Amiloride in Nephrotic Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Amiloride in Nephrotic Syndrome (NCT05079789), a randomized phase 3 study. The primary outcome is Decrease of Overhydration, %ECW After 8 Days.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, controlled interventional trial with a parallel-group design. The registry record lists an enrollment of 20, with 10 participants in the amiloride arm and 10 in the furosemide arm for the posted primary outcome. Random allocation is reported, but the method used to generate or conceal the allocation sequence is not reported in the registry record. Masking is listed as none, so the record describes the trial as open-label rather than masked.

The study compared amiloride with furosemide for treatment of edema in nephrotic syndrome. The arm descriptions give start doses of 5 mg for amiloride and 40 mg for furosemide. Further details about administration, dose adjustment, adherence, co-interventions, and the duration of assigned treatment are not reported in the registry record. The primary outcome was assessed after 8 days. Secondary outcomes listed in the record were decrease of overhydration, %ECW, after 16 days and decrease of body weight, in kg.

The record lists University Hospital Tuebingen as sponsor. The study start date is 2020-06-08 and the primary completion date is 2022-11-05. Its status is terminated. The reason for termination and whether termination affected recruitment, follow-up, or the planned analyses are not reported in the registry record. The number enrolled is recorded, but the record does not provide a fuller account of participant flow, such as how many completed the primary assessment or were included in each analysis.

Randomization can help balance measured and unmeasured participant characteristics between study groups on average, but it does not guarantee balance in a small trial. The small group sizes also mean that descriptive estimates may be sensitive to individual observations. The record does not describe a sample-size justification or the intended statistical analysis plan, so the design cannot be assessed against a prespecified precision or power target.

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

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 Decrease of Overhydration, %ECW After 8 Days, measured over 8 days.

The primary endpoint is the decrease in overhydration after 8 days, measured using bioimpedance spectroscopy and expressed as percent of extracellular water (%ECW). Bioimpedance spectroscopy estimates body-fluid compartments by measuring electrical properties of the body. In this trial, the endpoint is intended to capture change in excess hydration over the assessment period rather than relying only on a broader clinical impression of edema.

A decrease in overhydration is a quantitative measure: it describes the change in the measured hydration state, with larger decreases indicating more reduction in the measured overhydration. The record reports the endpoint as a median with an interquartile range for each arm. The amiloride median is 1.95, with an interquartile range from 0.8 to 6.4; the furosemide median is 5.15, with an interquartile range from 0.9 to 8.3. These are group summaries, not individual participant trajectories.

Using a measurement-based endpoint can support a more standardized comparison than an unstructured description of edema, but interpretation depends on how measurement and change were defined and collected. The record identifies the measurement method, unit, and assessment time. It does not report details such as baseline values, the precise calculation used to derive decrease, measurement reliability, or the handling of repeated or technically invalid readings. Those details are not reported in the registry record.

The primary measure should be interpreted alongside its scale and spread. It is not itself a patient-reported symptom, a measure of kidney function, or a direct account of how participants felt. Secondary outcomes include overhydration at 16 days and body-weight decrease, but the posted primary summary alone cannot describe those outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is reported as a median and an interquartile range, rather than as a mean and standard deviation. The median is the central ordered observation: half of the observations lie on either side, subject to the handling of ties and the calculation convention. It is often useful when a distribution is skewed or contains values that would pull the mean, although the registry record does not say why the median was chosen for this endpoint.

The interquartile range describes the middle half of the observed values, bounded by the lower and upper quartiles. For amiloride, the posted median is 1.95 and the interquartile range is 0.8 to 6.4. For furosemide, the median is 5.15 and the interquartile range is 0.9 to 8.3. These ranges convey variation among participants, not precision of the group medians. They should not be read as confidence intervals. The record does not specify the quartile convention used.

What would a treatment-effect estimate add?

