Effects of Nebivolol Versus Carvedilol on Cardiopulmonary Function at High Altitude in Healthy Subjects.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Nebivolol Versus Carvedilol on Cardiopulmonary Function at High Altitude in Healthy Subjects. (NCT00924833), a randomized phase 4 study. The primary outcome is Peak Exercise Oxygen Consumption.

2. Clinical Question

The study rationale treats high-altitude hypoxia as a model for selected cardiovascular, respiratory, metabolic, and exercise-performance changes that can resemble aspects of chronic heart failure. The stated aim was to evaluate how carvedilol and nebivolol affected those features and exercise performance at high altitude. That rationale does not make the study a direct test of treatment in people with heart failure: the described population is healthy subjects.

The primary endpoint was peak exercise oxygen consumption, a continuous measure reported in ml/Kg/min. The endpoint description identifies oxygen consumption at the peak of exercise, but does not report the observed values or a single comparison between treatments. The registry record identifies three measurement conditions and does not reduce the primary outcome to one comparison. The precise treatment contrast or contrasts intended for a primary conclusion are not reported in the registry record.

3. Trial Design

The registry record describes a completed Phase 4, randomized, triple-masked, parallel-group study sponsored by Istituto Auxologico Italiano. Enrollment was 27. The recorded study dates are 2006-05 for the start and 2006-11 for primary completion. The record lists hypoxia, altitude, and heart failure as conditions, while its study description specifies healthy subjects exposed to high-altitude hypoxia.

Three arms are described: placebo, carvedilol, and nebivolol. The placebo arm used one tablet twice daily. The carvedilol arm used 25 mg tablets, one tablet twice daily. The nebivolol arm used a 5 mg tablet daily along with one placebo tablet daily. The record labels the design parallel-group, so the interventions are described as allocated arms rather than as treatments all participants received in sequence. It does not report arm-specific enrollment or allocation counts.

The primary outcome was assessed at three listed times. Time 1 was sea level at baseline without treatment. Time 2 was sea level after three weeks of allocated treatment. Time 3 was within the first two days of high-altitude exposure, under treatment. Thus the record distinguishes both treatment status and environmental condition across the measurement schedule. Further details about the altitude exposure, visit procedures, or the timing of other outcomes are not reported in the registry record.

The registry record lists nine outcome measures and four analyses. It identifies several secondary outcomes, including peak exercise oxygen saturation, systolic pulmonary artery pressure, resting energy expenditure, and measures of blood pressure and heart rate. The record does not explain how those outcomes relate to the four listed analyses. It also does not report the randomization procedure, allocation concealment, or the operational details of triple masking. The study is marked completed, but that status alone does not establish which endpoint data were collected or analyzed.

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: 35 subjects were screened. Out of theese 7 subjects were excluded because they did not meet the inclusion/exclusion criteria. 27 subjects were randomized to the three treatment groups.

Overall Study

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.

6. Primary Endpoint

The registry lists the primary outcome as Peak Exercise Oxygen Consumption, measured over Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment..

The primary endpoint is peak exercise oxygen consumption, reported as a mean with standard deviation and measured in ml/Kg/min. It describes oxygen consumption at the peak of exercise. As a general statistical and physiological concept, oxygen consumption during peak exercise is used to characterize exercise capacity: it reflects the body’s oxygen use when the participant reaches the specified peak of an exercise assessment. The registry record does not provide the exercise protocol or a more detailed operational definition of peak.

The endpoint was scheduled for three conditions: untreated baseline at sea level, sea level after three weeks of allocated treatment, and high altitude under treatment during the first two days of exposure. These are not interchangeable settings. A treatment comparison at sea level would address a different setting from a comparison under high-altitude hypoxia, while a change from baseline would combine the passage of time and treatment exposure. The exact primary contrast is not reported in the registry record.

Peak exercise oxygen consumption is relevant to the study’s stated interest in exercise performance and cardiopulmonary responses. However, the measure alone does not capture every cardiovascular, respiratory, or metabolic outcome listed in the study rationale. No endpoint values, between-arm estimates, confidence intervals, or significance tests are reported in the registry record. Consequently, the endpoint’s clinical or statistical findings cannot be described from the registry entries available.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous and is characterized in the registry record by a mean and standard deviation. As a general explanation, a mean describes the average value in a group, while a standard deviation describes the spread of individual observations around that average. Reporting both can help readers understand the group’s measured values, but these summaries do not by themselves estimate a treatment difference or its precision. For that, the analysis would need to define a contrast and report an uncertainty measure, such as a confidence interval. Those outcome results are not reported in the registry record.

What is the treatment comparison?

