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 Safety and Efficacy of Chlorthalidone + Amiloride to Elderly Patients Treatment With Arterial Hypertension (NCT01191450), a randomized phase 3 study. The primary outcome is Number of Subjects With Serum Potassium Levels Below 4.0 mEq/l at Visit 4.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01191450 |
| Phase | Phase 3 |
| Condition | Arterial Hypertension |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 246 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eurofarma Laboratorios S.A. |
| Results posted | Yes |
2. Clinical Question
Population
Elderly patients with arterial hypertension. The registry record reports enrollment of 246 participants, but does not provide further eligibility criteria or an age range.
Intervention
Chlorthalidone 25 mg plus amiloride hydrochloride 5 mg, described as one oral tablet a day in the morning under the arm name Diupress®.
Comparator
Chlorthalidone 25 mg alone, described as one oral tablet a day in the morning under the arm name Higroton®.
Primary question
How many participants in each treatment group had serum potassium below 4.0 mEq/l at Visit 4? The registry record identifies this endpoint but does not report the arm-level counts or an estimated between-group effect.
The clinical question is framed around a laboratory threshold rather than a reported change in blood pressure. Blood Pressure is listed as a secondary outcome. The record describes the study purpose as assessing the efficacy and safety of the combination in elderly patients with arterial hypertension, but the posted primary endpoint specifically counts participants whose serum potassium is below the stated threshold at a scheduled visit.
Because the endpoint is a count, its interpretation depends on both the threshold and the number of participants assessed. The registry record notes that the analysis was intended to use the ITT population and that participant numbers differed across visits because attendance varied. It does not report how many participants in each arm met the threshold at Visit 4, how many were assessed for that endpoint, or a comparative estimate. Accordingly, the clinical question can be described, but the posted information does not establish whether the groups differed on this measure.
3. Trial Design
This was a phase 3, randomized, open-label, parallel-group study with 246 participants enrolled. The record lists Arterial Hypertension as the condition and describes the intended population as elderly patients. It does not give the eligibility criteria, participant age distribution, recruitment locations, or the method used to generate or conceal the random allocation sequence; those details are not reported in the registry record.
The two treatment groups differed in whether amiloride was included. Participants assigned to Diupress® received chlorthalidone 25 mg plus amiloride hydrochloride 5 mg as one oral tablet a day in the morning. Participants assigned to Higroton® received chlorthalidone 25 mg as one oral tablet a day in the morning. The record identifies no masking, so the study is described as open-label. It does not explain whether outcome assessors or laboratory personnel were masked.
The parallel-group structure means participants were assigned to one of the treatment groups rather than being described as crossing between them. The registry record does not state the allocation ratio or report the number randomized to each group as a separate result. The adverse-event information lists 121 participants at risk in Higroton® and 122 in Diupress®, but these are risk-set counts for those posted safety summaries and should not be treated as a complete account of randomization or attendance at every outcome visit.
The study began in 2011-08, had primary completion in 2013-08, and is listed as completed. The primary endpoint is the number of participants with serum potassium below 4.0 mEq/l at Visit 4. The record also lists Blood Pressure as a secondary outcome and reports two outcome measures, but does not give arm-level results for the primary endpoint. It lists zero analyses. Further details of the protocol, statistical analysis plan, and sample-size justification 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.
Overall Study
| Stage | Higroton® | Diupress® |
|---|---|---|
| STARTED | 121 | 122 |
| ITT Population | 121 | 122 |
| COMPLETED | 106 | 104 |
| NOT COMPLETED | 15 | 18 |
Analysis population for the primary outcome, as defined in the registry: Analysis of ITT. The number of participants differed across visits due to variations in attendance.
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: ITT population
| Characteristic | Unit | Higroton® | Diupress® | Total |
|---|---|---|---|---|
| Participants analysed | 121 | 122 | 243 | |
| Age, Continuous | years | 62 (SD 7) | 61 (SD 8) | 62 (SD 8) |
| Sex: Female, Male: Female | Participants | 65 | 74 | 139 |
| Sex: Female, Male: Male | Participants | 56 | 48 | 104 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Subjects With Serum Potassium Levels Below 4.0 mEq/l at Visit 4, measured over Visit 4 (75 ± 3 days of V1).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants whose serum potassium was below 4.0 mEq/l at Visit 4. It is a binary participant-level outcome—each assessed participant either falls below the stated threshold or does not—and the endpoint is expressed as a count. The record says the primary analysis was in the ITT population, while also noting that participant numbers varied across visits because attendance differed.