A randomized comparison is most directly interpreted through an estimate of the difference between groups, paired with an uncertainty interval. The appropriate effect measure depends on the endpoint and the planned analysis. A difference in group medians is one possible descriptive contrast, but it is not automatically the same as an effect estimated by a model or a prespecified statistical test. The registry record does not report a treatment-effect estimate, a confidence interval, or a p-value for the primary endpoint.

A confidence interval is a statistical range intended to communicate the uncertainty of an estimated effect under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, while the interval's position relative to a null value helps frame the evidence for a difference. No such interval is reported for this comparison. It would not be appropriate to infer one from the two medians and interquartile ranges without participant-level data and a justified method.

Why does the analysis method matter?

The endpoint is a change in a measured quantity, and the record reports medians. Analyses of change can depend on the distribution of the changes, baseline values, and whether the intended comparison is between changes, follow-up values adjusted for baseline, or another estimand. An estimand is the precise treatment effect the analysis seeks to describe, including the population, outcome, treatment conditions, and handling of events such as discontinuation or missing measurements. Those choices are not reported in the registry record.

General statistical practice is to select an analysis in advance and describe its assumptions. If data are highly skewed, a method based on a normal distribution may not describe them well. If variability differs between treatment groups, methods that assume equal variability may also be unsuitable. Randomization supports causal comparison, but the analysis still needs to account for the outcome's structure and the actual observations. The registry record does not identify a test, model, transformation, covariate adjustment, or diagnostic assessment.

Over-dispersion is a general issue for outcomes where observed variability is greater than a model's assumed variability. If ignored, standard errors can be too small and uncertainty intervals can be too narrow. It is not possible to determine from the posted medians and interquartile ranges whether over-dispersion is relevant to this endpoint; no model or dispersion assessment is reported.

What do the planning illustrations represent?

The planning illustrations use the observed effect as a basis for hypothetical sample-size scenarios, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. They are illustrations rather than the trial's own sample-size justification. The record does not report that these assumptions were used to design or conduct the trial. The displayed scenarios are not observed power and do not change the fact that only 10 participants per arm are reported for the primary outcome.

Sample-size planning depends on a target effect, outcome variability, the type of comparison, and the desired error and power criteria. An illustration tied to an observed effect can be especially uncertain in a small trial because that observed effect may not be a stable estimate of the underlying treatment effect. The registry record does not report the original target effect, assumed variability, desired power, or a prospective sample-size calculation. Thus, planning illustrations cannot establish whether the study was adequately sized for its intended question.

What can be inferred without a test result?

The posted summaries support a descriptive statement about the observed distributions and their medians. They do not support a claim that a difference is statistically significant, or that the treatments are equivalent. A non-significant result, if one had been reported, would not by itself prove equivalence; an equivalence conclusion requires a prespecified margin and an analysis designed for that purpose. Neither is reported in the registry record. Likewise, the absence of a p-value is not evidence that the groups are the same.

The record identifies values as missing or not estimable for a two-arm comparison for an other endpoint. That status should be understood as a limitation on the available comparison, not as a numerical result. No recalculated comparison is presented for the primary endpoint, and the record gives no basis for reconstructing an inferential analysis from the group-level summaries. Any additional analysis would need suitable participant-level data and clearly stated assumptions.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome: decrease of overhydration, %ECW, after 8 days. It also lists two secondary outcomes: decrease of overhydration, %ECW, after 16 days, and decrease of body weight, in kg. Considering multiple outcomes can increase the chance that at least one result appears noteworthy by chance if each is tested independently. A prespecified hierarchy, adjustment procedure, or other multiplicity strategy can help define how evidence across outcomes should be interpreted. Such a strategy is not reported in the registry record.

The record reports three outcome measures and two posted secondary outcomes, but lists zero analyses. It does not identify which outcomes were analyzed, whether any outcome was changed after the trial began, or whether additional outcomes were collected but not posted. An analysis plan, including any correction for multiple comparisons, is not reported in the registry record. For that reason, the primary outcome should not be treated as the only analysis that may have been considered, nor can a family of statistical tests be reconstructed.

