Radiation Following Percutaneous Balloon Aortic Valvuloplasty to Prevent Restenosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Radiation Following Percutaneous Balloon Aortic Valvuloplasty to Prevent Restenosis (NCT00538759), a randomized phase 2, phase 3 study. The primary outcome is Aortic Valve Area as a Continuous Variable, Measured by Echocardiography.

2. Clinical Question

The trial’s stated objective was to determine the impact of EBRT on aortic valve restenosis following successful BAV. The primary endpoint reported in the registry is aortic valve area (AVA), a continuous echocardiographic measure expressed in cm^2. The posted group means were 0.64 cm^2 for EBRT and 0.72 cm^2 for control. These are descriptive results from the trial record; they do not by themselves establish whether a difference between groups is compatible with chance or sufficiently precise to support a broader conclusion.

The registry also lists secondary outcomes concerning NYHA improvement, CHF rehospitalization, aortic valve reintervention, aortic valve area late loss index, and aortic valve mean gradient. Results or analyses for these secondary outcomes are not reported in the registry record. The record therefore offers a limited answer to the clinical question: it gives group-level primary endpoint summaries, but does not report an inferential comparison, confidence interval, or secondary-outcome analyses.

3. Trial Design

RADAR was a randomized, parallel-group trial registered as NCT00538759. The registry classifies it as Phase 2 and Phase 3. The sponsor was Minneapolis Heart Institute Foundation. The listed intervention groups were EBRT and sham control, with both interventions described as occurring after successful balloon aortic valvuloplasty. The masking classification was quadruple. The registry record does not report the specific roles or procedures covered by that masking label.

The record gives enrollment as 21. It lists the start date as 2007-09 and primary completion as 2010-07. The trial status is terminated. For the primary endpoint, the registry notes that the study was halted early due to a funding shortfall and did not reach its enrollment goal. The record does not report the original enrollment target or explain how the early halt affected the planned statistical analysis.

The primary outcome was aortic valve area measured by echocardiography at 6 months. It was analyzed as a continuous measure, with the registry reporting a mean and standard error for each group. The posted primary-endpoint summaries list 10 participants for EBRT and 7 for control. Those endpoint group counts should be understood as the counts attached to the reported summaries, not as a full account of enrollment, follow-up, or the analysis population. The registry record does not report a participant flow, reasons for missing endpoint measurements, or the number included in any adjusted analysis.

Although the design is described as randomized and quadruple-masked, details about sequence generation, allocation concealment, the masking procedures, and the statistical analysis plan are not reported in the registry record. The record lists five secondary outcomes and 7 outcome measures, but reports no analysis records. Thus, the design classification and group summaries are available, while important operational and analytical details are not.

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: Study was halted early due to funding shortfall. Did not reach enrollment goal

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 Aortic Valve Area as a Continuous Variable, Measured by Echocardiography, measured over 6 months.

The primary endpoint was aortic valve area measured by echocardiography at 6 months. AVA is a continuous measure of the opening area of the aortic valve, recorded in cm^2. A continuous endpoint retains the measured magnitude of the outcome rather than reducing it to categories such as improved or not improved. The registry reports the endpoint as a group mean with standard error.

In general, echocardiographic AVA can be used to describe valve opening and to assess its change over time or between groups. In this trial, the stated objective concerned restenosis after balloon aortic valvuloplasty, and the primary endpoint offered a quantitative measure relevant to valve status at the 6-month assessment. The registry record does not report a baseline AVA summary, a change-from-baseline analysis, or a definition of restenosis based on AVA. It is therefore not possible from the posted primary endpoint alone to assess the amount of within-person change or to apply a registry-defined restenosis threshold.

The reported group means were 0.64 cm^2 for EBRT and 0.72 cm^2 for control. Their accompanying standard errors were 0.06 and 0.07, respectively. A standard error describes the precision of an estimated mean, rather than the spread of individual participant measurements. Without the participant-level distribution, confidence intervals, or a reported between-group analysis, the endpoint summaries give only a limited account of uncertainty and do not establish the statistical significance or clinical importance of a group contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a continuous primary outcome as a mean and standard error for each randomized group. Understanding those summaries requires distinguishing the value of the mean, the variability among individual measurements, and the uncertainty in the estimated mean. The record provides the means and standard errors, but not the standard deviations or participant-level observations.

