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 Fixed Dose Combination of Bisoprolol and Amlodipine in the Treatment of Hypertension (NCT01977794), a randomized phase 3 study. The primary outcome is Mean Reduction In Systolic Blood Pressure (SBP) After 18 Weeks of Treatment From Baseline.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01977794 |
| Phase | Phase 3 |
| Condition | Hypertension |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 200 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck KGaA, Darmstadt, Germany |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned people with essential hypertension whose blood pressure was not well controlled on monotherapy with bisoprolol 5 mg or amlodipine 5 mg. The registry record describes separate groups according to which monotherapy had failed before trial inclusion. Further eligibility details, such as the blood-pressure thresholds used to define inadequate control, are not reported in the registry record.
Intervention
Participants in each group were assigned to receive a fixed-dose combination of bisoprolol and amlodipine. The record identifies the combination as the intervention for both the bisoprolol-failed group and the amlodipine-failed group. The combination's doses and any further treatment instructions are not reported in the registry record.
Comparator
The trial summary frames the study as testing whether the fixed-dose combination is superior to monotherapies. However, the intervention and arm descriptions in the registry record identify the combination in both groups, distinguished by the monotherapy that had failed before inclusion. The record does not report a concurrent monotherapy comparator arm or its results.
Primary question
The stated primary outcome is mean reduction in systolic blood pressure from baseline after 18 weeks of treatment. Baseline is defined as the latest systolic blood pressure under monotherapy. The central statistical question is whether the change in this continuous measure differs between relevant treatment groups. A numerical estimate of the primary outcome, a between-group contrast, and its uncertainty are not reported in the registry record, so the stated superiority question cannot be evaluated from the posted primary outcome information.
3. Trial Design
This was a randomized, comparative Phase 3 trial with a parallel-group model and no masking. The registry record lists enrollment of 200 and indicates that the trial is completed. Its start is recorded as 2014-03 and primary completion as 2015-03. The sponsor is Merck KGaA, Darmstadt, Germany.
The study addressed hypertension in people whose blood pressure was not well controlled on one of two monotherapies: bisoprolol 5 mg or amlodipine 5 mg. The arm descriptions divide participants according to which monotherapy had failed before trial inclusion. Participants in each described group were to receive the fixed-dose combination of bisoprolol and amlodipine. The record does not describe a concurrent arm continuing either monotherapy, even though the brief summary states that superiority over monotherapies was under investigation.
Randomization means assignment to study groups is determined by a chance process rather than chosen solely by the participant or investigator. In general, random assignment can help make groups comparable at the start of a trial, although it does not guarantee balance in every characteristic. The registry record does not report the randomization procedure, allocation ratio, or whether any stratification was used. No masking means the record does not describe treatment assignment as concealed from participants or study personnel after assignment.
The listed primary outcome is mean reduction in systolic blood pressure after 18 weeks, with baseline defined as the latest measurement under monotherapy. The record also lists secondary outcomes concerning diastolic blood pressure, controlled blood pressure, heart rate, and treatment-emergent adverse events. Details of visit schedules beyond the primary outcome timeframe, adherence assessment, and treatment exposure 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: A total of 200 subjects (100 subjects in the amlodipine failed group, and 100 subjects in the bisoprolol failed group) were enrolled and randomized in the trial. Out of which 196 subjects (97 subjects in amlodipine failed group and 99 subjects in bisoprolol failed group) were included in modified intent-to-treat (MITT) analysis set.
Overall Study
| Stage | Amlodipine Failed Group | Bisoprolol Failed Group |
|---|---|---|
| STARTED | 100 | 100 |
| COMPLETED | 92 | 94 |
| NOT COMPLETED | 8 | 6 |
Reasons for not completing this period:
| Reason | Amlodipine Failed Group | Bisoprolol Failed Group |
|---|---|---|
| Adverse Event | 2 | 2 |
| Lost to Follow-up | 2 | 1 |
| Protocol Violation | 1 | 0 |
| Death | 1 | 1 |
| Withdrew consent | 2 | 1 |
| Other | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: MITT analysis set was defined as all randomized and treated subjects with at least 1 SBP measurement after the date of first dose of IMP. Here "Number of subjects analyzed" signifies those subjects who were evaluable for this outcome measure.
