Study to Evaluate Symptoms in Patients Treated With Nebivolol or Metoprolol Extended-release (ER) for Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate Symptoms in Patients Treated With Nebivolol or Metoprolol Extended-release (ER) for Hypertension (NCT00547300), a randomized phase 3 study. The primary outcome is Change From Baseline in the Patient Symptoms Questionnaire (PSQ) Derived Score.

2. Clinical Question

In plain terms, the trial was designed to compare patient-reported symptom burden during treatment with nebivolol or metoprolol ER among people already taking HCTZ. The central statistical question would ordinarily be whether the groups changed differently in their PSQ-derived scores from baseline over the stated measurement period. The registry identifies that question but does not report a formal analysis or a primary endpoint result. It therefore does not support a conclusion about the size, direction or precision of a between-group difference in symptom change.

3. Trial Design

The registry describes a Phase 3, randomized, triple-masked, parallel-group study of nebivolol and metoprolol ER. Both were studied in patients with mild to moderate hypertension taking HCTZ. Nebivolol was described at 5 mg, 10 mg or 20 mg; metoprolol ER was described at 50 mg, 100 mg or 200 mg. The record does not explain how dose levels were assigned or adjusted, so the dose descriptions should not be read as a detailed dosing schedule.

Enrollment was recorded as 49. The study began on 2007-10-31, and primary completion was recorded as 2008-01-02. Its status is terminated. The registry states specifically that formal analysis of the primary endpoint was not conducted because the study was terminated before visit 10 was reached. The reason for termination is not reported in the registry record.

The primary measurement period was described as extending from visit 2 (week -2) to visit 10 (week 12), over a 14 week period. Secondary outcomes were peripheral blood pressure and pulse rate. The record lists 3 outcome measures and 0 analyses. It does not provide enough detail to reconstruct the full visit schedule, the treatment period actually completed by participants, or the extent of measurements collected before termination.

Randomization and masking describe design features, not evidence that a comparison was completed or that bias was eliminated. The record identifies the study as triple-masked but does not state which people or roles were masked. It also does not report the allocation procedure, concealment details, or other implementation information. The parallel design indicates that the intended comparison used separate groups assigned to the two interventions; additional operational details 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 week hydrochlorothiazide (HCTZ) run-in phase before randomization.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Formal analysis of the primary endpoint was not conducted in this abbreviated study as the study was terminated before visit 10 was reached.

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 Change From Baseline in the Patient Symptoms Questionnaire (PSQ) Derived Score, measured over Measurements occured over a 14 week period, from Visit 2 (Week -2) to Visit 10 (Week 12).

The primary endpoint was change from baseline in the Patient Symptoms Questionnaire (PSQ) derived score. The PSQ contained 44 possible symptoms, rated on a scale from 0, meaning no discomfort, to 5, meaning extreme discomfort. The endpoint was intended to represent change in patient-reported symptom burden during the measurement period specified in the registry: from visit 2 (week -2) to visit 10 (week 12), described as 14 weeks.

As a general statistical point, patient-reported symptom measures can capture experiences that may not be fully represented by physiological measurements alone. A change score compares a participant’s measurement after baseline with that participant’s baseline measurement. A treatment comparison of change scores would then assess whether the groups’ changes differed. The registry does not report the score’s calculation rules, handling of unanswered items, or whether symptoms were combined using a particular weighting method; these details are not reported in the registry record.

Crucially, the intended endpoint is not the same as an observed treatment effect. The registry says formal analysis was not conducted because termination occurred before visit 10 was reached. It reports no primary endpoint estimate, uncertainty interval or inferential result. Thus the endpoint definition describes what the study intended to measure, not a result demonstrating how either group’s score changed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and outcome description identify what the investigators intended to compare, but the registry does not report a formal analysis of the primary endpoint. The statistical concepts below are general explanations of how such analyses are usually understood; they are not a claim about methods actually used in this study.

What does randomization contribute?

