Esmolol vs. Labetalol in Endoscopic Sinus Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Esmolol vs. Labetalol in Endoscopic Sinus Surgery (NCT03661346), a randomized phase 2 study. The primary outcome is Intra-operative Surgical Visibility - Boezaart Scale.

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-masked, parallel Phase 2 trial comparing esmolol with labetalol in endoscopic sinus surgery. The condition listed is chronic sinusitis. The study is marked completed, and the registry enrollment is 28. The listed start date is 2017-03-01 and the primary completion date is 2018-03-30. The sponsor is The University of Texas Medical Branch, Galveston.

Both arm descriptions specify medication use when intra-operative mean arterial pressure was > 80 mmHg. The record does not describe the precise randomization procedure, allocation concealment, masking roles, or medication administration details, so these features cannot be characterized further from the registry record.

The primary outcome was intra-operative surgical visibility, assessed over the duration of the operation. The posted results give a mean and standard deviation for each arm and identify the analyzed patients as those with complete data. The reported primary-outcome group sizes are 13.0 for esmolol and 15.0 for labetalol. The registry also lists rate of blood loss, average mean arterial blood pressure, and average heart rate as secondary outcomes. Three secondary outcomes have posted results.

No sponsor-reported statistical analyses are listed. The comparisons discussed in the statistical interpretation are unadjusted recalculations from the posted summary statistics, rather than analyses reported in the registry. The record does not report a protocol-level sample-size justification or a detailed analysis plan.

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: Those analyzed had complete data

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: Patients with chronic rhinosinusitis undergoing FESS

6. Primary Endpoint

The registry lists the primary outcome as Intra-operative Surgical Visibility - Boezaart Scale, measured over Duration of operation.

The primary endpoint was intra-operative surgical visibility measured with the Boezaart scale over the duration of the operation. The registry describes the scale as ranging from 0 to 5. A score of 0 denotes no bleeding and optimal visibility; a score of 5 denotes severe bleeding, constant suctioning, and a compromised view. Intermediate categories describe increasing bleeding and suctioning requirements, including whether visibility is compromised when suction is removed.

This type of rating is used to characterize the surgeon’s view of the operating field, an aspect of surgical conditions that may be affected by bleeding. The trial reports the group results as means and standard deviations. The average score was 3.1 in each arm: the standard deviation was 0.69 for esmolol and 0.89 for labetalol.

As a general statistical point, the Boezaart scale consists of ordered categories. Reporting a mean treats score differences as suitable for arithmetic summaries, but the mean does not show how many patients received each individual score. The registry record does not report the score distribution, a separate ordinal analysis, or other details of how ratings were collected. The group means therefore describe average scores, not the full pattern of individual visibility ratings.

7. Results Posted in the Registry

• Labetalol: mean 3.10 versus 3.10 on control; difference 0.00 (95% CI -0.59 to 0.59), standardized effect d = 0.00; z-test p = 1.000.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Rate of Blood Loss

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Labetalol: mean 0.66 versus 0.59 on control; difference 0.07 (95% CI -0.17 to 0.31), standardized effect d = 0.21; z-test p = 0.570.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Labetalol and the control. The interval gives the range of effects that remain compatible with the data.

Average Mean Arterial Blood Pressure

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Labetalol: mean 79.40 versus 79.70 on control; difference -0.30 (95% CI -5.94 to 5.34), standardized effect d = -0.04; z-test p = 0.917.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Labetalol and the control. The interval gives the range of effects that remain compatible with the data.

Average Heart Rate

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Labetalol: mean 69.00 versus 72.00 on control; difference -3.00 (95% CI -10.58 to 4.58), standardized effect d = -0.29; z-test p = 0.438.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Labetalol and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes provide context about perioperative measurements alongside the primary visibility score. They cover blood loss, mean arterial blood pressure, and heart rate, so they address related but distinct features of the operation. The posted estimates do not show a consistent, clearly separated pattern between the two groups across these measures. Their confidence intervals include zero, and the unadjusted p-values do not provide a basis for strong claims of group differences.