The record gives two descriptions of timing: the primary endpoint timeframe is Visit 4 (75 ± 3 days of V1), while the visit schedule describes V4 as 90 ± 3 days after V0. It also describes V1 as 15 ± 3 days after V0. These timing details are reproduced as recorded; further clarification is not reported in the registry record.
In general, a threshold-based laboratory endpoint can summarize how many participants cross a prespecified concentration boundary at a particular assessment. Such an endpoint can be useful for describing a safety-related biochemical measure, while remaining distinct from the continuous potassium values themselves. The endpoint does not show how far an individual value lies below the threshold, nor does a count alone describe the distribution of values. Those additional summaries are not reported in the registry record.
Here, the posted record does not give the number below the threshold in either arm, the number assessed at Visit 4, or an effect estimate with a confidence interval. The endpoint definition is therefore available, but its observed comparative result and precision cannot be evaluated from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a randomized comparison of chlorthalidone plus amiloride against chlorthalidone alone, and defines the primary endpoint as the number of participants with serum potassium below 4.0 mEq/l at Visit 4. It does not report the observed primary endpoint count for either group. No between-group estimate, confidence interval, or p-value for this endpoint is reported in the registry record. Consequently, the available endpoint information is not sufficient to describe the direction, size, or statistical precision of a group difference.
The ITT population is named in the endpoint description. The same description notes that participant numbers differed across visits because attendance varied. This matters when reading a count: a smaller count of participants meeting a threshold could reflect fewer participants assessed as well as a different frequency of the outcome. The record does not give Visit 4 denominators or explain how absent assessments were handled, so the endpoint counts and their interpretation cannot be reconstructed.
The safety record provides separate counts for serious adverse events and other adverse events. For serious adverse events, Higroton® has 1 affected participant among 121 at risk, and Diupress® has 2 among 122 at risk. For other adverse events, the corresponding posted figures are 41 among 121 and 55 among 122. These are descriptive counts. The registry record does not provide comparative estimates or uncertainty measures for these summaries, and the counts alone do not establish that treatment caused an event or that the groups differ reliably.
The record lists three serious-event terms with percentages: Abdominal pain NOS, Myocardial ischaemia, and Innappetence, each at 0.8%. It does not identify an arm for each term in the information available for interpretation. Death counts are not reported in the registry record; a missing figure should not be read as evidence that no deaths occurred.
The study status is completed, but completion does not itself supply an outcome result. Since the posted record lists zero analyses and omits the primary comparison, the statistical interpretation must remain limited to the endpoint definition, design, and descriptive safety counts. Any claim about benefit, harm, or equivalence between treatments would go beyond the reported results.
9. Statistical Methods Explained
Statistical methods concern how a study turns observations into estimates and how uncertainty around those estimates is assessed. The registry record gives some design and endpoint information, but it does not report a detailed statistical analysis plan. The distinctions below explain what the available items mean in general and what cannot be determined from this record.
What does randomization contribute?
In general, randomization assigns participants to treatment groups through a chance-based process. Its purpose is to reduce systematic differences between groups at the point of assignment, including differences that may not be measured. Randomization does not guarantee that groups will be identical, and it does not remove the need to report baseline characteristics, outcome data, and the analysis used. This record identifies the study as randomized, but the sequence-generation and allocation-concealment procedures are not reported in the registry record.
The study is also listed as open-label and parallel-group. In general, open-label means treatment assignment is not masked from participants or study personnel, while a parallel-group design assigns participants to one treatment group for comparison with another. The record does not clarify whether any particular outcome assessor was masked. Lack of masking may be more relevant to outcomes that involve judgment or participant reporting than to a laboratory measurement, but the extent of any such influence cannot be assessed without more information about measurement procedures.
How should a threshold count be understood?
