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 Study to Evaluate the Effectiveness and Safety of a Fixed Dose Combination of Azilsartan Medoxomil and Chlorthalidone in Patients With High Blood Pressure Who do Not Achieve Target Blood Pressure Following Treatment With Azilsartan Medoxomil Alone (NCT01456169), a randomized phase 3 study. The primary outcome is Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01456169 |
| Phase | Phase 3 |
| Condition | Essential Hypertension |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 507 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Takeda |
| Results posted | Yes |
2. Clinical Question
The study asked whether adding chlorthalidone to azilsartan medoxomil was associated with a different change in clinic systolic blood pressure over the double-blind treatment period than continuing azilsartan medoxomil alone. It studied people with grades 2 or 3 essential hypertension who had not reached target blood pressure after treatment with azilsartan medoxomil alone. The registry describes two fixed-dose combinations, so the question concerns both the 40/12.5 mg and 40/25 mg combinations against the 40 mg azilsartan medoxomil regimen.
Population
Participants with grades 2 or 3 essential hypertension who did not achieve target blood pressure following azilsartan medoxomil 40 mg monotherapy. The registry lists total enrollment as 507.
Intervention
Once-daily azilsartan medoxomil 40 mg with chlorthalidone 12.5 mg, or azilsartan medoxomil 40 mg with chlorthalidone 25 mg, for up to 8 weeks.
Comparator
Azilsartan medoxomil 40 mg with placebo to chlorthalidone, taken orally once daily for up to 8 weeks.
Primary question
What was the change from baseline to Week 8 in trough, sitting, clinic systolic blood pressure, and how did the listed regimens compare?
The registry record does not report a single primary comparison result or the estimates needed to describe the size and precision of a treatment difference. The clinical question can therefore be identified from the design and endpoint, but the posted information does not establish the direction or magnitude of a comparison.
3. Trial Design
This was a Phase 3, randomized, parallel-group study with quadruple masking. Its official title describes a double-blind efficacy and safety study of fixed-dose combinations in subjects with grades 2 or 3 essential hypertension who did not achieve target blood pressure on TAK-491 40 mg monotherapy. TAK-491 is identified in the study record as azilsartan medoxomil. The listed regimens were azilsartan medoxomil 40 mg alone, azilsartan medoxomil 40 mg plus chlorthalidone 12.5 mg, and azilsartan medoxomil 40 mg plus chlorthalidone 25 mg.
Each regimen was described as an oral once-daily treatment for up to 8 weeks. The study summary says participants were assessed after not reaching target blood pressure following 4 weeks of azilsartan medoxomil 40 mg monotherapy. The registry lists enrollment of 507. The adverse-event entries list 133 participants at risk for the azilsartan-only group, 127 for the 40/12.5 mg combination, and 135 for the 40/25 mg combination. The registry also has a monotherapy safety entry with 507 participants at risk; the record does not fully explain how that entry relates to the treatment-period groups.
The study status is completed. The registry lists the start as 2011-10 and primary completion as 2012-12. These dates describe the recorded study timeline, not the timing or duration of individual participation beyond the treatment descriptions. Randomization and masking are stated, but the method used to generate assignments, conceal them, or maintain masking is not reported in the registry record. Details of the allocation ratio and the statistical design rationale are also 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: 507 participants entered the azilsartan medoxomil 40 mg Single-Blind Monotherapy Treatment Period and 395 participants were eligible to enter the Double-Blind Treatment Period and were randomly assigned to 1 of 3 active treatment arms.
Overall Study
| Stage | Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Azilsartan Medoxomil + Chlorthalidone 40/25 mg |
|---|---|---|---|
| STARTED | 133 | 127 | 135 |
| COMPLETED | 123 | 122 | 123 |
| NOT COMPLETED | 10 | 5 | 12 |
Reasons for not completing this period:
| Reason | Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Azilsartan Medoxomil + Chlorthalidone 40/25 mg |
|---|---|---|---|
| Adverse Event | 1 | 2 | 7 |
| Major Protocol Deviation | 3 | 2 | 3 |
| Voluntary Withdrawal | 3 | 0 | 2 |
| Lack of Efficacy | 2 | 0 | 0 |
| Other | 1 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set, consisting of all randomized participants who received at least 1 dose of double-blind study drug. A participant was included in the analyses only when there was both a baseline value and at least 1 value during the double-blind treatment period. Last observation carried forward (LOCF) was used.
