A Study of the Effect of Nebivolol to Evaluate Its Vasodilatory Effects in Hypertensive Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Effect of Nebivolol to Evaluate Its Vasodilatory Effects in Hypertensive Patients (NCT00648895), a randomized phase 3 study. The primary outcome is Percentage Change From Baseline to End of Treatment for the Difference Between the Post-ischemia and Pre-ischemia Forearm Vascular Resistance (FVR)..

2. Clinical Question

3. Trial Design

The registry identifies this as a phase 3, randomized, double-masked, parallel-group study. The listed interventions are nebivolol and Metoprolol ER (TM), and the arm descriptions use those same treatment names. The record gives total enrollment as 12. The study status is completed; the recorded start is 2007-11 and primary completion is 2009-07.

Randomization is a method for assigning participants to study groups by chance. In general, it is used to reduce systematic differences between groups at the point of assignment, although it does not guarantee that groups will be alike in a small study. The registry does not report the randomization procedure, allocation ratio, or method used to conceal assignments.

Double masking means that the registry classifies the study as masked at two levels, but it does not identify which roles were masked or describe how masking was maintained. A parallel design means participants are assigned to a group that receives its assigned intervention during the study rather than crossing between interventions, as a general design concept. The registry does not give additional details about treatment sequence, dose adjustment, or adherence.

The study’s stated purpose is to examine nebivolol’s mechanism of action, including forearm blood flow, nitric oxide availability, and other biomarkers, in comparison with another beta blocker. The brief summary lists nebivolol doses of 10, 20, and 40mg/day and a range of doses for extended-release metoprolol, but the registry does not map those doses to the arms or report dose-specific analyses. Further protocol details, including the sample-size justification and planned statistical analysis, 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.

Before assignment: All patients went through a 4-5 week, single blind, placebo washout phase before randomization.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Due to the small sample size, no efficacy conclusion could be made. 0 measured value primary outcome =Not applicable.

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 Percentage Change From Baseline to End of Treatment for the Difference Between the Post-ischemia and Pre-ischemia Forearm Vascular Resistance (FVR)., measured over Before treatment and after 10 weeks.

The primary endpoint is the percentage change from baseline to the end of treatment in the difference between post-ischemia and pre-ischemia forearm vascular resistance (FVR). The registry says FVR was calculated using forearm blood flow (FBF) and systolic blood pressure (SBP). It identifies the assessment as occurring at the trough, pre-meal time point, with measurements at baseline (visit 5) and at week 10. The stated timeframe is before treatment and after 10 weeks.

In general, comparing a post-ischemia measurement with a pre-ischemia measurement is intended to describe how the measured vascular resistance differs across those conditions. Expressing change relative to baseline can describe how that response changes over treatment. The registry’s summary says the study was designed to examine forearm blood flow, nitric oxide availability, and other biomarkers; the official title also names nitric oxide bioavailability and oxidative stress. These aims provide the mechanistic context for measuring a vascular response, but the endpoint itself is not a direct measurement of every biological process named in the title.

The registry does not report the formula used to derive the percentage change, a group mean, a standard deviation, or a treatment contrast. It records that no measured primary outcome value is applicable and states that the small sample size prevented an efficacy conclusion. Thus, the endpoint’s definition and timing are available, but its observed result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

Randomization assigns participants to study groups by chance. As a general statistical principle, this helps avoid deliberately or systematically assigning participants with particular characteristics to one intervention. It can support a fair comparison, but it does not ensure that groups will be balanced on every characteristic, especially when enrollment is small. The registry describes the study as randomized but does not report the assignment sequence, allocation concealment, or any details about how randomization was implemented. It therefore supports identifying the design as randomized, not evaluating the quality of its implementation.

What does masking mean for interpretation?

The registry classifies the study as double-masked. In general, masking is intended to reduce the influence of knowledge about assigned treatment on behavior, outcome assessment, or reporting. The record does not say which participants, investigators, assessors, or other roles were masked, nor does it describe the procedures used. The classification can be reported, but the effectiveness of masking cannot be assessed from the recorded details.

How should the continuous endpoint be understood?

The outcome is classified as continuous, with the mean as its parameter and the standard deviation as its dispersion measure. In general, a mean gives a central summary of measured values, while a standard deviation describes how spread out those values are around the mean. A mean alone does not show how variable the observations are, and a standard deviation alone does not identify a treatment difference. Both are needed to characterize the observed data, alongside an analysis that defines the comparison of interest.

Here the endpoint is a percentage change in a difference between post-ischemia and pre-ischemia FVR. The registry describes how FVR relates to FBF and SBP, and gives the assessment time points, but it reports no mean or standard deviation. It also does not provide a group contrast or an analysis result. Consequently, the continuous-outcome classification explains the type of summary that would be relevant, but it does not supply evidence about the size or precision of an effect.