The primary endpoint is a count of participants with serum potassium below 4.0 mEq/l at Visit 4. General statistical interpretation treats each participant as either meeting or not meeting that threshold at the assessment. To compare groups, an analysis would ordinarily need the number meeting the threshold and the number assessed in each group, as well as a defined measure of contrast. The registry record does not post those endpoint counts or a comparative result. It is therefore not possible to describe a risk difference, relative measure, confidence interval, or test result from the information recorded.
A confidence interval, in general, is a range of values compatible with the data and a specified statistical procedure. It communicates uncertainty around an estimate rather than certifying that a particular value is true. Without a reported endpoint estimate and interval, the precision of the treatment comparison cannot be assessed. A p-value, if reported, would address compatibility between the data and a specified null model under its assumptions; it would not by itself describe the size or practical importance of an effect. No primary-endpoint p-value is reported in the registry record.
What is the role of the ITT population?
The endpoint description says the analysis uses ITT. In general, an intention-to-treat approach analyzes participants according to their randomized assignment, regardless of whether they fully followed the assigned treatment. The principle helps preserve the comparability created by randomization. However, naming an ITT population does not explain how participants without an outcome measurement are handled. The registry record notes variation in attendance across visits but does not report the Visit 4 denominators, missing-data method, or whether the stated ITT analysis included all randomized participants for this endpoint.
Missing outcome data can affect an estimate when the probability of being observed is related to participant characteristics or outcomes. General approaches may include assumptions about the missingness process and methods for sensitivity analysis. Which assumptions and procedures were used in this study is not reported in the registry record. The size and direction of any effect of attendance differences therefore cannot be assessed.
What can safety counts establish?
The registry presents affected-participant counts for serious and other adverse events, along with numbers at risk in each arm. These are descriptive summaries. In general, a count is easier to interpret when its denominator, event definition, observation period, and handling of repeated events are clear. The record gives at-risk counts but does not report a comparative statistical analysis, confidence intervals, or details about whether the summaries count participants with one or more events versus event episodes beyond the labels used. The serious-event terms and percentages are listed without arm attribution in the registry entries.
Serious adverse events are distinct from all other adverse events in the posted grouping. A serious-event count should not be conflated with a count of every event, and a participant-level count should not be read as the total number of event episodes unless that is specified. The record does not supply enough detail to expand the interpretation beyond the posted group counts and term labels. Death counts are not reported in the registry record.
What do planning illustrations mean?
In general, sample-size planning calculations estimate how many participants may be needed under chosen assumptions about an effect, significance level, allocation, and statistical model. They are planning illustrations, not observed results and not observed power. The described illustration uses a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect expressed as a fraction of the observed effect. It specifies that non-time-to-event illustrations are expressed as participants per arm. Numerical planning outputs are not reported in the registry record. The illustration is explicitly not the trial's own design justification, and the trial's sample-size rationale is not reported in the registry record.
Overall, the record supports a description of the randomized design, the primary endpoint definition, and selected adverse-event counts. It does not document the inferential analysis needed to quantify the primary comparison or its uncertainty. General methods explanations cannot fill in those absent study-specific results or analytic details.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists two outcome measures, identifies Blood Pressure as a secondary outcome, and defines a primary endpoint based on serum potassium at Visit 4. It lists zero analyses. The record does not describe a hierarchy among secondary outcomes, a multiplicity adjustment, or a prespecified approach to interpreting multiple comparisons. These details are not reported in the registry record.
In general, multiplicity arises when several outcomes, time points, treatment contrasts, or subgroup analyses are tested. Considering many comparisons can increase the chance that at least one appears noteworthy by chance. A prespecified hierarchy or adjustment can help define how confirmatory conclusions are drawn. Because the registry record does not describe such procedures or report analyses, it is not possible to determine how multiplicity was handled in the trial's results.
The endpoint description identifies an ITT analysis and states that participant numbers differed across visits because attendance varied. The record does not provide Visit 4 denominators, the number of missing primary endpoint assessments, reasons for nonattendance, or a method for handling missing values. It also does not report sensitivity analyses assessing alternative missing-data assumptions. In general, missingness can affect both the precision and interpretation of a comparison; whether it did so in this study cannot be judged from the posted information.