What does a group mean describe?

A mean is the arithmetic average of the observed measurements in a group. For a continuous endpoint such as AVA, it gives a compact description of the group’s measured values at the specified assessment. It does not show the full distribution: groups with the same mean can differ in spread, skewness, or the presence of unusually high or low observations. Those features cannot be assessed from the registry summaries alone.

The reported means are 0.64 cm^2 for EBRT and 0.72 cm^2 for control. Each is a group-level summary at 6 months, not a description of every participant’s measurement. The registry does not report baseline means or a change-from-baseline result. It is therefore important not to interpret the endpoint means as within-person changes or as evidence about the trajectory of AVA over time.

What does the standard error mean?

A standard error describes the sampling uncertainty of an estimated statistic. For a mean, it indicates how much the estimate would tend to vary across repeated samples under the assumptions of the statistical model. It is not the same as the standard deviation, which describes variability among individual observations. A smaller standard error generally indicates a more precisely estimated mean, but it does not by itself show whether two group means differ statistically.

The registry reports standard errors of 0.06 for EBRT and 0.07 for control. The record does not report confidence intervals for either mean or for the between-group contrast. In general, a confidence interval expresses a range of values compatible with the data and a stated method, and conveys uncertainty about an estimate. The exact interval cannot be reconstructed as a registry result without the relevant analysis details, and no new interval should be inferred from these summaries.

How should a between-group comparison be evaluated?

For a randomized trial, the central efficacy comparison is ordinarily the difference between assigned groups, analyzed according to a defined statistical plan. The estimate of that contrast should be considered alongside its uncertainty and the endpoint’s clinical interpretation. A general principle is that a p-value addresses compatibility with a specified null model, whereas a confidence interval communicates a range of plausible effect values under its method. Neither replaces consideration of the design, missing observations, and relevance of the outcome.

In this record, the sponsor’s inferential comparison is not reported. There is no posted p-value, confidence interval, or analysis method for the primary endpoint. Therefore, the means can be described, but the statistical strength and precision of the between-group contrast cannot be stated from the registry. The absence of a reported analysis is not proof that no analysis was conducted; it means the corresponding result is not reported in the registry record.

What can planning illustrations tell readers?

Planning illustrations based on an observed effect are hypothetical calculations for future-study design, not measures of what this trial achieved. The stated assumptions for such illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Any resulting sample-size figure should be understood as a planning quantity, not as observed power or as evidence that the trial had adequate power. The registry record does not report the trial’s own sample-size justification, enrollment target, or a prospective effect size used for planning.

For this endpoint, the record indicates that values were missing or not estimable for a two-arm comparison and that no recalculated comparison is available. That is consistent with the absence of a reported inferential result: there is no simple unadjusted re-calculation to set beside a sponsor analysis. The distinction matters because a re-calculation from summary statistics, when possible, is not the same as the trial’s prespecified analysis and may not account for the actual design or missing data.

Why do early stopping and incomplete reporting matter?

The study was halted early due to a funding shortfall and did not reach its enrollment goal. In general, fewer observations can make estimates less precise, while early stopping can affect the amount and pattern of available follow-up. The registry does not report whether any interim analyses were conducted, the stopping procedures, or the statistical consequences of stopping. No conclusion about those procedures can be drawn from the termination status alone.

Likewise, the registry does not report a detailed analysis population, the handling of missing endpoint measurements, or the method used to address any departures from the planned follow-up. These details matter because analyses may differ depending on whether they include all randomized participants, only participants with measured outcomes, or a defined subset. The primary endpoint group counts describe the reported summaries, but the record does not establish how those counts relate to randomization, follow-up completeness, or the intended analysis set.

