Mineralocorticoid Receptor (MR) Antagonist (Eplerenone) vs Amlodipine and STRIATIN: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mineralocorticoid Receptor (MR) Antagonist (Eplerenone) vs Amlodipine and STRIATIN (NCT03683069), a randomized phase 4 study. The primary outcome is Systolic /Diastolic Supine Morning Liberal Salt Automated Blood Pressure.

2. Clinical Question

The study’s stated context is the relationship between striatin, salt-sensitive blood pressure, and mechanisms involved in blood-pressure regulation. The registry summary describes prior observations involving striatin risk-allele carriers and a heterozygous knockout mouse model, while noting that the mechanisms behind striatin-mediated salt-sensitive blood pressure were not clear. Those contextual statements motivate the research question; they are not results from this randomized comparison.

The central clinical comparison is whether blood-pressure measurements over the stated treatment period differ between participants assigned to eplerenone and participants assigned to amlodipine. The primary outcome combines systolic and diastolic pressure and includes measurements at baseline and subsequent visits. The registry record does not provide a single contrast, such as a specified follow-up visit or an average across visits, that can be interpreted as the definitive treatment comparison. It also does not report whether the comparison was intended to evaluate a difference between drugs, change within each arm, or both.

The population-level question should therefore be kept distinct from the broader biological motivation. A blood-pressure outcome under a liberal-salt diet can describe pressure in that study context, but the record does not state that this endpoint directly classifies individual participants as salt-sensitive. Nor does it report a genetic subgroup comparison for the randomized treatment contrast. The primary estimates, uncertainty intervals, and analysis of any relationship with striatin are not reported in the registry record.

3. Trial Design

The registry describes NCT03683069 as a randomized, triple-masked, parallel-design Phase 4 study sponsored by Brigham and Women's Hospital. The study status is completed. Enrollment is recorded as 90. The listed study dates are a start date of 2019-01-15 and a primary completion date of 2023-08-28. These administrative details describe the registered trial; they do not establish how many participants completed treatment or contributed to each outcome analysis.

The arms were eplerenone and amlodipine, both described as antihypertensive drugs. Randomization indicates that assignment was intended to use a chance-based process. A parallel design means participants are assigned to one treatment arm rather than crossing between the treatments as part of the stated design. The registry does not describe the randomization sequence, allocation concealment, or the parties included in the triple masking. Those implementation details are not reported in the registry record.

The primary blood-pressure outcome was scheduled around visits during randomized drug therapy: visit 2 at baseline, visit 3 at four weeks, visit 4 at 8 weeks, and visit 5 at 12 weeks. The record describes measurements after a liberal-salt diet period and a standardized morning procedure. The endpoint description says participants would be counseled regarding liberal salt intake and gives the dietary targets as Na+ (200 mEq), potassium (K+, 100 mEq), and calcium (800 mg). It also describes fasting, supine measurement with an automatic recording sphygmomanometer. The registry description is truncated, so additional procedure details are not reported in the registry record.

Enrollment is a planned or recorded study-level count, not necessarily the number of participants included in every analysis. The adverse-event record gives separate numbers at risk for the two arms, but the number analyzed for the primary outcome, the number completing each visit, and reasons for missing measurements are not reported in the registry record. The protocol’s sample-size justification and the planned statistical model are also not reported. The registry includes general assumptions for a planning illustration, but those assumptions alone do not establish the trial’s original design rationale or its analysis plan.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: baseline liberal salt diet

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.

6. Primary Endpoint

The registry lists the primary outcome as Systolic /Diastolic Supine Morning Liberal Salt Automated Blood Pressure, measured over Change in blood pressure between visit 2 (baseline), visit 3 (four weeks), visit 4 (8 weeks), visit 5 (12 weeks) of randomized drug therapy.

The primary endpoint is described as systolic and diastolic supine morning liberal-salt automated blood pressure. It is a continuous measure, with the outcome type identified as a mean and dispersion described using standard deviation. The stated timeframe is change in blood pressure between visit 2, the baseline visit, and visits 3, 4, and 5 during randomized therapy: four weeks, 8 weeks, and 12 weeks.

The registry describes a controlled measurement setting. Participants were to receive counseling about liberal salt intake, with stated dietary targets of Na+ (200 mEq), potassium (K+, 100 mEq), and calcium (800 mg). After 7 days on the diet, the procedure was to take place in the morning while participants were fasting. Participants were to remain supine for 60-90 mins before blood samples were obtained and blood pressure was measured using an automatic recording sphygmomanometer. Readings were to be taken every 2 mins for 20 mins, with the highest and lowest values discarded and the remaining readings averaged. A 24hr. urine collection was described as a check on balance and for storage for future analyses.