In general, randomization assigns participants to study groups using a chance-based procedure. Its purpose is to reduce systematic differences between groups at the point of assignment, including differences that may be known or unknown to investigators. Randomization does not guarantee that every characteristic will be balanced, especially in a small study, and it does not replace reporting the groups’ baseline characteristics or the analysis. The registry identifies the allocation as randomized, but the allocation sequence, implementation details and baseline results are not reported in the registry record.

A parallel-group design generally means each participant is assigned to one intervention group rather than receiving both interventions in sequence. That can make the group contrast interpretable as a comparison between assigned interventions, provided the analysis and follow-up are appropriately handled. The record identifies the model as parallel but does not report further details about treatment adherence, crossover or how participants were analyzed.

What does masking mean?

Masking is intended to limit the influence of expectations or knowledge of assignment on participant experience, care, outcome assessment or analysis. The registry labels the study triple-masked. As a general principle, a masking label alone does not identify which roles were masked, how masking was maintained, or whether it was successful. Those particulars are not reported in the registry record. The PSQ is patient-reported, so masking could be relevant to how responses are influenced, but the record does not describe any specific assessment of that possibility.

How would a change-score comparison work?

In general, a change score is calculated by comparing a participant’s follow-up measurement with that participant’s baseline measurement. A group-level analysis could then compare the distributions or average changes between randomized groups. An alternative approach may model follow-up values while accounting for baseline values. Different valid approaches can yield estimates with different precision, particularly when baseline and follow-up measurements are related. The registry does not report which approach was planned or used, and it reports no primary endpoint analysis.

The score’s construction also matters. The PSQ description gives the number of possible symptoms and the response scale, but the registry does not describe how item responses were combined into the derived score, how missing answers were handled, or whether all symptoms contributed equally. Those scoring details are not reported in the registry record. Without them, a reader cannot independently reproduce the derived endpoint from item-level responses.

What does precision mean?

As a general statistical concept, an estimate describes the observed size and direction of a comparison, while a confidence interval describes the range of values reasonably compatible with the data under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval. A p-value, when reported, addresses how compatible the observed data are with a specified null hypothesis under an analysis model; it does not measure the size or importance of an effect. None of these primary-endpoint results is reported in the registry record, so there is no estimate or interval to interpret for the intended PSQ comparison.

Precision depends on more than the number enrolled. It can also be affected by outcome variability, missing measurements, the analysis model and the amount of information available at the time of analysis. The enrollment field records 49, but the registry does not report the number with usable primary outcome data or the variation in PSQ scores. Because formal analysis was not conducted, precision for the primary treatment contrast cannot be assessed.

Why do outcome distributions matter?

As a general principle, an analysis should reflect the outcome’s scale and distribution. A score formed from symptom ratings may have a bounded range or may be concentrated at some values, but the registry does not report the observed distribution of the derived score. It would therefore be inappropriate to assert that a particular model was required or used. The registry also does not report an analysis plan describing assumptions, transformations, covariate adjustment or methods for checking model fit.

For other kinds of outcomes, such as counts, repeated measurements or time-to-event outcomes, different modeling approaches may be suitable. Over-dispersion is a general issue in count data: it occurs when observed variability exceeds what a simple model assumes, and ignoring it can make uncertainty appear too small. This is only a general statistical explanation; the registry does not identify the primary endpoint as a count outcome or report use of a count model.

The record names peripheral blood pressure and pulse rate as secondary outcomes, but does not give their results or analysis methods. It also lists 3 outcome measures and 0 analyses. There is no basis in the record to infer which statistical models, if any, were used for those secondary outcomes.

What can the safety counts tell us?

As a general matter, adverse-event counts describe how many participants were recorded as affected within the stated risk set. They do not by themselves estimate a causal treatment effect. A comparative safety analysis might also consider event definitions, observation time, severity, recurrence and uncertainty. The record reports group counts for serious and other adverse events and deaths, but does not supply these additional details or a formal safety comparison. The reported counts should therefore be read descriptively.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and secondary outcomes of peripheral blood pressure and pulse rate. It records 3 outcome measures and 0 analyses. The record does not describe a hierarchy among secondary outcomes, a strategy for controlling the chance of false-positive findings across multiple comparisons, or a multiplicity adjustment. These matters are not reported in the registry record.

