Comparing Blood Loss and Visualization After the Preoperative Use of Topical 0.05% Oxymetazoline Versus 1:1000 Epinephrine Prior to Endoscopic Sinus Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparing Blood Loss and Visualization After the Preoperative Use of Topical 0.05% Oxymetazoline Versus 1:1000 Epinephrine Prior to Endoscopic Sinus Surgery (NCT03228914), a randomized phase 4 study. The primary outcome is Surgical Field Visualization During Sinus Surgery as Indicated by Score on Boezaart Grading Scale.

2. Clinical Question

The comparison is about a surgical-field score, not directly about a patient-reported outcome. The registry also lists amount of blood loss in mL as a secondary outcome, but a result for that outcome is not reported in the registry record. The primary-outcome description presents both treatments within each participant, on opposite sides of the nasal cavity. That within-participant description is important for understanding the comparison: the two observations from a participant may be related. The registry metadata also labels the study as parallel, and does not explain the relationship between that label and the side-by-side treatment description. The record does not report the allocation procedure or the statistical method used to account for the two sides.

3. Trial Design

The registry describes this as a randomized, single-masked, parallel study in Phase 4. It is marked completed, with enrollment of 20. The recorded start date is 2018-06-14 and the primary completion date is 2018-08-29. The sponsor is The University of Texas Health Science Center, Houston. These details identify the trial as recorded but do not, by themselves, describe how randomization or masking was carried out.

The intervention descriptions specify topical pledgets for both treatments. Two pledgets containing 0.05% oxymetazoline were placed in the nasal cavity for the oxymetazoline treatment; the corresponding epinephrine description specifies two pledgets containing 1:1000 epinephrine. The primary-outcome population description adds that each participant who started the study received both treatments, one on each side of the nasal cavity. Thus, the posted outcome description is side-based and within-participant, even though the study model field says parallel. The registry record does not resolve that difference or state how the allocation was implemented.

The primary outcome was the surgical-field visualization score during surgery, with a timeframe described as during surgery, approximately 2-3 hours. The posted group summaries give n of 20.0 for each treatment, but the record’s population description indicates that these are treatment-side observations within participants rather than a description of separate sets of people. The record does not specify whether the reported analysis treated sides as paired, nor does it provide a detailed analysis plan. The secondary outcome listed is amount of blood loss in mL. Although the record indicates more than one outcome measure, a blood-loss result is not reported in the registry record. No protocol, allocation sequence details, or original sample-size justification is 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: For each participant who started the study, oxymetazoline was administered to one side of the nasal cavity and epinephrine was administered to the other side of the nasal cavity. Each participant has two sides of the nasal cavity, and each participant received both oxymetazoline and epinephrine, one drug per side.

Overall Study

Analysis population for the primary outcome, as defined in the registry: For each participant who started the study, oxymetazoline was administered to one side of the nasal cavity and epinephrine was administered to the other side of the nasal cavity. Each participant has two sides of the nasal cavity, and each participant received both oxymetazoline and epinephrine, one drug per side.

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: Adults greater than 18 years of age undergoing endoscopic sinus surgery. Age is an inclusion criteria and is not collected

6. Primary Endpoint

The registry lists the primary outcome as Surgical Field Visualization During Sinus Surgery as Indicated by Score on Boezaart Grading Scale, measured over during surgery approximately 2-3 hours.

The primary endpoint is the surgical-field visualization score during sinus surgery, measured with the Boezaart Grading Scale. The registry describes the score as ranging from 0, which indicates no bleeding under cadaveric conditions, to 5, which indicates severe bleeding requiring constant suctioning. The recorded summary is a mean score with standard deviation for each treatment.

This endpoint represents the surgeon’s view of the operative field in relation to bleeding. It is used in this study to compare the visibility associated with the two topical treatments during surgery. A lower score corresponds to less bleeding on the scale’s description, while a higher score indicates more severe bleeding and more need for suctioning. The posted mean was 3.0 for oxymetazoline and 2.55 for epinephrine.

The score is not the same measure as the amount of blood loss. The registry lists amount of blood loss in mL as a secondary outcome, but that outcome’s result is not reported in the registry record. The primary endpoint therefore addresses the recorded visualization score, and should not be interpreted as a numerical estimate of blood volume lost. The record does not report additional details about who assigned the score, whether scoring was performed separately for each side at a specified point, or how scores were combined across the operation.

7. Results Posted in the Registry

• Epinephrine: mean 2.55 versus 3.00 on control; difference -0.45 (95% CI -0.56 to -0.34), standardized effect d = -2.63; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous in the posted analysis and is summarized with a mean and standard deviation. A mean describes the central value of a set of measurements. A standard deviation describes how dispersed measurements are around that mean. These summaries are useful for describing the score distributions, but they do not show the individual observations or reveal whether the score differences varied systematically between participants.