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: Participants who were randomized into the double-blind treatment period. Baseline was defined as the last observed value while on monotherapy study drug and before the first dose of double-blind study drug.
| Characteristic | Unit | Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Azilsartan Medoxomil + Chlorthalidone 40/25 mg | Total |
|---|---|---|---|---|---|
| Participants analysed | 133 | 127 | 135 | 395 | |
| Age, Continuous | years | 57.9 (SD 10.18) | 59.2 (SD 10.72) | 57.7 (SD 10.46) | 58.2 (SD 10.45) |
| Age, Customized: < 45 years | participants | 13 | 10 | 12 | 35 |
| Age, Customized: 45 to < 65 years | participants | 87 | 79 | 88 | 254 |
| Age, Customized: ≥ 65 years | participants | 33 | 38 | 35 | 106 |
| Sex: Female, Male: Female | Participants | 46 | 54 | 44 | 144 |
| Sex: Female, Male: Male | Participants | 87 | 73 | 91 | 251 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | participants | 1 | 0 | 1 | 2 |
| Race/Ethnicity, Customized: Asian | participants | 0 | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Black or African American | participants | 1 | 0 | 0 | 1 |
| Race/Ethnicity, Customized: Native Hawaiian or Other Pacific Islander | participants | 0 | 0 | 1 | 1 |
| Race/Ethnicity, Customized: White | participants | 132 | 126 | 134 | 392 |
| Race/Ethnicity, Customized: Multiracial | participants | 1 | 0 | 1 | 2 |
| Region of Enrollment: Bulgaria | participants | 11 | 10 | 11 | 32 |
| Region of Enrollment: Estonia | participants | 18 | 16 | 18 | 52 |
| Region of Enrollment: France | participants | 2 | 1 | 2 | 5 |
| Region of Enrollment: Germany | participants | 29 | 29 | 28 | 86 |
| Region of Enrollment: Hungary | participants | 10 | 9 | 10 | 29 |
| Region of Enrollment: Italy | participants | 6 | 4 | 5 | 15 |
| Region of Enrollment: Lithuania | participants | 5 | 4 | 6 | 15 |
| Region of Enrollment: Netherlands | participants | 4 | 6 | 5 | 15 |
| Region of Enrollment: Poland | participants | 17 | 18 | 17 | 52 |
| Region of Enrollment: Serbia | participants | 4 | 3 | 4 | 11 |
| Weight | kg | 87.59 (SD 15.794) | 86.71 (SD 17.037) | 87.39 (SD 14.876) | 87.24 (SD 15.868) |
| Height | cm | 171.8 (SD 8.87) | 170.6 (SD 9.96) | 172.1 (SD 9.74) | 171.5 (SD 9.53) |
| Body Mass Index (BMI) | kg/m^2 | 29.63 (SD 5.066) | 29.78 (SD 5.206) | 29.52 (SD 4.572) | 29.64 (SD 4.937) |
| Smoking Classification: Never smoked | participants | 77 | 83 | 77 | 237 |
| Smoking Classification: Current smoker | participants | 31 | 25 | 30 | 86 |
| Smoking Classification: Ex-smoker | participants | 25 | 19 | 28 | 72 |
| Diabetes Status: Yes | participants | 20 | 27 | 20 | 67 |
| Diabetes Status: No | participants | 113 | 100 | 115 | 328 |
| Estimated Glomerular Filtration Rate (eGFR) | mL/min/1.73 m^2 | 84.8 (SD 16.41) | 81.5 (SD 16.25) | 82.4 (SD 16.51) | 82.9 (SD 16.41) |
| Baseline eGFR Categories (mL/min/1.73 m^2): 30 to < 60 ml/min/1.73 m^2 | participants | 11 | 10 | 11 | 32 |
| Baseline eGFR Categories (mL/min/1.73 m^2): 60 to < 90 ml/min/1.73 m^2 | participants | 78 | 85 | 80 | 243 |
| Baseline eGFR Categories (mL/min/1.73 m^2): ≥ 90 ml/min/1.73 m^2 | participants | 44 | 32 | 44 | 120 |
| Trough Clinic Systolic Blood Pressure (SBP) | mmHg | 150.7 (SD 10.69) | 149.6 (SD 11.54) | 149.8 (SD 10.95) | 150.0 (SD 11.04) |
| Trough Clinic SBP Category (mmHg): <140 mmHg | participants | 16 | 17 | 17 | 50 |
| Trough Clinic SBP Category (mmHg): ≥140 - <160 mmHg | participants | 86 | 87 | 93 | 266 |
| Trough Clinic SBP Category (mmHg): ≥160 - <180 mmHg | participants | 31 | 23 | 25 | 79 |
| Trough Clinic SBP Category (mmHg): ≥180 mmHg | participants | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure, measured over Baseline (of the double-blind treatment period) and Week 8.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | Standard Error |
| Unit | mm Hg |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline to Week 8 in trough, sitting, clinic systolic blood pressure, measured in mm Hg. The registry defines the endpoint as the change in trough systolic blood pressure at the final visit or Week 8 relative to baseline. Systolic pressure was the arithmetic mean of 3 trough sitting measurements. The reported summary measure was a least-squares mean, with standard error as the dispersion measure.
