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 ENAC Blockade and Arterial Stiffness (NCT03837626), a randomized phase 2, phase 3 study. The primary outcome is Carotid Femoral Pulse Wave Velocity.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03837626 |
| Phase | Phase 2, Phase 3 |
| Condition | Overweight and Obesity, Insulin Resistance |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 137 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Missouri-Columbia |
| Results posted | Yes |
2. Clinical Question
Population
The registry describes obese, insulin-resistant participants and lists overweight and obesity and insulin resistance as conditions. The study summary specifies premenopausal and postmenopausal women and age-matched men. The primary outcome is described for participants who finished the clinical trial; the number who finished is not reported in the registry record.
Intervention
Participants assigned to the active-treatment group received daily amiloride for 6 months, with a maximum dose of 5 mg. The registry names this intervention as an amiloride pill.
Comparator
The comparison group received daily placebo for 6 months. The study is described as randomized and placebo-controlled, with a parallel-group design and triple masking. Which roles were masked is not reported in the registry record.
Primary question
The central question was whether amiloride treatment changes carotid-femoral pulse wave velocity, a measure of arterial stiffness, from baseline through the 3- and 6-month assessments compared with placebo. The registry calls this measure the gold standard for arterial stiffness. It also describes a broader interest in endothelial function, but comparative results for either measure are not reported in the registry record. No treatment-effect estimate, confidence interval, or statistical test for the primary outcome is reported in the registry record.
3. Trial Design
The registry identifies this study as randomized, triple-masked, and parallel-group, with Phase 2 and Phase 3 designations. It lists enrollment of 137 and a completed status. The sponsor is the University of Missouri-Columbia. The study began on 2019-07-15, and its primary completion date is listed as 2024-10-05.
The parallel-group structure means participants were assigned to one of the treatment groups rather than being described as receiving both interventions in sequence. The registry lists daily amiloride, at a maximum dose of 5 mg, for 6 months in the active group and daily placebo for 6 months in the comparison group. It does not report the allocation ratio or explain how the random sequence was generated or concealed.
Triple masking is recorded, but the registry record does not identify which people involved in the trial were masked or describe the masking procedures. The brief summary indicates that the study examined premenopausal and postmenopausal women and age-matched men. It does not report group-specific enrollment or provide outcome results by sex or menopausal status.
Carotid-femoral pulse wave velocity was assessed at baseline, 3 months, and 6 months. The outcome description says measurements were taken during experimental visits under the same conditions and in a blinded manner. Details such as the precise measurement protocol, adherence monitoring, and handling of treatment discontinuation are not reported in the registry record. The primary-outcome population is described as participants who finished the clinical trial, but the number included and the rules for defining completion 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 | Placebo | Amiloride |
|---|---|---|
| STARTED | 47 | 90 |
| COMPLETED | 37 | 79 |
| NOT COMPLETED | 10 | 11 |
Reasons for not completing this period:
| Reason | Placebo | Amiloride |
|---|---|---|
| Adverse Event | 3 | 3 |
| Withdrawal by Subject | 2 | 4 |
| Physician Decision | 2 | 3 |
| Lost to Follow-up | 3 | 1 |
Analysis population for the primary outcome, as defined in the registry: Number of participants that finished clinical trial
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.
| Characteristic | Unit | Placebo | Amiloride | Total |
|---|---|---|---|---|
| Participants analysed | 47 | 90 | 137 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 42 | 86 | 128 |
| Age, Categorical: >=65 years | Participants | 5 | 4 | 9 |
| Sex: Female, Male: Female | Participants | 28 | 59 | 87 |
| Sex: Female, Male: Male | Participants | 19 | 31 | 50 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 3 | 3 | 6 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 44 | 87 | 131 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Asian | Participants | 0 | 2 | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 5 | 6 | 11 |
| Race (NIH/OMB): White | Participants | 40 | 80 | 120 |
| Race (NIH/OMB): More than one race | Participants | 1 | 2 | 3 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 47 | 90 | 137 |
6. Primary Endpoint
The registry lists the primary outcome as Carotid Femoral Pulse Wave Velocity, measured over baseline, 3 and 6 mo.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | m/s |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is carotid-femoral pulse wave velocity, abbreviated cfPWV in the registry description. It is measured in m/s and is presented as a continuous measure summarized by a mean and a 95% confidence interval. The registry describes cfPWV as the gold standard of arterial stiffness.