In general, repeated automated readings under specified conditions can make a blood-pressure measurement less dependent on a single reading or momentary fluctuation. Measuring both systolic and diastolic pressure captures two aspects of blood pressure. The liberal-salt context is relevant to the study’s stated interest in salt-sensitive blood pressure, but the endpoint alone does not establish a participant’s salt sensitivity. The registry record does not report the resulting means, standard deviations, changes, or comparison between arms.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

The outcome is identified as a mean of a continuous measure, with standard deviation as the dispersion measure. In general, a mean describes the central level of a set of measurements. A standard deviation describes how spread out individual measurements are around that mean. It is not the same as a confidence interval: the standard deviation describes variability among measurements, whereas a confidence interval describes uncertainty in an estimated quantity. The registry record does not report the primary-outcome means or standard deviations, so neither the central levels nor the observed variability can be assessed.

What does change from baseline mean?

In general, a change score compares a participant’s follow-up measurement with that participant’s baseline measurement. A group mean change then summarizes those participant-level changes. A comparison of mean changes between randomized arms asks whether the average change differed between the assigned groups. An analysis may instead model follow-up values while accounting for baseline, or use repeated measurements across visits. These methods can answer related but not identical questions and may make different assumptions. The registry record specifies change between baseline and later visits, but does not identify the model, the exact contrast, or whether baseline was included as a covariate.

Change scores can be useful because they express movement from the starting measurement, but their precision depends on variation in both baseline and follow-up measurements and on how those measurements are related within participants. Repeated readings from the same person are generally not independent observations. In general, an analysis that accounts for within-person correlation can represent this repeated-measure structure more appropriately than treating all visits as unrelated. The registry record does not report how repeated measurements were modeled or how correlations across visits were handled.

Why do the measurement procedures matter?

Blood pressure can vary across readings and circumstances. In general, consistent positioning, timing, preparation, and measurement procedures can reduce some avoidable variation and improve comparability across visits. The registry describes a morning, fasting, supine procedure after a liberal-salt diet period, automated readings, and an averaging rule that excludes the highest and lowest readings. These design features describe how the measurement was intended to be standardized. They do not establish that every participant followed the procedure, because adherence and deviations are not reported in the registry record.

The scheduled visits make the endpoint longitudinal: each participant could contribute measurements at baseline and at follow-up. A repeated-measures analysis can use information across visits, but interpretation depends on the planned contrasts and model assumptions. For example, a model may estimate separate arm differences at each visit or a pattern over time. The record does not state which estimand—the precise treatment effect the analysis is intended to estimate—was chosen. It also does not report how missing visit measurements were handled.

How should uncertainty and statistical significance be read?

In general, an estimated arm difference is more informative when paired with an uncertainty interval. The estimate conveys the direction and size of the contrast; the interval conveys how precisely it is estimated under the model. A p-value is one summary of evidence against a null hypothesis, but it does not replace the estimate or interval and does not describe clinical importance. No primary-outcome contrast, interval, or p-value is reported in the registry record. There is therefore no basis in the posted registry results for interpreting statistical significance or precision for the primary endpoint.

The registry lists four outcome measures and five analyses, while the primary outcome description includes more than one blood-pressure component and several time points. This makes multiplicity relevant in general: when many outcomes, visits, or contrasts are examined, the chance of at least one apparently unusual result can increase unless the analysis plan addresses the issue. The registry record does not describe a multiplicity adjustment or identify a hierarchy of primary comparisons. It would be inappropriate to assume either that an adjustment was used or that all comparisons were treated as equally confirmatory.

What do the planning assumptions establish?

The registry describes planning illustrations based on a two-sided significance level of 0.05, equal allocation between arms, a normal approximation, and effects defined as fractions of an observed effect. These are described as illustrations computed from the observed effect, not as the trial’s own design. The record does not provide numerical planning results in the information available for interpretation, nor does it report the original sample-size justification. These assumptions cannot establish what effect the trial was designed to detect or whether its enrollment was adequate for a particular endpoint.