Baseline was defined as baseline of the double-blind treatment period, and Week 8 was the stated endpoint visit. Clinic blood pressure provides a standardized measurement in the clinical setting. Using a mean of repeated measurements can represent the endpoint using more than one reading rather than relying on a single reading. In general, a change-from-baseline endpoint describes how the measurement differs from a participant’s starting value; comparing those changes between randomized groups can help estimate a treatment contrast.
Those general properties do not substitute for the actual estimates. The registry record does not report the primary endpoint values, a treatment contrast, confidence intervals, or a p-value. It therefore does not permit a numerical interpretation of the endpoint or a judgment about the precision of a group difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a clinically interpretable primary outcome: change in trough, sitting, clinic systolic blood pressure from baseline to Week 8. It also identifies the summary statistic as a least-squares mean and the dispersion as a standard error. However, it does not report the numerical primary outcome estimates or a single comparison of the combination regimens with azilsartan medoxomil alone. The direction, magnitude, and precision of any treatment contrast are therefore not reported in the registry record.
The record notes that the primary outcome has several categories or time points and is not reduced to one comparison. That matters for interpretation: without an estimate for each relevant comparison and its uncertainty, the endpoint definition alone cannot show whether observed changes differed between treatment groups. The enrollment figure and group sizes do not reveal an outcome effect. Nor can safety counts be used to infer a blood-pressure result.
In general, an estimate describes the observed difference or change, while a confidence interval describes the range of values compatible with the data under the analysis assumptions. A standard error describes the sampling uncertainty of an estimate, but the registry gives the type of dispersion rather than the endpoint’s numerical standard errors. No confidence interval or p-value for the primary endpoint is reported in the registry record. Statistical significance and clinical importance cannot be assessed from the endpoint definition alone.
The primary population is described as the full analysis set: randomized participants who received at least 1 dose of double-blind study drug, with both a baseline value and at least 1 value during the double-blind treatment period. The record says last observation carried forward, but its description is truncated after that phrase. The precise implementation, assumptions, and handling of missing values are not reported in the registry record. This limits assessment of how the stated analysis population and missing-data method may affect the reported estimates.
There are 15 outcome measures and 2 analyses listed in the record. The list includes clinic and ambulatory blood-pressure measures, but the registry information does not specify how conclusions across multiple outcomes or comparisons were controlled. Consequently, any interpretation should stay close to the endpoint definition and the reported estimates; where the estimate itself is absent, no treatment contrast can be reconstructed in the registry record recorded.
9. Statistical Methods Explained
The methods information describes a continuous endpoint, a randomized parallel-group design, a least-squares mean summary, and a standard error as the dispersion measure. The primary endpoint is change in clinic systolic blood pressure from baseline to Week 8. The registry also describes the full analysis set and mentions last observation carried forward. These details identify some features of the analysis, but they do not amount to a complete statistical analysis plan. The model formula, covariates, handling of repeated measures, and method for constructing comparisons are not reported in the registry record.
What does a least-squares mean represent?
In general, a least-squares mean is a model-based mean, often adjusted for variables included in the analysis model. Its interpretation depends on the model and the variables used. The registry names a least-squares mean but does not report the model specification or adjustment variables. It is therefore not possible to describe what adjustments were made or whether the reported means correspond to raw group averages.
What does the standard error convey?
In general, a standard error describes how much an estimate would vary across repeated samples under the statistical model and its assumptions. It is not the same as the spread of individual participants’ blood-pressure values. Confidence intervals are commonly constructed using an estimate and its standard error, with a method determined by the analysis. No numerical standard errors or confidence intervals for the primary endpoint are reported in the registry record, so the uncertainty around a treatment difference cannot be evaluated from the listed endpoint metadata.