In general, pulse wave velocity reflects how quickly a pressure wave travels through an artery. Greater arterial stiffness is associated with faster wave travel, so cfPWV provides a way to quantify arterial stiffness rather than relying only on a subjective assessment. This is a general explanation of the measure, not a finding from this trial.
The registry lists assessments at baseline, 3 months, and 6 months. Repeated measurements can describe the outcome over the course of treatment and allow a comparison of changes between randomized groups. The stated measurement conditions were the same across experimental visits, and the assessment was described as blinded. The registry does not specify the exact primary comparison, such as whether the principal contrast was change from baseline at a particular visit or an overall comparison across visits.
Although the registry gives the endpoint definition and its measurement schedule, it does not report group means, changes, treatment contrasts, or confidence intervals for cfPWV. It therefore does not establish from the posted results whether the groups differed or how precisely any difference was estimated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The trial record gives a design and an endpoint but does not report the comparative primary-outcome results. It lists carotid-femoral pulse wave velocity as the primary measure, measured at baseline, 3 months, and 6 months, but provides no group-specific means, changes from baseline, between-group estimates, confidence intervals, or p-values. As a result, the direction, size, and statistical precision of any treatment contrast cannot be described from the registry record.
The outcome is summarized as a mean with a 95% confidence interval. In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the analysis. Its width helps readers judge precision, while its position relative to a null value can be relevant when interpreting a treatment contrast. No primary-outcome confidence interval or treatment contrast is reported in the registry record, so those features cannot be assessed for this trial.
The scheduled measurements could support several distinct questions: the difference between groups at a visit, the difference in change from baseline, or a comparison using measurements across visits. Those approaches are not interchangeable, and the registry record does not specify which one formed the primary statistical contrast. It also does not report a statistical model, adjustment variables, or a test for the primary outcome. The outcome description alone is not enough to infer these choices.
The registry lists enrollment of 137, while the primary-outcome population is described as participants who finished the clinical trial. The number who finished and the number analyzed for cfPWV are not reported in the registry record. The enrollment figure therefore should not be treated as the denominator for a primary-outcome analysis without participant-flow information. Reasons for missing measurements and the treatment of missing values are also not reported in the registry record.
The registry lists 4 outcome measures and no posted analyses. It also does not report whether the investigators adjusted for multiple outcomes, time points, or subgroup comparisons. Without a defined analysis and its results, statistical significance, precision, and clinical importance cannot be judged. The record supports a description of the intended comparison and measurement schedule, not a conclusion about the effect of amiloride on arterial stiffness.
Safety information is reported separately from the primary endpoint. The registry lists no serious adverse events in either group, while other adverse events are reported for both groups. These counts describe the posted safety record; they do not substitute for the missing primary-outcome comparison and do not explain the nature or severity of the other adverse events.
9. Statistical Methods Explained
The registry describes the trial as randomized, triple-masked, and parallel-group. Random assignment is intended, in general, to make treatment groups comparable at the start by distributing measured and unmeasured factors through chance. That design can support a causal comparison when the assignment process is implemented as intended and the analysis preserves the randomized comparison. The registry does not report the sequence-generation or allocation-concealment methods, so those implementation details cannot be assessed.
What does the endpoint summary mean?
Carotid-femoral pulse wave velocity is a continuous outcome, measured in m/s. The registry says it is summarized as a mean with a 95% confidence interval. A mean describes the center of observed measurements; a confidence interval describes the uncertainty around an estimated mean or contrast under a specified statistical model. In general, neither a mean nor its confidence interval alone establishes a treatment effect: interpretation depends on the quantity being estimated and the comparison being made.
The record lists measurement at baseline, 3 months, and 6 months. A treatment comparison could focus on a follow-up value, change from baseline, or a repeated-measures model that uses observations across visits. These strategies answer different questions and can rely on different assumptions. The primary contrast and model are not reported in the registry record. No analysis results are posted for these time points.
Why does masking matter?
The study is labeled triple-masked, and the endpoint description says cfPWV was assessed in a blinded manner under the same conditions at experimental visits. In general, masking can reduce the influence of expectations on care, reporting, and measurement. The registry does not identify the three masked roles or describe how masking was maintained, so the label should not be expanded into assumptions about which trial personnel or participants were unaware of assignment.
What can the registry say about sample size?
