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 Phase 4 Study to Assess the Effect of Bisoprolol on Glycemic Level in Type II Diabetic Subjects With Suboptimal Blood Pressure Control (NCT01066039), a na phase 4 study. The primary outcome is Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Month 6.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01066039 |
| Phase | Phase 4 |
| Condition | Hypertension, Diabetes Mellitus, Type II |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 202 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck KGaA, Darmstadt, Germany |
| Results posted | Yes |
2. Clinical Question
Population
The registry describes people with type 2 diabetes and hypertension, with suboptimal blood pressure control. The primary endpoint population was the full analysis set: participants who received at least one dose of investigational product and had a primary endpoint HbA1c measurement. The registry does not report additional demographic or clinical eligibility details in the record.
Intervention
Participants received bisoprolol in a prospective, open-label study lasting 24 weeks. The registry does not describe a dose or dosing schedule in the record.
Comparator
There was no separate comparator arm. The study is recorded as single group, with allocation listed as not applicable. The primary endpoint compares HbA1c at Month 6 with baseline within the study population; it does not compare bisoprolol with another treatment or with a concurrent untreated group.
Primary question
The primary question was how mean HbA1c changed from baseline to Month 6 among participants in the defined analysis population. The registry describes the study hypothesis as no change in glycemic level and lipid metabolism, with HbA1c identified as the measure of glycemic level. The numerical result, its uncertainty, and any test of that hypothesis are not reported in the registry record.
3. Trial Design
This was a Phase 4, prospective, multicenter, open-label, single-arm study of bisoprolol. The registry lists enrollment of 202 participants and a study duration of 24 weeks. The study is recorded as completed. Its title and description concern people with type 2 diabetes and suboptimal blood pressure control; hypertension and type 2 diabetes are the listed conditions.
Because the design had one group, there was no concurrent control arm and no randomized treatment allocation. Participants' HbA1c at Month 6 was compared with their own baseline value for the primary endpoint. That within-person comparison can describe change over the study period, but by itself cannot separate a treatment-associated change from changes over time or other influences. The registry does not report a control group or a method for estimating what would have happened without bisoprolol.
The study was open label, so masking is listed as none. The registry does not report the rationale for this design, the sample-size justification for enrollment of 202, or detailed eligibility criteria. It also does not report the dosing schedule or a fuller account of how participants were recruited. Those details should not be inferred from the study title or from the single-arm structure.
The primary analysis population is described as the full analysis set. It included participants who received at least one dose of investigational product and had the primary efficacy endpoint measured. This definition makes availability of a Month 6 HbA1c measurement relevant to inclusion in that endpoint population. The registry does not state how many participants met this definition or how missing endpoint measurements were handled.
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 |
|---|---|
| STARTED | 202 |
| Treated | 200 |
| COMPLETED | 158 |
| NOT COMPLETED | 44 |
Reasons for not completing this period:
| Reason | Bisoprolol |
|---|---|
| Adverse Event | 6 |
| Withdrawal by Subject | 17 |
| Protocol Violation | 2 |
| Inclusion/Exclusion Criteria Violation | 9 |
| Investigator's Request | 1 |
| Dropout due to Insulin Administration | 1 |
| Additional Antihypertensive Required | 4 |
| Volunteer Failed to Make the Next Visit | 2 |
| Failure to Control Blood Pressure | 1 |
| Drug/Dose Adjustment Required | 1 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) included all participants who received at least one dose of investigational product and for whom the primary efficacy endpoint (HbA1c) was measured.
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.