These outcomes do not replace the primary visibility result. Blood loss is a volume-rate measure, while the primary outcome is a surgeon-rated score of the operating field. Blood pressure and heart rate are physiological measurements. Similarity or difference in one measure does not automatically establish a corresponding result in another. The registry record does not report an analysis linking changes in these secondary measures to visibility scores.

The secondary comparisons are recalculations from posted summary statistics, and no sponsor-reported analyses are listed. Their p-values are unadjusted. As a general statistical matter, examining multiple outcomes creates more opportunities for apparently notable results to arise by chance, so secondary results without an adjustment or prespecified interpretive hierarchy deserve less weight than a clearly specified primary analysis. The record does not report a multiplicity strategy or identify which secondary outcome, if any, was intended to be most important.

Accordingly, the secondary results are most useful as descriptive context and as estimates that could inform future study planning, rather than as independent confirmation of the primary finding. They neither resolve the uncertainty around the visibility comparison nor establish a coherent difference across all measured perioperative outcomes.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Rate of Blood Loss
• Average Mean Arterial Blood Pressure
• Average Heart Rate

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports continuous outcomes as means and standard deviations. The posted comparisons are unadjusted recalculations from the group summaries, not sponsor-reported analyses. For the primary outcome, the reported group means are 3.1 in each arm, with standard deviations of 0.69 for esmolol and 0.89 for labetalol. The recalculated mean difference is 0.0, and the unadjusted p-value is 1.0. No adjustment for other variables is reported.

What does a mean difference describe?

A mean difference expresses how far apart the two group averages are, using the outcome’s original scale. In the posted comparisons, the difference is expressed as labetalol relative to esmolol. A positive value means the labetalol average is higher; a negative value means it is lower. For the Boezaart scale, higher scores correspond to more bleeding and poorer visibility, according to the scale description. This direction is specific to the endpoint and does not by itself imply a clinical benefit or harm.

For the primary endpoint, the two reported means are equal, so the recalculated difference is 0.0. A zero difference in the observed averages does not mean every patient had the same score, nor does it prove that the underlying group averages are identical. Standard deviations describe variation of individual scores around each group mean. They are not measures of uncertainty in the difference itself; the confidence interval addresses that uncertainty.

How should the p-value be read?

In general, a p-value describes how compatible the observed data are with a specified statistical null model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The primary comparison has an unadjusted p-value of 1.0. That result is consistent with the equal observed means, but it does not prove equivalence. The registry record does not report a prespecified threshold for interpreting the primary analysis, or details of a sponsor-run inferential analysis.

The p-values for secondary outcomes are also unadjusted recalculations. Because several outcomes are examined, interpreting each p-value as if it were the only analysis can overstate the strength of evidence. The record does not report a multiplicity adjustment or a hierarchy for interpreting secondary outcomes.

Why does uncertainty matter?

A confidence interval gives a range of values compatible with the data under the statistical method used. For the primary comparison, the interval includes zero and extends in both directions. This means the posted summary statistics do not pin down the direction of a possible difference. General statistical interpretation of a confidence interval also depends on the assumptions and method used; the registry record does not report the specific interval-construction method.

The primary score is an ordered scale, but results are reported as means and standard deviations. As a general point, a mean can be a useful compact summary, yet it does not reveal whether scores cluster around the average or are spread across categories. The record does not give score frequencies, medians, or an ordinal-model analysis. The reported mean comparison should therefore be read as a comparison of average scores, not as a complete description of the score distributions.

What do the planning illustrations mean?

The sample-size illustrations are based on observed effects and are explicitly not the trial’s own design justification. They assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Their entries estimate participants per arm for 80% or 90% power when planning to detect a stated fraction of an observed effect. For example, for planning at 75% of the observed blood-loss effect, the illustration gives 626 participants per arm for 80% power and 838 participants per arm for 90% power.

These are planning illustrations, not observed power and not evidence that the trial was designed around those assumptions. Since the illustrations use effects observed in this trial, their values can be strongly influenced by the estimates from the posted groups. The record does not report the original sample-size assumptions, a formal justification for the registry enrollment, or interim analyses.

