Study of the Efficacy and Safety of Nebivolol in Younger Patients (18 - 54 Years): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of the Efficacy and Safety of Nebivolol in Younger Patients (18 - 54 Years) (NCT01415531), a randomized phase 4 study. The primary outcome is Trough Seated Diastolic Blood Pressure (DBP).

2. Clinical Question

The main comparison concerns the mean change in diastolic blood pressure between the randomized groups, rather than a comparison of individual patients’ responses. A more negative change represents a larger reduction from baseline on this measure. The registry reports group means and standard deviations, along with a sponsor-reported ANCOVA comparison. The analysis therefore provides information about the average Week 8 change and its statistical uncertainty, not about the response of every participant or about outcomes beyond the stated measurement and follow-up period.

3. Trial Design

This was a Phase 4, multicenter, randomized, triple-masked, placebo-controlled, parallel-group study. It enrolled 641 patients and is recorded as completed. The registry lists the start as 2011-08 and primary completion as 2012-03. Its stated purpose was to assess the efficacy, safety, and tolerability of 8 weeks of nebivolol compared with placebo in younger patients aged 18 - 54 years with stage 1 or stage 2 essential hypertension.

The intervention was oral nebivolol in a 5, 10 or 20 mg tablet; the comparator was dose-matched placebo. The record identifies the sponsor as Forest Laboratories. Random allocation and the parallel-group structure mean the primary comparison is between participants assigned to the two groups, with each participant allocated to one group. The registry calls the masking triple but does not identify the masked parties or give further operational details about concealment.

There were 211 participants in the posted placebo summary and 423 in the nebivolol summary for the primary endpoint. The primary outcome population is described separately: 641 patients were randomized, the safety population included 641 who received at least one dose, and the intent-to-treat population included 634 with at least one postbaseline seated diastolic blood pressure measurement. The registry does not explain the difference between the randomized totals and the endpoint group counts, or provide additional details on analysis-set construction beyond those descriptions.

The primary endpoint was change from baseline to Week 8 in trough seated diastolic blood pressure. Trough seated systolic blood pressure was posted as a secondary outcome. The registry lists one analysis for the primary endpoint and does not provide a reported analysis for the secondary outcome. Further trial-protocol details, including the original sample-size justification and the planned statistical analysis beyond the information in the record, 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:

Analysis population for the primary outcome, as defined in the registry: 641 patients were randomized to receive double-blind treatment. The Safety population consisted of 641 patients who received at least 1 dose of double-blind treatment. The Intent to Treat population (ITT) consisted of 634 patients who had at least 1 postbaseline seated diastolic blood pressure (DBP) assessment

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 Trough Seated Diastolic Blood Pressure (DBP), measured over Change from Baseline to Week 8.

The primary endpoint is change from baseline to Week 8 in mean seated trough cuff diastolic blood pressure, measured in mmHG using an Omron device. A trough measurement is intended to capture blood pressure at the specified point in the dosing interval; the registry identifies this as a seated measurement but does not give further measurement-timing details. Change from baseline expresses the Week 8 measurement relative to the participant’s starting measurement, and the posted summaries report the mean change for each group.

Diastolic blood pressure is the lower of the two routinely measured blood pressure values. The registry uses a continuous outcome: each participant’s measurement contributes to a group mean, and the standard deviation describes variation among observations in the group. Comparing changes between randomized groups addresses whether the average change differs between the assigned treatments over the stated follow-up. It does not describe the full distribution of individual responses or establish what happened after Week 8.

General explanation: continuous blood pressure outcomes can capture a range of observed changes rather than classifying participants into a small number of categories. A change-from-baseline endpoint also uses each participant’s baseline measurement as a reference. The registry reports that the primary analysis used the intent-to-treat population and a last-observation-carried-forward approach for missing follow-up values. The specific rationale for choosing this endpoint, its clinical importance threshold, and the trial’s prespecified handling of other missing data are not reported in the registry record.

7. Results Posted in the Registry

• Nebivolol: mean -11.80 versus -5.50 on control; difference -6.30 (95% CI -7.83 to -4.77), standardized effect d = -0.70; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Trough Seated Systolic Blood Pressure (SBP)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Nebivolol: mean -13.70 versus -5.50 on control; difference -8.20 (95% CI -10.53 to -5.87), standardized effect d = -0.57; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Nebivolol than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcome is change from baseline to Week 8 in trough seated systolic blood pressure. Its group means show a decrease in both arms, with a more negative average change in the nebivolol arm than in the placebo arm. This direction is broadly consistent with the pattern of the primary diastolic endpoint. It provides a related measure of blood pressure, but it is a separate outcome and does not replace the primary result.

