Effect of an H1 Receptor Antagonist on Exercise Performance in Hypoxia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of an H1 Receptor Antagonist on Exercise Performance in Hypoxia (NCT03192488), a randomized phase 4 study. The primary outcome is Performance Time.

2. Clinical Question

The trial addresses a specific exercise-performance question under laboratory conditions. It does not, from the registry information alone, answer broader questions about other exercise settings, other doses, longer exposure, or people outside the described population. Its crossover design means that the conditions are repeated within a study framework, but the registry record does not report the order in which participants received them or whether a washout period was used. Those omissions matter when interpreting how cleanly an observed difference can be attributed to the condition rather than to order or carryover.

3. Trial Design

The registry describes a randomized, double-blind, Phase 4 crossover study sponsored by Indiana University. The study status is completed. The stated enrollment is 13. The listed conditions are hypoxia and altitude, and the interventions include cetirizine, an oral placebo capsule, and hypoxia. In the crossover model, participants are exposed to more than one condition rather than being assigned to a single parallel group for the entire study. The registry record does not report the treatment sequence, the randomization method, or the duration or use of a washout period.

The three outcome conditions were cetirizine with hypoxia, placebo with hypoxia, and placebo with normoxia. The arm descriptions state that the pills were taken 60 min before exercise. Cetirizine and placebo were given as 10 mg doses. Hypoxia was described as a normobaric environment with 14.3% oxygen, while normoxia was described as room air with 20.9% oxygen. The registry's descriptions of the altitude simulated by the hypoxic condition differ: one gives 3,000m/9,000ft, while the brief summary gives 3000m (9900ft).

The primary outcome analysis was limited to subjects who completed all three interventions, according to the outcome description. Each condition has a reported sample size of 8 for the primary outcome. The adverse-event population is reported separately, with 11 at risk for each condition. Enrollment, outcome sample sizes, and safety denominators therefore should not be treated as interchangeable. The registry record does not provide a participant flow explaining these counts, nor does it describe whether all randomized participants completed every condition.

Randomization and masking can reduce certain forms of bias, but the registry's labels do not reveal how these procedures were implemented. In a crossover study, the within-participant structure can be informative because each participant contributes measurements under multiple conditions. Appropriate interpretation also depends on information about sequence, period effects, carryover, and the statistical handling of repeated observations. Those details are not reported in the registry record. The posted analysis is described as ANOVA, but the registry does not state enough about the model to determine how it accounted for the crossover structure.

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: Enrolled participants were excluded prior to arm/group assignment if they had abnormal pulmonary function, or voluntarily discontinued with study procedures after completing a graded maximal exercise test and familiarization trial of exercise performance tests on a cycle ergometer. Two subjects withdrew prior to initial group assignments.

First Intervention (d1)

First Washout (>6d)

Reasons for not completing this period:

Second Intervention (d1)

Second Washout (>6d)

Analysis population for the primary outcome, as defined in the registry: Subjects who completed all three interventions were included in the outcome analysis.

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: The baseline characteristics for subjects completing all three study arms (Hypoxia/Cetirizine, Hypoxia/Placebo, Normoxia/Placebo) are included.

6. Primary Endpoint

The registry lists the primary outcome as Performance Time, measured over Performed 60min after pill ingestion.

The primary endpoint is performance time, measured in minutes: the time required to complete an 8km cycling time trial. It was assessed 60min after pill ingestion. The registry reports a mean and standard deviation for each of the three conditions. A time-to-completion measure is a direct measure of task performance in this laboratory exercise setting: shorter times indicate faster completion of the specified trial. It is not a measure of every aspect of exercise capacity, nor does it by itself explain why performance differed.

Using the same distance and a defined exercise task gives the outcome a clear interpretation within the study. Reporting means describes average completion time within each condition, while standard deviations describe how spread out the observed times were around those means. The reported means are 17.03 for cetirizine and hypoxia, 18.08 for placebo and hypoxia, and 16.32 for placebo and normoxia. The corresponding standard deviations are 1.92, 2.87, and 1.98. These summaries describe the posted condition-level results; they do not show the individual paired differences that would be especially informative in a crossover design.

The choice of a time trial makes the endpoint relevant to the stated exercise-performance question, but the registry record does not report a clinically meaningful threshold for a difference in completion time. Nor does it explain how the primary endpoint was selected from the listed exercise tests in the study summary. Results for other performance tasks are not described in the posted primary outcome details. Interpretation should therefore stay focused on the measured 8km cycling time trial and its stated analysis population.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a continuous outcome summarized as a mean with standard deviation. This is a natural descriptive summary for a measurement such as completion time, where each participant's result is numeric. A mean gives the arithmetic center of the observed values, while the standard deviation describes their spread. Neither statistic alone shows the full shape of the observations or how much each participant changed between conditions.

