadjusted secondary findings should be regarded cautiously and should not be elevated on the basis of a nominal p-value alone.

The primary analysis population is described as the safety analysis set, consisting of participants who received one of the study treatments. For the primary outcome, the recorded number analyzed means the number evaluable for the measure. The endpoint summaries give group-specific counts, but the registry does not explain why those counts differ or how missing measurements were handled. It does not report whether missingness was related to treatment, surgery, outcome status, or other factors.

The record also does not state whether analyses followed an intention-to-treat principle, whether participants were analyzed according to assigned treatment, or how protocol deviations were addressed. These details are not reported in the registry record. Because the endpoint is measured after surgery, unavailable measurements could matter to interpretation, but the record does not provide enough information to characterize that possibility or its impact.

The sample-size justification, planned interim analyses, and methods for handling missing data are not reported in the registry record. Their absence limits assessment of the original inferential plan and of whether the posted analyses represent all planned comparisons. It is not appropriate to infer a specific analysis strategy from the outcomes or results that are listed.

13. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiovascular disorder (20.0%), wound infection (20.0%), cardiac arrest (11.1%), cardiogenic shock (11.1%), myocardial infarction (11.1%).

The registry reports serious adverse events among participants at risk in each treatment group. For sitaxsentan at 1 mg/kg, 2 of 9 participants at risk had a serious adverse event; for sitaxsentan at 2 mg/kg, 5 of 10 did; and for placebo, 4 of 10 did. These are descriptive counts from a small study and should not be treated as precise estimates of comparative risk. The record also lists other adverse events for 9 of 9 participants in the 1 mg/kg group, 9 of 10 in the 2 mg/kg group, and 9 of 10 in the placebo group.

The most frequently listed serious-event terms include cardiovascular disorder and wound infection, each recorded as 20.0%; cardiac arrest, cardiogenic shock, myocardial infarction, and ventricular tachycardia are each listed as 11.1%. These terms describe events recorded in the registry, not necessarily events judged to be caused by study treatment. The record does not provide enough detail to assess event timing, duration, severity grading, or attribution by treatment.

Death counts are not reported in the registry record. The group counts should be read as safety summaries, not as a controlled estimate of relative safety. With limited group sizes and no detailed event-level context, apparent differences cannot establish a treatment-related pattern.

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

The results describe a randomized comparison of two sitaxsentan doses with placebo for short-term percentage change in PVR after separation from CPB. The arm summaries show different mean values, but they also show substantial variability. The sponsor’s ANCOVA estimates have broad 95% confidence intervals that include zero, leaving considerable uncertainty about the size and direction of each dose-versus-placebo contrast.

That uncertainty does not mean the groups are proven identical. A wide interval can remain compatible with a range of effects, and the posted estimates do not precisely distinguish among those possibilities. Conversely, the point estimates alone do not establish an important effect. The registry record does not define a clinically meaningful threshold for PVR change, so clinical importance cannot be judged against a prespecified threshold from these registry entries.

The primary outcome is a physiological measure at a specific postoperative time, not a direct measure of survival, long-term recovery, or later cardiovascular events. The registry lists several other perioperative outcomes, but their presence does not mean that the primary result predicts those outcomes. The registry entries do not support conclusions beyond the measures and time points recorded.

The study’s randomized design is relevant to the intended treatment comparisons, but the registry does not report enough detail about allocation procedures, analysis populations, missing data, or model covariates to assess all potential sources of bias. Its unmasked status is recorded. The study’s size and the variation in the primary endpoint also limit the precision of its estimates.

Accordingly, the posted results are best understood as uncertain estimates from a phase 2 dose-confirmation study in cardiac surgery participants requiring CPB. They neither establish a definitive treatment effect nor demonstrate the absence of one. They do not provide medical advice, and they should not be generalized automatically to other populations, procedures, or outcomes.

15. Why This Trial Matters Statistically

This study illustrates why a numerical difference between group means is not enough to establish a clear statistical conclusion. The primary arm summaries point in different directions for placebo and the sitaxsentan groups, but their variability is substantial. The sponsor’s ANCOVA estimates add a formal comparison, while the broad confidence intervals make clear that the estimates are imprecise.

It also shows the distinction between descriptive statistics and model-based comparisons. The group means summarize the observed outcome values. The ANCOVA results are estimates from a model, but the registry does not identify its covariates or full specification. Readers should not assume that the ANCOVA estimates can be recreated simply by subtracting the displayed means, or that the adjustment is fully assessable from the posted record.

The endpoint itself is a derived physiological measure assembled from several components and taken at a defined perioperative time. This makes the clinical question specific, while also underscoring the need for clear measurement and missing-data details. Those details are not reported in the registry record.

Finally, the record lists many outcome measures and secondary results. That breadth can be useful for describing what was assessed, but it makes prespecification and multiplicity important. Without a reported analysis plan or multiplicity strategy, isolated secondary findings deserve less weight than a clearly prioritized primary analysis. The study is therefore a useful example of how design information, outcome definitions, uncertainty, and reporting completeness all shape interpretation—not just the direction of a point estimate.

16. 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.

Several limitations specific to this record constrain interpretation. The study enrolled 29 participants, and the primary outcome summaries include 9, 9, and 10 evaluable participants across the treatment groups. The confidence intervals are wide, and the reported standard deviations indicate considerable variation. The estimates are therefore imprecise for the primary physiological outcome.

The registry records no masking. It does not report allocation concealment, the randomization method, or whether outcome assessors were masked. These details are not reported in the registry record, so the possibility of bias in treatment delivery or measurement cannot be fully assessed.

The sponsor’s ANCOVA comparisons are reported, but the covariates, model specification, assumptions, and diagnostic checks are not. The record also does not explain missing outcome data, provide reasons for the outcome-specific analyzed counts, or state the analysis population strategy beyond defining the safety analysis set and evaluable participants. These gaps limit assessment of robustness.

The study has a short-term primary endpoint and several perioperative secondary outcomes. Longer-term outcomes and a detailed clinical interpretation threshold for the primary measure are not reported in the registry record. The record does not provide a sample-size justification, interim-analysis information, or a complete statistical analysis plan. It also does not report how multiplicity was handled across outcomes and comparisons.

Finally, the safety summaries give group counts and selected serious-event terms, but detailed event-level information and death counts are not reported in the registry record. These limitations do not invalidate the posted summaries; they define how cautiously the estimates and safety counts should be interpreted.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Confirming The Sitaxsentan Dose In Patients Undergoing Heart Surgery — NCT00838383.
• Registry record last updated 2022-09-08; status last verified 2022-08.
• Results first posted 2022-09-08.
• 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.

20. Record Summary

NCT00838383 is a completed randomized, unmasked, parallel-group phase 2 study of intravenous sitaxsentan at 1 mg/kg or 2 mg/kg versus placebo in people undergoing elective cardiac surgery requiring CPB. The registry lists enrollment of 29, a start date of 2006-08-10, and primary completion on 2008-03-31.

The primary outcome was percentage change in PVR at 0.5 hour after separation from CPB. The arm summaries show substantial variability, and the sponsor’s ANCOVA comparisons with placebo have broad 95% confidence intervals that include zero. The record also lists perioperative secondary outcomes and safety results, but important details about the analysis plan, missing data, model specification, and multiplicity are not reported in the registry record.