Why are confidence intervals and p values useful?

As a general statistical explanation, a confidence interval expresses uncertainty around an estimate under specified assumptions. It can help readers judge whether the data are compatible with a range of effect sizes, not just whether a result passes a significance threshold. A p value describes how unusual data at least as incompatible with a specified null model would be, assuming that model and the analysis assumptions. Neither measure provides the probability that a treatment works, and neither substitutes for the observed estimate and its clinical or scientific context.

No confidence interval or p value for the primary endpoint is reported in the registry record. There is also no reported effect estimate to which an interval or significance test could be attached. This absence prevents a judgment about statistical precision or the evidence for a difference from these registry results.

What can the sample-size illustration establish?

The stated sample-size framework is a planning illustration based on an observed effect, not the trial’s own design. It specifies a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. For continuous outcomes, the planning quantity is described as participants per arm. The registry record does not report the resulting planning values in the registry record for this analysis, nor does it report the assumptions used to design the trial itself.

In general, a sample-size calculation estimates the enrollment needed to meet specified statistical goals under stated assumptions. A retrospective planning illustration is not observed power and does not show that the study had a particular probability of finding an effect. It cannot replace an effect estimate or its uncertainty. The registry reports enrollment of 12 and explicitly says that no efficacy conclusion could be made because of the small sample size; it does not give a sample-size justification or a protocol-based target.

What analysis details are absent?

The registry reports zero analyses. It does not report the statistical model, covariate adjustment, treatment contrast definition, handling of repeated measurements, or method for addressing missing observations. These details matter in general because they describe how observed values are converted into an estimate and how uncertainty is quantified. The record also does not report an analysis population or explain whether all randomized participants were included in any analysis. Without those details and without outcome estimates, the posted information supports a design-level description rather than a reconstruction or evaluation of the treatment analysis.

Over-dispersion is a general concern for certain count-data models when variability exceeds what a simple model assumes. It is not a reported feature of this continuous endpoint, and the registry does not identify a count model. The relevant limitations are instead the lack of reported continuous-outcome summaries, analysis details, and a single interpretable comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, but the primary outcome description includes pre-ischemia and post-ischemia measurements and assessments at baseline and the end of treatment. It indicates that the outcome has several categories or time points and was not reduced to one comparison. The registry record does not describe a multiplicity strategy, such as how statistical interpretation would account for testing multiple outcomes, contrasts, time points, or doses. It also does not report which comparisons, if any, were designated in advance for formal testing. The protocol’s statistical plan is not reported in the registry record.

In general, multiplicity matters when several statistical tests are conducted because interpreting each test separately can increase the chance of finding at least one apparently notable result by chance. That general issue does not establish that a particular adjustment was required or used in this study. The registry does not report enough analysis detail to determine how multiplicity was addressed.

Missing-data handling is also not reported. The record does not give the number of participants with observed primary outcome data, describe reasons for missing measurements, or state how missing values were handled. The statement that no measured primary outcome value is applicable does not supply a missing-data method or an analysis result.

The registry does not identify an intention-to-treat, per-protocol, or other analysis population. It also does not explain whether participants were analyzed according to random assignment, treatment received, or another rule. These omissions limit assessment of the analysis population and its relationship to randomization. No interim analyses or stopping rules are reported in the registry record; their use or absence cannot be inferred from the completed status alone.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for 0 of 6 participants in the nebivolol group and 0 of 6 participants in the Metoprolol ER (TM) group. It reports other adverse events for 5 of 6 participants in each group. The top serious adverse-event terms list is empty. The death entries are null, so deaths are not reported in the registry record; null should not be read as a confirmed count of zero.

These figures describe the adverse-event entries recorded for the listed groups. They do not show event severity beyond the serious-versus-other grouping, provide event names for the other adverse events, or establish whether the events were considered related to treatment. The registry does not report additional details about onset, duration, recurrence, or how events were collected. It also does not provide a safety analysis or statistical comparison between groups.

In general, an adverse-event count is descriptive: it records events or participants meeting a reporting category and does not by itself establish causation. With enrollment of 12, the registry’s figures should be read as limited descriptive counts, not as a precise estimate of comparative safety. The record does not support conclusions about risks beyond the entries it reports.

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

The study was designed to compare nebivolol with extended-release metoprolol and to examine a vascular response relevant to the stated mechanistic aims. The primary endpoint is defined as percentage change from baseline to the end of treatment in the difference between post-ischemia and pre-ischemia FVR. The record identifies measurements at baseline and week 10 and says they were assessed at the trough, pre-meal time point.