The secondary outcome’s unadjusted mean difference is -8.2 mm Hg, with a recalculated 95% confidence interval from -10.53 to -5.87 and an unadjusted p-value of <0.001. The registry does not list a sponsor-reported analysis for this endpoint. These figures are descriptive and inferential summaries of the posted secondary outcome; they should not be treated as an independent confirmation without considering the full analysis plan.

Multiplicity matters when several outcomes or comparisons are examined. General explanation: as the number of statistical tests increases, the chance of observing at least one apparently strong result by chance can increase if no adjustment or prespecified testing strategy is used. The registry lists two outcome measures, but does not report a multiplicity adjustment, hierarchical testing procedure, or other plan for interpreting multiple outcomes. The secondary result therefore carries less weight than the designated primary analysis, particularly because the record does not give its own reported analysis or explain how secondary testing was controlled.

The overall pattern across the posted endpoints is directionally aligned: both diastolic and systolic group summaries show more negative mean change in the nebivolol group. This observation does not establish that all outcomes were prespecified, that their analyses were independent, or that the results address a broader clinical benefit. The registry record gives one secondary endpoint and no multiplicity details, so conclusions from it should remain limited to the measurement and time point recorded.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Trough Seated Systolic Blood Pressure (SBP)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous, so the registry reports means and standard deviations for the two groups. The mean is the arithmetic average of the observed change values. The standard deviation describes how spread out individual changes are around that average. The placebo group had a mean change of -5.5 mmHG and standard deviation of 9.5; the nebivolol group had a mean change of -11.8 mmHG and standard deviation of 8.8. These summaries do not show the exact distribution of measurements or the experience of each participant.

What does the mean difference represent?

The mean difference compares the groups’ average changes. For the primary endpoint, the recalculated unadjusted estimate is -6.3 mmHG, defined as the nebivolol group mean relative to the placebo group mean. A negative value means the nebivolol group’s average change was more negative. Since the endpoint is change from baseline, this corresponds to a larger mean decrease in that group. General explanation: a difference in group means is a summary of average separation, not a statement that each participant’s outcome differed by that amount.

How does the sponsor analysis differ from the recalculation?

The registry reports an ANCOVA analysis with a least-squares mean difference of -6.3, a 95% confidence interval from -7.7 to -4.8, and p < 0.001. ANCOVA is a regression-based method that can compare group outcomes while accounting for specified covariates. The registry does not report which covariates were included or the model details. The recalculated comparison uses the posted group means and standard deviations without covariate adjustment; its estimate is -6.3, its 95% confidence interval is -7.832 to -4.768, and its unadjusted p-value is <0.001. The methods differ, so their intervals and p-values need not match exactly.

General explanation: adjustment can change an estimate or its uncertainty when the model includes information related to the outcome. Without the model specification and participant-level data, the posted summaries cannot reproduce an adjusted ANCOVA result. The recalculation is consequently a transparent summary-statistic comparison, not a replacement for the sponsor’s model-based analysis.

What does the confidence interval convey?

A confidence interval expresses uncertainty around an estimated difference under the assumptions of the method used. The sponsor’s interval gives a range of values compatible with its ANCOVA analysis at the stated 95% confidence level. The recalculated interval reflects the unadjusted method and posted summary statistics. Neither interval describes the range of individual participant changes; both concern uncertainty about a group-level difference. General explanation: a narrower interval indicates greater statistical precision, while a wider interval indicates more uncertainty about the estimated group contrast.

What do the p-values mean?

The registry reports p < 0.001 for its ANCOVA analysis, while the unadjusted recalculation reports p <0.001. A p-value is a measure of how incompatible the observed data are with a specified null hypothesis, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it measure clinical importance. The record does not report further details about the p-value calculation beyond identifying the sponsor analysis as ANCOVA; the recalculation is explicitly unadjusted.

Why can over-dispersion matter?

General explanation: for a continuous outcome, greater variability relative to the size of the mean difference makes it harder to estimate the group contrast precisely. The standard deviations describe variability in this trial’s posted summaries. Here, the standard deviations are 9.5 for placebo and 8.8 for nebivolol, while the unadjusted estimated difference is -6.3. The standardized effect estimate in the recalculation is -0.697. This standardized value expresses the mean contrast relative to pooled variability; it is not in mmHG and should not be read as a blood pressure change.

