A Study to Evaluate the Use and Safety of CARDIOLITE® in Pediatric Patients With Kawasaki Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Use and Safety of CARDIOLITE® in Pediatric Patients With Kawasaki Disease (NCT00162032), a non-randomized phase 3 study. The primary outcome is Determine the Predictive Value of Cardiolite® Rest and Stress MPI to Define Pediatric Populations With Kawasaki Disease at High and Low Risk of Developing Cardiac Events..

2. Clinical Question

3. Trial Design

The registry describes a Phase III, open-label, non-randomized, international, multicenter trial with a single-group model. It lists 445 participants enrolled and a completed study status. The recorded study start was 2005-08, and primary completion was 2010-05. Sestamibi was the listed intervention. The study evaluated CARDIOLITE® rest and stress myocardial perfusion imaging in pediatric patients with Kawasaki Disease.

Participants were described in two age cohorts: children ages 4-11 and adolescents ages 12-16. These are descriptive cohorts, not randomized treatment groups. Because allocation was non-randomized and there was no masking, this design does not provide a randomized comparison of imaging against an alternative diagnostic strategy or against no imaging. The primary comparison instead divided participants according to their scan classification: SSS >=4 was labeled high risk, while SSS <4 was labeled low risk.

The stated purpose was to assess the predictive value of rest and stress MPI for defining groups at higher and lower risk of subsequent cardiac events. The secondary objectives concerned detection of myocardial ischemia versus coronary angiography, including assessment focused on the left anterior descending artery, incidence of hard cardiac events, and prediction of cardiac events. These are listed as objectives; outcome values are not reported in the registry record.

The registry does not report additional protocol details such as how participants were recruited, how imaging interpretations were standardized, or how clinical events were adjudicated. Those details should not be inferred from the trial title or design labels.

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: Had SPECT Myocardial perfusion imaging tests and experienced a cardiac event

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 Determine the Predictive Value of Cardiolite® Rest and Stress MPI to Define Pediatric Populations With Kawasaki Disease at High and Low Risk of Developing Cardiac Events., measured over 3 years.

The primary endpoint concerns the proportion of participants experiencing cardiac events among those with abnormal and normal CARDIOLITE® MPI scans during the stated 3 years follow-up period. The registry defines an abnormal, high-risk scan as SSS >=4 and a normal, low-risk scan as SSS <4. It describes the event rate as a cumulative rate based on a Kaplan-Meier estimate conditional on the SPECT MPI score result. The specified comparison is cardiac event-free survival between the high-risk and low-risk groups.

This endpoint addresses prognosis: whether scan classification separates participants into groups with differing subsequent event experience. In general, a prognostic endpoint can help assess whether a test result is associated with future outcomes. It does not, by itself, estimate the effect of assigning a treatment, because scan classification is not randomized treatment assignment.

The registry lists a 95% confidence interval as the dispersion measure, but numerical event rates and confidence limits are not reported in the registry record. The primary endpoint description also does not provide detailed definitions of each cardiac event, event adjudication procedures, or the number of participants with evaluable follow-up.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary analysis is described as a comparison of cardiac event-free survival between groups defined by the MPI score. The registry identifies a Kaplan-Meier estimate of cumulative event rate conditional on the SPECT MPI score result, together with a log-rank statistic. Numerical estimates and test results are not reported in the registry record, so the methods can be described but their findings cannot be interpreted from the record.

What does Kaplan-Meier estimation do?

In general, Kaplan-Meier estimation describes the probability of remaining free of an event over follow-up while allowing participants to contribute information for different lengths of time. A participant who has not had an event by the end of observed follow-up may be censored: their event time is not known beyond that point, but their observed time contributes information up to censoring. Interpretation depends on how censoring occurs. If the chance of being censored is related to event risk in a way not addressed by the analysis, the estimate may be biased. The registry does not report censoring details or checks of this assumption.

The endpoint description says the cumulative event rate is conditional on scan score result. In practical terms, the estimate is calculated separately for the groups defined by the score threshold, rather than for all participants as if they formed one undivided group. The registry does not provide the estimated event rates, numbers at risk over time, or confidence intervals needed to assess the amount of uncertainty in those group-specific estimates.

What does the log-rank comparison test?

In general, the log-rank test compares event-free survival experience across groups over follow-up. It evaluates whether the observed pattern of events over time is compatible with a common survival experience under the test's null hypothesis. The registry specifies a two-sided test and alpha = 0.05. A two-sided test allows for a difference in either direction; the stated alpha is the threshold specified for the test, not evidence that a difference was found. No test statistic or p-value is reported in the registry record.

The log-rank test is an overall comparison and does not, on its own, quantify the size of a difference in a way that replaces group-specific event estimates and their confidence intervals. It also does not adjust for other participant characteristics unless a separate adjusted model is used. No adjusted model is reported in the registry record. In general, when survival patterns differ over time in ways that do not fit the test's assumptions, a single overall comparison may be harder to summarize. The registry does not report assessments of this issue.

