Spironolactone in Patients With Single Ventricle Heart: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Spironolactone in Patients With Single Ventricle Heart (NCT00211081), a non-randomized na study. The primary outcome is Change in Flow Mediated Dilation.

2. Clinical Question

The study’s stated rationale is to use ultrasound to assess blood-vessel function in patients with heart failure and to examine the effect of spironolactone on that function. Its registered title focuses on endothelial function in patients with single ventricle heart. These descriptions establish the clinical context, but they do not establish who was actually enrolled beyond the record’s overall enrollment figure or whether every participant had the conditions mentioned in the brief summary.

The design supports a before-and-after question within a single group, rather than a randomized comparison between spironolactone and an alternative. That distinction matters: a change observed over time would not, by itself, separate a drug effect from other explanations for change. Because no primary outcome values or analysis results are reported in the registry record, the clinical question cannot be answered from the posted information.

3. Trial Design

The registry lists a completed study sponsored by Emory University, with a start date of 2004-11 and primary completion in 2008-06. It records enrollment of 12. The trial is classified as non-randomized, single-group, and unmasked. The intervention is spironolactone, described as a drug; the arm is identified as open label. No separate comparator arm is described.

The primary endpoint is scheduled for measurement at baseline and post-intervention, with the post-intervention timepoint specified as 4 weeks. The primary population is described as subjects that completed all study visits. The registry does not report how many participants completed the visits, whether every enrolled participant contributed primary endpoint data, or how missing measurements were handled.

The record does not specify the spironolactone dose or schedule, adherence assessment, or other treatment details. It also does not report a protocol-level statistical plan, a sample-size justification for the trial, interim analyses, or stopping rules. These details should not be inferred from the study’s completed status or its enrollment figure.

The design is important for interpreting any change in the endpoint. With a single group measured before and after intervention, the comparison is within participants over time, not between randomized groups. Such a design can describe observed change, but it does not independently control for time-related changes, measurement variation, or other influences. In this record, even the observed change is not reported, so the design can be described but its endpoint findings cannot be assessed.

The registry also lists secondary outcomes concerning inflammatory markers and the 6 Minute Walk Test. The presence of these outcomes indicates a broader set of measurements, but the registry record does not report their results or explain how they were incorporated into the analysis.

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: Subjects that completed all study visits.

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 Change in Flow Mediated Dilation, measured over Baseline, Post-Intervention (4 Weeks).

The primary endpoint is change in flow-mediated dilation of the brachial artery, expressed as a percentage of brachial artery diameter. The registry describes high-resolution ultrasound measurement of arterial diameter above the small cavity in the elbow joint. Diameter is assessed at rest and in response to an increase in blood flow to the area, with measurements planned at baseline and after the 4-week intervention.

Flow-mediated dilation is used as a non-invasive measure of the artery’s response to increased blood flow. In general, a vascular response of this kind can provide information about endothelial function, the function of the inner lining of blood vessels. The measure is an indirect physiological endpoint: it is not itself a measure of symptoms, daily functioning, or a clinical event. The registry’s stated rationale is to examine vessel function using ultrasound in patients with heart failure.

The endpoint is described as a mean of a continuous measure, with standard deviation as its dispersion measure. In general, a mean describes the average measurement in a group, while a standard deviation describes how spread out measurements are around that average. For a change endpoint, a clear interpretation depends on knowing how change was calculated, the observed measurements, and their variability. The registry record does not report those outcome values, the mean change, or its standard deviation.

The listed primary population includes subjects who completed all study visits. The record does not report whether the endpoint was analyzed as a within-participant difference, whether all available measurements were used, or what approach was taken for participants with incomplete visits.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous measurement: flow-mediated dilation expressed as a percentage of brachial artery diameter. The registry identifies the summary parameter as a mean and the dispersion measure as standard deviation. In general, a mean gives the central average of the recorded measurements. A standard deviation describes how variable individual measurements are around that mean; it is not the same as the uncertainty in the estimated mean or in a mean change.

For a before-and-after study, a natural analysis would compare each participant’s post-intervention measurement with that participant’s baseline measurement. In general, analyzing within-participant changes accounts for the fact that measurements from the same person are related. However, the registry record does not state the exact calculation or model used for change, and it does not report outcome values. It is therefore not possible to reconstruct or assess an analysis from the record.

A confidence interval is a statistical range that conveys uncertainty around an estimated effect. A narrower interval generally indicates greater precision, while a wider interval indicates greater uncertainty. Its interpretation depends on the analysis and assumptions used. For this trial, no confidence interval for the primary endpoint is reported in the registry record, so the precision of an estimated change is unknown. The absence of an interval is not evidence that the effect was precisely estimated or that there was no change.

A p-value measures how compatible the observed data are with a specified null model under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The registry record does not report a primary endpoint p-value, a test method, or a null hypothesis. No conclusion about statistical significance can therefore be made.