Why can randomization matter?
In general, random assignment aims to make treatment groups comparable at the start with respect to both measured and unmeasured characteristics, on average. This supports interpretation of between-group comparisons, subject to adherence, outcome measurement, missing data, and analysis choices. The registry states that allocation was randomized and the model was parallel. The assignment procedure and allocation ratio are not reported in the registry record, so those operational details cannot be assessed.
What is the role of the analysis population?
The registry defines the full analysis set as all randomized participants who received at least 1 dose of double-blind study drug. It further says a participant was included in analyses only when there was both a baseline value and at least 1 value during the double-blind treatment period. This definition identifies eligibility for the primary analysis, but it does not clarify whether participants were analyzed according to their randomized group in every circumstance or how deviations from assigned treatment were handled. Such details are not reported in the registry record.
What does last observation carried forward mean?
In general, last observation carried forward replaces a missing later measurement with an earlier observed measurement. This can preserve a record for analysis, but it makes assumptions about the unobserved values and can understate or distort uncertainty if those assumptions are unsuitable. The primary-population description ends after mentioning last observation carried forward. The registry record does not report the full missing-data procedure, the timing of carried-forward measurements, or any sensitivity analyses. No conclusion about the suitability or impact of that approach can be drawn from the fragment alone.
How should multiple outcomes be considered?
The registry lists 15 outcome measures and 2 analyses. Several secondary measures concern clinic or ambulatory blood pressure, including systolic and diastolic measurements and daytime, nighttime, and 24-hour summaries. In general, when many hypotheses are assessed, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for multiplicity. The registry record does not report a multiplicity strategy, the hierarchy of outcomes, or which analyses were intended to support formal conclusions. It is therefore not possible to establish how the listed outcomes were prioritized or how error rates were managed.
The record’s stated primary endpoint uses a mean of 3 trough sitting systolic readings. In general, averaging repeated measurements can reduce the influence of short-term reading variability, although the amount of benefit depends on the measurement process. The registry does not describe the measurement-device procedures or quality-control details. Its endpoint definition tells readers what was summarized, but not all the procedures needed to reproduce the measurement or statistical analysis.
Overall, the registry supplies an endpoint definition and some analysis-population language, but not a complete account of the inferential methods. Numerical estimates, standard errors, confidence intervals, p-values, model details, and the full missing-data strategy are not reported in the registry record. Statistical conclusions should not be inferred from the study design alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 15 outcome measures and 2 analyses. The primary measure is change in trough, sitting, clinic systolic blood pressure from baseline to Week 8. Listed secondary measures include clinic diastolic pressure and ambulatory systolic and diastolic pressure, with 24-hour, daytime, and nighttime summaries. This is a family of related outcomes, but the registry record does not report which outcomes were confirmatory, whether one comparison was designated as primary for each measure, or how multiplicity was addressed.
In general, testing many outcomes or treatment contrasts without adjustment can increase the chance of a false-positive finding across the collection of tests. A prespecified hierarchy, adjustment procedure, or distinction between confirmatory and exploratory analyses can clarify how such results should be interpreted. None of those details is reported in the registry record. The record also does not provide enough primary-outcome results to assess the role of any multiplicity procedure in the conclusions.
The described full analysis set includes randomized participants who received at least 1 dose of double-blind study drug and had both a baseline value and at least 1 value during the double-blind period. The endpoint description mentions last observation carried forward, but the accompanying text is incomplete. The number and pattern of missing outcome measurements, reasons for missingness, full imputation procedure, and sensitivity analyses are not reported in the registry record. In general, missing-data assumptions matter because observed outcomes may differ systematically from unobserved outcomes. The available description is insufficient to evaluate that possibility or the robustness of the analysis.