Population: Analysis population included all the participants who were enrolled in this study.
| Characteristic | Unit | Bisoprolol |
|---|---|---|
| Participants analysed | 202 | |
| Age, Continuous | years | 59.1 (SD 8.8) |
| Sex: Female, Male: Female | Participants | 92 |
| Sex: Female, Male: Male | Participants | 110 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Month 6, measured over Baseline, Month 6.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Percent HbA1c |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in glycosylated hemoglobin, or HbA1c, at Month 6. HbA1c is recorded as a percentage, and the registry describes it as the percentage of glycosylated hemoglobin. The change was defined as the Month 6 value minus the baseline value. Under that definition, a negative change would indicate a lower measured HbA1c at Month 6 than at baseline, while a positive change would indicate a higher value; the registry record does not report the observed mean change.
HbA1c is used as a measure of glycemic level because it summarizes glycosylated hemoglobin as a percentage. In general, a continuous endpoint such as HbA1c can be described with a mean and a measure of variability. The registry specifies the mean as the summary parameter and standard deviation as the dispersion measure. The numerical mean, standard deviation, participant count for the endpoint, and any confidence interval are not reported in the registry record.
The endpoint represents change over the study period in the defined analysis population. It is not a direct comparison against another treatment, because this study had a single group. The registry also lists change in HbA1c at Month 3 as a secondary outcome, alongside blood pressure, insulin-resistance, insulin, C-peptide, lipid, and urine-related measures at specified follow-up times.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive constraint is that the registry record does not report the numerical result for the primary endpoint. It identifies the endpoint, its timing, its units, and the analysis population, but gives no mean change, standard deviation, confidence interval, or p-value. Therefore the direction and size of the observed HbA1c change, and the precision with which it was estimated, cannot be described from this record. The stated hypothesis of no change is not itself evidence that the result was zero or that a statistical test supported that hypothesis.
The study planned to assess change from baseline to Month 6. A mean change would describe the average within-participant difference for those represented in the endpoint analysis. It would not show whether every participant changed in the same direction. A standard deviation, if reported, would describe variation in the observed values around the mean; it would not by itself quantify uncertainty in the mean. A confidence interval would ordinarily help show the range of values compatible with the data and analysis, but one is not reported in the registry record.
The single-arm design also limits causal interpretation. A before-and-after change can be observed in participants receiving bisoprolol, but without a concurrent comparator it cannot establish how much of any change was attributable to the study treatment rather than other factors or the passage of time. The open-label design means masking was not used. The registry does not report further design details that would clarify how measurement or other potential influences were addressed.
The registry lists 202 enrolled participants, while the serious-adverse-event record gives 200 at risk and the primary analysis population requires both at least one dose and a measured primary endpoint. These figures describe different registry entries and should not be treated as interchangeable analysis denominators. The endpoint-specific participant count is not reported in the registry record, so the extent of missing primary measurements cannot be determined from the record.
Several secondary outcomes are listed, including HbA1c at Month 3 and multiple metabolic, blood-pressure, and urine measures. Their numerical results are not reported in the registry record. The record also does not report a statistical analysis plan or a method for addressing multiple outcome tests. Consequently, no conclusion about secondary results or the handling of multiple comparisons can be drawn.
Overall, the record establishes what the investigators intended to measure and how the primary change was defined, but it does not provide the numerical outcome needed to characterize the observed glycemic change. This distinction matters: a study objective, a stated hypothesis, and an endpoint definition do not substitute for an effect estimate and its uncertainty.
9. Statistical Methods Explained
The endpoint is a continuous measure, and the registry identifies the mean as its summary parameter and the standard deviation as its measure of dispersion. The record does not report the statistical test, model, confidence interval method, or other detailed analysis procedure. The explanations below distinguish those recorded details from general statistical context.
What does a mean change describe?
General statistical context: for a continuous endpoint, a mean change summarizes the average of the individual changes in the analysis population. Here, each change was defined as the Month 6 HbA1c value minus the baseline HbA1c value. The sign of the change therefore has a clear direction: values below zero represent a lower follow-up measurement than baseline, and values above zero represent a higher follow-up measurement. The registry does not report the mean change, so neither its direction nor its magnitude can be stated.