The record lists enrollment of 137, but a sample-size justification for the trial is not reported in the registry record. The stated sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The illustration is described as detecting a stated fraction of the observed effect; for non-time-to-event outcomes, the convention is participants per arm. These are planning assumptions, not evidence of the trial's original design rationale or its achieved power. A sample-size calculation based on an observed effect is not observed power, and no numerical planning results are reported in the registry record.
How should confidence intervals and tests be read?
In general, a confidence interval is useful for assessing both the range of effects compatible with the data and the precision of an estimate. A p-value, when reported, addresses compatibility with a specified null hypothesis under the analysis assumptions; it does not measure the probability that a treatment works. The registry record does not report a p-value, effect estimate, or confidence interval for cfPWV. No statistical conclusion about the primary comparison can therefore be reconstructed from the endpoint description alone.
Why can variation affect the analysis?
General statistical context: continuous clinical measurements can vary between people and across visits. Greater variability makes a treatment contrast less precise if other aspects of the design are unchanged. Repeated measurements may also be correlated within a participant, so a model that uses several visits should account for that structure. The registry does not state how within-person correlation or other distributional features were handled. It also does not report whether transformations, robust methods, or alternative analyses were planned or used.
What can be inferred from the posted record?
The record supports statements about the randomized parallel-group design, the interventions, the stated measurement schedule, and the endpoint's planned summary. It does not supply the analysis specification or comparative primary-outcome results. Consequently, no recalculated treatment estimate is described, and no claim about statistical significance or precision is warranted. Any planning illustration should be understood as a design aid rather than a description of the observed evidence.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 4 outcome measures, but the record does not describe a procedure for controlling multiplicity across outcomes, visits, or possible subgroup comparisons. The primary endpoint has measurements at baseline, 3 months, and 6 months; the primary contrast among these measurements is not specified. Without a prespecified testing hierarchy or adjustment method in the record, it is not possible to determine how the risk of false-positive findings across multiple tests was addressed.
The registry lists no posted analyses. It does not report whether the primary comparison was adjusted for baseline values or other covariates, whether subgroup analyses were planned, or whether any interim analyses took place. These details are not reported in the registry record and should not be inferred from the randomized design or from the outcome schedule.
The primary-outcome population is described as participants who finished the clinical trial. However, the number who finished, the number with measurements at each visit, and the analysis population are not reported in the registry record. The record does not state whether analyses followed intention-to-treat principles, used a per-protocol population, or applied another definition.
Missing-data reasons and methods for handling missing observations are also not reported in the registry record. In general, missingness can affect estimates if the availability of measurements is related to treatment or outcome. Statistical approaches depend on assumptions about why data are missing; without the participant flow and analysis details, those assumptions cannot be evaluated for this trial.
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 |
|---|---|---|---|
| Placebo | 0 | 47 | 0.0% |
| Amiloride | 0 | 90 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo | 0 of 47 |
| Amiloride | 0 of 90 |
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 |
|---|---|
| Placebo | 5 of 47 |
| Amiloride | 9 of 90 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | Amiloride |
|---|---|---|---|
| Headache | Nervous system disorders | 5 of 47 | 9 of 90 |
The registry reports serious adverse events separately for the placebo and amiloride groups. The placebo group lists 47 participants at risk and 0 affected by serious adverse events; the amiloride group lists 90 at risk and 0 affected. Deaths are listed as 0 in both groups. These are the serious-event and death counts recorded in the registry.
For other adverse events, the registry lists 47 at risk and 5 affected in the placebo group, and 90 at risk and 9 affected in the amiloride group. The record does not provide event descriptions in the serious-event terms list, which is empty. It also does not identify the types, severity, timing, or relatedness of the other adverse events in the registry record for this analysis.
These figures describe counts of participants reported as affected, not a comparison adjusted for follow-up time or other factors. The registry does not report a statistical safety comparison, and these counts alone cannot establish whether the groups differed in risk. The event counts also do not indicate whether participants had more than one event. They should be read as the posted safety summary, not as a complete account of tolerability.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, placebo-controlled comparison was conducted to examine amiloride and arterial stiffness in obese insulin-resistant participants. It identifies cfPWV as the primary outcome, names its unit and summary format, and gives the planned assessment times. It also reports the treatment duration and maximum amiloride dose. These details clarify the question the trial was designed to address.