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: MITT analysis set was defined as all randomized and treated subjects with at least 1 SBP measurement after the date of first dose of investigational medicinal product (IMP).
| Characteristic | Unit | Amlodipine Failed Group | Bisoprolol Failed Group | Total |
|---|---|---|---|---|
| Participants analysed | 97 | 99 | 196 | |
| Age, Continuous | years | 63.4 (SD 11.62) | 59.6 (SD 12.05) | 61.5 (SD 11.96) |
| Gender: Female | Participants | 77 | 72 | 149 |
| Gender: Male | Participants | 20 | 27 | 47 |
6. Primary Endpoint
The registry lists the primary outcome as Mean Reduction In Systolic Blood Pressure (SBP) After 18 Weeks of Treatment From Baseline, measured over Baseline, Week 18.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | millimeters of mercury (mmHg) |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is mean reduction in systolic blood pressure from baseline after 18 weeks of treatment, measured in millimeters of mercury (mmHg). Baseline is defined as the latest systolic blood pressure measured under monotherapy. The outcome is continuous: each participant's blood-pressure change can take a range of values, and the group mean describes the average change among participants included in the analysis.
Systolic blood pressure is the pressure recorded during heart contraction. In general, measuring change from a baseline value can describe how an outcome shifts during treatment while using each participant's pre-treatment measurement as a reference. Comparing mean changes between groups can address whether the average change differs between assigned treatment strategies. The clinical interpretation depends on the size and precision of that difference, not merely on whether a statistical test crosses a significance threshold.
The registry record defines the baseline and timeframe but does not report the primary endpoint's group means, standard deviations, between-group estimate, confidence interval, or p-value. The record notes that the primary outcome has several categories or time points and was not reduced to one comparison. As a result, the numerical magnitude and precision of the primary blood-pressure result cannot be described from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically interpretable primary measure: mean change in systolic blood pressure from the latest measurement under monotherapy to the 18-week assessment. It also describes the MITT analysis set as randomized and treated participants with at least 1 systolic blood-pressure measurement after the first dose of investigational medicinal product, with the number analyzed referring to participants evaluable for this outcome. These definitions clarify what the endpoint is intended to represent and which participants could contribute to its analysis.
However, the numerical primary outcome is not reported in the registry record. There are no reported group means, standard deviations, treatment contrast, confidence interval, or p-value in the available primary-outcome information. The record indicates that the outcome has several categories or time points and was not reduced to one comparison. Therefore, it is not possible to state the observed mean reduction, compare numerical changes, or assess the precision of a treatment contrast from this information.
This absence matters because the trial summary describes a superiority question. A superiority conclusion requires an estimate comparing the relevant groups, along with an assessment of uncertainty. A mean change within a group alone would not establish that the change differs from another group's change. In addition, the arm descriptions identify the fixed-dose combination in both groups, with group membership based on the monotherapy that had failed before inclusion. The registry record does not report a concurrent monotherapy comparator result that would permit evaluation of the summary's stated comparison.
The adverse-event information is descriptive and should be read separately from efficacy. The registry record lists serious adverse events affecting 1 participant in the amlodipine-failed group and 2 in the bisoprolol-failed group, with 100 at risk in each group. It also lists other adverse events affecting 63 and 53 participants, respectively. These counts do not supply a primary blood-pressure estimate, and they do not by themselves establish a causal difference in safety between the groups. Death counts are not reported in the registry record.
In general, a confidence interval communicates the range of treatment differences compatible with the data under the statistical model, and its width indicates precision. A p-value addresses compatibility with a specified null hypothesis under that model; it does not measure clinical importance. Neither can be interpreted for the primary treatment contrast because those results are not reported in the registry record. No claim about the size, direction, statistical significance, or clinical importance of the primary comparison is supported by the posted primary outcome information.
9. Statistical Methods Explained
The registry record describes a continuous primary outcome summarized as a mean, with standard deviation as the dispersion measure. It defines the outcome as reduction in systolic blood pressure from baseline after 18 weeks. The baseline is the latest systolic blood-pressure measurement under monotherapy. These definitions identify the measurement and the intended summary, but the numerical summaries and treatment comparison are not reported in the registry record.
What does a mean describe?
General: a mean is the arithmetic average of observed values in an analysis group. For a change outcome, the mean summarizes the average participant-level change under the endpoint definition. It does not show how much participants differ from one another. Two groups can have similar means but different spreads, or different means with substantial overlap in individual observations.