11. Confidence Intervals and Precision

The primary comparison is centered on no observed difference: the mean score was 3.1 in each group, and the recalculated mean difference is 0.0. The confidence interval extends on both sides of zero. Thus, the estimate does not determine whether the underlying average score is higher with esmolol or with labetalol. The interval is the main indication of the uncertainty in the comparison; equal sample means alone do not establish that the true difference is exactly zero.

The primary groups include 13.0 patients receiving esmolol and 15.0 receiving labetalol. The standard deviations are 0.69 and 0.89, respectively. These describe observed variation in scores, while the confidence interval describes uncertainty around the estimated difference. They answer related but distinct questions. The registry record does not report the interval-construction method or a prespecified range of differences that would be considered unimportant.

The p-value of 1.0 is an unadjusted recalculation and should not be read as proof of no effect. A p-value does not express the probability that the treatments are identical. Nor does a confidence interval that crosses zero establish equivalence: that would require a suitable prespecified margin and an analysis designed to assess it, neither of which is reported in the registry record.

For the secondary outcomes, the posted confidence intervals also extend across zero. Their widths and the underlying estimates reflect uncertainty in those comparisons as well. Given the group sizes and the absence of reported sponsor analyses, the results are best treated as estimates with substantial uncertainty rather than definitive evidence that small or moderate differences are absent.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists three secondary outcomes with posted results: rate of blood loss, average mean arterial blood pressure, and average heart rate. It also records five outcome measures overall, but the registry record does not identify the remaining measures in the posted outcome information. No reported analyses are listed. Consequently, the available record does not establish whether the reported outcomes represent all planned analyses or how any additional outcomes were handled.

The secondary comparisons are unadjusted. The registry record does not report a multiplicity correction, a testing hierarchy, or a plan for interpreting several outcomes together. In general, when many outcomes are tested, the chance of at least one apparently unusual result can increase. An adjustment or a prespecified hierarchy can address that issue, but the record does not say whether either was used. The secondary p-values should therefore be read cautiously rather than as stand-alone confirmatory findings.

For the primary outcome, the record says that those analyzed had complete data. It does not report how many patients lacked primary-outcome data, why data might be missing, or whether missingness differed between arms. It also does not describe imputation, sensitivity analyses, or how the analysis population was defined beyond the complete-data statement. The displayed primary group sizes are the posted analyzed group sizes; the registry record does not explain their relationship to every enrolled patient.

Randomization is listed, but the record does not report the sequence-generation or concealment procedures. Double masking is recorded, without identifying which roles were masked or how masking was maintained. The registry does not report a detailed statistical analysis plan, interim analyses, or a sample-size justification. These omissions limit assessment of prespecification, potential missing-data bias, and the interpretation of multiple outcomes; they do not establish that any particular problem occurred.

13. 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.

The adverse-event figures list zero serious adverse events and zero other adverse events in the esmolol group, with 13 patients at risk in each category. For labetalol, the record likewise lists zero serious adverse events and zero other adverse events, with 15 patients at risk in each category. Deaths are listed as zero in both groups. No serious-event terms are listed.

These entries describe the events recorded in the registry, not proof that no adverse events of any kind occurred. The record does not give additional details about event collection, definitions, duration of safety follow-up, or completeness of reporting. Zero recorded events in these groups should therefore be interpreted as a limited observation from this trial, not as a precise estimate of risk or a comparison establishing equal safety between treatments.

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

The posted primary data show equal average visibility scores in the esmolol and labetalol groups: each mean is 3.1. The unadjusted recalculated mean difference is 0.0, with p = 1.0. The confidence interval extends to both sides of zero, so the data do not establish the direction of a possible underlying difference. These results describe the observed averages and their statistical uncertainty; they do not establish that the treatments are equivalent.

The score has an interpretable direction: higher Boezaart values indicate more bleeding and poorer visibility. However, a group mean does not reveal the distribution of individual scores, and the registry does not provide score frequencies. The scale rating also differs from the secondary blood-loss rate, so the primary result should not be read as a direct statement about measured blood volume.