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 |
|---|---|---|---|
| Monotherapy: Azilsartan Medoxomil 40 mg | 3 | 507 | 0.6% |
| Azilsartan Medoxomil 40 mg | 2 | 133 | 1.5% |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | 0 | 127 | 0.0% |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | 0 | 135 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Monotherapy: Azilsartan Medoxomil 40 mg | 15 of 507 |
| Azilsartan Medoxomil 40 mg | 15 of 133 |
| Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | 13 of 127 |
| Azilsartan Medoxomil + Chlorthalidone 40/25 mg | 26 of 135 |
Most frequent serious adverse event terms
| Event term | Organ system | Monotherapy: Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Azilsartan Medoxomil + Chlorthalidone 40/25 mg |
|---|---|---|---|---|---|
| Cerebrovascular accident | Nervous system disorders | 1 of 507 | 1 of 133 | 0 of 127 | 0 of 135 |
| Myocardial infarction | Cardiac disorders | 0 of 507 | 1 of 133 | 0 of 127 | 0 of 135 |
| Acute myocardial infarction | Cardiac disorders | 1 of 507 | 0 of 133 | 0 of 127 | 0 of 135 |
| Ventricular tachycardia | Cardiac disorders | 1 of 507 | 0 of 133 | 0 of 127 | 0 of 135 |
| Blood pressure increased | Investigations | 1 of 507 | 0 of 133 | 0 of 127 | 0 of 135 |
| Renal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 507 | 0 of 133 | 0 of 127 | 0 of 135 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Monotherapy: Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil 40 mg | Azilsartan Medoxomil + Chlorthalidone 40/12.5 mg | Azilsartan Medoxomil + Chlorthalidone 40/25 mg |
|---|---|---|---|---|---|
| Blood creatinine increased | Investigations | 2 of 507 | 4 of 133 | 4 of 127 | 11 of 135 |
| Headache | Nervous system disorders | 9 of 507 | 2 of 133 | 3 of 127 | 5 of 135 |
| Nasopharyngitis | Infections and infestations | 6 of 507 | 4 of 133 | 2 of 127 | 4 of 135 |
| Dizziness | Nervous system disorders | 3 of 507 | 0 of 133 | 2 of 127 | 6 of 135 |
| Hypotension | Vascular disorders | 0 of 507 | 1 of 133 | 2 of 127 | 4 of 135 |
| Viral infection | Infections and infestations | 0 of 507 | 4 of 133 | 0 of 127 | 0 of 135 |
Serious events with the highest arm-level rate: myocardial infarction (0.8%), cerebrovascular accident (0.8%), acute myocardial infarction (0.2%), ventricular tachycardia (0.2%), blood pressure increased (0.2%).
The registry lists serious adverse events and other adverse events separately for the treatment groups. In the azilsartan medoxomil 40 mg group, 2 of 133 participants were listed with serious adverse events and 15 of 133 with other adverse events. In the 40/12.5 mg combination group, the corresponding entries are 0 of 127 and 13 of 127. In the 40/25 mg combination group, they are 0 of 135 and 26 of 135. A separate monotherapy entry lists 3 of 507 participants with serious adverse events and 15 of 507 with other adverse events.
These are counts of participants recorded as affected against the listed numbers at risk. They are not a comparison adjusted for follow-up time, and the registry does not provide enough information to interpret differences as causal. The record lists serious-event terms and percentages, including myocardial infarction and cerebrovascular accident at 0.8% each, and acute myocardial infarction, ventricular tachycardia, blood pressure increased, and renal cancer at 0.2% each. The terms are not mapped to treatment groups in the information recorded.
Deaths are not reported in the registry record. The safety entries should be read as descriptive counts, not as a complete assessment of risk or as proof that events did or did not differ between regimens.
12. What the Result Does, and Does Not, Mean
The study record identifies a randomized comparison of azilsartan medoxomil alone with two azilsartan medoxomil–chlorthalidone combinations in people with grades 2 or 3 essential hypertension who did not reach target blood pressure after azilsartan monotherapy. It defines a primary clinic systolic blood-pressure endpoint and several secondary blood-pressure measures. Those elements describe the question the trial was designed to address.
What the record does not establish is the primary treatment effect. Numerical endpoint estimates, a treatment contrast, confidence intervals, and p-values are not reported in the registry record. The direction and magnitude of the comparison, and the precision with which it was estimated, cannot be determined from the design description or the enrollment count. No conclusion about the efficacy of any regimen should be drawn from these registry entries alone.
In general, a statistically significant result is not automatically large or important, and a non-significant result does not by itself show that treatments are equivalent. Interpretation depends on the estimate, its uncertainty, the prespecified question, and the analysis methods. The registry record does not contain the endpoint results or enough detail about the statistical plan to make those distinctions for this study.
