Spironolactone in Adult Congenital Heart Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Spironolactone in Adult Congenital Heart Disease (NCT01069510), a randomized phase 2 study. The primary outcome is Extracellular Volume Fraction.

2. Clinical Question

The study’s stated purpose was to examine whether spironolactone reduces fibrous stiffening in heart muscle tissue and improves heart function. The primary outcome addresses myocardial extracellular volume rather than heart function directly. It is therefore a structural imaging measure related to the fibrosis question, not a complete account of the study’s broader aims. The record also names six-minute walk distance and procollagen 3 NT peptide as secondary outcomes.

3. Trial Design

This was a Phase 2, randomized, double-masked, parallel-group study sponsored by Oregon Health and Science University. The registry lists an enrollment of 40 and a completed status. The recorded start was 2010-02, and the primary completion date was 2016-06. The study title places the treatment sub-study within research on heart failure and myocardial fibrosis in congenital heart disease.

Participants were assigned to spironolactone or placebo. The spironolactone arm received 25 mg daily, while the placebo arm received placebo. Randomization means assignment was intended to use a chance-based process; the specific sequence-generation method and allocation concealment procedures are not reported in the registry record. Double masking indicates that masking was part of the design, but the record does not specify which roles were masked or how masking was maintained. Parallel-group design means the treatment groups were followed as separate arms rather than participants crossing between assigned treatments.

The main outcome was extracellular volume fraction, expressed as a percentage of myocardium and measured by T1 mapping with MRI at 12 month. The posted primary-outcome summaries include 8 participants in the placebo arm and 7 in the spironolactone arm. These outcome counts are not the same information as the overall enrollment figure; the registry record does not explain the relationship between enrollment and the participants contributing to this outcome.

The trial record names six-minute walk distance and procollagen 3 NT peptide as secondary outcomes, and reports three outcome measures overall. It does not provide posted analyses for those outcomes. The protocol’s detailed eligibility criteria, treatment adherence, concomitant care, and follow-up procedures 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

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 Extracellular Volume Fraction, measured over 12 month.

The primary endpoint was extracellular volume fraction, expressed as a percentage of myocardium. It was measured using T1 mapping with MRI, with a stated timeframe of 12 month. The posted summaries report a mean and standard deviation for each treatment arm.

As general statistical context, extracellular volume fraction describes the proportion of myocardial tissue represented by extracellular space. The trial’s stated rationale concerns myocardial fibrosis, described in the study summary as fibrous stiffening of heart muscle. An MRI-derived extracellular volume measure can therefore serve as an imaging outcome relevant to that rationale. It is not itself a direct measurement of symptoms, exercise capacity, or heart function.

The choice of a continuous endpoint allows the outcome to be described across a range of values rather than only as an event that did or did not occur. The arm-level mean gives the average reported value among participants contributing data, while the standard deviation describes the spread of individual values around that mean. These summaries do not by themselves establish whether the arms differ beyond what could be expected from sampling variation. The registry record does not post a confidence interval, p-value, or estimable two-arm result for this endpoint.

The registry also identifies six-minute walk distance and procollagen 3 NT peptide as secondary outcomes. Those measures relate to other aspects of the study’s stated interests, but the record does not provide their results or explain their analysis in detail.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, double-masked, parallel-group trial. Randomization is a design method intended to make treatment assignment independent of participants’ measured and unmeasured characteristics, on average. It supports a fair comparison when implemented as intended, but does not guarantee that small groups will be balanced. The registry does not report how the random sequence was generated, how assignments were concealed, or whether the final groups were comparable at baseline.

What do the arm summaries describe?

The primary outcome is continuous: extracellular volume fraction, measured as a percentage of myocardium. For a continuous outcome, a mean gives the average value among the observations included in a group summary. The standard deviation describes how dispersed individual observations are around that average. It is not a measure of the precision of the mean and is not an estimate of the uncertainty in a treatment comparison. The posted values are 30.1 with standard deviation 3.8 for placebo, based on 8 participants, and 25.3 with standard deviation 1.5 for spironolactone, based on 7 participants.

A comparison between randomized groups generally targets the difference in outcome under the assigned strategies, subject to the analysis plan and data available. To interpret such a comparison, readers need an effect estimate and an account of its uncertainty, commonly expressed with a confidence interval, and often a test statistic or p-value. A confidence interval is a range of values compatible with the data and the assumptions of the analysis; its width communicates precision. These are general statistical concepts. The registry record does not report a confidence interval, p-value, or estimable two-arm comparison for the primary endpoint.

Why does the missing comparison matter?

The record states that values were missing or not estimable for a two-arm comparison of the continuous endpoint. As a result, the arm-specific means and standard deviations cannot substitute for the unreported comparison. Readers should not infer a formal test, a confidence interval, or a treatment-effect estimate from the separate summaries. No sponsor analysis is posted for this endpoint in the registry record, and the record gives no analysis details that would explain the unavailable comparison.