The secondary measurements offer additional descriptive information, but they are unadjusted comparisons and are not a substitute for a prespecified primary analysis. No sponsor-reported analyses are listed. The record also does not report an equivalence margin, a detailed analysis plan, or a multiplicity strategy. Those absences limit the strength of conclusions that can be drawn from nonsignificant comparisons.

The results apply to the trial’s recorded groups and outcomes. The registry lists enrollment as 28 and says the primary analysis included patients with complete data. It does not report detailed missing-data handling or enough information to assess whether the posted groups represent all enrolled patients for each outcome. The observed zero adverse-event counts also should not be generalized as proof of no risk. Overall, the record supports a cautious description of the observed results, not a treatment recommendation or a definitive conclusion about clinical equivalence.

15. Why This Trial Matters Statistically

This trial illustrates an important distinction between observing similar group averages and demonstrating that two treatments are equivalent. The primary means are both 3.1, and the recalculated difference is 0.0. Yet the confidence interval extends in both directions, so the estimate retains uncertainty about the underlying difference. Without a prespecified equivalence margin and an analysis designed around that question, equal observed averages are not enough to support an equivalence claim.

It also shows why outcome choice matters. Surgical visibility is measured with a graded rating scale, while blood loss is reported as a rate and blood pressure and heart rate are physiological measures. These measures describe different aspects of the operation. An average score gives a compact summary, but without the individual score distribution it cannot show how ratings were spread across the scale.

The registry’s planning illustrations offer another statistical lesson. They use observed effects to estimate participants per arm under stated assumptions, but they are not the trial’s original design justification and are not observed power. Planning values can change substantially according to the effect size a future study aims to detect. They should be treated as illustrations, not as evidence about the adequacy of the completed trial.

Finally, the record distinguishes posted summary data from sponsor-reported analyses: no reported analyses are listed. That makes transparent labeling of unadjusted recalculations and their limitations important. The trial provides estimates useful for understanding the observed data and considering future research, while the uncertainty and reporting gaps constrain stronger inferences.

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.

The primary result is based on posted group summaries and a recalculated, unadjusted comparison. The registry record lists no sponsor-reported analyses, so it does not provide a reported model or analysis details against which to assess the recalculation. The record also does not report a prespecified equivalence margin, a detailed analysis plan, or a multiplicity strategy. These omissions limit confirmatory interpretation.

The primary endpoint is reported as a mean and standard deviation on the Boezaart scale, but the individual score distribution is not reported. Because the scale uses ordered categories, the mean alone cannot show whether group scores were concentrated in particular categories or spread across them. The record does not report ratings by surgeon, inter-rater reliability, or procedures for standardizing assessments beyond the scale description.

The registry says that the primary analysis included those with complete data, but does not report the amount or reasons for missing data, how missingness was handled, or sensitivity analyses. The posted primary groups are small, and the confidence interval includes differences in either direction. The record does not provide enough detail to assess whether all randomized patients were included in each outcome analysis.

Further trial-specific details are not reported in the registry record, including the randomization procedure, allocation concealment, masking roles, and medication administration details. The registry enrollment is 28, but the record does not provide a design justification for that enrollment. Safety reporting lists no recorded events, but does not describe event-collection methods or follow-up details. These limitations identify what cannot be evaluated from the record; they do not show that a particular bias or procedural problem occurred.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Esmolol vs. Labetalol in Endoscopic Sinus Surgery — NCT03661346.
• Registry record last updated 2021-02-08; status last verified 2017-03.
• Results first posted 2021-02-08.
• 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

The registry describes a completed, randomized, double-masked, parallel Phase 2 trial of esmolol versus labetalol in endoscopic sinus surgery for chronic sinusitis. Enrollment is listed as 28. The primary endpoint was intra-operative visibility on the Boezaart scale over the duration of the operation.

Posted primary means were 3.1 in both groups. An unadjusted recalculation gives a mean difference of 0.0 and p = 1.0; the confidence interval includes values on either side of zero. The record also posts results for rate of blood loss, mean arterial blood pressure, and heart rate. No sponsor-reported analyses are listed. The registry describes the primary analyzed population as patients with complete data, but does not report detailed missing-data handling, a multiplicity strategy, or a sample-size justification.