This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Randomized Controlled Study to Assess the Effects of Bisoprolol and Atenolol on Resting Heart Rate and Sympathetic Nervous System's Activity in Subjects With Essential Hypertension (NCT01251146), a randomized phase 4 study. The primary outcome is Change From Baseline in Baroreflex Sensitivity (BRS) at Attainment of Heart Rate Goal.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01251146 |
| Phase | Phase 4 |
| Condition | Hypertension |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 177 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck KGaA, Darmstadt, Germany |
| Results posted | Yes |
2. Clinical Question
Population
People with essential hypertension were the population of interest. The registry describes the primary-outcome analysis population as the intention-to-treat population: randomized participants who received at least 1 dose of study medication. For the measure, “N” denotes participants evaluated for the measure, and “n” denotes participants evaluated at a specified time point. The registry record does not give primary-outcome group counts or further participant characteristics.
Intervention
One study arm received bisoprolol. The registry identifies it as a drug intervention, but does not describe dose, titration details, or other treatment procedures in the arm description.
Comparator
The other study arm received atenolol, also identified as a drug intervention. The record does not provide an active-comparator treatment schedule or additional arm details.
Primary question
The primary question was how change from baseline in baroreflex sensitivity differed between the bisoprolol and atenolol groups when participants attained the heart-rate goal. The goal was a heart rate less than or equal to 65 beats per minute. The registry record does not report the numerical change in either group, a between-group estimate, or a confidence interval or test result for this comparison.
3. Trial Design
This was a prospective, randomized, parallel-group Phase 4 study comparing bisoprolol with atenolol in people with essential hypertension. The record describes the study as multi-centric. Masking was listed as none, so the study was not masked according to the registry record. Randomization was used to assign participants to the two treatment arms, but the method used to generate or conceal the allocation is not reported in the registry record.
The registry lists enrollment as 177. That figure is the recorded enrollment, not a statement about how many participants contributed data to the primary endpoint. The primary-outcome description distinguishes participants evaluated for a measure from those evaluated at a specified time point, but outcome-specific counts are not reported in the registry record.
The study began in 2010-11, had primary completion in 2012-02, and is listed as completed. The primary endpoint was change from baseline in baroreflex sensitivity when the heart-rate goal was attained. The registry defines goal attainment as a heart rate less than or equal to 65 beats per minute and gives the possible attainment time points as Week 2, Week 4, or Week 6. The study also listed outcomes concerning heart-rate variability, heart-rate-goal attainment, adverse events, serious adverse events, and treatment compliance.
The registry record does not describe the dose regimens, treatment duration beyond the listed assessment times, eligibility criteria, or the reasons for selecting the enrollment target. It also does not report a statistical analysis plan or numerical primary-outcome results.
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
| Stage | Bisoprolol | Atenolol |
|---|---|---|
| STARTED | 86 | 91 |
| COMPLETED | 83 | 81 |
| NOT COMPLETED | 3 | 10 |
Reasons for not completing this period:
| Reason | Bisoprolol | Atenolol |
|---|---|---|
| Lost to Follow-up | 3 | 10 |
Analysis population for the primary outcome, as defined in the registry: Intention to treat (ITT) population included all randomized participants who received at least 1 dose of study medication. "N" signifies those participants who were evaluated for this measure. "n" signifies those participants who were evaluated for this measure at the specified time point for each treatment arm group respectively.
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.
| Characteristic | Unit | Bisoprolol | Atenolol | Total |
|---|---|---|---|---|
| Participants analysed | 86 | 91 | 177 | |
| Age, Continuous | years | 45.44 (SD 9.78) | 46.30 (SD 9.87) | 45.88 (SD 9.81) |
| Sex: Female, Male: Female | Participants | 31 | 38 | 69 |
| Sex: Female, Male: Male | Participants | 55 | 53 | 108 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Baroreflex Sensitivity (BRS) at Attainment of Heart Rate Goal, measured over Baseline and attainment of heart rate goal (Week 2 or Week 4 or Week 6).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | millisecond per millimeter of mercury |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in baroreflex sensitivity (BRS) at attainment of the heart-rate goal. BRS was reported as a mean continuous measure, with units of milliseconds per millimeter of mercury. The stated assessment was at the time the goal was attained, which could be Week 2, Week 4, or Week 6. The goal was a heart rate less than or equal to 65 beats per minute.