What does the mean difference represent?

The comparison is expressed as epinephrine minus oxymetazoline. The reported mean difference is -0.45, based on a mean score of 2.55 for epinephrine and 3.0 for oxymetazoline. The sign tells the direction of the comparison: the epinephrine mean was lower. Since the scale description associates higher scores with more bleeding and poorer visualization, the lower mean is consistent with a lower bleeding-related score for epinephrine in the observed data. The difference is in score units, not in mL of blood loss.

The comparison also reports d of -2.629. In general, a standardized effect expresses a difference relative to a measure of variability, rather than in the original score units. The registry reports a pooled standard deviation of 0.171 for this calculation. The record does not specify in detail how the standardized effect was derived, or whether the within-participant structure was incorporated. It is therefore appropriate to describe the posted statistic without assuming a particular model or treating it as a complete account of the design.

What does the p-value tell the reader?

The unadjusted p-value is <0.001. In general, a p-value is calculated under a null hypothesis and the assumptions of a statistical procedure. It describes the compatibility of the data with that null model; smaller values indicate that data as extreme as those observed would be less compatible with the model. A p-value is not the probability that the null is true, a measure of the size of an effect, or a measure of the practical importance of a difference. The registry labels the value unadjusted. It does not report the full test procedure, its degrees of freedom, or a detailed model specification.

The p-value needs particular caution because the outcome description says both treatments were used by each participant on opposite sides of the nasal cavity. General statistical practice distinguishes an analysis of independent groups from an analysis of paired observations. Paired methods use the within-participant relationship, while independent-group methods do not. Pairing can affect both the estimated uncertainty and the test result. The registry record does not report whether the primary comparison used a paired analysis or how the side-level observations were handled. It is therefore not possible to verify from the record whether the posted interval and p-value reflect the described structure.

Why does the registry’s design description matter?

The study metadata identifies random allocation, single masking, and a parallel model. Separately, the primary-outcome population text says each participant received oxymetazoline on one side and epinephrine on the other. These are different kinds of information: the metadata gives broad design labels, whereas the population description states how treatment was applied to the two nasal sides. The record does not explain how the parallel label relates to the within-participant treatment description. It also does not report who was masked, how masking was maintained, or how treatment side was assigned. These missing details affect the ability to reconstruct the analysis, not the numerical values that were posted.

In general, a confidence interval describes a range of effect values compatible with the data and the procedure used to construct it. It reflects statistical uncertainty under that procedure and its assumptions. The registry comparison reports an interval for the mean difference, and both reported limits are negative. The record does not state the confidence level or provide the statistical method used to form the interval. The direction is consistent with the lower epinephrine mean, but interpretation of the interval’s coverage depends on the underlying analysis.

What is not documented about the analysis?

The record does not provide a detailed statistical analysis plan, explain handling of missing scores, identify an analysis population, or report whether there were interim analyses. The number of analysis entries is 0. This absence does not establish that no analyses were conducted; it means that analysis details are not reported in the registry record. The record also does not provide a result for the listed blood-loss outcome.

These gaps matter because a reproducible comparison requires knowing how observations were selected and modeled, how within-participant dependence was handled, and how incomplete measurements were treated. They also matter for multiplicity: if several outcomes or tests were examined, the interpretation of an unadjusted p-value can depend on how those analyses were planned. The record lists a primary visualization endpoint and a secondary blood-loss endpoint but does not report a multiplicity procedure. No adjustment should be assumed.

General statistical interpretation should therefore separate the descriptive finding from claims about its reliability beyond the recorded analysis. The descriptive means and reported mean difference are clear. The unadjusted p-value and interval are also posted. However, the absent analysis details mean readers cannot confirm the method behind them or establish whether the uncertainty calculations fully reflect the side-by-side design.

10. Confidence Intervals and Precision

The estimated mean difference is -0.45, expressed as epinephrine minus oxymetazoline. The reported confidence interval has both limits below zero. In the analysis as posted, the interval therefore supports a negative difference in the same direction as the observed means: a lower average visualization score for epinephrine. The registry comparison also reports p < 0.001.

A confidence interval is useful because it communicates uncertainty around an estimate rather than presenting the estimate as exact. In general, a narrower interval indicates greater precision under the assumptions of the method used, while a wider interval indicates more uncertainty about the plausible values. The posted interval is relatively close to the estimated difference, but its interpretation depends on the statistical method. The registry record does not report the confidence level or enough analysis detail to assess how the interval was constructed.

The most important qualification is the treatment structure. The primary-outcome description says both treatments were given to each participant on opposite sides of the nasal cavity. If measurements on the two sides are related, the method used to account for that relationship can affect precision. The record does not state whether the interval used a paired analysis or otherwise modeled that dependence. The interval and p-value should therefore be read as the registry’s posted comparison, with this uncertainty about the method in mind.