The term ITT indicates an analysis population concept, but it does not by itself specify the complete analysis set or the treatment of missing measurements. The registry record does not report a per-protocol analysis, a safety analysis population definition, or further population-specific results. Any assertion about the effect of missing data, multiplicity, or deviations from assigned treatment would therefore be unsupported by the information recorded.
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 |
|---|---|---|---|
| Higroton® | 1 | 121 | 0.8% |
| Diupress® | 2 | 122 | 1.6% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Higroton® | 41 of 121 |
| Diupress® | 55 of 122 |
Most frequent serious adverse event terms
| Event term | Organ system | Higroton® | Diupress® |
|---|---|---|---|
| Myocardial ischaemia | Cardiac disorders | 0 of 121 | 1 of 122 |
| Abdominal pain NOS | Gastrointestinal disorders | 1 of 121 | 0 of 122 |
| Innappetence | Psychiatric disorders | 0 of 121 | 1 of 122 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Higroton® | Diupress® |
|---|---|---|---|
| Metabolism and Nutrition Disorders | Metabolism and nutrition disorders | 25 of 121 | 31 of 122 |
| Investigations | Investigations | 5 of 121 | 7 of 122 |
| Vascular Disorders | Vascular disorders | 1 of 121 | 7 of 122 |
| General Disorders and Administration Site Conditions | General disorders | 2 of 121 | 3 of 122 |
| Gastrointestinal Disorders | Gastrointestinal disorders | 1 of 121 | 4 of 122 |
| Musculoskeletal and Connective Tissue Disorders | Musculoskeletal and connective tissue disorders | 2 of 121 | 2 of 122 |
| Renal and Urinary Disorders | Renal and urinary disorders | 2 of 121 | 0 of 122 |
| Reproductive System and Breast Disorders | Reproductive system and breast disorders | 1 of 121 | 1 of 122 |
| Nervous System Disorders | Nervous system disorders | 1 of 121 | 0 of 122 |
| Immune System Disorders | Immune system disorders | 1 of 121 | 0 of 122 |
Serious events with the highest arm-level rate: abdominal pain nos (0.8%), myocardial ischaemia (0.8%), innappetence (0.8%).
The registry record reports serious adverse events separately from other adverse events. In the Higroton® group, 1 participant was affected by a serious adverse event among 121 at risk; in the Diupress® group, 2 were affected among 122 at risk. For other adverse events, it reports 41 affected among 121 at risk in Higroton® and 55 among 122 at risk in Diupress®. These are descriptive participant counts, not adjusted comparisons.
The record also lists Abdominal pain NOS, Myocardial ischaemia, and Innappetence as serious-event terms, each with a reported percentage of 0.8%. It does not specify which arm each term belongs to in the information recorded. The percentages should therefore be read as listed, without assigning them to a treatment group or inferring a comparative rate.
Counts alone do not show whether events were caused by treatment, how severe or persistent they were, or whether a participant experienced multiple events. The registry record does not report a statistical comparison or uncertainty interval for these safety summaries. Death counts are not reported in the registry record; that absence should not be interpreted as a reported count of zero.
12. What the Result Does, and Does Not, Mean
The record establishes that this was a randomized, open-label, parallel-group phase 3 study of chlorthalidone plus amiloride versus chlorthalidone alone in elderly patients with arterial hypertension. It specifies the primary endpoint as the number of participants with serum potassium below 4.0 mEq/l at Visit 4. It also provides selected serious and other adverse-event counts. These registry entries describe the study question and some recorded safety data.
The record does not provide the observed primary endpoint counts by arm, a between-group effect estimate, or a confidence interval. It therefore does not allow a reader to determine the direction or size of the primary endpoint difference, or how precisely that difference was estimated. The status of completed does not substitute for those results. The secondary outcome Blood Pressure is listed, but its results are not reported in the registry record.
Likewise, the adverse-event counts do not by themselves establish a causal relationship with either treatment or show that one group had a reliably higher risk. They are descriptive figures with no reported comparative uncertainty. The terms and percentages listed for serious events are not attributed to an arm in the information available, and deaths are not reported.