The registry describes BRS as a characteristic of baroreflex control, commonly assessed noninvasively by relating fluctuations in heart rate to fluctuations in blood pressure. In general, this type of measure is used to describe how heart-rate responses relate to blood-pressure changes. The endpoint therefore focuses on a physiological measure rather than only whether participants reached a heart-rate threshold.
Change from baseline expresses how the measured value at the specified assessment differs from the starting value. A comparison between randomized groups could describe whether the average change differed under the study’s treatment assignments. The registry specifies that the measure is summarized by a mean and standard deviation, but does not report either group’s values, the difference in mean change, or uncertainty around a comparison. The magnitude and precision of the primary endpoint result therefore cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a randomized comparison of bisoprolol and atenolol, with change in BRS at attainment of the heart-rate goal as the primary endpoint. It does not report numerical primary-outcome results. In particular, there are no reported group means or standard deviations, no between-group estimate, and no confidence interval or significance test for the primary comparison. The direction, size, and precision of any difference cannot be determined from the record.
The primary measure is tied to a post-baseline event: reaching the specified heart-rate goal. Assessment could occur at Week 2, Week 4, or Week 6. Because the numerical results and the number assessed at each time point are not reported, it is not possible to tell how observations were distributed across those assessment times or how many participants contributed to the endpoint. The record also does not explain how participants who did not reach the goal were handled in the primary analysis.
The safety figures report 0 serious adverse events among 86 participants at risk in the bisoprolol group and 0 among 91 at risk in the atenolol group. The record lists 6 other adverse events in each group. These counts are descriptive and do not establish that the treatments have identical safety profiles. The registry does not provide event details for the listed other adverse events, and deaths are not reported in the record.
Other planned outcomes concerned heart-rate variability, including low-frequency and high-frequency power and their ratio; reaching the heart-rate goal at different treatment dosages and assessment weeks; adverse events and serious adverse events; and treatment compliance. Numerical results for these outcomes are not reported in the registry record. The record lists no analyses, so it does not permit evaluation of analysis choices, adjusted comparisons, or uncertainty for those outcomes.
Overall, the registry describes the study question and design, but the available results are insufficient to quantify the primary comparison. The absence of a reported estimate should not be interpreted as evidence of no difference; it means the registry record does not report the information needed to assess the result.
9. Statistical Methods Explained
What does randomization contribute?
Randomization assigns participants to treatment groups using a chance-based process. In general, this is intended to make the groups comparable, on average, with respect to factors measured and unmeasured at the start of a study. It does not guarantee identical groups, and the value of randomization for interpretation depends on how assignment was generated, whether it was implemented as planned, and how participants were followed and analyzed. The registry identifies the study as randomized but does not report the allocation-generation or concealment procedures.
What does the parallel-group design mean?
In a parallel-group trial, participants are assigned to a treatment arm and followed in that arm rather than crossing between treatments as part of the design. Here, the two listed arms were bisoprolol and atenolol. The registry describes no masking. In general, lack of masking can matter when treatment knowledge could influence behavior, care, measurement, or reporting. The record does not describe safeguards for outcome assessment or whether BRS measurement was performed by assessors unaware of treatment assignment.
How should change from baseline be read?
Change from baseline compares a follow-up measurement with the participant’s starting measurement. A group mean change describes the average change among the participants included in that calculation. A between-group comparison of mean changes would address whether average changes differed between randomized arms. The registry identifies the primary measure as a mean and specifies standard deviation as its dispersion measure. General statistical interpretation distinguishes the average effect estimate from its precision: the standard deviation describes variability among observations, while a confidence interval, when reported, describes uncertainty around an estimated quantity under the analysis assumptions. No numerical mean, standard deviation, estimate, or confidence interval for BRS is reported in the registry record.
Why does the assessment time matter?
The primary assessment was linked to attainment of the heart-rate goal, with possible assessment at Week 2, Week 4, or Week 6. This means the endpoint is not described as a single fixed calendar-time measurement for every participant. In general, when measurement timing depends on reaching a target, interpretation may depend on how participants who reach the target at different times are handled and how participants who do not reach it are included. The registry record does not report those analysis details or the numbers evaluated at each time.