Precision for the primary score does not resolve uncertainty about other outcomes. Amount of blood loss in mL is listed as secondary, but a result is not reported in the registry record. The small enrollment also means the record offers limited information about the range of results that might occur in broader populations or about uncommon safety events. These are limits on interpretation, not reasons to replace the posted estimate with a different one.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are illustrations based on the observed effect, not the trial’s original design assumptions. The registry record does not report the original sample-size justification. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; each scenario uses the stated fraction of the observed effect as the effect to detect.

Planning for 100% of the observed effect gives estimates of 3 participants per arm for 80% power and 4 participants per arm for 90% power. Planning for 75% of the observed effect gives estimates of 5 participants per arm for 80% power and 6 participants per arm for 90% power. Planning for 50% of the observed effect gives estimates of 10 participants per arm for 80% power and 13 participants per arm for 90% power. The accompanying curve represents the same general planning relationship across assumed effect sizes.

In plain terms, 80% power is the probability, under the planning assumptions and for the effect specified, that the planned analysis would meet its significance criterion if that effect were the true effect. The 90% power column describes a higher target probability under those assumptions. A smaller effect is harder to detect, so planning to detect a smaller fraction of the observed effect requires more participants per arm in these illustrations.

These figures are not observed power and are not evidence that the completed study was planned to use those sample sizes. They are planning calculations anchored to the observed effect, and their values depend on the assumptions used. They also do not resolve the registry’s missing details about how the within-participant side measurements were analyzed.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.450; pooled standard deviation σ = 0.171.
2. n = 2 × (1.96 + 0.842)² × 0.171² / -0.450² = 2.3, rounded up to 3 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.45                      # observed difference in means
sigma <- 0.171172427686237                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3228914)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 3 (80% power), 4 (90% power)
 75% of observed effect: n per arm = 5 (80% power), 6 (90% power)
 50% of observed effect: n per arm = 10 (80% power), 13 (90% power)
power.t.test: 3.5 
Simulated power at n = 3 per arm: 0.678 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists the visualization score as the primary outcome and amount of blood loss in mL as a secondary outcome. It reports 2 outcome measures and 1 posted secondary outcome, but the blood-loss result is not reported in the registry record. The record lists 0 analysis entries. It does not describe a multiplicity adjustment, a hierarchy of tests, or how interpretation would be handled if several outcomes or comparisons were examined.

In general, multiplicity refers to the increased chance of a false-positive result when several hypotheses are tested. Statistical plans may address this by defining one primary test, adjusting significance thresholds, or using another prespecified approach. The registry record does not report whether any such approach was planned or used. The posted p-value is explicitly unadjusted; no adjustment should be inferred from the record.

The record also does not report how missing primary-outcome scores were handled, whether any observations were excluded, or which analysis population was used. The enrollment count and posted treatment-side counts do not substitute for a missing-data description. It is not stated whether every enrolled participant contributed usable measurements to each outcome or whether any incomplete observations occurred. Those details are not reported in the registry record.

A further analysis issue is the within-participant description: each participant received both treatments on opposite nasal sides. The record does not explain whether a paired analysis was used, how treatment side was assigned, or how the relation between two sides from one participant was modeled. These are not necessarily errors in the posted analysis; they are items needed to judge and reproduce it. The broad metadata labels the model parallel, but the record does not clarify how that label relates to the stated side-by-side treatment arrangement.

Finally, interim analyses and a detailed statistical analysis plan are not reported in the registry record. Their absence from the record should not be taken as proof that they did not occur. With these limits, interpretation can describe the reported primary comparison and its unadjusted p-value, but cannot establish the complete analysis strategy, multiplicity handling, or treatment of missing data.

14. 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 registry reports 0 serious adverse events in the oxymetazoline group and 0 in the epinephrine group. It also reports 0 other adverse events and 0 deaths in each group. The at-risk count is 20 for each group for serious adverse events and 20 for each group for other adverse events.

These figures are event counts as recorded, not proof that the treatments have no safety risks. A study of this size can provide only limited information about uncommon events, and zero recorded events does not establish that an event cannot occur. The registry record does not provide further detail about adverse-event definitions, collection procedures, or follow-up beyond these entries. The safety figures should be read as the events reported for this study, not as a general safety conclusion.

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

The result supports a limited descriptive statement: the posted mean Boezaart score was lower on the epinephrine-treated side than on the oxymetazoline-treated side. The means were 2.55 and 3.0, respectively, and the reported mean difference for epinephrine relative to oxymetazoline was -0.45. Since the scale associates higher scores with more bleeding and worse visualization, the observed direction corresponds to a lower bleeding-related score for epinephrine in this study.