The safety counts provide descriptive information about serious and other adverse events in the listed groups. They do not, on their own, establish whether one regimen has a higher or lower risk. The record does not report deaths, detailed event timing, or a formal safety comparison. These limitations mean the event counts should not be treated as comprehensive evidence about comparative safety.
The appropriate reading is therefore bounded: the registry records a completed randomized Phase 3 study, its treatment regimens, endpoint definitions, analysis-population language, and some adverse-event counts. It does not provide a single primary comparison result. A quantitative claim about treatment differences or their clinical importance is not supported by the recorded information.
13. Why This Trial Matters Statistically
This trial is statistically notable for the structure of its clinical question: it compares continued azilsartan medoxomil with two fixed-dose combinations after participants did not achieve target blood pressure on azilsartan monotherapy. The randomized, parallel-group design and stated masking are relevant features for interpreting comparisons, while the 3 listed regimens make it important to identify exactly which treatment contrast answers each question.
The endpoint is a continuous change from baseline, based on the mean of 3 trough sitting systolic blood-pressure measurements. In general, a continuous outcome retains information about the size of changes, while a change-from-baseline comparison focuses on differences in change during treatment. The registry specifies a least-squares mean and standard error, but does not provide model details or the numerical estimates needed to interpret the treatment contrasts.
The record also lists multiple blood-pressure outcomes, including clinic and ambulatory measures. In general, multiple related outcomes can describe different aspects of a response, but they require a clear analysis hierarchy to distinguish primary evidence from additional or exploratory findings. That hierarchy and any multiplicity approach are not reported in the registry record. The incomplete description of last observation carried forward also highlights why missing-data methods matter for a longitudinal endpoint.
Finally, this record illustrates the difference between a trial’s design information and its reported results. The design and endpoint can clarify what investigators intended to compare, but they cannot replace treatment estimates and uncertainty intervals. Because a single primary comparison result is not reported in the registry record, the central statistical question remains unanswered by the recorded data.
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 principal limitation for interpreting efficacy is the absence of a single reported primary comparison result. The registry defines the Week 8 endpoint but does not report group estimates, a contrast between regimens, confidence intervals, standard errors, or p-values for that endpoint. It is therefore not possible to characterize the observed treatment effect or its precision.
The primary outcome is described as having several categories or time points and is not reduced to one comparison. The record does not explain the comparisons represented by those categories or how they relate to the study question. It also does not describe the statistical model, adjustment variables, handling of repeated observations, or the planned multiplicity strategy. These omissions limit reproducibility and make it difficult to connect the endpoint definition with an inferential conclusion.
The population description includes a full analysis set and a requirement for baseline and at least 1 double-blind treatment-period value. It mentions last observation carried forward, but the description is incomplete. The number and reasons for missing measurements, the full missing-data procedure, and sensitivity analyses are not reported in the registry record. These details are relevant to evaluating the reliability of a change-from-baseline estimate.
For safety, the registry gives counts of participants with serious and other adverse events but does not report deaths, event timing, a formal between-group analysis, or a full account of follow-up. The listed serious-event terms are not assigned to individual groups in the record. The adverse-event counts therefore support only a limited descriptive reading and cannot establish comparative safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate the Effectiveness and Safety of a Fixed Dose Combination of Azilsartan Medoxomil and Chlorthalidone in Patients With High Blood Pressure Who do Not Achieve Target Blood Pressure Following Treatment With Azilsartan Medoxomil Alone — NCT01456169.
- Registry record last updated 2014-04-23; status last verified 2014-03.
- Results first posted 2014-04-23.
- 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 3 randomized, quadruple-masked, parallel-group study enrolled 507 participants with essential hypertension who did not achieve target blood pressure following azilsartan medoxomil 40 mg monotherapy. The listed regimens were azilsartan medoxomil 40 mg alone and fixed-dose combinations with chlorthalidone 12.5 mg or 25 mg, taken once daily for up to 8 weeks.
The primary endpoint was change from baseline to Week 8 in trough, sitting, clinic systolic blood pressure, summarized as a least-squares mean with standard error. The registry describes the full analysis set and mentions last observation carried forward, but the missing-data description is incomplete. It lists 15 outcome measures and 2 analyses.
The record contains some serious and other adverse-event counts. It does not report a single primary treatment comparison, numerical primary endpoint estimates, uncertainty intervals, p-values, deaths, or several details of the statistical analysis. Accordingly, the recorded information describes the trial question and selected safety counts but does not permit a quantitative conclusion about the primary treatment difference.