How should the score threshold be understood?

The registry defines SSS >=4 as abnormal and high risk, and SSS <4 as normal and low risk. This creates two scan-defined categories for the stated comparison. In general, converting a score into categories simplifies group interpretation but discards distinctions among values within each category. The record does not report how the threshold was selected, whether it was fixed before the study, or whether alternative thresholds were examined. Those details are not reported in the registry record and should not be presumed.

The study's objective is predictive: whether scan findings help distinguish groups with differing future event experience. A predictive association is not the same as diagnostic accuracy for detecting current ischemia, which appears among the secondary objectives, nor is it a treatment-effect comparison. The registry lists comparisons with coronary angiography for ischemia-detection objectives, but it does not provide their analysis results.

What can planning calculations establish?

The registry describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. For time-to-event illustrations, the quantity is total events using the Schoenfeld method; for other outcomes, it is participants per arm. These assumptions describe a planning illustration, not the trial's non-randomized, single-group design. The trial's own sample-size justification is not reported in the registry record. Such planning calculations are not observed power and should not be interpreted as proof that the study could or could not detect an effect.

In general, over-dispersion means that observed variability is greater than a model assumes. When present, standard errors based on an under-dispersed model may be too small, leading to confidence intervals that are too narrow and tests that are too optimistic. The registry does not identify over-dispersion as an issue or report a model for it; this general concept does not establish that over-dispersion affected this study.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Children (4 -11 Years) Normal", "Adolescents (12-16 Years) Normal", "Children (4-11 Years) Abnormal", "Adolescents (12-16 Years) Abnormal")
n      <- c(287, 93, 26, 19)
events <- c(0, 0, 0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Children (4 -11 Years) Normal  287  0  0.0  0.0  1.3  0.0  1.3  0.0  1.3
ARM  Adolescents (12-16 Years) Normal  93  0  0.0  0.0  3.9  0.0  4.0  0.0  3.8
ARM  Children (4-11 Years) Abnormal  26  0  0.0  0.0  13.2  0.0  12.9  0.1  12.8
ARM  Adolescents (12-16 Years) Abnormal  19  0  0.0  0.0  17.6  0.0  16.8  0.1  16.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures: the primary predictive-value objective and secondary objectives concerning ischemia detection, hard cardiac events, left anterior descending artery ischemia detection, and prediction of cardiac events. It does not report a multiplicity strategy, such as an adjustment across tests or a hierarchy defining which comparisons would be confirmatory. The intended interpretation of multiple outcome tests is therefore not reported in the registry record. In general, examining multiple outcomes can increase the chance of at least one apparently notable result by chance if each is interpreted separately.

No analyses are listed in the registry record. Numerical results for the primary or secondary outcomes are not reported, so there is no basis to determine which measures were analyzed, whether all planned outcomes were reported, or whether additional analyses were performed. The registry does specify the primary log-rank comparison as two-sided with alpha = 0.05, but does not describe how that threshold relates to the secondary objectives.

Missing-data procedures are not reported in the registry record. This includes the handling of missing scan results, incomplete follow-up, withdrawals, and missing event information. The analysis population and the number contributing to each outcome are also not reported. In general, these details matter because missing measurements or follow-up can affect both denominators and time-to-event estimates. The registry's description of participants who had SPECT imaging and experienced a cardiac event is not a complete account of the analysis population or missing-data handling.

There is no reported description of interim analyses, stopping rules, or sensitivity analyses. Their presence or absence should not be inferred from the completed status alone.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: overdose (0.3%).

The registry lists serious adverse events separately for children ages 4-11 and adolescents ages 12-16. In the children cohort, 1 participant among 329 at risk was listed with a serious adverse event. In the adolescents cohort, 0 participants among 116 at risk were listed with a serious adverse event. These counts describe the registry's reported safety data; they do not establish that an event was caused by Sestamibi or by imaging.

For other adverse events, the registry lists 8 participants among 329 at risk in the children cohort and 5 among 116 at risk in the adolescents cohort. The leading serious adverse-event term is listed as Overdose, 0.3%. The registry does not provide further detail about event timing, severity beyond the serious classification, recurrence, or attribution. Death counts are not reported in the registry record.

These safety figures should be read as counts within the listed age cohorts, not as a comparison of risk between treatments. The trial was non-randomized and did not include a like-for-like control group. The registry does not describe whether participants could contribute more than one event to the event-term summaries, or the method used to assess relatedness. Accordingly, the listed counts alone do not establish comparative safety or causation.

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

The study was designed to examine whether rest and stress CARDIOLITE® MPI could identify pediatric patients with Kawasaki Disease whose later cardiac-event experience differed by scan classification. Its primary question is prognostic: whether the SSS-defined high-risk and low-risk groups have different cardiac event-free survival. The registry specifies the score categories and statistical comparison, but it does not report numerical primary results. No conclusion about the observed separation, its magnitude, or its precision can be drawn from the registry record.