A trial with three allocated arms can support more than one possible comparison, such as each active treatment against placebo or one active treatment against the other. The scientifically relevant comparison depends on the question the analysis was designed to answer. Here, the registry record identifies the three arms but does not specify a primary contrast or a hierarchy among possible contrasts. It also does not report whether analyses adjusted for baseline values or other covariates.

The measurement schedule adds another choice. Peak exercise oxygen consumption was measured at untreated sea-level baseline, after three weeks of allocated treatment at sea level, and during the first two days at high altitude under treatment. An analysis could focus on a particular time point, compare changes from baseline, or model measurements jointly. These approaches answer different questions and rely on different assumptions. The statistical analysis plan and the method used to handle the repeated measurements are not reported in the registry record.

What do masking and allocation tell readers?

The study is labeled randomized, triple-masked, and parallel-group. Randomization is a general design method intended to make allocation independent of participant characteristics, on average, and thereby support fair treatment comparisons. Masking can reduce the influence of treatment knowledge on behavior, measurement, or assessment. The registry record does not describe the randomization process, who was masked, or how masking was maintained. The parallel-group label indicates that the arms were designed as separate groups; it does not provide arm sizes or establish how participants were assigned.

How should the planning calculations be read?

The registry’s planning assumptions describe illustrative sample-size calculations, not the trial’s own design justification. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is expressed as a stated fraction of the observed effect. Such calculations ask what sample size might be needed under the specified assumptions to detect a target effect. They are planning illustrations, not observed power, and they do not show that the completed study had that probability of detecting an effect. The record does not report the trial’s original sample-size justification.

These illustrations depend on the observed effect used as their reference. When an observed effect is uncertain, a planning calculation based on it is also uncertain. The registry record does not provide the primary endpoint results needed to judge the size or precision of that reference effect. Nor does it identify a particular one of the possible treatment comparisons as the basis for the calculation. Accordingly, the assumptions should not be read as evidence that a comparison was prespecified or adequately powered.

What statistical details remain unclear?

The record lists four analyses and nine outcome measures, but does not describe the statistical tests, model form, adjustment choices, or contrast definitions. The number of analyses alone does not reveal whether the analyses were prespecified, exploratory, or associated with particular endpoints. The record also does not report diagnostic checks or assumptions for the analysis of continuous outcomes. In general, a model’s assumptions matter because departures can affect standard errors, confidence intervals, and tests; which assumptions are relevant depends on the method actually used.

As a general concept, over-dispersion means that observed variability is greater than a model expects. It can make uncertainty estimates too narrow if the analysis does not accommodate that extra variability. The registry record does not identify a count outcome or report an over-dispersion assessment; the primary endpoint described is continuous. This general concept therefore should not be mistaken for a reported feature of this trial’s analysis.

The analysis populations, handling of missing measurements, and use of any interim analysis are not reported in the registry record. Those details matter because results can depend on which participants are included and how incomplete follow-up is treated. No statistical method can be attributed to this study beyond the design labels and assumptions explicitly described in the record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists nine outcome measures and four analyses, but does not explain how those analyses map to outcomes or comparisons. It does not report whether one outcome was designated as the sole confirmatory endpoint, whether treatment contrasts were prioritized, or whether any adjustment for multiple testing was planned. The primary outcome is identified, but its measurement at three time points leaves the intended primary contrast unclear. Multiplicity procedures and their rationale are not reported in the registry record.

As a general statistical issue, examining several outcomes, time points, or treatment comparisons can increase the chance that at least one result appears noteworthy by chance. Adjustment methods can address some forms of this issue, but their appropriateness depends on the hypotheses and analysis plan. Without the planned hypothesis structure and results, it is not possible to determine whether multiplicity affects interpretation of this trial.

The registry record does not report missing-data counts, reasons for missingness, or methods for handling incomplete endpoint measurements. It also does not state whether analyses used an intention-to-treat population, a per-protocol population, or another defined analysis set. Arm-specific participant counts and endpoint denominators are not reported. These omissions prevent assessment of whether participants with available data differed systematically from those without data, or whether the analysis population followed the randomized allocation.

Use of interim analyses, stopping rules, and any changes to the planned analyses are not reported in the registry record. Their absence from the record is not evidence that a particular procedure was or was not used. The available description does not support conclusions about these aspects of the study’s statistical conduct.

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

The registry record establishes that the trial was designed to compare carvedilol, nebivolol, and placebo in healthy subjects, including assessment during high-altitude exposure. It identifies peak exercise oxygen consumption as the primary outcome and specifies three measurement conditions. These details define the intended topic and structure of the assessment; they do not establish what the measurements showed.

No primary outcome estimates or uncertainty measures are reported in the registry record. It is therefore not possible to state which arm had a higher or lower mean, whether any difference was precise, or whether the observed data were compatible with a range of treatment effects. The record does not support a claim that one treatment was better, worse, or equivalent to another on the primary endpoint.

