Effects of the Beta-blocker Nebivolol (Bystolic) on Subjects With High Normal Blood Pressure and/or a Family History of Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of the Beta-blocker Nebivolol (Bystolic) on Subjects With High Normal Blood Pressure and/or a Family History of Hypertension (NCT01202175), a randomized phase 4 study. The primary outcome is Aortic Systolic Blood Pressure (SBP).

2. Clinical Question

The trial’s stated rationale focuses on people at elevated risk of developing hypertension, including people with high-normal blood pressure and/or a family history of hypertension. The summary also describes interest in biological markers in blood and urine, including microscopic protein in urine and C-reactive protein in blood. The listed secondary outcomes include urinary nitric oxide, isoprostane and hydrogen peroxide excretion, as well as plasma interleukin levels.

The primary endpoint is aortic systolic blood pressure, a continuous measurement reported in mm Hg. The intended measurement occasions are baseline (visit 1) and 8 weeks (visit 2). The clinical question is therefore about the blood-pressure measure over the stated trial period, not about long-term prevention of hypertension. Whether the trial’s participants or results support any conclusion about that question cannot be determined from the registry record because primary outcome results are not reported.

3. Trial Design

The registry describes a randomized, single-masked, parallel-group Phase 4 trial sponsored by the University of California, San Diego. Enrollment is listed as 50. The two groups are identified as nebivolol and sugar pill. Randomization means assignment was intended to be based on chance, while a parallel design means participants were assigned to one group rather than crossing between treatments. The record does not identify who was masked, so the meaning of single masking for participants, clinicians, or outcome assessors cannot be established from the registry entry.

The recorded study start is 2010-07, and primary completion is recorded as 2012-06. The status is completed. The primary endpoint is aortic systolic blood pressure, with measurements specified at baseline and 8 weeks. The brief summary describes before-and-after evaluation, but it does not provide a detailed schedule for treatment, visits, or other assessments. Dose, adherence procedures, and treatment duration beyond the endpoint timing are not reported in the registry record.

The registry lists pre-hypertension and hypertension as conditions. Its summary describes the intended population as people with high-normal blood pressure and/or a family history of hypertension, but detailed inclusion and exclusion criteria are not reported in the registry record. The two arm-description fields contain no additional descriptions. As a result, the record does not clarify whether eligibility could be met by either risk characteristic, how each was defined for enrollment, or whether other clinical characteristics were required.

The record lists 12 outcome measures, including the primary blood-pressure measure and secondary biological measures. It lists 0 analyses. That entry does not establish whether analyses were conducted but not entered; it means the registry record does not provide analysis results or a detailed analysis plan. The specific method used to compare groups, any adjustment variables, and the approach to repeated measurements are not 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.

Overall Study

Reasons for not completing this period:

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 Aortic Systolic Blood Pressure (SBP), measured over Basline (visit 1) and 8 weeks (visit 2).

Aortic systolic blood pressure is the primary endpoint. It measures the systolic component of pressure in the aorta, the major artery leaving the heart, and the record specifies the unit as mm Hg. The endpoint is continuous, and the registry identifies the planned summary as a mean with standard deviation. Measurements are specified at baseline (visit 1) and 8 weeks (visit 2).

In general, a continuous measure can show the distribution of observed values and how they differ between groups or over time. A mean describes the center of a set of measurements, while a standard deviation describes their spread around that mean. Aortic systolic pressure is relevant to the trial’s stated question because the study concerns people with high-normal blood pressure and risk of future hypertension. The endpoint is a measure of blood pressure during the trial, however, not a direct measure of whether participants later develop hypertension.

The registry record does not report the mean or standard deviation for either group at either visit, nor does it report a change estimate, between-group contrast, confidence interval, or p-value. Consequently, the direction, size, and precision of any primary endpoint difference cannot be described from the registry record. The use of this endpoint and measurement schedule identifies what was intended to be assessed, but does not itself establish what the measurements showed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. It identifies the trial as randomized, single-masked, and parallel, and identifies a continuous primary endpoint summarized as a mean with standard deviation. It does not name the test or model used to analyze the endpoint, provide an analysis plan, or report estimates. The concepts below explain how such design and summary choices are generally understood; they do not describe an unreported analysis from this trial.

What does randomization contribute?

In general, random assignment helps limit systematic differences between groups at the time of assignment. It does not guarantee identical groups, particularly in a trial with limited enrollment. Checking baseline characteristics can help readers understand how the groups began, but the baseline results are not reported in the registry record. Randomization also does not resolve questions about later adherence, missing measurements, or how participants were included in the analysis. Those issues require additional information about conduct and analysis.

What do the mean and standard deviation describe?

For a continuous outcome, the mean is an average that describes the center of the observed measurements. The standard deviation describes how spread out the individual measurements are around that average. A mean alone does not show how much individual values vary, while a standard deviation alone does not show the estimated difference between groups. Both are descriptive summaries; an inferential comparison generally also needs an estimate of the contrast and an assessment of its uncertainty.