The record does not report the comparative cfPWV results. It therefore cannot show whether the mean outcome changed, whether changes differed between groups, or how precise any estimated difference might be. No conclusion about benefit, lack of benefit, or equivalence follows from the absence of posted outcome estimates. A completed status and an enrollment figure are not substitutes for outcome data.
In general, a statistically significant finding would not by itself establish that an effect is clinically important. Conversely, a non-significant result would not establish that groups are equivalent; estimates and their precision would be needed to understand what effects remain compatible with the data. Here, the registry does not report the estimates or tests needed for either interpretation.
The findings also cannot be extended to subgroups on the basis of the study summary alone. Although premenopausal and postmenopausal women and age-matched men are mentioned, no subgroup results or interaction analyses are reported in the registry record. The safety counts provide limited descriptive information but do not replace efficacy results or a formal safety comparison.
The appropriate interpretation is therefore bounded: the registry describes a trial designed to compare amiloride with placebo on arterial stiffness, but the posted record does not report the primary comparative result. Statistical and clinical conclusions about the treatment effect remain undetermined from the registry record.
13. Why This Trial Matters Statistically
This trial is statistically interesting because its central question concerns a continuous physiological measure collected repeatedly over treatment. The registry identifies cfPWV as the primary endpoint and schedules measurements at baseline, 3 months, and 6 months. Repeated measurements can provide information about the trajectory of an outcome, but they also require clear definition of the primary contrast and appropriate handling of within-participant dependence.
Randomization and masking are relevant features of the design. Random assignment is intended to reduce systematic differences between groups, while blinded measurement can limit observer influence. The record reports both a randomized design and blinded assessment under the same conditions, but does not give enough procedural detail to evaluate implementation fully. It also does not identify which roles were masked.
The registry's reporting gap is important for statistical interpretation. Without group-level results, effect estimates, confidence intervals, and an analysis description, readers cannot judge magnitude, precision, or robustness. Nor can they determine how the multiple outcomes and visits were handled or how missing measurements affected the analysis. The design may be informative in principle, but the posted record does not expose the evidence needed to evaluate its primary comparison.
Finally, the record distinguishes the planned endpoint from the safety summary. The available adverse-event counts are descriptive and do not answer the efficacy question. Keeping these evidence types separate avoids treating enrollment, completion status, or event counts as indirect evidence about change in arterial stiffness.
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 interpretation is that comparative primary-outcome results are not reported in the registry record. Although cfPWV, its measurement unit, summary format, and assessment times are described, there are no reported group means, treatment contrasts, confidence intervals, or p-values. The treatment effect and its precision therefore cannot be assessed.
The primary-outcome population is defined as participants who finished the trial, but the number who finished and the number analyzed are not reported in the registry record. Participant flow, withdrawals, adherence, and reasons for missing measurements are also not described. This prevents assessment of whether follow-up differed between groups or how missing data may have influenced the results.
The record does not report the exact primary contrast, statistical model, baseline adjustment, or handling of repeated measurements. It also does not describe a multiplicity strategy across the listed outcome measures and scheduled visits. The absence of these details limits assessment of the analysis choices and the risk of selective emphasis among possible comparisons.
Although the study is labeled triple-masked and the measurement description says assessments were blinded, the identities of masked roles and masking procedures are not reported in the registry record. The record also does not report subgroup estimates for the women and men described in the study summary. Finally, other adverse events are not characterized by type or severity in the available safety summary. These reporting limits constrain interpretation; they do not establish that the trial lacked these procedures or data.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: ENAC Blockade and Arterial Stiffness — NCT03837626.
- Registry record last updated 2025-12-30; status last verified 2025-11.
- Results first posted 2025-12-30.
- 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
The registry describes ENAC Blockade and Arterial Stiffness as a randomized, triple-masked, parallel-group trial with Phase 2 and Phase 3 designations. It lists enrollment of 137, a completed status, and the University of Missouri-Columbia as sponsor. The study compared daily amiloride, with a maximum dose of 5 mg, against daily placebo for 6 months.
The primary endpoint was carotid-femoral pulse wave velocity, measured at baseline, 3 months, and 6 months and summarized as a mean with a 95% confidence interval. The registry identifies it as a measure of arterial stiffness and describes blinded assessment under the same conditions. Comparative outcome results and the statistical analysis are not reported in the registry record.
Safety counts include 0 serious adverse events and 0 deaths in each group, with other adverse events reported for both groups. The registry lists no posted analyses.