What does the ANOVA result represent?

ANOVA is a method for evaluating whether observed means differ across multiple conditions, using a model that compares variation associated with condition against variation not explained by condition. The record describes the reported analysis as ANOVA and lists the three conditions together. It reports a mean difference (final values) of 1.06, a 95% confidence interval of 0.01 to 2.11, and p = 0.047. The record does not specify the ANOVA model, its assumptions, or the exact contrast underlying the mean-difference estimate. The listed result should therefore be presented as the sponsor-reported analysis rather than reconstructed as a specific pairwise comparison.

In a general statistical explanation, a confidence interval conveys uncertainty in an estimate under the model and its assumptions. A narrower interval indicates greater precision than a wider interval for the same scale and context. An interval is not a range containing a fixed proportion of individual participant results, nor is it a probability statement about the parameter after observing the data. Interpreting the reported interval also depends on whether the model reflects the design and whether other relevant analyses were considered.

Why does the crossover structure matter?

In general, crossover studies collect observations under multiple conditions from the same participants. Those observations are often correlated: a participant's results across conditions may be more alike than results from different participants. A statistical model that recognizes this dependence can distinguish within-participant changes from differences between participants. Treating condition samples as independent when they are not can misstate uncertainty. The registry identifies the design as crossover, but does not report the analysis details needed to tell how dependence was handled.

Sequence and period can also matter in a crossover. Sequence refers to the order in which conditions are received; period refers to the place of a measurement within the sequence. Carryover describes an influence of a previous condition on a later measurement. These are general considerations, not claims that such effects occurred in this study. The registry record does not report the condition order, washout approach, or modeling of period and carryover. Thus, the posted description is insufficient to evaluate those aspects of the design.

What does the p-value say?

In general, a p-value quantifies how compatible the observed data are with a specified null model, given the analysis assumptions. The reported p-value is 0.047. It is not the chance that the treatment has no effect, and it does not measure the size or practical importance of a difference. A smaller p-value does not automatically mean a larger or more meaningful effect. The estimated difference and its confidence interval are needed to describe magnitude and precision, while design and analysis details inform whether the estimate is trustworthy.

The record reports 2 outcome measures and 3 analyses. It names one secondary outcome, plasma histamine concentrations at baseline and post-exercise. However, the registry record does not state whether the reported p-value was adjusted for multiple outcomes, analyses, or comparisons, or whether a hierarchy of testing was specified. When several analyses are conducted, the chance of at least one result appearing unusual can increase if each is interpreted without accounting for multiplicity. This is a general statistical concern; the record does not establish what adjustment, if any, was used.

Why is over-dispersion relevant?

Over-dispersion is a general issue when observed variability is greater than a statistical model expects. It is especially relevant to count outcomes, where a simple model may underestimate variability if the counts are more heterogeneous than assumed. The primary endpoint is continuous performance time, not a count, so count over-dispersion is not the central concern for interpreting this endpoint. For this continuous outcome, the relevant questions include the distribution of times, the dependence among repeated measurements, and whether the model captures their variability. The registry does not report diagnostic checks or model assumptions.

Can the posted summaries be recalculated?

Recalculation from group means and standard deviations is limited because the record does not give participant-level observations or the within-participant covariance information needed for a crossover comparison. The registry notes that values are missing or not estimable for a two-arm comparison of the continuous endpoint. No recalculated pairwise estimate is therefore available from the posted summaries. A simple calculation that treats the conditions as independent would not be a suitable substitute for a model that respects the repeated-measures design.

Planning sample sizes, when displayed as illustrations, answer a different question from the observed analysis. In general, a planning calculation uses assumptions about an effect, variability, significance level, allocation, and model to estimate the number of participants needed for a future study. It is not an observed power calculation and does not establish the probability that the present study detected an effect. The registry's planning description says its illustrations use a stated fraction of the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions are not reported as the design basis for this trial. The record does not report the trial's sample-size justification or its original planning assumptions.

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("Cetirizine and Hypoxia", "Placebo and Hypoxia", "Placebo and Normoxia")
n   <- c(8, 8, 8)
m   <- c(17.03, 18.08, 16.32)
sp  <- c(1.92, 2.87, 1.98)
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  Cetirizine and Hypoxia  8  17.030  1.920  15.425  18.635
CARM  Placebo and Hypoxia  8  18.080  2.870  15.681  20.479
CARM  Placebo and Normoxia  8  16.320  1.980  14.665  17.975

11. Analyses Reported by the Sponsor

The sponsor-reported analysis is an ANOVA across the three listed conditions. It gives a mean difference (final values) of 1.06, a 95% confidence interval of 0.01 to 2.11, and p = 0.047. The registry record does not make the contrast behind that mean-difference estimate fully explicit, so it should not be relabeled as a particular pairwise comparison. The condition means and standard deviations are also reported, but those summaries do not contain the within-participant information needed to independently reproduce a crossover analysis.

