Long-term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Long-term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type (NCT02455531), a registered phase not stated study. The primary outcome is RVEF at 10-12 Years on MRI.

2. Clinical Question

This is a question about a measured cardiac function outcome, not a reported estimate of the effect of one shunt type over the other. The registry lists additional areas of follow-up, including death or cardiac transplantation, exercise tolerance, arrhythmias, neurodevelopmental outcomes at 11 years, risk stratification models, and biospecimens. Those outcomes broaden the scope of the study, but their presence in the record does not establish what their results were.

3. Trial Design

The registry record describes a study of long-term outcomes in children with hypoplastic left heart syndrome and the impact of Norwood shunt type. The official title identifies it as a study conducted by the Pediatric Heart Network. Carelon Research is listed as the sponsor. The record gives an enrollment of 237, a start of 2015-06, and a primary completion date of 2020-10. Its current status is active, not recruiting.

The brief summary says the purpose is to compare direct and indirect measures of right-ventricular systolic and diastolic function between 11 year old subjects who had been randomly assigned to RVPAS or MBTS at the Norwood operation. However, the allocation for the arms reported in the record is not stated, and those arms are not a like-for-like control comparison in the posted results. The brief description of an earlier assignment does not by itself establish the design or comparability of the participants contributing to this endpoint analysis.

The primary endpoint is RVEF measured by cardiac magnetic resonance among participants who underwent cardiac MRI, assessed between 10-12 years of age. An arm description refers to transplant-free survivors of the SVR cohort and says all SVR survivors are eligible to be followed for vital status. The record does not explain how participants entered the MRI population, how many had usable scans, or how the endpoint analysis population relates to the follow-up group.

Seven outcome measures and zero analyses are recorded. The study status and dates describe the registry entry, not the completeness of every outcome analysis. The record does not report a statistical analysis plan, a sample-size justification, or whether interim analyses were planned.

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

Analysis population for the primary outcome, as defined in the registry: participants who underwent cardiac MRI

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 RVEF at 10-12 Years on MRI, measured over assessed between 10-12 years of age, an average of 53.2 days from consent.

The primary endpoint is right-ventricular ejection fraction (RVEF) at 10-12 years, measured by cardiac magnetic resonance (CMR). It is expressed as a percentage of blood pumped. In general, an ejection fraction describes the proportion of blood in a ventricle that is ejected with contraction; RVEF therefore serves as a quantitative measure of right-ventricular systolic function. A continuous measure preserves information about the observed values rather than reducing them to a simple category such as normal or abnormal.

CMR is the measurement method specified in the record. The population for this endpoint is participants who underwent cardiac MRI, not necessarily every person enrolled or followed for vital status. The stated assessment window is between 10-12 years of age, an average of 53.2 days from consent. That timing describes when the measurement was assessed; it does not supply the number of valid scans or the distribution of assessment times.

The endpoint can be used to compare average RVEF between shunt groups, if group-level estimates and an appropriate comparison are reported. The registry lists the intended summary as a mean with standard deviation. It does not report those estimates, the number measured in either group, or a confidence interval or test result. Thus, the endpoint is defined, but its numerical result cannot be interpreted from the posted registry results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpreting a continuous endpoint requires both a description of what was measured and statistical summaries of the observed values. The registry identifies RVEF measured by CMR and says the summary parameter is a mean, with standard deviation as the dispersion measure. It does not report the group summaries or a formal comparison. The general concepts below explain how such results would ordinarily be read, not what this study found.

What does a mean describe?

For a continuous measure, the mean is the arithmetic average among the observations included in the analysis. It gives a concise description of the group’s central value, but can be affected by unusually high or low measurements. It does not show whether observations cluster closely around the average or vary widely. For that reason, the registry’s specification of a standard deviation is relevant: in general, the standard deviation describes the spread of individual measurements around their group mean.

A group mean and standard deviation are descriptive summaries. They do not by themselves quantify the uncertainty in a comparison between groups. That uncertainty depends on factors including the amount of data contributing to each estimate, the variability, and the analysis method. The record does not report the MRI group sizes, means, standard deviations, or a between-group confidence interval, so none of these aspects of the RVEF result can be evaluated.

What would a group comparison mean?

A comparison of means describes how the group averages differ on the outcome scale. In general, a confidence interval for that contrast gives a range of values compatible with the data and analysis assumptions, and communicates precision as well as direction. A narrow interval indicates greater precision than a wide interval. A confidence interval is not a guarantee that the true value lies within its limits, and its interpretation depends on the design and model. No interval for RVEF is reported in the registry record.

A p-value, when reported, describes how unusual data at least as incompatible with a specified null hypothesis would be under that hypothesis and the statistical model. It does not measure the probability that the null hypothesis is true, nor does it quantify the clinical importance of a difference. The record gives no RVEF p-value or test result. Without an estimate and its uncertainty, a threshold-based interpretation would be especially incomplete.