The registry describes a continuous endpoint and identifies standard deviation as the dispersion measure. In general, continuous measurements can vary between participants, and some statistical models rely on assumptions about the distribution of errors. If observations have more variability than a model allows, standard errors and uncertainty estimates may be too small; this is one reason model fit and distributional assumptions matter. The record does not report diagnostic checks, transformations, robust methods, or any other adjustment for unusual variability.

The design is a single group with baseline and post-intervention assessments. In general, a paired analysis can estimate the average within-participant change, while an unpaired analysis would treat the timepoint measurements as independent and may not reflect their relationship. The registry does not identify which approach was used. It also does not report whether the analysis included covariate adjustment or whether any participants were excluded from the primary analysis beyond the stated completed-visits population.

Planning calculations are not the same as analyses of observed results. The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of the observed effect. These assumptions do not describe a reported trial analysis. The trial itself is recorded as single-group, so assumptions about equal allocation between two arms do not match its registered design. The observed effect used for such illustrations is not reported in the registry record, and no sample-size outputs can be interpreted from the information recorded. Planning illustrations are not observed power and do not establish what the trial could detect after the fact.

In general, power is a design-stage probability of detecting an effect of a specified size under assumed conditions. It is not a measure of whether the observed findings are reliable, and calculating power from an observed effect does not resolve uncertainty in the findings. A sample-size planning exercise can be informative only when its assumptions, target effect, and design align with the intended study. Because the record does not report the trial’s own sample-size justification, one should not infer that enrollment was adequate or inadequate.

Multiplicity arises when several outcomes or analyses are tested. In general, testing many outcomes can increase the chance of at least one apparently notable result, so researchers may specify a primary outcome, a testing hierarchy, or an adjustment method. The registry names the primary endpoint and lists secondary outcomes, but does not report an analysis hierarchy or multiplicity adjustment. No multiplicity-adjusted result is reported.

Missing-data methods are also part of statistical interpretation. In general, excluding participants with missing measurements can change the composition of the analyzed group, while imputation or model-based methods require assumptions about why data are missing. The endpoint population is described as subjects who completed all study visits, but the record does not say how many participants met this definition, how missing data were handled, or whether sensitivity analyses were performed.

These general concepts explain what would be needed to interpret a continuous before-and-after endpoint. They do not fill in missing trial-specific results. The registry record does not report the estimates, analysis details, or assumptions needed to assess the statistical findings.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Spironolactone")
n   <- c(10)
m   <- c(5.5)
sp  <- c(2.1)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Spironolactone  10  5.500  2.100  3.998  7.002

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies change in flow-mediated dilation as the primary endpoint and lists secondary outcomes involving C-Reactive Protein, Interleukin-6, Interleukin 1 Beta, Interleukin-10, Tumor Necrosis Factor-Alpha, and change in the 6 Minute Walk Test score. This set of outcomes creates a multiplicity question: when researchers examine several endpoints, a notable result may arise by chance even if no individual outcome has a meaningful effect. In general, a prespecified hierarchy or adjustment can help control the interpretation of multiple tests.

The registry record does not report a multiplicity adjustment, an outcome-testing hierarchy, or a statistical analysis plan. It also does not report results for the primary or secondary outcomes. It is therefore not possible to determine which analyses were conducted, whether the primary endpoint was treated as confirmatory, or how any multiple comparisons were interpreted.

The primary endpoint population is described as subjects that completed all study visits. The record does not report the number of participants in that population, the amount or pattern of missing endpoint data, or a method for handling missingness. In general, complete-case analysis can be vulnerable to bias if the participants with complete data differ in relevant ways from those without complete data. Imputation and model-based approaches also depend on assumptions that need to be described and assessed.

The registry does not report whether an intention-to-treat analysis, a complete-case analysis, or another analysis population was used. The enrollment figure alone does not establish who contributed to the primary analysis. Without these details and without outcome estimates, the robustness of the findings cannot be assessed.

12. 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 0% reporting threshold.

The registry lists 12 participants at risk for serious adverse events in the spironolactone group and records 0 serious adverse events. It also lists 12 at risk for other adverse events and records 0 other adverse events. Deaths are recorded as 0. These figures describe the safety information entered in the registry for the recorded group.

Zero reported events should be read narrowly. It means the registry reports no events in these categories for the group and risk population shown; it does not prove that the intervention has no safety risks. Small studies may provide limited information about uncommon events, and the record does not describe how adverse events were defined, collected, assessed for relation to treatment, or monitored over time. It also does not report a detailed adverse-event listing or explain whether all participants had the same duration of safety follow-up.

The figures are not a comparison with an untreated or alternative-treatment group because the study is recorded as single-group and no comparator is described. They therefore cannot establish whether event rates differed from another treatment or from the background experience of the population. The registry’s adverse-event entries should be interpreted as descriptive counts, not as comparative evidence.