In general, a treatment comparison is best interpreted using the outcome definition, group-specific denominators, an effect estimate, and its uncertainty, alongside details about missing observations and the analysis population. Several of these elements are absent for the primary outcome. The posted information can support a careful account of design and endpoint definitions, but not a conclusion about comparative efficacy, equivalence, or overall safety. Such conclusions would require results and methods that are not reported in the registry record.
13. Why This Trial Matters Statistically
This study illustrates why a registered clinical question and a reported clinical result are not the same thing. The record specifies a randomized comparison, describes the two drug regimens, and defines a threshold-based primary endpoint. Those details allow readers to understand what investigators intended to compare. However, without group-specific endpoint counts or an estimated contrast, the central statistical comparison cannot be evaluated.
The endpoint also makes clear why denominators matter. The record states that attendance varied across visits and that participant counts differed. A count of participants below a threshold is most interpretable alongside the number assessed in each group. Without those denominators and the method for handling missing assessments, neither the observed frequency nor the possible influence of nonattendance can be fully appraised.
The safety summaries offer a second statistical lesson: descriptive counts are not, on their own, comparative evidence. Counts should be read in the context of their risk sets, event definitions, observation period, and uncertainty. The registry provides some group counts but no comparative analysis, and it does not assign the listed serious-event terms to a treatment arm in the information recorded.
Finally, the record distinguishes a planning illustration from the trial's own design. General sample-size illustrations rely on assumptions and should not be mistaken for an analysis of observed outcomes or for evidence that a study had a particular probability of detecting an effect. The trial's own sample-size justification is not reported in the registry record. Together, these features show why transparent reporting of outcomes, denominators, analysis methods, and uncertainty is necessary for a statistical reading of a clinical trial.
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 interpretation is that the registry record does not report arm-level results for the primary endpoint. It identifies what was counted and when, but not how many participants in each group had serum potassium below 4.0 mEq/l, how many were assessed at Visit 4, or the estimated comparison and its uncertainty. The primary result therefore cannot be independently interpreted from the posted information.
The timing description is not fully aligned within the record: the endpoint timeframe is stated as Visit 4 (75 ± 3 days of V1), while the visit schedule describes V4 as 90 ± 3 days after V0. V1 is described as 15 ± 3 days after V0. Further clarification of this timing is not reported in the registry record.
Attendance differed across visits, but the record does not provide visit-specific denominators, reasons for missing assessments, or missing-data procedures. Although the endpoint description names an ITT analysis, it does not explain how incomplete outcome data were handled. The allocation sequence, concealment procedures, eligibility criteria, age distribution, and any masking of assessors are also not reported in the registry record.
For safety, the registry provides counts but not comparative estimates or uncertainty intervals. It does not clarify all event-counting details, attribute the listed serious-event terms to an arm, or report death counts. The record lists a secondary Blood Pressure outcome but gives no results and lists zero analyses. Multiplicity procedures, the trial's own sample-size justification, and further statistical analysis details are not reported in the registry record. These omissions restrict both efficacy and safety interpretation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Efficacy of Chlorthalidone + Amiloride to Elderly Patients Treatment With Arterial Hypertension — NCT01191450.
- Registry record last updated 2025-06-12; status last verified 2025-03.
- Results first posted 2025-06-12.
- 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.
Continue through the Clinical Biostats statistical pathway
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18. Record Summary
NCT01191450 is a completed phase 3 randomized, open-label, parallel-group study with 246 enrolled participants. It compares chlorthalidone 25 mg plus amiloride hydrochloride 5 mg with chlorthalidone 25 mg alone in elderly patients with arterial hypertension. The study began in 2011-08 and had primary completion in 2013-08.
The primary endpoint is the number of participants with serum potassium below 4.0 mEq/l at Visit 4. Blood Pressure is listed as a secondary outcome. The endpoint description refers to an ITT analysis and notes varying attendance across visits. The registry record does not report the primary endpoint counts by arm, a comparative estimate, or uncertainty around that comparison.
Posted safety summaries list serious adverse events affecting 1 of 121 participants in Higroton® and 2 of 122 in Diupress®, and other adverse events affecting 41 of 121 and 55 of 122, respectively. Three serious-event terms are listed at 0.8% each, without arm attribution in the information recorded. Death counts and detailed statistical analysis methods are not reported in the registry record.