In general, a sample-size calculation estimates the number of participants needed under specified assumptions about the target effect, variability, significance level, and desired power. Such calculations are planning tools, not results about the trial. Power calculated after observing a treatment estimate is not a measure of how persuasive the observed result is. The registry’s planning-illustration description should not be read as observed power or as a documented prospective rationale for enrollment.

The statistical analysis plan, the analysis population, missing-data procedures, and model diagnostics are not reported in the registry record. In general, these details matter because they describe which observations contribute, how incomplete data are treated, and whether the method’s assumptions are plausible. Without them—and without the outcome estimates—the posted information supports understanding the measurement plan and design, but not reproducing or fully evaluating the primary statistical analysis.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome description includes systolic and diastolic blood pressure measured at baseline and three later visits. The registry also records four outcome measures and five analyses. In general, examining multiple outcomes, visits, and contrasts creates a multiplicity issue: the more comparisons considered, the greater the chance that at least one result may appear notable by chance alone. A prespecified testing hierarchy or adjustment can address some multiplicity concerns. The registry record does not report whether such a strategy was planned or used, which comparisons were treated as primary, or whether results were adjusted for multiple testing.

Missing-data information is also limited. The number enrolled is recorded as 90, but the number with primary-outcome measurements at baseline and each follow-up visit is not reported in the registry record. Reasons for missing measurements, participant withdrawals, treatment discontinuations, and the method used to handle missing values are not reported. In general, incomplete outcome data can affect both precision and the validity of a comparison, depending on why measurements are missing and how the analysis handles them. The extent and consequences of missing data cannot be assessed from the registry information.

The analysis populations are not reported in the registry record. It is not stated whether the primary analysis included all randomized participants, participants who completed treatment, or another defined group. Nor is it stated how treatment assignment, protocol deviations, or adherence were handled in the primary analysis. The adverse-event denominators do not define the population used for the blood-pressure analysis.

These omissions limit the ability to assess the risk of selective reporting, reproduce the analysis, and understand which participants underpin any eventual estimate. The registry record also does not report a statistical analysis plan or the procedures used to address multiple testing and incomplete follow-up. These are unknowns, not evidence that the trial did or did not use a particular method.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists 33 participants at risk in the Epleronone Arm and 32 in the Amlodipine Arm. It reports 0 serious adverse events in each arm and 0 deaths in each arm. For other adverse events, it reports 0 affected in the Epleronone Arm and 3 affected in the Amlodipine Arm. The record’s arm label spells the first drug “Epleronone”; the intervention and primary arm description elsewhere name eplerenone.

These figures should be read as the registry’s reported counts, with the listed at-risk group sizes as their context. The registry does not provide event descriptions in the serious-adverse-event terms, as the top serious terms list is empty. It does not give further detail about the three other adverse events, their nature, timing, duration, or relationship to treatment. It is therefore not possible to characterize those events beyond their recorded category and count.

In general, an observed count of zero does not establish that an event cannot occur. Safety estimates depend on how events were defined, collected, and followed, and on the number and duration of observation. The record does not provide enough detail to evaluate those aspects or to compare safety risks statistically. The counts also do not replace the missing primary blood-pressure results, and they should not be interpreted as evidence for or against a treatment effect.

12. What the Result Does, and Does Not, Mean

The registry record establishes that a completed randomized, triple-masked, parallel Phase 4 study compared eplerenone with amlodipine and planned to assess systolic and diastolic supine morning blood pressure under a liberal-salt dietary condition. It also gives a schedule of baseline and follow-up visits and describes standardized blood-pressure measurement procedures. These details clarify the study question and intended measurement setting.

They do not establish the size, direction, or precision of a treatment difference. Numerical primary-outcome results are not reported in the registry record. Without arm-specific changes and a between-arm estimate, readers cannot determine whether the measured blood pressure differed between treatments, how large any difference was, or how uncertain an estimate might be. The absence of posted values must not be interpreted as a finding of no difference.

The study’s biological motivation concerns striatin and salt-sensitive blood pressure. That motivation does not show that this trial identified a mechanism or demonstrated a genetic treatment interaction. The registry record does not report a primary analysis of striatin-related subgroups, a treatment-by-genotype comparison, or a result that establishes individual salt sensitivity. The endpoint is a blood-pressure measure in a specified dietary context; it is not, by itself, a direct classification of salt sensitivity.

The adverse-event record reports no serious adverse events and no deaths in either listed arm, and reports three other adverse events in the amlodipine arm and none in the eplerenone arm. These are descriptive counts with limited event detail, not a complete statistical comparison of safety. Enrollment and completion status also do not reveal how many participants contributed to the primary analysis.