Standard deviations also help describe how much the participant-level measurements vary within each group. General statistical context: when outcome variability is substantial relative to the size of a group, the mean may be estimated less precisely. With limited numbers of observations, individual values can have considerable influence on a mean. The registry’s summaries do not include participant-level values, so the shape of the distributions, possible outliers, and the sensitivity of the means to individual observations cannot be assessed.

What does the planning illustration represent?

The stated sample-size assumptions describe a planning illustration based on the observed effect, not the trial’s own design. The assumptions specify a two-sided significance level of 0.05, equal allocation between arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. Such a calculation is a prospective illustration of the number of participants per arm that would be needed under those assumptions. It is not an observed trial result and is not evidence that the completed study had a particular probability of detecting an effect.

The record does not include numerical planning estimates for participants per arm. It also does not report the trial’s own sample-size justification or the assumptions used in its original design. The planning illustration should not be mistaken for an account of the enrollment target, nor should it be interpreted as observed power. General statistical context: sample-size planning depends on the target effect, outcome variability, allocation, significance threshold, and chosen power. Changing those assumptions changes the planning result.

The registry identifies the outcome parameter as a mean and its dispersion as a standard deviation. It does not report an adjusted model, covariate set, or analysis method for the primary endpoint. No particular test or model should therefore be attributed to the study based on the posted record. The record reports three outcome measures and two named secondary outcomes, but no analyses are posted. Any claims about multiplicity adjustment, subgroup analyses, interim monitoring, or sensitivity analyses would go beyond the recorded information.

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("Placebo", "Spironolactone")
n   <- c(8, 7)
m   <- c(30.1, 25.3)
sp  <- c(3.8, 1.5)
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  Placebo  8  30.100  3.800  26.923  33.277
CARM  Spironolactone  7  25.300  1.500  23.913  26.687

11. Multiplicity, Missing Data and Analysis Populations

The registry record names two secondary outcomes: six-minute walk distance and procollagen 3 NT peptide. It reports three outcome measures overall, but does not post analyses for the secondary outcomes. The record does not describe a multiplicity strategy, such as adjustment of significance thresholds or a hierarchy for interpreting several outcomes. It is therefore not possible to determine how the study planned to control the chance of false-positive findings across outcomes, if that was addressed in the protocol.

No analyses are recorded for the primary comparison, and the record states that values were missing or not estimable for a two-arm comparison of the continuous endpoint. It does not explain whether the obstacle was missing observations, data quality, an analytic issue, or another reason. Details of missing measurements, withdrawals, exclusions, imputation, and sensitivity analyses are not reported in the registry record.

The posted outcome counts are 8 for placebo and 7 for spironolactone. The record does not specify whether these participants represent all randomized participants with available measurements, a per-protocol group, or another analysis population. It also does not state whether participants were analyzed according to their randomized assignment. Thus, the analysis population and the handling of missing outcome data cannot be established from the posted record.

General statistical context: missing outcome data can affect both precision and interpretation. The direction and size of any resulting bias depend on why values are missing and how missingness relates to participants’ outcomes and treatment assignment. Without those details, neither the impact of missing data nor the robustness of the arm summaries can be assessed.

12. Safety Results

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

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 serious adverse event information separately for the two arms. For placebo, 8 participants were recorded as at risk and 0 as affected by a serious adverse event. For spironolactone, 7 participants were recorded as at risk and 0 as affected. These are the serious-event counts recorded in the registry for the groups and populations listed.

Zero affected participants in these summaries means no serious adverse events were recorded among the listed participants in the posted results. It should not be read as proof that no event occurred outside the recorded reporting period or population. The registry record does not report further details about the event collection window, definitions, adjudication, or completeness of reporting. Deaths are not reported in the record.

General statistical context: when event counts are low or absent in small groups, the data may provide limited information about the frequency of uncommon harms. An observed count of zero does not establish that the underlying risk is zero. These figures should be interpreted as descriptive safety reporting, not as a precise estimate of comparative risk. The registry also lists zero participants affected by other adverse events in both arms, but the record does not provide additional event descriptions.

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

The posted primary-outcome information describes extracellular volume fraction at 12 month among the participants with arm-level summaries. The placebo mean was 30.1 with standard deviation 3.8 among 8 participants, and the spironolactone mean was 25.3 with standard deviation 1.5 among 7 participants. These data describe the observed groups, not a fully reported statistical comparison.

The record does not provide an estimable two-arm comparison, confidence interval, or p-value for this outcome. Consequently, the precision of any treatment contrast is not quantified, and the record does not establish whether the observed arm means are distinguishable beyond sampling variability. The summaries alone do not support a conclusion that spironolactone changed extracellular volume fraction.