The main inferential result in the registry is the ANCOVA comparison. The recalculated unadjusted estimate is useful for understanding the posted group summaries and their uncertainty, but it does not contain the adjustment or other details of the sponsor’s model. The registry does not report the original statistical plan, covariates, model diagnostics, assumptions checks, interim analyses, or further sensitivity analyses. Those omissions limit how fully the analysis can be independently assessed from the record alone.

11. Confidence Intervals and Precision

The primary endpoint’s recalculated unadjusted mean difference is -6.3 mmHG, with a 95% confidence interval from -7.832 to -4.768. This interval gives a range of plausible values for the population mean difference under the unadjusted method and its assumptions. Its endpoints are both negative, consistent with the direction of the group means. It does not mean that 95% of individual participants had changes within this range, nor does it give a prediction interval for an individual response.

The sponsor’s ANCOVA estimate is also -6.3, with a reported 95% confidence interval from -7.7 to -4.8. These limits are reported to one decimal place, whereas the recalculated limits are reported with three decimal places. The displayed numerical precision should not be mistaken for greater certainty: the interval width and interpretation depend on the method and data, not on the number of digits printed. The registry does not report a direct comparison of these interval methods.

In general, confidence intervals capture sampling uncertainty conditional on the analysis assumptions. They do not account automatically for every possible source of uncertainty, including bias from missing data, errors in measurement, or model misspecification. The record describes last observation carried forward for the primary analysis but does not report sensitivity analyses that test alternative missing-data assumptions. The numerical interval therefore needs to be read alongside the endpoint definition, analysis population, and limitations of the posted record.

The interval indicates that the estimated group-average contrast is not pinpointed to one exact value. It conveys statistical precision for the average difference, not clinical relevance. The registry does not state a minimum clinically important difference, so the interval cannot be classified against such a threshold from this record.

12. Planning a Similar Trial: Sample Size

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

The sample-size figures are planning illustrations based on the observed effect, not the trial’s original design calculations. They report participants per arm for 80% power and participants per arm for 90% power; these are not total event counts. The planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect.

For each assumed effect size, the 80% power column gives the estimated number of participants needed in each arm for an 80% chance of detecting an effect of that size under the stated assumptions, if the effect and assumptions are correct. The 90% power column uses a higher target chance of detection and therefore requires more participants per arm in the listed scenarios. These are design-planning quantities, not outcomes measured in the study.

The rows consider planning for 100%, 75%, and 50% of the observed effect. The smaller the effect a study aims to detect, the more participants are generally needed to distinguish it from random variation under otherwise comparable assumptions. This is why the figures increase as the assumed fraction of the observed effect becomes smaller. The listed counts are not a recommendation for a future study: a real design would also depend on its target outcome, population, analysis plan, anticipated missingness, and other protocol choices.

This is not observed power. It is a planning illustration calculated from the posted effect estimate under the listed assumptions. The trial’s own original sample-size assumptions and justification are not reported in the registry record, so these figures should not be interpreted as evidence about how the trial was designed or whether its planned sample size was achieved.

13. How the Sample Size Is Derived

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

Formula

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

Worked calculation for this trial

1. Observed difference Δ = -6.300; pooled standard deviation σ = 9.039.
2. n = 2 × (1.96 + 0.842)² × 9.039² / -6.300² = 32.3, rounded up to 33 participants per arm for 80% power.

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

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -6.3                      # observed difference in means
sigma <- 9.03861091881779                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

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

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1415531)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 33 (80% power), 44 (90% power)
 75% of observed effect: n per arm = 58 (80% power), 77 (90% power)
 50% of observed effect: n per arm = 130 (80% power), 174 (90% power)
power.t.test: 33.3 
Simulated power at n = 33 per arm: 0.798 (20000 replicates)

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

14. Analyses Reported by the Sponsor

The sponsor-reported primary analysis is an ANCOVA comparison of least-squares mean changes. It estimates a difference of -6.3, with a 95% confidence interval from -7.7 to -4.8 and p < 0.001. This is the registry’s reported inferential analysis for the primary endpoint.

The recalculated comparison is an unadjusted estimate based on the posted group means and standard deviations. It gives a mean difference of -6.3, a 95% confidence interval from -7.832 to -4.768, and p <0.001. The two estimates agree when expressed to one decimal place, and both intervals lie below zero. The recalculation is not the same model as the ANCOVA: it does not reproduce covariate adjustment or the least-squares means.