In short, the registry supports a description of trial design, measurement procedures, and limited safety counts. It does not support a conclusion about comparative blood-pressure effects, statistical significance, clinical importance, the adequacy of the analysis, or the role of striatin in treatment response. Those questions require outcome estimates and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically relevant because it combines a randomized treatment comparison with repeated measurements of a continuous physiological outcome in a defined measurement setting. Random assignment can support a fair comparison between treatment groups when implemented and analyzed appropriately. Repeated visits can describe how blood pressure changes over time, while standardized measurement conditions may help limit avoidable variability. These design features make the analysis plan important: the chosen contrast and method determine how those measurements are translated into a treatment estimate.

The liberal-salt context also links the endpoint to the study’s stated interest in salt-sensitive blood pressure and striatin. That connection makes it important to distinguish the general research motivation from the estimand actually tested. A blood-pressure difference during the described dietary condition would answer a question about measurements in that context; a claim about genetic mechanisms or individual salt sensitivity would require additional analyses and evidence. The registry record does not report such analyses.

From a biostatistical perspective, multiple visits and both systolic and diastolic outcomes raise questions about correlation, choice of primary contrast, multiplicity, and missing measurements. These questions are not merely technical: they affect what a reported estimate means and how confidently it can be interpreted. The registry record does not describe the model, missing-data approach, or multiplicity strategy, and it does not post the primary numerical results. Consequently, the record cannot be used to evaluate how these design features were handled in the analysis.

The trial also illustrates why completion status and enrollment are not substitutes for outcome reporting. A completed study can still be difficult to interpret when the primary estimates, uncertainty, and analysis population are absent. The posted information is useful for understanding the research question and intended procedures, but it is insufficient for assessing the comparative treatment result or its precision.

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 central limitation is that the registry record does not report numerical results for the primary blood-pressure endpoint. No mean changes, standard deviations, treatment contrasts, confidence intervals, or p-values are available for interpretation. The stated measurement schedule therefore cannot be connected to an estimated effect or its precision.

The primary outcome description includes systolic and diastolic pressure across multiple visits, but the registry does not identify a single treatment contrast as the principal result. The analysis model, handling of repeated measurements, and approach to multiplicity are not reported. The record lists four outcome measures and five analyses, but does not describe how these outcomes and analyses relate to one another or which findings were prespecified as confirmatory.

Participant-flow information is incomplete for interpreting the primary endpoint. Although enrollment is recorded as 90, the primary-outcome analysis counts at each visit, completion of follow-up, reasons for missing data, and analysis population are not reported in the registry record. The adverse-event arm counts do not fill this gap because they are safety entries rather than primary-outcome analysis counts.

The record does not report detailed eligibility criteria, baseline characteristics, adherence to the liberal-salt diet or randomized therapy, or deviations from the planned measurement procedure. It also does not provide the original sample-size justification or a complete statistical analysis plan. The planning-illustration assumptions do not establish the trial’s prospective design rationale.

Finally, the registry’s description of the primary endpoint is truncated. The available information describes the intended measurement procedures, but not every procedural detail or the final analytic implementation. These limitations restrict reproducibility and prevent assessment of whether the posted design was followed as intended.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Mineralocorticoid Receptor (MR) Antagonist (Eplerenone) vs Amlodipine and STRIATIN — NCT03683069.
• Registry record last updated 2025-03-19; status last verified 2025-03.
• Results first posted 2025-03-19.
• 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.

18. Record Summary

NCT03683069 is a completed, randomized, triple-masked, parallel Phase 4 study sponsored by Brigham and Women's Hospital. The registry records enrollment of 90 and a comparison of antihypertensive eplerenone with amlodipine. The study’s stated context concerns hypertension, salt-sensitive blood pressure, and striatin.

The primary outcome was systolic and diastolic supine morning automated blood pressure under a liberal-salt dietary condition, assessed as change from baseline at four weeks, 8 weeks, and 12 weeks. The registry describes a standardized morning measurement procedure and a 7-day diet period.

The registry record does not report the primary blood-pressure estimates, uncertainty intervals, p-values, analysis model, analysis populations, or missing-data procedures. It reports 0 serious adverse events and 0 deaths in each listed arm, along with 0 other adverse events in the Epleronone Arm and 3 in the Amlodipine Arm. The numerical safety details are limited, and the primary comparative result cannot be determined from the posted registry information.