The standard deviation describes spread around a group mean. It is not the same as the standard error, which describes uncertainty in an estimated mean, and it is not a confidence interval. The registry record identifies standard deviation as the dispersion measure but does not report its value for the primary endpoint. Without the group summaries and a defined contrast, the precision of the mean difference cannot be assessed.
What would a between-group comparison mean?
General: a treatment comparison for a continuous endpoint commonly estimates the difference between group means, based on the change measured in each group. The estimate describes the direction and magnitude of the observed contrast; an uncertainty interval indicates how precisely that contrast is estimated. Interpretation depends on the comparison actually made, the analysis population, and the assumptions of the statistical method. The registry record does not report a numerical contrast or identify a numerical primary comparison that can be interpreted.
The trial summary states that the study investigated superiority of the fixed-dose combination over monotherapies. Yet the listed arm descriptions specify that both described groups received the combination, with group identity based on prior failure of bisoprolol or amlodipine monotherapy. The registry record does not report a contemporaneous monotherapy group's primary outcome. This distinction is important: a comparison between participants with different prior monotherapy failures would not, by itself, be the same as a randomized comparison of the combination against either monotherapy.
How should a confidence interval and p-value be read?
General: a confidence interval expresses uncertainty around an estimated effect using a stated procedure and model. A narrow interval indicates greater precision than a wide interval, while the interval's location helps indicate which effect values are compatible with the data. A p-value measures how unusual the observed data, or more extreme data, would be under a specified null hypothesis and statistical model. It does not quantify the probability that the null hypothesis is true, nor does it establish whether an effect is practically important.
No confidence interval or p-value for the primary comparison is reported in the registry record. Therefore, statistical significance, compatibility with no difference, and the range of plausible treatment effects cannot be assessed. The record also does not report the analysis model or the assumptions used for the primary endpoint comparison.
What does the analysis population include?
The MITT analysis set is defined as randomized and treated participants with at least 1 systolic blood-pressure measurement after the date of first dose of investigational medicinal product. The record clarifies that the number analyzed means participants evaluable for this outcome. This definition is not identical to a population that includes every randomized participant regardless of post-dose measurement availability. The number analyzed in each group and the reasons any randomized participants were not evaluable are not reported in the registry record.
General: restricting an analysis to participants with an observed post-treatment measurement can affect interpretation if missing measurements are related to health status, treatment response, or treatment discontinuation. Methods for handling missing endpoint measurements can include assumptions or statistical models, but the appropriate approach depends on the data and prespecified plan. The registry record does not report the amount or pattern of missing primary endpoint data, an imputation method, or sensitivity analyses.
What do the planning assumptions represent?
The registry record describes a sample-size planning illustration based on the observed effect, not the trial's own design. It specifies a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For non-time-to-event outcomes, the described planning quantity is participants per arm for 80% or 90% power. These are planning assumptions, not observed power and not evidence that the trial was designed around those values.
The numerical planning results and the observed primary effect are not reported in the registry record. A planning illustration based on an observed effect is conditional on that effect estimate and its assumptions; it does not establish the probability that the completed trial detected a true effect. The registry record does not report the original sample-size justification, its target effect, or the statistical plan underlying the trial's enrollment.
General: over-dispersion refers to variability greater than a model expects. When present, a model that assumes less variability can understate uncertainty and make statistical evidence appear more precise than it is. The record does not identify over-dispersion as an issue or describe a model for it; it would be inappropriate to infer that it occurred in this trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary outcome with several categories or time points and indicates that it was not reduced to one comparison. It also lists secondary outcomes: change from baseline in diastolic blood pressure after 18 weeks, percentage of participants with controlled blood pressure, change from baseline in heart rate after 18 weeks, and counts of treatment-emergent adverse events, serious treatment-emergent adverse events, adverse events leading to discontinuation, and adverse events leading to death.
General: when several outcomes, time points, or group comparisons are tested, the chance of at least one apparently unusual result can rise if each is assessed without accounting for the family of tests. Multiplicity procedures can control that risk, but the choice depends on which comparisons were planned and how they were prioritized. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a prespecified plan for interpreting multiple primary categories or time points.