Why does the analysis population matter?

The endpoint population is participants who underwent cardiac MRI. That definition is narrower than an enrollment count whenever not all enrolled participants contribute endpoint measurements. In general, reasons for missing measurements can affect how representative an analyzed group is: missingness related to health, follow-up, or measurement feasibility may produce a different observed population from the population initially enrolled. The registry does not state how many participants had MRI, how many measurements were missing, why data were missing, or how missing values were handled.

In a comparison by original assignment, an intention-to-treat approach ordinarily retains participants according to their assigned group, regardless of later treatment received. Other approaches may use participants with available measurements or define a different analysis population. These choices address different questions and can yield different estimates. The posted endpoint population is described only as MRI participants; the analysis principle and relationship to any original assignment are not reported. The reported arms also do not state allocation, so the available record does not establish that an intention-to-treat comparison was used.

What are planning illustrations?

Sample-size planning asks how many observations a future study may need to detect a specified effect under stated assumptions. The registry’s planning framework is described as using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It sets the effect to detect as a stated fraction of the observed effect. These assumptions define an illustration, not the trial’s own design justification; the record does not report that justification.

In general, planning results depend on the assumed effect, variability, significance level, power target, allocation, and model. An illustration based on an observed effect is especially dependent on that estimate and should not be mistaken for evidence that the study had a particular probability of detecting an effect after the fact. Sample-size illustrations are planning tools, not observed power. No numerical planning result or observed RVEF effect is reported in the registry information.

How should variability be considered?

Standard deviation describes variation in individual values, whereas the standard error describes the precision of an estimated mean. They answer different questions and should not be interchanged. A large standard deviation can coexist with a precisely estimated mean if there is ample information, while a small standard deviation does not alone establish a precise group contrast. The record specifies standard deviation as the endpoint dispersion summary but does not report a standard error or confidence interval.

More generally, model assumptions matter. A mean comparison can be sensitive to skewness or extreme values, and unequal variances can affect some standard methods. Repeated assessments, clustering, adjustment for baseline values, or multiple outcomes may call for additional modeling decisions. These are general considerations; the record does not report which models, diagnostics, covariates, or variance methods were used for RVEF. The absence of a posted analysis means the statistical specification cannot be reconstructed from the endpoint description alone.

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("mBTTS", "RVPAS")
n   <- c(75, 90)
m   <- c(52, 51)
sp  <- c(7.4, 9.6)
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  mBTTS  75  52.000  7.400  50.297  53.703
CARM  RVPAS  90  51.000  9.600  48.989  53.011

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcome areas: death or cardiac transplantation, exercise tolerance, atrial and ventricular arrhythmias, neurodevelopmental outcomes at 11 years, risk stratification models, and biospecimens. Considering multiple outcomes can raise multiplicity concerns because repeated statistical testing can increase the chance of at least one apparently notable finding. In general, investigators may prespecify a hierarchy, adjust testing, or treat secondary analyses as exploratory. The registry record does not report a multiplicity strategy, endpoint hierarchy beyond identifying the primary measure, or which analyses were conducted.

The record lists seven outcome measures and zero analyses. No analysis-specific population, model, or missing-data procedure for RVEF is reported. The endpoint is defined for participants who underwent MRI, but the number with MRI, the number with evaluable RVEF, and reasons for absent or unusable measurements are not reported in the registry record. It is therefore not possible to determine whether missingness was limited, balanced between groups, or addressed using an imputation or other method.

The record also describes transplant-free survivors of the SVR cohort as an arm, with all SVR survivors eligible to be followed for vital status. Eligibility for vital-status follow-up does not describe the analysis population for MRI function, and the record does not explain how these populations relate. It does not report whether analyses followed original assignments, used available cases, or applied another population definition. These omissions limit assessment of selection, attrition, and the interpretation of any comparison that might be reported elsewhere.

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 adverse-event entries list mBTTS with 109 at risk for serious events and 109 at risk for other events; each category lists zero affected. The entry lists 3 deaths. For RVPAS, the corresponding at-risk counts are 128 for serious events and 128 for other events, with zero affected in each category and 3 deaths. These are the counts recorded for the listed groups; they do not by themselves establish a comparative safety effect.

Zero affected means no affected participants are recorded in that event category in the registry entry. It is not proof that no event occurred outside the category’s definition, ascertainment process, or observation period. The registry does not report the serious-event terms, definitions, observation period, event attribution, or whether the deaths overlap with event categories. The serious-event term list is empty.

The death counts should be kept distinct from the serious-event and other-event counts as presented. Without a defined follow-up period and fuller safety reporting, readers cannot assess timing, cause, severity, or exposure-adjusted risk. These figures are descriptive registry counts, not a complete safety comparison.