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

This study asks a focused physiological question: whether brachial artery flow-mediated dilation changed after spironolactone in patients with single ventricle heart. It uses ultrasound and specifies baseline and post-intervention measurement, with the latter scheduled at 4 weeks. The registry record establishes the endpoint and the general design, but it does not report the observed endpoint results.

Because the primary mean change, variability, and inferential statistics are not reported in the registry record, there is no basis for describing the direction or size of the observed result or how precise it was. The same limitation applies to the listed secondary outcomes. The record therefore cannot show whether the measured vascular function changed, whether any change was statistically distinguishable from no change, or whether a change would be clinically important.

Even a reported before-and-after difference in a single-group study would not by itself demonstrate that spironolactone caused that difference. In general, a change could reflect the intervention, natural variation over time, measurement conditions, or other factors. A randomized comparator can help address some competing explanations, but none is described in this registry record.

The endpoint is a physiological measure of vascular response, not a direct measure of symptoms, quality of life, hospitalization, or survival. The registry lists a 6 Minute Walk Test among secondary outcomes, but does not report its result. The presence of a physiological endpoint should not be treated as evidence of a clinical outcome.

The safety entries report no serious or other adverse events and no deaths in the recorded group, but those figures are descriptive and do not establish the absence of risk. Taken together, the posted information is useful for understanding the study question and design, while leaving efficacy, precision, and broader clinical implications unresolved.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between a registered question and an interpretable result. The registry identifies a primary continuous endpoint, a measurement method, a planned timepoint, and a single-group design. Yet without the outcome values and analysis, readers cannot estimate the observed change or assess its uncertainty. A clear endpoint definition is necessary for interpretation, but it does not substitute for reporting the result.

The design also makes the role of a comparator especially important. A within-group before-and-after measurement can describe change, but it cannot isolate the intervention’s contribution from other changes over time. This distinction is central to causal interpretation and should remain visible even when the outcome is a laboratory or imaging measure.

The record’s endpoint population is limited to subjects who completed all study visits, while the enrolled population is recorded separately. Without the number analyzed and a missing-data account, readers cannot judge how representative the analyzed data may be. This is a general reporting issue for longitudinal studies: the handling of incomplete follow-up can influence both the estimate and its precision.

The study also lists several secondary outcomes. That makes a transparent analysis plan valuable, because readers need to know which questions were primary and how multiple results were evaluated. The registry does not report those methods or the results, leaving the statistical interpretation incomplete.

Finally, planning assumptions should not be confused with observed evidence. The registry describes planning illustrations, but those are not an observed-power calculation or a substitute for an estimate with uncertainty. The record’s value is therefore chiefly in documenting the intended physiological question and design, while highlighting how outcome reporting, analysis details, and clear treatment of missing data are needed for a complete statistical assessment.

15. 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 of the registry record for statistical interpretation is the absence of primary outcome results. It does not report baseline or post-intervention measurements, mean change, standard deviation, confidence interval, or p-value. Without those quantities, neither the magnitude nor precision of the endpoint can be assessed.

The record describes a single-group, non-randomized, unmasked design and does not describe a control group. This limits causal interpretation of any possible before-and-after change. The intervention details are also incomplete: the drug is named, but dose and schedule are not reported in the registry record.

The primary endpoint population is defined as subjects that completed all study visits, but the record does not report how many participants completed the visits or contributed data. It does not describe missingness, exclusions, the analysis population, or sensitivity analyses. Although enrollment is recorded as 12, that figure alone cannot establish the endpoint sample size.

The registry lists secondary outcomes but does not report their results, the analysis plan, or a strategy for multiplicity. It also does not report the trial’s own sample-size justification, interim analyses, or statistical model. Details about ultrasound measurement procedures beyond the brief endpoint description, measurement reliability, and assessor blinding are not reported in the registry record.

The record’s safety entries are limited to counts in the listed categories and do not describe event definitions, collection methods, or follow-up duration. These limitations mean that both the efficacy interpretation and the safety interpretation must remain descriptive and constrained to what the registry records.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Spironolactone in Patients With Single Ventricle Heart — NCT00211081.
• Registry record last updated 2017-11-06; status last verified 2017-10.
• Results first posted 2014-12-16.
• 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.

19. Record Summary

The registry describes a completed, non-randomized, single-group, open-label study of spironolactone in patients with single ventricle heart. Emory University is listed as the sponsor. The record gives enrollment as 12, with a start date of 2004-11 and primary completion in 2008-06.

The primary endpoint is change in brachial artery flow-mediated dilation, expressed as a percentage of artery diameter and measured by high-resolution ultrasound at baseline and post-intervention, with the post-intervention timepoint specified as 4 weeks. The primary population is subjects who completed all study visits. Secondary outcomes include inflammatory markers and change in 6 Minute Walk Test score.

The registry records 0 serious adverse events, 0 other adverse events, and 0 deaths in the spironolactone group. It does not report primary or secondary outcome results, statistical estimates, confidence intervals, p-values, or detailed analysis methods. The record therefore describes the study question and design but does not support conclusions about the measured effects.