The registry does not report the ANCOVA covariates, model specification, or diagnostics, so the adjusted analysis cannot be independently reconstructed from the posted summary statistics. The sponsor’s result should be read as the trial’s reported analysis, while the recalculation offers a simple check of the group-summary contrast. Differences in interval limits and p-value format are consistent with the analyses being reported using different methods and precision. The record does not identify a discrepancy between them.

15. Multiplicity, Missing Data and Analysis Populations

The primary outcome description states that the efficacy analysis used the intent-to-treat population with last observation carried forward. The registry defines that population as 634 patients who had at least one postbaseline seated diastolic blood pressure measurement. It also reports that 641 patients were randomized and that the safety population consisted of 641 patients who received at least one dose of double-blind treatment. These definitions distinguish the analysis populations; the record does not give a participant flow accounting for every exclusion or missing measurement.

Last observation carried forward uses a participant’s last available observation to stand in for a missing later measurement. General explanation: this approach can preserve a record for analysis when follow-up data are missing, but it relies on assumptions about how the participant’s unobserved outcome relates to the last observed value. The registry does not report the amount or pattern of missing Week 8 data, the reasons for missingness, or sensitivity analyses using alternative assumptions. The influence of missing data on the result therefore cannot be fully assessed from this record.

The registry identifies the primary analysis as ANCOVA but does not report model covariates, diagnostics, or detailed estimation procedures. It lists one secondary outcome and does not report a sponsor analysis for that endpoint. A multiplicity adjustment or planned testing sequence is not reported in the registry record. As a result, the record does not establish how the secondary result was positioned relative to the primary test, or how the overall chance of false-positive findings across outcomes was handled.

The original sample-size justification, any interim analyses, and a fuller prespecified statistical plan are not reported in the registry record. Those details matter when assessing whether outcomes and analyses were selected in advance and how missingness, multiplicity, or model assumptions were handled. Their absence does not change the posted estimates, but it limits independent evaluation of the design and statistical analysis beyond the information recorded.

16. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fall (0.5%), non-cardiac chest pain (0.5%), prostate cancer (0.5%), splenic rupture (0.5%), transient ischaemic attack (0.5%).

The registry reports serious adverse events among 214 participants at risk in the placebo group and 427 at risk in the nebivolol group. Four participants in each group were recorded as affected by a serious adverse event. For other adverse events, the at-risk counts are again 214 and 427, with 21 affected in the placebo group and 37 in the nebivolol group. These are counts of participants recorded as affected, not measures of the blood pressure endpoint.

The listed serious adverse event terms and percentages are Fall (0.5%), Non-cardiac chest pain (0.5%), Prostate cancer (0.5%), Splenic rupture (0.5%), Transient ischaemic attack (0.5%), and Hypersensitivity (0.2%). The registry does not provide further contextual detail for these terms in the posted summary. Death counts are not reported in the record; this should not be read as evidence that no deaths occurred.

Safety counts describe what was recorded during the trial and are not, on their own, proof that an event was caused by an assigned treatment. The at-risk denominators differ from the primary endpoint group counts, and the registry does not explain that difference. These figures should be read as descriptive safety information, alongside the limited follow-up and the details available in the record.

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

The posted primary result describes average change in trough seated diastolic blood pressure from baseline to Week 8 in a randomized comparison of nebivolol and placebo among patients aged 18 - 54 years with stage 1 or stage 2 essential hypertension. The group summaries show a more negative mean change for nebivolol than placebo, and the sponsor’s ANCOVA estimate of the between-group difference is -6.3, with a 95% confidence interval from -7.7 to -4.8 and p < 0.001. This is evidence about the stated endpoint and analysis, not a complete account of every possible effect of treatment.

The result does not show that every person in the nebivolol group experienced a decrease, or that any one participant’s change would match the group mean. The standard deviations indicate variation in individual measurements, while the confidence interval concerns uncertainty in the estimated average difference. Neither summary conveys the whole distribution of responses.

The record covers an 8-week treatment period and reports blood pressure changes at Week 8. It does not establish what happens after that time, nor does it report outcomes beyond the listed diastolic and systolic blood pressure measures and safety summaries. No clinical-importance threshold is reported, so the statistical evidence should not be equated with a judgment about the size or importance of a difference for an individual patient.