The outcome is an MRI-derived measure relevant to the study’s interest in myocardial fibrosis. It does not directly measure heart function, symptoms, exercise capacity, or every aspect of heart failure. The study summary describes broader aims, while the primary endpoint addresses one specific imaging measure. The secondary outcomes named in the record are not accompanied by posted results.

The enrollment figure is 40, while the posted primary outcome summaries are based on 8 participants in placebo and 7 in spironolactone. The registry does not explain the difference, identify the analysis population, or describe missing data. Those gaps limit conclusions about representativeness and completeness. The safety record reports zero participants affected by serious adverse events among the listed groups, but the record does not provide enough detail to infer that risk is absent.

Overall, the registry supports a descriptive reading of the reported endpoint values and adverse-event counts. It does not support a definitive estimate of treatment effect, an assessment of statistical significance, or a broad conclusion about the study’s stated goals.

14. Why This Trial Matters Statistically

This trial illustrates why arm-level summaries and an arm-to-arm analysis answer different statistical questions. Means and standard deviations describe the outcome values within each group. A treatment comparison needs an estimate of the contrast and information about its uncertainty. In this record, the arm summaries are available, but the two-arm comparison is reported as missing or not estimable. The distinction prevents a descriptive difference between group means from being mistaken for a formal finding.

The outcome counts also matter. The registry lists an overall enrollment of 40, but the primary endpoint summaries include 8 participants in placebo and 7 in spironolactone. Without an explanation of the analysis population or missing measurements, readers cannot judge why only those participant counts appear in the endpoint summaries, or how the unavailable observations might affect interpretation.

The trial’s primary outcome is an imaging measure related to the study’s fibrosis rationale. A statistical interpretation should stay aligned with what that outcome measures, rather than treating it as a direct measure of every clinical aim named in the study summary. The secondary outcomes are identified but do not have posted analyses, so they cannot fill the gaps in the primary comparison.

Finally, safety counts and efficacy summaries have different interpretive limits. Zero serious adverse events were recorded among the listed participants, but small event counts do not demonstrate that the underlying risk is zero. Taken together, the record highlights the value of complete analysis reporting: outcome estimates, uncertainty, analysis populations, missing-data handling, and safety definitions are all needed for a more informative 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 primary endpoint has arm-level means, standard deviations, and participant counts, but the registry record does not provide an estimable two-arm comparison. There is no posted confidence interval or p-value to quantify uncertainty in the contrast. The registry does not explain why the comparison is unavailable, so the reason cannot be determined from the record.

The difference between the overall enrollment of 40 and the endpoint counts of 8 in placebo and 7 in spironolactone is not explained. There is no account of participant flow, withdrawals, exclusions, missing MRI measurements, or the population used for analysis. Without these details, it is not possible to assess the completeness or representativeness of the outcome data.

Baseline characteristics, treatment adherence, and details about follow-up and concomitant care are not reported in the registry record. The record also does not describe the randomization sequence, allocation concealment, masking procedures, or primary analysis method. These gaps prevent a detailed assessment of how the design was implemented and how the endpoint summaries were generated.

The secondary outcomes, six-minute walk distance and procollagen 3 NT peptide, are named but have no posted analyses. The record does not report a multiplicity plan, an analysis population, or methods for addressing missing data. It also does not provide participant-level observations, which would be needed to examine distributional features or the influence of individual values.

Safety reporting is limited to counts of participants at risk and affected. The record does not provide event definitions, collection details, or reported death counts. These omissions restrict interpretation of both the outcome comparison and the safety information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Spironolactone in Adult Congenital Heart Disease — NCT01069510.
• Registry record last updated 2019-08-21; status last verified 2019-07.
• Results first posted 2019-08-21.
• 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 record describes a completed Phase 2, randomized, double-masked, parallel-group trial sponsored by Oregon Health and Science University, with enrollment of 40. The recorded start was 2010-02, and primary completion was 2016-06. The treatment arms were spironolactone 25 mg daily and placebo.

The primary outcome was extracellular volume fraction, expressed as a percentage of myocardium and measured by T1 mapping with MRI at 12 month. The placebo summary was a mean of 30.1 with standard deviation 3.8 among 8 participants; the spironolactone summary was a mean of 25.3 with standard deviation 1.5 among 7 participants. The registry reports that a two-arm comparison was missing or not estimable.

Six-minute walk distance and procollagen 3 NT peptide are listed as secondary outcomes, without posted analyses. Serious adverse event summaries record 0 affected participants among 8 at risk in placebo and 0 among 7 at risk in spironolactone. The record does not report a comparative efficacy estimate, missing-data handling, or detailed analysis methods.