The record specifies means and standard deviations for aortic systolic blood pressure, but does not post those values. It also does not state whether the primary analysis was intended to compare the endpoint at 8 weeks, changes from baseline, or a model incorporating both visits. These are distinct analytical approaches. In general, a model that uses repeated measurements can account for the relationship between measurements from the same participant, but the choice of model and its assumptions must be described before its results can be evaluated.

How should uncertainty be assessed?

In general, a confidence interval presents a range of values compatible with the data and the statistical model at a stated confidence level. Its width reflects the precision of the estimate: narrower intervals indicate greater precision, while wider intervals indicate greater uncertainty. A point estimate without an interval can obscure how precisely the effect is estimated. The registry record does not report a confidence interval for the primary endpoint or for the secondary outcomes.

A p-value, in general, measures how unusual data at least as incompatible with a specified null hypothesis would be under that hypothesis and the model’s assumptions. It is not the probability that the null hypothesis is true, and it does not communicate the size or clinical importance of an effect. No p-value for the primary endpoint is reported in the registry record. The two-sided significance level of 0.05 appears among the sample-size planning assumptions; it should not be taken as evidence that the trial’s analysis used that threshold unless the analysis plan says so.

What do the planning assumptions mean?

The registry’s planning description specifies a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It also describes illustrations based on fractions of an observed effect. In general, sample-size calculations estimate how many participants would be needed under stated assumptions about the target effect and variability. Changing the target effect changes the planning requirement: planning to detect a smaller effect generally requires more information than planning to detect a larger one.

These calculations are planning illustrations, not observed power. Observed power is not a substitute for reporting an effect estimate and its uncertainty. A planning value also does not establish that the trial was designed with that target, because the registry record does not report the trial’s own sample-size justification. The record does not provide numerical planning outputs in the registry record for this analysis, so no specific required sample size can be stated.

Why can variation matter?

In general, greater variability makes it harder to distinguish a group contrast from the natural spread of measurements, all else being equal. The standard deviation is one way to describe such spread for a continuous measure. If a statistical model assumes a particular distribution or variance structure, departures from that assumption can affect uncertainty estimates. This trial’s primary endpoint is continuous, and the record does not report evidence of over-dispersion or a model that addresses it. No claim about such a problem can therefore be made for these data.

What cannot be reconstructed?

The registry does not give the group-level endpoint values, the number with measurements at each visit, or a primary contrast. A simple recalculation from summary statistics is therefore not possible from the registry record. The specific test, covariate adjustment, treatment of repeated observations, and approach to outliers are not reported. Without those details and results, statistical significance, effect magnitude, and precision cannot be independently assessed.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 12 outcome measures, including blood pressure and secondary measures of urinary excretion and plasma interleukin levels. When a study evaluates multiple outcomes or multiple comparisons, the chance of at least one apparently notable result can increase if each is assessed separately. In general, a prespecified hierarchy, adjustment procedure, or clear distinction between primary and exploratory outcomes can help readers interpret multiple tests. The registry record does not report a multiplicity strategy or explain how the primary and secondary outcomes were prioritized beyond naming the primary endpoint.

The record lists 0 analyses. This means analysis results are not displayed in the registry record; it does not establish that no analyses were undertaken. There is no reported account of which comparisons were performed, whether any were prespecified, or how results across the outcome measures were handled. No analysis-specific multiplicity adjustment can be identified.

Missing-data handling is not reported in the registry record. The record does not give the number of participants measured at each visit, describe reasons for missing measurements, or state whether missing values were imputed, excluded, or addressed by a model. In general, missingness can affect an estimate when the probability of having an observed measurement is related to participant characteristics or outcomes. The possible direction and extent of any such effect cannot be judged without the missingness information and analysis approach.

The analysis populations are also not described. For example, the registry record does not state whether the primary analysis included everyone randomized, only participants who completed treatment, or another defined group. These choices can change the question an analysis answers. The record’s enrollment of 50 participants does not, by itself, indicate how many contributed to each endpoint analysis.

11. 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 adverse-event entry lists 50 participants at risk for serious events, with 0 serious events reported, and 50 participants at risk for other events, with 1 other event reported. It also lists 0 deaths. The serious adverse event terms field contains no listed terms. The type and severity details of the other event are not reported in the registry record.

These figures are counts, not a detailed comparison of safety between nebivolol and the sugar pill. The registry presents the counts for all study participants rather than separating them by treatment group, and it does not provide event timing, duration, attribution, or participant-level context. The at-risk counts indicate the number represented in the adverse-event entry; they do not show how completely events were collected or whether every participant had the same observation period.

In general, a lack of reported serious events in a trial does not rule out uncommon events or establish that an intervention is free of risk. A small trial may provide limited information about events that occur infrequently. The record’s descriptive counts should therefore be read narrowly: 0 serious events and 0 deaths are recorded, alongside 1 other event, without enough detail to characterize that event or compare groups.

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

The record establishes that a randomized, single-masked, parallel Phase 4 trial was conducted, with nebivolol and a sugar pill as the groups and aortic systolic blood pressure as the primary endpoint. It also gives the endpoint timing as baseline and 8 weeks and lists 12 outcome measures. These details describe the trial’s structure and intended measurements; they do not show what happened to the endpoint values.