A mean is a compact description of the group, not a description of every participant. Individual changes may vary around that average. The standard deviation is a descriptive measure of that variability. It is not the same as a confidence interval, and it does not directly state how precisely the mean has been estimated. The registry names standard deviation as the planned or recorded dispersion measure but does not give its numerical value.
Why use a change score?
General statistical context: a change score puts baseline and follow-up measurements on the same within-participant scale by subtracting the baseline value from the later value. This makes the endpoint directly express the average shift over the specified interval. A change score does not, on its own, solve all challenges of longitudinal data. Its interpretation depends on which participants contribute measurements and on how incomplete follow-up is handled. The registry defines the primary analysis population but does not report the number contributing to the endpoint or the procedure used for missing measurements.
The primary assessment was at Month 6, while HbA1c at Month 3 was listed as a secondary outcome. These are distinct assessment times and should not be treated as interchangeable. The record does not provide numerical results for either time point.
What can a confidence interval add?
General statistical context: a confidence interval expresses uncertainty around an estimated quantity under a specified statistical method. For a mean change, it would help readers judge which values remain compatible with the data and analysis, rather than focusing only on a single point estimate. Its width depends on factors including the variability in the data, the amount of information available, and the method used. No confidence interval or interval method is reported in the registry record, so precision cannot be assessed numerically.
A p-value, when reported, addresses compatibility between data and a specified null hypothesis under a statistical model; it is not a measure of effect size or clinical importance. The registry record does not report a p-value, test statistic, or testing procedure for the primary endpoint. The study's stated no-change hypothesis should not be mistaken for a reported statistical finding.
Why does the single-arm design matter?
General statistical context: a within-group before-and-after estimate describes change among participants in the observed group. A concurrent comparison can help distinguish a treatment contrast from changes that would also have occurred over time, though its usefulness depends on the design and analysis. This study is recorded as single group, with allocation not applicable, so the primary endpoint is not a randomized between-group contrast. The record does not report a comparator-based estimate.
The open-label structure means masking was not used. This describes the study design but does not, by itself, establish the direction or size of any bias. The registry does not report additional procedures for reducing or evaluating potential measurement or conduct effects. Interpretation should therefore remain tied to the design that is recorded rather than assuming safeguards not described in the record.
How should planning calculations be read?
General statistical context: sample-size calculations based on an effect estimate are planning illustrations under assumptions; they are not observed outcomes and are not evidence that a study had a particular probability of finding a result. The planning assumptions associated with this record specify a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. The effect to detect is defined as a stated fraction of the observed effect. Such calculations are not the original design rationale for this single-arm study, and their assumptions do not turn the study into a two-arm comparison.
The record does not report the original sample-size justification or the statistical plan used for the trial. It also does not report a numerical primary effect estimate in the results. Any planning illustration should consequently be kept separate from the observed trial findings: it does not supply the missing endpoint result, and it should not be described as observed power.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the primary endpoint as change from baseline in HbA1c at Month 6. It also lists secondary outcomes covering HbA1c at Month 3; systolic, diastolic, and mean blood pressure at Month 6; insulin-resistance measures, insulin, and C-peptide at Months 3 and 6; lipid measures at Month 6; and urine-related measures at Month 6. The record lists 10 outcome measures in total. Numerical results for these outcomes are not reported in the registry record.
When several outcomes or time points are examined, multiplicity is a general statistical concern: repeated testing can increase the chance of at least one apparently notable finding under a set of null hypotheses. Methods for prioritizing outcomes or adjusting interpretation can address this, but the registry record does not report a multiplicity procedure, testing hierarchy, or statistical analysis plan. It is therefore not possible to determine how the listed outcomes were handled inferentially.
The full analysis set is defined as participants who received at least one dose of investigational product and had the primary efficacy endpoint HbA1c measured. The number included in that population is not reported in the registry record. The record also does not report the amount or pattern of missing data, whether participants with incomplete follow-up were excluded or otherwise included, or whether any imputation or sensitivity analysis was used.