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("EBRT", "Control")
n   <- c(10, 7)
m   <- c(0.64, 0.72)
sp  <- c(0.06, 0.07)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
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  EBRT  10  0.640  0.190  0.504  0.776
CARM  Control  7  0.720  0.185  0.549  0.891

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five secondary outcomes: NYHA improvement, CHF rehospitalization, aortic valve reintervention, aortic valve area late loss index, and aortic valve mean gradient. It also records 7 outcome measures. The registry record does not report results or analysis records for the secondary outcomes, and it does not describe a multiplicity strategy. It is therefore not reported in the registry record whether the trial planned to adjust inference for testing multiple outcomes or how it prioritized them relative to the primary endpoint.

Multiplicity is a general statistical concern when several outcomes or comparisons are tested: the chance of at least one apparently notable result can increase as the number of tests grows. A prespecified hierarchy or adjustment may be used to manage that issue, but the registry does not report such a plan. Since secondary results are not posted, their direction, precision, and relationship to the primary endpoint cannot be evaluated from this record.

The primary endpoint entry states that the study was halted early due to a funding shortfall and did not reach its enrollment goal. The registry reports primary endpoint summaries for 10 EBRT participants and 7 control participants, but does not provide participant flow, missingness by group, or reasons for unavailable measurements. Missing-data methods, imputation, and sensitivity analyses are not reported in the registry record.

The analysis population is also not described beyond the group summaries. The record does not say whether the primary analysis followed intention-to-treat principles, included only participants with observed measurements, or used another defined population. This makes it difficult to assess how the reported endpoint summaries relate to the randomized groups and whether missing outcome data could affect interpretation. No assumption about missingness or analysis-set membership should be made without those details.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: congestive heart failure exacerbation (38.5%), arrhythmia (25.0%), aortic valve replacement (23.1%), aortic valve restenosis (23.1%), respiratory/copd (15.4%).

The adverse-event record gives group-specific counts for serious events, other events, and deaths. For serious events, the record lists 13 at risk and 12 affected in the EBRT group, and 8 at risk and 7 affected in the control group. For other events, it lists 13 at risk and 13 affected in the EBRT group, and 8 at risk and 8 affected in the control group. The death counts are 8 for EBRT and 3 for control. These are separate safety entries from the primary endpoint summaries and should not be treated as the primary analysis population.

The registry also lists serious adverse-event terms with percentages: Congestive Heart Failure Exacerbation, 38.5%; Arrhythmia, 25.0%; Aortic Valve Replacement, 23.1%; Aortic Valve Restenosis, 23.1%; Respiratory/COPD, 15.4%; and Balloon Valvuloplasty, 12.5%. The record does not provide enough detail in these entries to establish the event-level counting rules, whether a participant could contribute to multiple terms, or the precise denominator for each percentage. These figures should therefore be read as the registry’s reported safety summaries, not as a basis for recalculating rates or making direct comparisons.

Safety counts are descriptive. The registry record does not report an inferential comparison of adverse events between groups, follow-up time for these events, or an account of event attribution. The counts alone do not establish whether an event was caused by an intervention.

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

The posted result describes echocardiographic AVA at 6 months in a randomized comparison of EBRT and sham control after successful balloon aortic valvuloplasty. The reported mean was 0.64 cm^2 for EBRT and 0.72 cm^2 for control, with standard errors of 0.06 and 0.07. Those data allow a descriptive statement about the group summaries, but the registry does not report a formal comparison, confidence interval, or p-value.

The result does not establish the size or precision of a treatment effect. A group mean is not an individual outcome, and a difference in descriptive means is not by itself a test of a hypothesis. Without an inferential estimate, it is not possible to determine from the record how compatible the observations are with a range of possible between-group effects. Clinical importance also cannot be judged from the endpoint summaries alone, particularly because the record does not state a threshold for meaningful change or provide a change-from-baseline analysis.

The early halt and the failure to reach the enrollment goal are important context. The registry attributes the halt to a funding shortfall, but does not report its statistical consequences or describe any interim analyses. The available endpoint summaries may not capture all randomized participants or planned follow-up; the registry does not report enough detail to determine this. Therefore, the results should be interpreted as limited descriptive evidence rather than as a definitive estimate.