Because the primary endpoint results are not reported in the registry record, the direction and size of any difference between groups are unknown from this record. There is no reported estimate, confidence interval, or p-value with which to evaluate the evidence or its precision. The secondary outcomes likewise lack numerical results. Neither the study title nor its stated rationale can substitute for outcome data.

The endpoint addresses a short-term blood-pressure measurement, not whether participants later developed hypertension. The registry’s description of an at-risk population and its interest in biological markers do not establish an effect on future disease or on those markers. Follow-up beyond the stated 8-week visit is not described in the primary endpoint entry.

The adverse-event counts are also limited. The record lists 0 serious events and 0 deaths, and 1 other event, without identifying the other event or reporting counts by group. These data do not support a detailed comparative safety assessment. A registry record that lacks outcome estimates should not be read as evidence that the groups had the same results, just as it should not be read as evidence of a difference.

In general, interpreting a clinical trial requires the estimated effect, its uncertainty, and enough information about the analysis and conduct to judge possible biases. Those details are not reported for the primary comparison. The available record therefore supports a description of the design and planned endpoint, but not a conclusion about the magnitude, precision, or clinical meaning of an effect.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its design places a randomized treatment comparison alongside a continuous blood-pressure endpoint and a set of biological secondary outcomes. That combination illustrates why a clear primary endpoint is important: it focuses interpretation on a defined measure and time frame, even when the research question also involves several other markers. Here, the primary measure is aortic systolic blood pressure at baseline and 8 weeks.

The record also illustrates the difference between a trial’s design information and its evidential results. Randomization and masking describe intended protections against bias, but readers still need reported group values, a treatment contrast, and uncertainty to assess what the study found. The record reports the design features but no primary analysis results. That gap prevents an assessment of effect magnitude and precision, regardless of the scientific rationale.

Multiple outcomes raise a further statistical issue. With 12 outcome measures listed, readers would benefit from knowing which analyses were prespecified and how multiplicity was handled. The record does not report that information. Nor does it describe missing-data procedures or analysis populations. These are not minor technical details: they help determine which observations contributed to an estimate and how confidently a result can be interpreted.

Finally, the enrollment of 50 and the planning description should not be confused with evidence about the observed effect. Planning calculations depend on assumptions and are not observed power. The record does not state its own sample-size justification. This makes the trial a useful example of why transparent reporting needs to include not just a planned design, but also outcomes, uncertainty, and analysis details.

14. 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 principal limitation for statistical interpretation is that the registry record does not report the primary endpoint results. No group means or standard deviations are given for aortic systolic blood pressure, and there is no estimated contrast, confidence interval, or p-value. This prevents assessment of direction, magnitude, and precision. The record also does not report results for the listed secondary outcome measures.

Important design and conduct details are limited. The arm descriptions are empty beyond the group labels, and the dose, treatment instructions, and adherence information are not reported in the registry record. Although the study is described as single-masked, the masked party or parties are not identified. Detailed eligibility criteria are also absent, limiting assessment of how closely the enrolled population matches the broad description of people with high-normal blood pressure and/or a family history of hypertension.

The primary endpoint is specified at baseline and 8 weeks, but the registry record does not state the planned statistical comparison or how it handled within-participant repeated measurements. It does not report baseline characteristics, the number assessed at each visit, missing-data methods, the analysis population, or an approach to multiplicity across the 12 outcome measures. The listing of 0 analyses means results are not displayed; it does not resolve whether analyses were carried out elsewhere.

The adverse-event information is sparse and not separated by treatment group. The record lists 0 serious events, 1 other event, and 0 deaths, but does not identify the other event or provide further context. Thus, the safety entry cannot support a detailed comparison. Finally, while planning assumptions are described, the trial’s own sample-size justification is not reported in the registry record. These limitations constrain what can be concluded from the registry entry, not necessarily what may be available from other sources.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effects of the Beta-blocker Nebivolol (Bystolic) on Subjects With High Normal Blood Pressure and/or a Family History of Hypertension — NCT01202175.
• Registry record last updated 2019-08-21; status last verified 2019-07.
• Results first posted 2019-08-21.
• 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.

18. Record Summary

The registry describes a completed, randomized, single-masked, parallel Phase 4 trial sponsored by the University of California, San Diego, with enrollment of 50. The groups are nebivolol and sugar pill. The primary endpoint is mean aortic systolic blood pressure, measured at baseline and 8 weeks.

The stated population is people at risk of hypertension, including those with high-normal blood pressure and/or a family history of hypertension. The record lists 12 outcome measures and 0 analyses. Numerical primary and secondary outcome results, a detailed analysis plan, missing-data procedures, and analysis populations are not reported in the registry record.

The adverse-event entry lists 0 serious events, 1 other event, and 0 deaths. The other event is not described, and the counts are not broken down by treatment group. The registry record therefore supports a description of the trial’s design and recorded safety counts, but not a statistical conclusion about the primary endpoint or a comparative safety assessment.