What do the safety counts convey?
In general, an adverse-event count is a descriptive tally and does not by itself characterize event severity, timing, duration, recurrence, or whether an event was considered related to treatment. The registry reports 0 serious adverse events among 86 participants at risk in the bisoprolol arm and 0 among 91 at risk in the atenolol arm. It also lists 6 other adverse events in each arm. The record does not provide the terms for those other events or a detailed safety analysis. A count of zero observed serious events does not show that the underlying risk is zero.
What can planning illustrations establish?
General sample-size calculations estimate how many participants might be needed under stated assumptions to detect a specified effect with a chosen significance level and power. The registry describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. Such illustrations are not the trial’s own design rationale, and they are not observed power. The registry record does not report the study’s sample-size justification. Without the primary effect estimate and the related numerical planning results, the illustrations cannot be interpreted as evidence about the strength or reliability of the observed comparison.
10. Multiplicity, Missing Data and Analysis Populations
The record lists multiple outcomes and assessment points. Secondary outcomes include changes in low-frequency and high-frequency heart-rate variability power and their ratio at attainment of the heart-rate goal and at the end of follow-up. Other outcomes concern goal attainment by treatment dosage and at Week 2, Week 4, and Week 6, as well as adverse events, serious adverse events, and treatment compliance. Considering multiple outcomes or time points can increase the chance of finding an apparently notable result by chance if many tests are performed. In general, statistical plans may address this through a hierarchy of outcomes or other multiplicity procedures. The registry record does not report whether any such approach was planned or used.
The registry describes an intention-to-treat population for the primary measure as randomized participants who received at least 1 dose of study medication. It also distinguishes the number evaluated for a measure from the number evaluated at a specified time point. However, it does not report the primary endpoint’s participant counts, a missing-data strategy, or how participants without a measurement or without heart-rate-goal attainment were handled. The approach to protocol deviations and any additional analysis populations are not reported in the registry record.
The record lists 0 analyses. It therefore does not provide analysis outputs or enough detail to determine the statistical model, any covariate adjustment, the handling of repeated or time-specific measurements, or the procedure for missing observations. These omissions limit assessment of both multiplicity and the way the stated analysis population was applied.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Bisoprolol | 0 | 86 | 0.0% |
| Atenolol | 0 | 91 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Bisoprolol | 6 of 86 |
| Atenolol | 6 of 91 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Bisoprolol | Atenolol |
|---|---|---|---|
| Elevated Triglyceride | Metabolism and nutrition disorders | 4 of 86 | 4 of 91 |
| Dizziness | Nervous system disorders | 0 of 86 | 2 of 91 |
| Elevated Cholesterol | Metabolism and nutrition disorders | 2 of 86 | 0 of 91 |
| Headache | Nervous system disorders | 0 of 86 | 1 of 91 |
| Bradycardia | Cardiac disorders | 0 of 86 | 1 of 91 |
| Chest distress | General disorders | 0 of 86 | 1 of 91 |
The registry lists serious adverse events for each treatment arm. In the bisoprolol group, 0 serious adverse events were reported among 86 participants at risk. In the atenolol group, 0 serious adverse events were reported among 91 participants at risk. The record also lists 6 other adverse events in each group.
These are counts, not estimates of comparative risk. The registry record does not give event descriptions for the other adverse events, nor does it report their severity, timing, duration, or relationship to treatment. The deaths information is not reported in the registry record; a missing death count should not be read as a count of zero.
In general, observing no serious adverse events in a group does not prove that serious events cannot occur or that the underlying risk is absent. Interpretation depends on follow-up, event ascertainment, and the amount and quality of safety information available. The record does not provide enough detail to make a broader comparative safety assessment.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized Phase 4 study compared bisoprolol with atenolol in people with essential hypertension. Its primary question concerned change from baseline in BRS when participants reached a heart-rate goal of less than or equal to 65 beats per minute. The record also identifies additional outcomes involving heart-rate variability, goal attainment, adverse events, and treatment compliance.
What the record does not establish is the numerical result for the primary comparison. It contains no reported group means, dispersion values, between-group estimate, confidence interval, or test result for BRS. Without those quantities, the size and direction of a difference and the precision of the estimate cannot be judged. This absence is not evidence that the groups had the same result; it is a limitation of what the registry record reports.