Missing-data methods and analysis populations are also not reported in the registry record. The record does not say whether the primary analysis included all randomized participants, only participants with observed measurements, or another group; it does not report the number with missing outcome data or why any data may be missing. It also does not specify an intention-to-treat approach, a per-protocol approach, imputation, or sensitivity analyses. These omissions matter because the pattern and handling of missing data can affect both the estimate and its uncertainty.

The registry record identifies values as missing or not estimable for a two-arm comparison for an other endpoint. This does not supply an analysis method or establish why values could not be estimated. Without fuller reporting on outcome availability and analysis populations, the posted information cannot show how missingness was handled or whether the primary summaries include every randomized participant.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: delayed discharge from hospital due to macrohematuria after kidneybiopsy (10.0%), myocardial infarction (10.0%), pericardial effusion with in-hospital monitoring (10.0%), abdominal pain with diarrhea with inhospital treatment (10.0%), aki stage 2 with in-hospital treatment (10.0%).

For serious adverse events, the registry record lists 1 affected participant among 10 at risk in the amiloride group and 4 among 10 at risk in the furosemide group. It lists zero deaths in each group. These are counts of participants affected as recorded in the registry; they are not a comparison adjusted for chance, baseline risk, exposure time, or other factors. With 10 participants at risk in each arm, the counts are descriptive and should not be treated as precise estimates of comparative safety.

The record also lists other adverse events for 9 of 10 participants in the amiloride group and 10 of 10 in the furosemide group. “Other” adverse events and serious adverse events are separate registry categories; the counts should not be added together. The record does not provide enough detail to determine overlap between categories or to reconstruct the number of distinct events experienced by participants.

Five serious-event terms are listed, each with 10.0%: delayed discharge from hospital due to macrohematuria after kidneybiopsy; myocardial infarction; pericardial effusion with in-hospital monitoring; abdominal pain with diarrhea with inhospital treatment; and AKI stage 2 with in-hospital treatment. The list does not assign these terms to a treatment arm, and the registry record does not report further event-level timing, duration, outcome, or attribution. The listed terms therefore cannot establish that a study drug caused an event. Small-group counts and incomplete event detail limit comparative interpretation.

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

The registry record reports a randomized, open-label, parallel comparison of amiloride and furosemide for edema in nephrotic syndrome. For the primary outcome, the posted median decrease in overhydration after 8 days is 1.95 in the amiloride arm and 5.15 in the furosemide arm. The interquartile ranges are 0.8 to 6.4 and 0.9 to 8.3, respectively. These summaries describe observed outcomes among 10 participants per arm.

The values support a limited descriptive reading: the median change is higher in the furosemide group in the posted summary. A larger decrease corresponds to a greater reduction in the measured overhydration. But the record does not report an inferential comparison, confidence interval, or p-value. The summaries alone do not establish that the apparent difference is statistically reliable, clinically important, or attributable to treatment. They also do not demonstrate that the treatments are equivalent.

The results concern a specific measurement and assessment time. They do not by themselves address longer-term outcomes, other features of nephrotic syndrome, kidney function, quality of life, or every aspect of edema. The record lists secondary outcomes at 16 days and body-weight decrease, but does not provide results for those measures in the posted primary summary. Conclusions should not be extended to outcomes that are not reported.

The registry status is terminated, with enrollment recorded as 20. The reason for termination, the intended enrollment target, participant flow, and the completeness of outcome data are not reported in the registry record. These gaps prevent assessment of whether termination affected the planned comparison or which participants contributed to the summaries.

Safety counts are also descriptive. The serious-event counts are 1 among 10 participants in the amiloride group and 4 among 10 in the furosemide group, with zero deaths in either group. Those numbers cannot establish a comparative safety effect or determine causality, particularly without event-level detail and an inferential analysis. Overall, the record offers a small set of descriptive outcome and safety data, not a complete statistical evaluation of efficacy or safety.