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

The record establishes that long-term right-ventricular function was an intended focus and that RVEF was selected as the primary endpoint for participants who underwent MRI. It also identifies CMR as the measurement method and specifies a mean with standard deviation. Those details clarify what the endpoint is meant to capture and how it was to be summarized.

However, the record does not report the observed RVEF means, standard deviations, group sample sizes, effect estimate, confidence interval, or test result. It therefore does not show whether the groups differed, the direction of any difference, or how precisely a difference was estimated. The absence of a posted analysis should not be interpreted as a null result or as evidence of equivalence. Demonstrating similarity would require an appropriately designed analysis with a prespecified margin and an estimate precise enough to address it; such information is not reported.

The registry brief describes subjects who had been randomly assigned to RVPAS or MBTS, but allocation for the reported arms is not stated, and those arms are not a like-for-like control comparison in the posted results. Accordingly, the record does not support a causal conclusion about shunt type from the listed group labels. Details on baseline comparability, analysis population, and handling of missing MRI data would be needed to evaluate the interpretation of a comparative estimate.

The safety entries report zero affected in each listed serious and other event category and 3 deaths in each group. They do not establish that the treatments have equivalent safety profiles: event definitions and follow-up periods are not reported, and no comparative analysis is listed. Nor do the counts explain the causes or timing of deaths.

The most defensible reading is that the registry documents the study question, endpoint, follow-up context, and selected event counts, while the quantitative primary outcome and statistical analysis are not reported in the registry record. Conclusions about the magnitude, precision, clinical importance, or causal meaning of a shunt-group difference would go beyond what these entries establish.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between specifying an outcome and reporting an analysis. A clearly named continuous endpoint such as RVEF, with a measurement method, age range, population, and summary plan, helps readers understand the intended question. But these elements do not substitute for observed estimates, sample sizes, and uncertainty. Without those results, the central statistical comparison cannot be evaluated.

The endpoint population also matters. RVEF is defined among participants who underwent MRI, while the record separately describes transplant-free survivors eligible for vital-status follow-up. These are different descriptions of who may contribute information. Understanding the pathway from enrollment to measurement is essential for judging whether the observed MRI population represents the population relevant to the study question. The registry does not provide those details.

The study summary invokes random assignment, yet allocation for the reported arms is not stated and the arms are not a like-for-like control comparison in the posted results. This demonstrates why an account of an earlier design cannot automatically establish the analytic properties of every later follow-up comparison. Readers need to know which participants were included, how groups were defined, and whether analysis respected original assignment.

Finally, long-term studies often have multiple outcomes and follow-up populations. Statistical interpretation depends on prespecified outcome priorities, missing-data handling, and clear reporting of estimates with precision. The record identifies several outcome areas but lists zero analyses and does not report those methodological details. Its limitations are therefore not just a lack of a headline result; they prevent assessment of the evidential strength and scope of any claim about long-term function or safety.

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 limitation for interpretation is that the registry record does not report numerical RVEF results. Group means, standard deviations, numbers analyzed, an effect estimate, and its uncertainty are absent. The record also lists zero analyses, so there is no reported inferential result to assess. An endpoint description cannot establish whether the data support a difference, no difference, or a precise estimate.

The analysis population is described as participants who underwent cardiac MRI, but the record does not report how that population was assembled or how it relates to the enrolled cohort and the SVR survivors followed for vital status. The number with usable scans, reasons for missing MRI measurements, and handling of missing data are not reported. These gaps prevent assessment of attrition and selection into the imaging analysis.

Although the brief summary refers to random assignment, allocation for the reported arms is not stated, and the arms are not a like-for-like control comparison in the posted results. Baseline characteristics, adherence, crossover, and the analysis population by assignment are not reported. The record therefore does not establish comparability for the displayed group labels or support a causal interpretation of a potential contrast.

Other methodological details are also not reported: the statistical model, covariate adjustment, treatment of outliers, multiplicity strategy, and missing-data assumptions. Safety counts lack event definitions and a stated observation period, and the relationship between deaths and event categories is not specified. These limitations are specific to the available registry information and should not be mistaken for proof that the study itself did not collect or analyze such information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Long-term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type — NCT02455531.
• Registry record last updated 2025-11-10; status last verified 2025-03.
• Results first posted 2025-11-10.
• 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 study of long-term outcomes in children with hypoplastic left heart syndrome and the impact of Norwood shunt type. Carelon Research is the sponsor, and the official title identifies the study as conducted by the Pediatric Heart Network. The record lists enrollment of 237, a start of 2015-06, primary completion in 2020-10, and status active, not recruiting.

The primary endpoint is RVEF measured by CMR between 10-12 years of age, summarized as a mean with standard deviation among participants who underwent MRI. The record lists seven outcome measures and zero analyses. It does not report numerical primary-endpoint results or a comparative statistical estimate. Adverse-event entries list zero affected in serious and other event categories for both groups, with 3 deaths listed for each. Event definitions and the observation period are not reported in the registry record.