As a general statistical concept, multiplicity arises when several outcomes, time points, subgroups or treatment comparisons are examined. With more opportunities to test hypotheses, the chance of at least one apparently notable result can increase if all tests are treated as independent confirmatory findings. Prespecifying a primary outcome and defining how secondary analyses will be interpreted can help distinguish confirmatory questions from exploratory ones. The registry’s endpoint descriptions alone do not establish what analysis hierarchy or decision rules were planned.

The primary measurement window was described from visit 2 (week -2) to visit 10 (week 12), over 14 weeks. The registry says the study was terminated before visit 10 was reached and formal analysis of the primary endpoint was not conducted. It does not report how many participants had measurements at each visit, whether earlier measurements were available for analysis, or how incomplete follow-up was handled. Missing-data assumptions and methods are not reported in the registry record.

The record also does not specify the analysis population, such as whether an intended analysis would include all randomized participants, participants who received treatment, or another defined group. Although enrollment was 49, enrollment alone does not identify the number included in any endpoint analysis. No formal primary analysis is reported, and the registry’s analysis count is 0. Accordingly, neither the handling of missing data nor the population underlying a treatment-effect estimate can be assessed from this record.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events in both groups as 0 affected participants among 25 at risk in the nebivolol group and 0 among 26 at risk in the metoprolol ER group. Deaths are recorded as 0 for both groups. The record lists no serious-event terms. These entries describe what is recorded; they do not establish that no event could occur outside the observation captured by the study.

For other adverse events, the registry reports 5 affected among 25 at risk with nebivolol and 3 affected among 24 at risk with metoprolol ER. The at-risk counts differ by outcome category in the metoprolol ER group: 26 for serious adverse events and 24 for other adverse events. These counts should be read with their stated denominators, not combined into a new total. The registry does not give event-level details, observation time by participant, severity for the other events, or a formal statistical comparison.

In general, an adverse event recorded during a trial is not necessarily caused by the study treatment. Causal attribution requires clinical and design information beyond a count of affected participants. The posted figures are descriptive and do not, by themselves, establish a difference in safety between the treatments. The reason for termination is not reported in the registry record.

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

The record supports a description of the trial’s purpose and design: a randomized, triple-masked, parallel-group comparison of nebivolol and metoprolol ER in patients with mild to moderate hypertension taking HCTZ. The intended primary outcome was change from baseline in the PSQ-derived score. The study also listed peripheral blood pressure and pulse rate as secondary outcomes. These details explain what the study set out to assess, but they are not treatment-effect findings.

The registry explicitly states that formal analysis of the primary endpoint was not conducted because termination occurred before visit 10 was reached. No primary estimate, confidence interval or p-value is reported. It is therefore not possible to quantify the groups’ difference in symptom change, judge its precision, or determine whether the observed data support a particular statistical conclusion. The absence of an analysis is not evidence that the treatments had equal effects, nor is it evidence that one had a greater effect.

The adverse-event entries are limited descriptive information. They report no serious adverse events and no deaths in either group, along with counts for other adverse events. Those records do not prove the absence of risk, establish treatment causation, or provide a formal comparison. The different risk-set denominators for other and serious adverse events in the metoprolol ER group should be retained when reading those entries.

More broadly, the registry does not report the reason the study was terminated, the primary-outcome analysis population, missing-data methods, the analysis plan or the results for the listed secondary outcomes. These gaps prevent a full evaluation of the intended efficacy and safety comparisons. A reader should distinguish the registered question, the limited safety counts and an analyzed result: only the first two are described in the posted record, while a formal primary endpoint result is not reported.