The primary analysis population is described as randomized and treated participants with at least 1 post-dose systolic blood-pressure measurement; participants counted as analyzed were evaluable for the endpoint. The number analyzed and the extent of missing primary outcome data are not reported in the registry record. The record does not report how missing measurements were handled, whether participants with incomplete measurements were excluded, or whether sensitivity analyses assessed the effect of missing data.
Other analysis populations and the statistical analysis plan are not reported in the registry record. The record also does not report interim analyses or any adjustment associated with them. These omissions limit assessment of how the primary comparison was selected and whether the posted results, if reported, would reflect all planned analyses.
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 |
|---|---|---|---|
| Amlodipine Failed Group | 1 | 100 | 1.0% |
| Bisoprolol Failed Group | 2 | 100 | 2.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Amlodipine Failed Group | 63 of 100 |
| Bisoprolol Failed Group | 53 of 100 |
Most frequent serious adverse event terms
| Event term | Organ system | Amlodipine Failed Group | Bisoprolol Failed Group |
|---|---|---|---|
| Cardio-respiratory arrest | Cardiac disorders | 1 of 100 | 0 of 100 |
| Cholelithiasis | Hepatobiliary disorders | 0 of 100 | 1 of 100 |
| Craniocerebral injury | Injury, poisoning and procedural complications | 0 of 100 | 1 of 100 |
| Multiple injuries | Injury, poisoning and procedural complications | 0 of 100 | 1 of 100 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Amlodipine Failed Group | Bisoprolol Failed Group |
|---|---|---|---|
| Sinus bradycardia | Cardiac disorders | 30 of 100 | 25 of 100 |
| Bradycardia | Cardiac disorders | 20 of 100 | 15 of 100 |
| Oedema peripheral | General disorders | 9 of 100 | 9 of 100 |
| Urinary tract infection | Infections and infestations | 6 of 100 | 9 of 100 |
| Overdose | Injury, poisoning and procedural complications | 8 of 100 | 7 of 100 |
| Upper respiratory tract infection | Infections and infestations | 4 of 100 | 5 of 100 |
Serious events with the highest arm-level rate: cardio-respiratory arrest (1.0%), cholelithiasis (1.0%), craniocerebral injury (1.0%), multiple injuries (1.0%).
The registry record reports serious adverse events for the amlodipine-failed group and the bisoprolol-failed group. Each group had 100 participants at risk. The number reported as affected was 1 in the amlodipine-failed group and 2 in the bisoprolol-failed group. The record also lists serious-event terms with percentages of 1.0%: cardio-respiratory arrest, cholelithiasis, craniocerebral injury, and multiple injuries. It does not identify a group association for each listed term in the information reported.
Other adverse events were reported as affecting 63 participants in the amlodipine-failed group and 53 in the bisoprolol-failed group, with 100 at risk in each. The record does not provide additional detail about event severity, duration, recurrence, or whether individual participants experienced more than one event. Death counts are not reported in the registry record.
General: serious adverse events and other adverse events are different categories, and event counts should not be treated as equivalent to participant counts unless the reporting definition confirms that equivalence. These descriptive figures do not establish that treatment caused an event or that one group had a greater underlying risk. The groups also represent participants with different failed prior monotherapies, so a direct safety comparison would require context about assignment, follow-up, exposure, and analysis that is not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record establishes the trial's stated clinical question and endpoint: it was a randomized Phase 3 study of a fixed-dose combination of bisoprolol and amlodipine in people with hypertension whose blood pressure was not well controlled on bisoprolol 5 mg or amlodipine 5 mg monotherapy. The primary endpoint was mean reduction in systolic blood pressure from the latest measurement under monotherapy to the assessment after 18 weeks.
That description is not itself evidence of the size or direction of an effect. The numerical primary result and a treatment contrast are not reported in the registry record. Consequently, the record does not support a statement that the combination produced a larger or smaller reduction than a comparator, nor does it show the precision or statistical significance of such a comparison. The brief summary's stated interest in superiority over monotherapies cannot be evaluated without the relevant comparative results.
The arm descriptions also matter for interpretation. Both described groups received the fixed-dose combination, while the group distinction was the monotherapy that had failed before trial inclusion. This record does not describe a concurrent monotherapy arm or its primary outcome. A difference between the described groups, if one were reported, would not automatically answer whether the combination is superior to either monotherapy.