These omissions matter because an analysis based only on participants with measured outcomes can describe that observed subset, while missing outcomes may limit how well it represents all enrolled participants. Without the endpoint-specific denominator and missing-data procedures, that potential limitation cannot be quantified. The registry's definition of the full analysis set should be reported as written, without assuming that other analysis populations or missing-data methods were used.
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 | 7 | 200 | 3.5% |
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 | 61 of 200 |
Most frequent serious adverse event terms
| Event term | Organ system | Bisoprolol |
|---|---|---|
| Fracture lower limb | Musculoskeletal and connective tissue disorders | 1 of 200 |
| Fracture rib | Musculoskeletal and connective tissue disorders | 1 of 200 |
| Fracture upper limb | Musculoskeletal and connective tissue disorders | 1 of 200 |
| Musculoskeletal disorder | Musculoskeletal and connective tissue disorders | 1 of 200 |
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 200 |
| Gallbladder carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 200 |
| Hepatic neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 200 |
| Neoplasm metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 200 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Bisoprolol |
|---|---|---|
| Headache | Nervous system disorders | 8 of 200 |
| Dizziness | Nervous system disorders | 6 of 200 |
| Coughing | Respiratory, thoracic and mediastinal disorders | 4 of 200 |
| Weakness generalized | General disorders | 3 of 200 |
| Diarrhoea | Gastrointestinal disorders | 3 of 200 |
| Common cold | Infections and infestations | 3 of 200 |
| Numbness | Nervous system disorders | 2 of 200 |
| Abdominal discomfort | Gastrointestinal disorders | 2 of 200 |
| Constipation | Gastrointestinal disorders | 2 of 200 |
| Dyspepsia | Gastrointestinal disorders | 2 of 200 |
Serious events with the highest arm-level rate: fracture lower limb (0.5%), fracture rib (0.5%), fracture upper limb (0.5%), musculoskeletal disorder (0.5%), breast cancer (0.5%).
The safety record lists 200 participants at risk for the bisoprolol group. It reports 7 in the serious adverse-event affected count and 61 in the other adverse-event affected count. These are registry counts; the record does not provide further detail about event timing, duration, severity grading beyond the serious category, or whether participants could appear in both categories. The counts should not be treated as a comparison with another treatment group, because the study had only one arm.
The listed serious adverse-event terms are fracture lower limb, fracture rib, fracture upper limb, musculoskeletal disorder, breast cancer, and gallbladder carcinoma. Each term is reported at 0.5%. The registry does not state in this record whether these terms represent unique participants, event episodes, or a particular coding convention, so they should be read as reported terms rather than interpreted as mutually exclusive categories.
Deaths are not reported in the registry record. The adverse-event counts alone do not establish a causal relationship to bisoprolol. In general, adverse-event reporting describes events recorded during a study; attribution and comparative risk require additional information and an appropriate comparison. No such comparative safety estimate is reported for this single-arm study.
12. What the Result Does, and Does Not, Mean
The record establishes that investigators planned to examine HbA1c change from baseline to Month 6 in participants with type 2 diabetes and hypertension who received bisoprolol. It also defines how the change was calculated and specifies a full analysis set based on treatment exposure and availability of the primary measurement. These details identify the scientific question and the outcome framework, but they do not establish what happened to HbA1c during the study.
The numerical primary endpoint result is not reported in the registry record. Without the mean change and a measure of its uncertainty, the size, direction, and precision of any observed change cannot be described. The stated hypothesis of no change is an objective for evaluation, not a result. The registry record also does not report a statistical test or confidence interval from which to assess compatibility with that hypothesis.
Even if a within-group change were available, the single-arm design would limit what it could establish. A change between baseline and Month 6 is not a randomized contrast against another treatment or a concurrent control. It could describe change among observed participants, but it could not by itself isolate the effect attributable to bisoprolol. The record contains no comparator arm against which to estimate such a contrast.