The registry describes the randomized design and the primary analysis, but does not report the full statistical plan, details of the ANCOVA model, or sensitivity analyses for missing data. The safety summary also does not provide enough context to determine causation for individual adverse events. General explanation: interpreting a trial result requires attention to the population, intervention, comparator, endpoint, follow-up, analysis assumptions, and uncertainty, rather than relying on a p-value alone.

Accordingly, the posted findings support a limited statistical interpretation of the average Week 8 blood pressure changes in the analyzed groups. They do not constitute medical advice, establish outcomes for people outside the studied population, or settle questions that the registry did not measure or report.

18. Why This Trial Matters Statistically

This trial illustrates the distinction between a sponsor-reported adjusted analysis and an unadjusted recalculation from group summaries. Both give a mean difference of -6.3 when reported to one decimal place, but their confidence intervals and p-values arise from different procedures. Knowing which result is adjusted, and what information is unavailable about the adjusted model, is essential for reading the registry’s evidence accurately.

It also shows why estimates and intervals are more informative than a significance label alone. The mean difference describes the direction and size of the average contrast, while the confidence interval conveys uncertainty in that contrast. Neither answers whether a difference is clinically important; the registry does not state a threshold for that judgment. The standard deviations add context about variability among participants, which is distinct from uncertainty in the group-average estimate.

The analysis populations are another important statistical detail. The record identifies 641 randomized patients, a safety population of 641 who received at least one dose, and an intent-to-treat population of 634 with at least one postbaseline diastolic measurement. The primary analysis also used last observation carried forward. These details affect how results are interpreted, while missing-data quantities and sensitivity analyses are not reported.

Finally, the secondary endpoint has a direction consistent with the primary endpoint, but no sponsor-reported analysis or multiplicity plan is listed for it. This illustrates why related outcomes should not automatically be treated as independent confirmation. Statistical interpretation depends not just on the numerical pattern, but also on prespecification, multiplicity, analysis choices, and the limits of the registry record.

19. 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 report the original sample-size justification, the trial’s planned design assumptions, or the full statistical analysis plan. The sample-size figures accompanying the posted summaries are planning illustrations based on the observed effect and cannot establish how the original trial was powered or designed. The registry also does not report whether interim analyses were conducted.

Although the primary analysis is identified as ANCOVA, the covariates, model specification, diagnostics, and handling of model assumptions are not reported. The unadjusted recalculation uses posted means and standard deviations and cannot reproduce the adjusted analysis. This limits independent assessment of the sponsor-reported model using the registry summaries alone.

The primary efficacy population is defined as participants with at least one postbaseline diastolic blood pressure measurement, and the analysis used last observation carried forward. The record does not state the amount, timing, or reasons for missing measurements, or report sensitivity analyses under alternative missing-data assumptions. It also does not explain the difference between randomized totals and the group counts in the endpoint summaries.

The registry lists a secondary systolic outcome but no sponsor-reported analysis for it, and it does not report a plan for controlling multiplicity. It gives no clinical-importance threshold for the blood pressure differences. Follow-up for the stated treatment period is 8 weeks, and no longer-term endpoint is reported in these results.

Safety reporting is also limited in the posted summary: event counts and selected serious-event terms are available, but contextual details and death counts are not reported. These limitations do not erase the numerical results, but they constrain interpretation of precision, robustness, broader relevance, and safety beyond the information recorded.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study of the Efficacy and Safety of Nebivolol in Younger Patients (18 - 54 Years) — NCT01415531.
• Registry record last updated 2013-05-16; status last verified 2013-03.
• Results first posted 2013-05-16.
• 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.

23. Record Summary

NCT01415531 is a completed Phase 4 randomized, triple-masked, parallel-group study of nebivolol versus dose-matched placebo in patients aged 18 - 54 years with stage 1 or stage 2 essential hypertension. The registry records 641 randomized patients and an 8-week treatment period. The primary endpoint was change from baseline to Week 8 in trough seated diastolic blood pressure.

The posted group means were -5.5 mmHG for placebo and -11.8 mmHG for nebivolol. The sponsor-reported ANCOVA estimate was -6.3, with a 95% confidence interval from -7.7 to -4.8 and p < 0.001. The registry also posts a secondary systolic blood pressure outcome, but does not report a sponsor analysis for it.

The record describes the primary intent-to-treat analysis as using last observation carried forward. The original sample-size justification, full statistical plan, and several details needed to assess missing data, multiplicity, and the adjusted model are not reported in the registry record.