Even if a difference between scan-defined groups were reported, that finding would concern association and prediction in the studied population. Because participants were not randomized to scan categories, the comparison would not establish that imaging itself changes cardiac-event risk. Nor would it show that acting on the scan result improves outcomes. Those are different questions from whether scan results are associated with subsequent events.

The stated secondary objectives address related but distinct issues. Detection of myocardial ischemia versus coronary angiography concerns diagnostic performance, while incidence and prediction of cardiac events concern clinical outcomes over time. Evidence about one objective would not automatically answer the others. The registry lists these objectives but does not report their numerical results.

More generally, an estimate should be considered alongside its uncertainty, endpoint definition, follow-up, and analysis population. The registry identifies a 95% confidence interval for the primary measure but does not report its limits or the event counts on which it would be based. It also does not report missing-data methods or analysis denominators. These omissions prevent assessment of precision and completeness from the registry record.

The completed status and enrollment of 445 describe study conduct, not the direction or reliability of the results. The posted information supports describing the trial's question, design, and listed safety counts, but not a claim that the imaging did or did not predict events.

14. Why This Trial Matters Statistically

This trial is statistically notable for framing a diagnostic imaging question as a time-to-event prediction problem. Rather than treating scan categories as randomized interventions, the primary comparison asks whether groups classified by SSS have different cardiac event-free survival. That distinction matters: prognostic separation can be informative about risk classification, but it does not by itself demonstrate a causal effect of testing or of a treatment decision based on testing.

The stated use of Kaplan-Meier estimation and a log-rank comparison reflects the time-to-event structure of the primary objective. These methods can account for participants having different lengths of follow-up, provided the relevant assumptions are reasonable. The registry record, however, does not provide the estimates, confidence intervals, test result, or analysis details needed to evaluate how well the methods were applied or how much uncertainty remained.

The study also illustrates why design labels and outcome evidence should be read separately. It is Phase III and completed, with 445 enrolled, yet the registry record does not report numerical primary or secondary analyses. A completed study objective is not itself evidence that the objective was met. Likewise, the listed safety counts are descriptive and do not create a controlled safety comparison.

Finally, the study's objectives span prediction of events and detection of ischemia, which require distinct interpretations. Keeping those questions separate helps prevent a diagnostic-performance objective from being mistaken for evidence about future-event prediction, or either from being mistaken for a randomized treatment effect.

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 central limitation for interpretation is that numerical primary-outcome results are not reported in the registry record. The event rates, confidence intervals, log-rank statistic, and p-value are unavailable, as are numerical results for the secondary outcomes. Thus, the record does not permit assessment of effect size or precision, regardless of the completed study status.

The non-randomized, single-group design does not offer a randomized control comparison. The main groups are defined by scan score, so differences in their outcomes could reflect characteristics associated with those classifications as well as any predictive information in the scan. No adjusted analysis is reported. The record also does not report how the SSS threshold was selected or whether it was prespecified.

Important follow-up and analysis details are not reported in the registry record, including the number of participants contributing to the primary analysis, censoring patterns, loss to follow-up, event definitions, and event-adjudication procedures. Missing-data handling and analysis populations are not reported either. Without these details, the completeness and robustness of the time-to-event comparison cannot be evaluated.

The record lists multiple outcome measures but does not report a multiplicity strategy or any analyses. It does not report interim analyses or sensitivity analyses. The trial's own sample-size justification is not reported; planning illustrations based on observed effects are not the same as a justification for this design and are not observed power.

The safety summaries are also limited: the registry lists cohort counts and a serious-event term but does not report attribution, event-level detail, or death counts. These limitations restrict interpretation to the information explicitly recorded, rather than supporting conclusions about comparative safety or causation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Use and Safety of CARDIOLITE® in Pediatric Patients With Kawasaki Disease — NCT00162032.
• Registry record last updated 2019-07-23; status last verified 2019-07.
• Results first posted 2013-12-06.
• 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 NCT00162032, a completed Phase III, open-label, non-randomized, international, multicenter study of CARDIOLITE® myocardial perfusion imaging in pediatric patients with Kawasaki Disease. It lists 445 enrolled participants, Sestamibi as the intervention, and cohorts of children ages 4-11 and adolescents ages 12-16. The study began in 2005-08 and reached primary completion in 2010-05.

The primary objective was to assess whether cardiac-event experience differed between participants with SSS >=4 and those with SSS <4 over 3 years, using Kaplan-Meier estimation and a two-sided log-rank comparison at alpha = 0.05. Numerical primary and secondary outcome results, confidence limits, and analysis details are not reported in the registry record. The listed adverse-event counts are descriptive and do not provide a randomized safety comparison.