What the posted information does show is the study’s randomized, double-masked, parallel-group classification, total enrollment of 12, treatment names, endpoint definition, and limited adverse-event counts. It also says that no efficacy conclusion could be made because of the small sample size and records no measured primary outcome value. These registry entries describe the design and reporting status; they do not identify the direction, size, or precision of a treatment effect.

What the record does not show is a numerical primary outcome result, a statistical comparison, or an interval expressing uncertainty around an effect. It does not establish that nebivolol was better, worse, or equivalent to the comparator. Nor does the absence of a reported efficacy conclusion demonstrate that the interventions had identical effects. Without an estimate and its uncertainty, no treatment-effect interpretation can be drawn from the primary endpoint.

The study’s mechanistic aims should also be distinguished from evidence of a clinical effect. The title and summary name forearm blood flow, nitric oxide availability, other biomarkers, and oxidative stress, but the record does not report results for these measures in the registry record. The endpoint definition alone cannot establish a mechanism or demonstrate a broader clinical outcome.

In general, trial interpretation depends on the observed effects, the uncertainty around those effects, the prespecified analysis, and the study context. The registry record does not report enough outcome or analysis information to make that assessment for this study. Its findings, as posted, support a cautious account of what was planned and recorded, not a conclusion about comparative efficacy.

13. Why This Trial Matters Statistically

This trial is statistically notable as an example of the difference between a well-specified measurement and a reported treatment result. The registry describes a particular continuous endpoint, its relationship to forearm blood flow and systolic blood pressure, its assessment conditions, and its timing. Those details make the intended measurement understandable. They do not, on their own, answer whether the intervention groups differed.

The registry reports enrollment of 12 and explicitly states that no efficacy conclusion could be made because of the small sample size. That statement highlights why enrollment and outcome reporting need to be considered together. In general, small studies can yield uncertain estimates, but the degree of uncertainty must be assessed from the data and an appropriate estimate; it cannot be quantified from enrollment alone. In this record, the outcome value and analysis are not reported.

The design labels also illustrate what can and cannot be learned from registry descriptions. Randomized, double-masked, and parallel-group identify important features of the planned study structure. The record does not give implementation details or the statistical analysis plan, so those labels cannot establish how randomization and masking worked in practice or how the primary contrast was estimated.

Finally, the record shows the value of distinguishing descriptive safety counts from efficacy results. It includes group counts for serious and other adverse events, while leaving deaths unreported and providing no comparative safety analysis. Clear interpretation depends on recognizing the limits of each kind of information. For this study, the most defensible statistical conclusion is about the incompleteness of the reported efficacy analysis, not the presence or absence of a treatment effect.

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 central limitation for interpreting the primary endpoint is that the registry reports no measured value and no efficacy analysis. It supplies the endpoint definition and measurement schedule but no group summaries, treatment contrast, measure of uncertainty, or p value. The registry itself says the sample size was too small for an efficacy conclusion. Without outcome estimates, the magnitude and precision of any difference cannot be assessed.

The registry does not report the statistical analysis plan, sample-size justification, analysis population, randomization implementation, or handling of missing data. It also does not specify how the stated range of doses was assigned to the two treatment arms or report dose-specific results. The endpoint description involves multiple measurement conditions and time points, and the registry notes that it was not reduced to one comparison. Details about the intended comparison and multiplicity handling are not reported.

Safety reporting is limited to counts of participants with serious and other adverse events. Serious-event terms are not listed, the other adverse events are not named, and the death values are null rather than reported counts. The registry does not give event attribution or a statistical comparison of safety outcomes.

These limitations are specific to the information recorded for this study. They prevent a full assessment of efficacy, precision, analysis choices, and safety, but do not demonstrate that unreported analyses were or were not conducted outside the registry. Further protocol and results information is not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of the Effect of Nebivolol to Evaluate Its Vasodilatory Effects in Hypertensive Patients — NCT00648895.
• Registry record last updated 2010-09-20; status last verified 2010-08.
• Results first posted 2010-09-20.
• 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 phase 3, randomized, double-masked, parallel-group study of nebivolol and Metoprolol ER (TM) in hypertension, with total enrollment of 12. The brief summary describes nebivolol doses of 10, 20, and 40mg/day and a range of doses for extended-release metoprolol. The primary endpoint concerns percentage change from baseline to the end of treatment in the difference between post-ischemia and pre-ischemia FVR, assessed at baseline and week 10.

The registry states that no efficacy conclusion could be made because of the small sample size and records no measured primary outcome value. It reports 0 serious adverse events among 6 participants in each group and other adverse events among 5 of 6 participants in each group. Deaths are not reported in the registry record. The primary analysis results and further statistical details are not reported.