Even if a treatment contrast were available, interpretation would depend on the contrast, its precision, and the conditions under which it was measured. An estimate from sea level after treatment would not automatically answer the question of performance under high-altitude hypoxia. Likewise, a comparison with untreated baseline would need to be interpreted in light of the timing and conditions of measurement. The registry record does not specify the primary contrast or analysis used.

The study’s rationale relates high-altitude hypoxia in healthy subjects to selected features seen in chronic heart failure. This is a model rationale, not direct evidence about treatment effects in patients with heart failure. The listed condition of heart failure does not change the population described in the study summary. The registry record does not report outcomes in people with heart failure or establish how results in this model would generalize to them.

These distinctions are statistical as well as clinical. A study’s design and endpoint description show what it was intended to investigate. Conclusions about observed effects require the outcome data, a defined comparison, and an account of uncertainty. Those results are not reported in the registry record, so the trial’s treatment effects cannot be characterized from the available record.

12. Why This Trial Matters Statistically

This study is statistically notable for separating measurement conditions: untreated baseline at sea level, treated assessment at sea level, and assessment under treatment during early high-altitude exposure. That schedule makes the target question dependent on both treatment and environment. A result tied to one condition cannot be assumed to describe another, and a change across conditions needs a clearly defined contrast and analysis.

The parallel, randomized design and three-arm structure make the comparison strategy important. Active-treatment-versus-placebo questions differ from a direct comparison of the two active treatments. The registry record identifies the arms but does not specify which contrast was primary. This illustrates why a trial’s endpoint label alone is not sufficient to interpret its analysis: the timing, comparison, and analysis population also matter.

The record reports enrollment of 27, but not arm-specific counts or endpoint denominators. These details would be needed to understand how much information supported each comparison. The stated planning calculations are illustrations based on an observed effect and specified assumptions, not observed power or a record of the original design justification. Without endpoint results and the calculation outputs, they cannot establish the precision achieved in the completed study.

Finally, the study illustrates the boundary between a physiological model and a patient population. The rationale invokes similarities between high-altitude responses in healthy subjects and selected features of chronic heart failure, but the described participants were healthy subjects. Statistical interpretation must preserve that distinction. No conclusion about treatment effects in this population—or about generalization to people with heart failure—can be drawn from the registry record without reported results and a carefully specified estimand.

13. 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.

A central limitation of the available registry description is that it does not report primary endpoint values or treatment-effect estimates. Without group summaries, uncertainty intervals, or test results, readers cannot assess the magnitude, direction, or precision of the primary outcome. The record also does not give arm-specific enrollment or the number with measurements at each time point, limiting assessment of the information available for each comparison.

The primary endpoint is measured under three conditions, but the primary contrast is not specified. This leaves uncertainty about whether the intended inference concerns treatment at sea level, performance under high-altitude exposure, change from baseline, or another comparison. The record does not describe how repeated measures were analyzed, how baseline measurements were used, or whether the analysis adjusted for any participant characteristics.

The study description identifies healthy subjects and a high-altitude hypoxia model, while heart failure appears among the listed conditions and in the scientific rationale. The record does not describe a patient population with heart failure. Consequently, the model’s relevance to clinical heart failure remains a rationale, not a direct population-level finding in the information reported.

Further limitations include the absence of reported randomization procedures, masking details, missing-data methods, analysis-population definitions, multiplicity strategy, and statistical analysis plan. Details of altitude exposure and the exercise assessment are also not reported in the registry record. These gaps do not establish that the procedures were inadequate; they restrict what can be evaluated from the registry description.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Effects of Nebivolol Versus Carvedilol on Cardiopulmonary Function at High Altitude in Healthy Subjects. — NCT00924833.
• Registry record last updated 2009-09-02; status last verified 2009-02.
• Results first posted 2009-06-19.
• 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.

17. Record Summary

NCT00924833 is a completed Phase 4 randomized, triple-masked, parallel-group study sponsored by Istituto Auxologico Italiano, with enrollment of 27. It compared placebo, carvedilol, and nebivolol in healthy subjects, with assessment at sea level and during high-altitude exposure. The primary outcome was peak exercise oxygen consumption, recorded at untreated sea-level baseline, after three weeks of allocated treatment at sea level, and during the first two days at high altitude under treatment.

The registry record lists nine outcome measures and four analyses. It does not report primary endpoint results, arm-specific counts, the primary treatment contrast, or the statistical analysis plan. As a result, the treatment effects and their precision cannot be assessed from the record. The study rationale concerns a high-altitude model of selected features associated with chronic heart failure; the described participants were healthy subjects.