The serious and other adverse-event counts are descriptive. They do not establish causation or a comparative safety effect, and deaths are not reported in the registry record. In general, statistical results should be interpreted alongside design, measurement, analysis population, missingness, and uncertainty. Those details are incomplete for this trial in the registry record.
The appropriate conclusion is therefore limited: the registry record describes a randomized trial and defines a primary blood-pressure endpoint, but it does not report the numerical primary outcome needed to quantify or assess the stated efficacy comparison. No treatment recommendation follows from these data.
13. Why This Trial Matters Statistically
This trial is statistically interesting because its stated objective, endpoint, and listed arms do not align transparently in the registry record. The brief summary describes testing superiority of a fixed-dose combination over monotherapies, whereas the two arm descriptions both identify the combination as the treatment and distinguish participants by which monotherapy had failed before inclusion. Knowing the actual comparator is essential to interpreting a treatment contrast.
The primary endpoint is a continuous measure defined as change from a stated baseline to an 18-week assessment. That design can yield an estimate of average change and, when compared across relevant randomized groups, an estimate of a between-group difference. But the registry record does not report the numerical primary result, its uncertainty, or a comparison that answers the summary's superiority question. The endpoint definition alone cannot establish efficacy or precision.
The record also illustrates why the analysis population and missing-data approach matter. The MITT set requires participants to be randomized and treated and to have at least 1 post-dose systolic blood-pressure measurement. The number analyzed and the handling of missing measurements are not reported in the registry record. Without these details, readers cannot assess the extent to which the analysis represents all randomized participants or the possible influence of missing outcomes.
Finally, the record lists multiple secondary outcomes and indicates several primary categories or time points, while not reporting a single primary comparison. General statistical practice requires clarity about which contrasts were planned and how multiplicity was addressed, because selective interpretation across many tests can overstate evidence. The registry record does not report that plan. These issues make the limits of the reported information as important as the trial's design labels.
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 main limitation for interpreting efficacy is that the registry record does not report a numerical primary outcome or a between-group comparison. It therefore offers no estimate of mean systolic blood-pressure change, no standard deviation, and no confidence interval or p-value for the stated primary question. The record's note that the primary outcome has several categories or time points and was not reduced to one comparison further prevents a clear account of which result would represent the main test.
The described treatment comparison is also unclear from the arm information. Both groups are described as receiving the fixed-dose combination, separated according to prior failure of bisoprolol or amlodipine monotherapy. Although the brief summary describes superiority over monotherapies, a concurrent monotherapy comparator and its results are not reported in the registry record. The doses of the combination and additional treatment details are not reported in the registry record.
Further methodological information is absent. The registry record does not report the randomization procedure, allocation ratio, primary statistical model, sample-size justification, multiplicity strategy, interim analyses, or a detailed statistical analysis plan. The numerical planning illustration is described as based on the observed effect, but the effect and planning results are not reported in the registry record.
The analysis population requires a post-dose systolic blood-pressure measurement, but the number analyzed, missing-data extent, reasons for missingness, and methods for handling missing observations are not reported in the registry record. These omissions limit assessment of potential selection and uncertainty. Safety information is also limited: death counts and detailed event-level context are not reported in the registry record. The adverse-event counts are descriptive and do not resolve the unreported efficacy comparison.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Fixed Dose Combination of Bisoprolol and Amlodipine in the Treatment of Hypertension — NCT01977794.
- Registry record last updated 2017-01-30; status last verified 2017-01.
- Results first posted 2016-08-11.
- 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
NCT01977794 is a completed, randomized, parallel-group, unmasked Phase 3 trial sponsored by Merck KGaA, Darmstadt, Germany. Enrollment is recorded as 200, with start in 2014-03 and primary completion in 2015-03. The trial concerns hypertension in people whose blood pressure was not well controlled on bisoprolol 5 mg or amlodipine 5 mg monotherapy.
The listed intervention in both described groups is fixed-dose bisoprolol and amlodipine; the groups differ by which monotherapy had failed before trial inclusion. The primary endpoint is mean reduction in systolic blood pressure from baseline after 18 weeks. Secondary outcomes include diastolic blood pressure, controlled blood pressure, heart rate, and adverse events.
The numerical primary outcome and its comparative estimate are not reported in the registry record. The record also does not report a concurrent monotherapy comparator result, the missing-data approach, or several elements of the statistical plan. Serious and other adverse-event counts are listed, but deaths are not reported in the registry record.