No recalculated two-arm comparison is available from the posted summaries; the record notes that values are missing or not estimable for that continuous comparison. Accordingly, there is no independent recalculated estimate to set against the sponsor's result. The record does not flag a discrepancy between a sponsor result and a recalculation. The sponsor's reported analysis is therefore the inferential result available in the registry, while the condition-level means remain useful descriptive statistics. This does not resolve questions about the model specification, crossover handling, or multiplicity, which are not reported in the registry record.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures and 3 analyses. It identifies performance time as the primary outcome and plasma histamine concentrations at baseline and post-exercise as a secondary outcome. The record does not describe how the analyses relate to each outcome, whether they include multiple contrasts, or whether testing followed a prespecified hierarchy. It also does not report whether the p-value was adjusted for multiple comparisons or outcomes.

Multiplicity matters because conducting several statistical tests can increase the chance of obtaining at least one result that appears unusual even if none of the underlying effects is real. Adjustment methods and testing hierarchies address that issue in different ways. This is a general statistical consideration, not a claim that the reported p-value is necessarily invalid. Without a stated plan, readers cannot determine how the p-value should be interpreted in relation to the other analyses.

The primary outcome population is described as subjects who completed all three interventions. This is a completer-based description. The registry record does not report an intention-to-treat analysis, a per-protocol definition, reasons for non-completion, or how missing outcome data were handled. It does not give participant-level missingness by condition or indicate whether imputation was used. As a result, the extent and consequences of missing data cannot be assessed from the posted information.

The record reports enrollment of 13, an outcome sample size of 8 for each condition, and 11 participants at risk for adverse events in each condition. These denominators refer to different registry entries. Because the study is a crossover, condition-specific sample sizes should not be added to estimate the number of participants. The registry does not explain the differences among enrollment, outcome, and safety counts or provide a flow diagram. It is therefore not possible to reconstruct participant disposition or infer the number of unique participants contributing to all analyses.

Other analysis details are also not reported in the registry record, including the specific crossover model, treatment sequence, period effects, carryover handling, and any prespecified interim analyses. The absence of these details does not prove that the procedures were not used; it means the posted record does not allow readers to evaluate them.

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.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events in each of the three condition groups. It lists 11 participants at risk for serious adverse events in each group and no deaths in any group. For other, non-serious adverse events, it reports 1 in the cetirizine and hypoxia condition and 0 in each placebo condition; the reported at-risk count is 11 for each condition.

These figures are condition-specific registry summaries. In a crossover design, a participant may contribute to more than one condition, so the entries should not be added to estimate the number of unique people with events or exposed across the study. The record does not provide descriptions of the single other adverse event, its timing, severity, or relationship to treatment. It also does not give enough detail to assess how adverse events were collected or whether the same participant contributed to more than one condition's safety denominator.

Zero reported serious events means none were recorded in these registry entries; it does not establish that the conditions carry no risk. Safety results should be interpreted in light of the reported denominators, the study's size, and the limited event detail. The registry lists no serious adverse-event terms.

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

The posted results describe performance times for an 8km cycling time trial under three laboratory conditions. The condition means were 17.03 minutes with cetirizine and hypoxia, 18.08 minutes with placebo and hypoxia, and 16.32 minutes with placebo and normoxia. The sponsor-reported ANOVA gives a mean difference (final values) of 1.06, with a 95% confidence interval of 0.01 to 2.11 and p = 0.047. These figures characterize the reported data and analysis; they do not establish how the result would generalize beyond this study setting.

The outcome is a completion time, so a shorter time represents faster completion of the specified task. The condition averages show a shorter mean time in the cetirizine/hypoxia condition than in the placebo/hypoxia condition. However, the reported mean-difference contrast is not fully specified, and the registry does not provide the participant-level paired results or the model details needed to verify a particular treatment contrast. The descriptive ordering of means should not be substituted for a clearly defined causal estimate.

The result also does not show that any difference is practically important. The registry does not report a threshold for meaningful change in performance time. A confidence interval describes statistical uncertainty under the analysis assumptions, not clinical relevance, and the p-value does not measure the magnitude of a difference. Missing information about multiplicity and crossover analysis further limits a complete assessment of precision and robustness.

These results concern the study's stated population and laboratory exercise conditions. They do not establish effects for other exercise tasks, environments, doses, or populations. The registry record does not report all aspects of treatment sequence, washout, or handling of repeated measurements, and it gives no participant flow explaining the outcome and safety denominators. Those uncertainties should remain part of any interpretation.