Consequently, the record can inform readers about the study’s planned comparison and its reported status, but it cannot support a claim that either treatment performed better or worse on the primary symptom endpoint. It also cannot establish that the treatments were equivalent. Such conclusions would require analyzed outcome data and appropriate estimates of uncertainty, which are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because its registry record makes a clear distinction between an intended endpoint and an analyzed result. The primary outcome is described in detail: change from baseline in a PSQ-derived score, using a questionnaire covering 44 possible symptoms rated from 0 to 5. Yet the record says that formal analysis was not conducted because the study was terminated before visit 10 was reached. The presence of a defined endpoint therefore does not imply that a treatment comparison is available.

That distinction is important when interpreting randomized trials. Randomization is a design feature that can support a fair comparison, but it cannot supply missing outcome estimates. Likewise, triple masking is a design label, not a substitute for reporting the analysis, uncertainty or missing-data handling. Here, the registry reports the design but does not report the primary estimate, its precision or the statistical methods used to obtain it.

The record also illustrates why descriptive safety counts require restraint. Counts of affected participants can be informative as a record of observed events, but without event detail, follow-up information or formal comparisons, they cannot establish causation or a reliable difference between groups. The reported zero serious adverse events in each group is a limited observation, not a general assurance about safety.

Finally, a terminated study can still document a meaningful research question, planned outcomes and the boundary between available and unavailable evidence. The registry identifies the comparison and the reason the primary endpoint was not formally analyzed, while leaving important questions—including the termination reason and secondary outcome results—not reported in the registry record. This makes transparent interpretation more important than filling gaps with assumptions.

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 most consequential limitation is that the formal primary endpoint analysis was not conducted. The registry attributes this to termination before visit 10 was reached. As a result, no primary treatment-effect estimate or measure of its precision is reported. The reason for termination is not reported in the registry record, so it cannot be linked to efficacy, safety, recruitment, operations or any other cause.

Enrollment was recorded as 49, but the record does not state how many participants completed particular visits or contributed usable data to any outcome. The primary measurement period was described as extending from visit 2 (week -2) to visit 10 (week 12), over 14 weeks, yet the available record does not detail how much of that follow-up was obtained. The amount and pattern of missing outcome data are not reported in the registry record.

The endpoint description specifies the PSQ content and response anchors but does not explain how the derived score was calculated, how incomplete questionnaires were handled, or which analysis model was intended. The analysis population, prespecified covariates and treatment of deviations from assigned intervention are also not reported. No formal primary analysis is listed, and the registry reports 0 analyses.

Secondary outcomes include peripheral blood pressure and pulse rate, but their results and analysis methods are not reported. Although the record provides adverse-event counts, it does not provide serious-event terms, detailed descriptions of other events, or a formal comparison. The triple-masked label is not accompanied by information about which roles were masked. These limitations restrict interpretation of both the intended treatment comparison and the descriptive safety entries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Evaluate Symptoms in Patients Treated With Nebivolol or Metoprolol Extended-release (ER) for Hypertension — NCT00547300.
• Registry record last updated 2019-05-21; status last verified 2019-04.
• Results first posted 2019-05-21.
• 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 Phase 3, randomized, triple-masked, parallel-group study comparing nebivolol with metoprolol ER in patients with mild to moderate hypertension taking HCTZ. The arm descriptions list nebivolol at 5 mg, 10 mg or 20 mg and metoprolol ER at 50 mg, 100 mg or 200 mg. Enrollment was 49; the study began on 2007-10-31, primary completion was recorded as 2008-01-02, and status is terminated.

The primary endpoint was change from baseline in the PSQ-derived score, measured over a period described as 14 weeks from visit 2 (week -2) to visit 10 (week 12). The registry states that formal analysis was not conducted because termination occurred before visit 10 was reached. Peripheral blood pressure and pulse rate were listed as secondary outcomes. The record lists 3 outcome measures and 0 analyses.

Safety entries report 0 serious adverse events and 0 deaths in each group, with other adverse events recorded for 5 of 25 at risk in the nebivolol group and 3 of 24 at risk in the metoprolol ER group. The reason for termination and a formal primary endpoint result are not reported in the registry record.