The result does not quantify the difference in blood volume lost. Although amount of blood loss in mL is listed as a secondary outcome, its result is not reported in the registry record. Nor does a difference in the recorded score by itself establish how meaningful that difference is for surgical decisions or outcomes. The registry supplies no threshold for interpreting a clinically important score difference.

The posted unadjusted p-value is <0.001, and the reported confidence interval has negative limits. These statistics describe the posted analysis, but the registry does not report enough detail to determine whether its uncertainty estimates account for the described paired treatment arrangement. The record also does not explain the relationship between the parallel-model label and its statement that each participant received both treatments on opposite sides. This limits independent assessment of the comparison’s methods.

The findings apply to the enrolled study population and the recorded surgical setting. They do not establish that the same difference would occur in other populations or procedures. The registry record does not report the original sample-size justification or a detailed analysis plan, and the study’s limited enrollment means the safety entries cannot rule out uncommon events. The correct interpretation is therefore neither a broad treatment claim nor a dismissal of the reported comparison: it is a lower observed mean score for epinephrine, with methodological and generalizability limits that remain unresolved in the record.

16. Why This Trial Matters Statistically

This trial is statistically notable because its primary-outcome description is within-participant: each participant received oxymetazoline on one nasal side and epinephrine on the other. In general, a within-participant design can control for characteristics shared by the two sides of the same person. It also creates related observations, which should be reflected in the analysis. The registry record does not state whether that relation was incorporated into the reported comparison.

The posted means and mean difference are straightforward to describe, but the design details are essential for interpreting their precision. Treating paired side measurements as unrelated observations can yield different uncertainty estimates than a method that uses the pairing. The available record does not provide sufficient detail to determine which approach was used. The parallel-model metadata label, alongside the side-by-side treatment description, further makes it important to distinguish recorded labels from the actual outcome population description.

The study also illustrates why an endpoint’s meaning should be kept separate from its numerical result. A Boezaart score represents a graded assessment of the surgical field in relation to bleeding. It is not interchangeable with blood loss measured in mL. The secondary blood-loss outcome is listed, but its result is not reported in the registry record. Accordingly, the posted primary result addresses visualization scoring, not every aspect of bleeding during surgery.

Finally, the registry reports an unadjusted p-value and confidence interval but no detailed analysis plan or multiplicity procedure. That makes transparent reporting of design, analysis, missing-data handling, and outcome results particularly important. The numerical comparison is informative as a record of what was posted, while the missing methods and secondary result limit how fully it can be evaluated.

17. 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 arise from the information recorded for this particular trial. The most consequential is that the primary-outcome description says each participant received both treatments, one on each side of the nasal cavity, while the study model field is labeled parallel. The registry does not explain this difference. Nor does it state how treatment side was assigned or whether the analysis treated the two sides as paired. These gaps make it difficult to independently assess the reported p-value and interval.

The registry gives group means, standard deviations, and treatment-side counts, but does not provide individual measurements or a detailed statistical analysis plan. It does not report how missing scores were handled, what analysis population was used, whether any observations were excluded, or whether there were interim analyses. The absence of these details should be understood as incomplete reporting in the registry record, rather than evidence about what did or did not occur.

The listed secondary outcome is amount of blood loss in mL, but its result is not reported in the registry record. Thus, interpretation of the posted primary score cannot be supplemented with a posted blood-volume comparison. The record also does not report a threshold for a clinically important difference in the visualization score.

Enrollment was 20, and the adverse-event entries report no events in the recorded categories. Those data offer limited information about uncommon safety outcomes. The record does not provide further adverse-event collection details. It also does not report the original sample-size justification, so the planning illustrations based on the observed effect cannot be used to reconstruct the trial’s own design rationale.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Comparing Blood Loss and Visualization After the Preoperative Use of Topical 0.05% Oxymetazoline Versus 1:1000 Epinephrine Prior to Endoscopic Sinus Surgery — NCT03228914.
• Registry record last updated 2021-01-13; status last verified 2021-01.
• Results first posted 2021-01-13.
• 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.

21. Record Summary

The registry record describes a completed Phase 4 randomized, single-masked study sponsored by The University of Texas Health Science Center, Houston. It lists enrollment of 20, a start date of 2018-06-14, and a primary completion date of 2018-08-29. The intervention comparison was topical 0.05% oxymetazoline versus topical 1:1000 epinephrine before endoscopic sinus surgery.

The primary endpoint was the mean Boezaart surgical-field visualization score during surgery. The posted means were 3.0 for oxymetazoline and 2.55 for epinephrine, with a reported mean difference of -0.45 for epinephrine relative to oxymetazoline and an unadjusted p-value of <0.001. The record describes both treatments as given to each participant on opposite sides, but does not report how the analysis handled that structure. Blood loss in mL is listed as a secondary outcome, but its result is not reported in the registry record. No serious adverse events, other adverse events, or deaths are recorded in either group.