13. Why This Trial Matters Statistically

This trial raises a central biostatistical issue: randomized assignment and a numerical difference between group summaries do not, by themselves, provide a complete treatment-effect estimate. The trial reports medians and interquartile ranges for a measured change in overhydration, which makes it possible to describe the observed distributions. But readers also need an appropriate between-group estimate and its uncertainty to judge how compatible the data are with a range of possible effects.

The group sizes are small, and the primary endpoint is summarized with a median. This combination highlights why distributional summaries and inferential methods must be distinguished. The interquartile ranges give information about spread among participants, whereas an uncertainty interval for the treatment contrast would address the precision of the comparison. One cannot substitute for the other. The record does not report that contrast or an analysis method, so the statistical evidence remains limited to descriptive results.

The record also illustrates the importance of transparent reporting beyond a primary outcome value. Details about participant flow, analysis populations, missing measurements, multiplicity, and the reason for termination are not reported in the registry record. These items help readers understand what data entered an analysis and how planned comparisons relate to posted findings. Their absence does not tell readers what happened, but it restricts what can be concluded from the record.

Finally, safety figures in small trials require careful framing. Counts of affected participants and listed event terms can identify what was recorded, but they do not establish causation or comparative risk. Distinguishing descriptive counts from modeled or adjusted estimates is essential, especially when group sizes are limited. The trial is statistically informative as an example of why a posted numerical result needs context about design, analysis, precision, and reporting completeness.

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 primary endpoint summaries are available for 10 participants in each arm, but the registry record does not report participant-level observations. Without those data, the distribution cannot be examined beyond the reported median and interquartile range, and alternative summaries or analyses cannot be checked. The record does not provide a confidence interval or p-value for the primary comparison.

The registry lists no analyses. It does not report a statistical analysis plan, the prespecified estimand, a method for comparing groups, or whether the analysis accounted for baseline overhydration. The reason for using the median is not stated. Details about how the decrease was calculated, measurement procedures, and measurement reliability are also not reported in the registry record.

The status is terminated, but the reason and consequences of termination are not described. Enrollment is listed as 20, but the record does not state the planned sample size or whether the listed enrollment was the target. Participant flow, withdrawals, adherence, treatment exposure, and the number with an observed primary outcome are not reported. Missing-data handling and analysis populations are not specified.

The record identifies secondary outcomes but does not provide their results in the primary summary. It does not describe how multiplicity was handled or whether additional outcome analyses were conducted. Masking is listed as none; the record does not describe whether outcome measurement procedures included safeguards against observer influence. Treatment details beyond the stated start doses are not reported.

Finally, adverse-event reporting is limited to group-level counts and a list of serious-event terms. The terms are not assigned to treatment groups, and timing, severity details, attribution, and outcomes are not reported. The small groups and incomplete analysis information mean that these safety data should be read descriptively rather than as a dependable comparative assessment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Amiloride in Nephrotic Syndrome — NCT05079789.
• Registry record last updated 2025-01-14; status last verified 2025-01.
• Results first posted 2025-01-14.
• 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

The registry record describes a Phase 3, randomized, open-label, parallel trial comparing amiloride with furosemide for edema in nephrotic syndrome. Enrollment is 20, with 10 participants in each arm for the posted primary outcome. The listed start doses are 5 mg for amiloride and 40 mg for furosemide. The primary outcome is decrease of overhydration, %ECW, after 8 days, measured by bioimpedance spectroscopy.

The posted medians are 1.95 for amiloride and 5.15 for furosemide, with interquartile ranges of 0.8 to 6.4 and 0.9 to 8.3. The record does not report an inferential comparison. Secondary outcomes listed are overhydration decrease after 16 days and body-weight decrease. The study is listed as terminated; its reason is not reported in the registry record. Analysis methods, missing-data handling, analysis populations, and a sample-size justification are not reported.