The safety information is similarly limited. The record reports no serious adverse events in either arm during the recorded assessment and lists 6 other adverse events in each arm. Those counts do not describe event types or provide a full comparative safety analysis. Deaths are not reported in the registry record.
In general, a trial’s design and a result’s interpretation are separate matters. Randomization supports a comparative design, but conclusions also depend on complete outcome reporting, appropriate analysis, and precision. The registry record does not report the statistical analysis details or the numerical outcome results needed to assess those features. It also does not establish effects beyond the study population, treatments, outcomes, and follow-up described in the record.
13. Why This Trial Matters Statistically
This study is statistically notable for asking a question about a physiological endpoint measured when participants attain a treatment target, rather than relying only on whether the target was reached. BRS was defined through the relation between heart-rate fluctuations and blood-pressure fluctuations, and the primary endpoint was change from baseline at goal attainment. The endpoint therefore combines a continuous measure with an assessment time tied to a clinical threshold.
That structure makes the analysis details important. Participants could reach the goal at Week 2, Week 4, or Week 6, while some might not reach it during the specified period. In general, the handling of different assessment times and participants without an eligible measurement affects what a mean change represents. The registry record does not report those details or the outcome-specific counts, so readers cannot assess their influence on the primary comparison.
The randomized, parallel-group design gives the comparison a clear structure, while the absence of masking is relevant when considering possible influences on measurement and reporting. The registry identifies the study as completed and reports enrollment as 177, but does not provide numerical primary-endpoint results. The resulting gap between a clearly described question and unavailable estimates illustrates why registration details alone cannot answer an efficacy question statistically.
The record also lists multiple secondary outcomes and safety measures. Their presence makes it important to know how outcomes were prioritized and whether multiplicity was addressed. Those analysis details are not reported. The trial is therefore useful for identifying the intended comparison and endpoint structure, but the registry record does not support a quantitative assessment of the primary result or a comprehensive evaluation of the analyses.
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 in the registry record is the absence of numerical primary-outcome results. No group-specific BRS change, standard deviation, between-group estimate, confidence interval, or test result is reported. The record therefore does not allow assessment of the primary comparison’s magnitude, direction, or precision.
The primary endpoint was assessed when the heart-rate goal was attained, with possible timing at Week 2, Week 4, or Week 6. The record does not give the number of participants evaluated at each time, explain how people who did not attain the goal were treated in the analysis, or describe how different attainment times were handled. These details matter for understanding which participants contributed to the reported mean, if such a mean were available.
The registry lists no analyses and does not report a statistical analysis plan, missing-data methods, multiplicity procedures, covariate adjustment, or sensitivity analyses. It identifies an intention-to-treat population for the primary measure, but does not provide the endpoint-specific counts needed to assess how that population was represented in the analysis.
The arm descriptions contain no dosing or treatment-procedure details. The record also does not report participant characteristics, the randomization procedure, masking of outcome assessors, or the sample-size rationale. For safety, the counts are limited: the registry lists 6 other adverse events in each arm but does not describe them, and deaths are not reported in the registry record. These gaps constrain interpretation of both the primary comparison and the broader safety profile.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Randomized Controlled Study to Assess the Effects of Bisoprolol and Atenolol on Resting Heart Rate and Sympathetic Nervous System's Activity in Subjects With Essential Hypertension — NCT01251146.
- Registry record last updated 2017-03-08; status last verified 2017-01.
- Results first posted 2012-11-30.
- 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.
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18. Record Summary
The registry describes a completed, prospective, multi-centric, randomized, unmasked, parallel-group Phase 4 study of bisoprolol versus atenolol in people with essential hypertension. Enrollment is listed as 177. The primary endpoint was change from baseline in BRS at attainment of a heart-rate goal of less than or equal to 65 beats per minute, assessed at Week 2, Week 4, or Week 6.
Other listed outcomes include heart-rate variability measures, goal attainment, adverse events, serious adverse events, and treatment compliance. The record reports 0 serious adverse events in each arm and 6 other adverse events in each arm. It does not report numerical results for the primary endpoint, deaths, or analysis outputs. The primary comparison’s direction, magnitude, and precision cannot be assessed from the registry record.