In short, the registry contains descriptive condition means and a sponsor-reported ANOVA result for the time-trial endpoint. The result should be read as evidence about this recorded analysis, with its stated uncertainty and reporting limits, rather than as a general claim about treatment effectiveness.

15. Why This Trial Matters Statistically

This trial is statistically interesting because its crossover design and three conditions raise questions that are not answered by group means alone. In a crossover, participants can serve as their own comparison across conditions. That structure can be useful when outcomes vary substantially between people, but it also requires an analysis that accounts for repeated measurements and their dependence. The registry identifies the design but does not describe the statistical model in enough detail to assess how that dependence was handled.

The conditions also combine medication and environment in different ways: cetirizine with hypoxia, placebo with hypoxia, and placebo with normoxia. This makes the interpretation of any single contrast important. The listed sponsor analysis includes all three groups and reports a mean difference, but the contrast is not fully explicit in the registry record. Clear contrast definitions are necessary to connect an estimate to a specific question, such as the comparison of cetirizine with placebo under hypoxia.

The primary endpoint is easy to understand as a measured task outcome: time to complete an 8km cycling time trial. Yet a simple, interpretable measure does not remove the need for a transparent analysis plan. The record does not specify the model, multiplicity approach, missing-data handling, or crossover details such as sequence and period. These omissions constrain how precisely readers can judge the estimate and its robustness.

The trial also illustrates why enrollment, outcome sample sizes, and safety denominators should be reported with a clear participant flow. The registry lists enrollment of 13, condition-level outcome samples of 8, and safety denominators of 11 per condition. In a crossover study, these figures cannot be added as if they were separate parallel arms. Without an explanation of the differences, the relationship among the analysis populations remains unclear.

Finally, the registry reports a confidence interval and p-value alongside condition means, allowing a distinction between descriptive patterns and inferential results. The result is most informative when read with its uncertainty and the limits of the registry's methodological detail, rather than treated as a standalone yes-or-no finding.

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 registry record does not provide the crossover sequence, the randomization procedure, or whether a washout period was used. It does not describe the model sufficiently to determine how within-participant correlation, period effects, or possible carryover were handled. These are important design and analysis details for interpreting repeated conditions, but their omission from the record does not establish that they were not addressed in the study.

The reported mean difference is not linked unambiguously to a specific pairwise contrast, even though the analysis lists all three conditions. The condition-level means are descriptive and the posted summaries do not include individual paired changes or the covariance information needed for a crossover recalculation. The registry notes that a two-arm continuous comparison is not estimable from the posted values. This limits independent verification of the sponsor-reported result.

The record lists 2 outcome measures and 3 analyses but does not report a multiplicity adjustment, testing hierarchy, or full analysis plan. It also does not state the assumptions and diagnostic checks used for the ANOVA. The primary outcome population is described as participants completing all three interventions, but missing-data methods and reasons for incomplete outcomes are not reported. A participant flow explaining enrollment, outcome sample sizes, and safety denominators is also absent.

The simulated altitude is described inconsistently: the arm descriptions state 3,000m/9,000ft, while the brief summary states 3000m (9900ft). The record does not resolve this discrepancy. It also does not report a threshold for a practically meaningful performance-time difference, which limits interpretation of the result's importance beyond statistical uncertainty.

Generalizability is limited by the described laboratory task and population. The registry does not establish how the findings relate to other exercise settings, populations, or outcomes. The safety information is brief: one other adverse event is reported for the cetirizine/hypoxia condition, but its details are not given. No serious adverse events or deaths are listed, but the record does not provide enough context to characterize safety comprehensively.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Effect of an H1 Receptor Antagonist on Exercise Performance in Hypoxia — NCT03192488.
• Registry record last updated 2020-06-16; status last verified 2020-06.
• Results first posted 2020-06-16.
• 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-blind, Phase 4 crossover study sponsored by Indiana University, with enrollment of 13. Its primary outcome was time in minutes to complete an 8km cycling time trial, assessed 60min after pill ingestion. The reported conditions were cetirizine with hypoxia, placebo with hypoxia, and placebo with normoxia.

Condition means were 17.03, 18.08, and 16.32, respectively, with standard deviations of 1.92, 2.87, and 1.98. The sponsor-reported ANOVA gives a mean difference (final values) of 1.06, a 95% confidence interval of 0.01 to 2.11, and p = 0.047. The record does not clearly identify the contrast represented by that mean difference.

The registry lists plasma histamine concentrations at baseline and post-exercise as a secondary outcome. It reports zero serious adverse events and zero deaths in each condition, and one other adverse event in the cetirizine/hypoxia condition. Important crossover-model details, multiplicity handling, missing-data methods, and a participant flow are not reported in the registry record.