The listed secondary outcomes broaden the intended assessment to blood pressure and several metabolic and urine measures. Their numerical results and the approach to interpreting multiple outcomes are not reported in the registry record. The safety counts describe recorded events among participants at risk, but do not provide comparative rates or establish causality.
Accordingly, the study record supports a description of the design, endpoints, and reported safety counts, but not a conclusion about the magnitude or clinical importance of a glycemic change. Those questions require outcome estimates and their uncertainty, interpreted in light of the single-arm design and the analysis population.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of how an endpoint definition and a study design jointly shape interpretation. The primary outcome is a continuous measure, specified as mean change in HbA1c from baseline to Month 6. The subtraction order is explicit, so the direction of a change would be interpretable if the numerical estimate were available. The record also identifies standard deviation as the dispersion measure, which is conceptually distinct from uncertainty in the estimated mean.
At the same time, the record illustrates why a protocol question and a result are not interchangeable. A stated hypothesis of no change does not report whether the data were consistent with that hypothesis, nor does an endpoint definition reveal the observed effect. Here, the numerical primary result and its precision are not reported in the registry record. Statistical interpretation must recognize that boundary rather than infer a result from the study title or objective.
The single-arm design is central. A pre-to-post change can summarize what occurred within the group, but it cannot provide the same information as a between-group comparison. This is an important distinction for clinical researchers reading studies of change over time. The design can describe an observed trajectory, but causal attribution requires evidence beyond a within-group difference.
The record also identifies multiple secondary outcomes and a full analysis set tied to measured HbA1c. That makes multiplicity and missing outcome data relevant questions, yet the corresponding methods and endpoint-specific participant count are not reported. The study therefore serves as a reminder to read outcome definitions alongside analysis populations, missing-data procedures, and the availability of numerical estimates, rather than treating an outcome label as a complete statistical report.
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 immediate limitation for statistical interpretation is that the numerical primary endpoint result is not reported in the registry record. The mean change, standard deviation, endpoint participant count, confidence interval, and p-value are not available in the record. The observed direction, magnitude, and precision therefore cannot be evaluated.
The single-arm structure means there is no concurrent comparison group. Change from baseline can describe within-group movement, but it cannot separate a treatment-associated change from other influences over the study period. The study is also open label, with masking listed as none. The registry does not report further design details that would allow assessment of additional protections against potential sources of bias.
The record lists 202 enrolled participants, but the primary analysis set requires at least one dose and a measured primary endpoint, and its size is not reported. The safety record lists 200 at risk. These counts cannot be assumed to represent the same population or endpoint denominator. The registry does not report missing-data amounts, reasons for missingness, or how missing primary measurements were handled.
Although several secondary outcomes are listed, their numerical results and any procedure for handling multiple outcomes are not reported in the registry record. The record also does not report the detailed statistical analysis plan, the original sample-size justification, or further eligibility and dosing details. These limits constrain assessment of both the statistical findings and how broadly they may apply.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase 4 Study to Assess the Effect of Bisoprolol on Glycemic Level in Type II Diabetic Subjects With Suboptimal Blood Pressure Control — NCT01066039.
- Registry record last updated 2014-07-04; status last verified 2014-06.
- Results first posted 2014-07-04.
- 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
This completed Phase 4 study assessed bisoprolol in a prospective, multicenter, open-label, single-arm design. The registry lists enrollment of 202 and describes a 24-week study among people with type 2 diabetes and hypertension, with suboptimal blood pressure control identified in the title and summary.
The primary endpoint was mean change in HbA1c from baseline to Month 6, defined as the Month 6 measurement minus baseline. The full analysis set included participants who received at least one dose and had the primary HbA1c endpoint measured. Numerical primary and secondary outcome results are not reported in the registry record.
The safety record lists 200 at risk, 7 in the serious adverse-event affected count, and 61 in the other adverse-event affected count. The study had no comparator arm, and deaths are not reported in the registry record.