The record also does not provide analyses of its listed secondary outcomes or details about missing data and the analysis population. Those omissions limit assessment of consistency across outcomes and robustness to incomplete observations. The adverse-event counts and listed serious-event terms add descriptive safety information, but no inferential comparison or event-attribution analysis is reported.

In general, randomized assignment can support a causal comparison when the study is conducted and analyzed according to appropriate procedures, but the registry record does not document enough analytical detail to evaluate those procedures fully. The posted results neither establish a treatment benefit nor establish its absence. They report group-level endpoint values in a trial that ended early, without the uncertainty estimates and analysis details needed for a firm conclusion.

14. Why This Trial Matters Statistically

This trial illustrates why a randomized label and a numerical endpoint summary are not sufficient on their own to convey the strength of evidence. The registry identifies a randomized, parallel-group comparison with quadruple masking and reports means for a continuous echocardiographic endpoint. Yet the primary comparison’s inferential result, confidence interval, and statistical method are not reported. Readers can see the direction of the descriptive means, but cannot evaluate the precision of the contrast from the posted record.

The distinction between a mean and a standard error is particularly important. Means summarize group values, while standard errors describe uncertainty in those estimated means. Neither the two means nor their individual standard errors directly substitute for a reported confidence interval for the between-group effect. A careful statistical interpretation keeps those quantities separate and avoids treating descriptive separation as proof of a group difference.

The record also highlights the importance of interpreting results in light of trial conduct. The study was halted early due to a funding shortfall and did not reach its enrollment goal. The registry does not report the planned enrollment target, analysis population, missing-data procedures, or any interim-analysis information. Without these details, statistical precision and potential vulnerabilities in the analysis cannot be fully assessed.

Finally, the listed secondary outcomes and safety summaries show why reporting plans matter. Multiple outcomes can raise multiplicity questions, while event counts require clear definitions and denominators for interpretation. The registry does not report a multiplicity approach or a comparative safety analysis. This case therefore demonstrates a broader principle of clinical-trial reading: distinguish what the observed summaries say from what requires an inferential analysis, and treat missing methods and reporting details as genuine limits rather than filling them in by assumption.

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 key trial-specific limitation is that the study was terminated after a funding shortfall and did not reach its enrollment goal. The registry gives enrollment as 21 but does not report the planned target or explain how stopping affected the timing or conduct of the primary analysis. The endpoint summaries are based on 10 participants in the EBRT group and 7 in the control group; the registry does not explain how these counts relate to the overall enrolled population or describe participant flow.

The primary endpoint is reported only as a mean with standard error at 6 months. Baseline AVA, change from baseline, participant-level distributions, and a between-group effect estimate are not reported in the registry record. A confidence interval, p-value, and primary analysis method are also not reported, so neither the inferential evidence nor the precision of a contrast can be assessed from this entry.

Additional design and analysis details are absent. The registry does not report eligibility criteria beyond the brief description of elderly patients with severe calcific aortic stenosis after successful BAV, allocation procedures, masking procedures, the intended analysis population, missing-data handling, or sensitivity analyses. It also does not report whether interim analyses were conducted or how early termination was reflected in the analysis plan.

Five secondary outcomes are listed, but their results and analysis records are not reported. The record does not describe an approach to multiplicity. Safety entries give counts and selected serious-event terms, but do not provide event-level definitions, follow-up time, attribution, or a reported inferential comparison. These limitations do not negate the descriptive information in the registry; they define the boundaries of what can be concluded from it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Radiation Following Percutaneous Balloon Aortic Valvuloplasty to Prevent Restenosis — NCT00538759.
• Registry record last updated 2019-10-01; status last verified 2019-09.
• Results first posted 2019-10-01.
• 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

NCT00538759, titled “Radiation Following Percutaneous Balloon Aortic Valvuloplasty to Prevent Restenosis,” is a randomized, parallel-group Phase 2 and Phase 3 trial sponsored by Minneapolis Heart Institute Foundation. It compared external beam radiation therapy to sham treatment after successful balloon aortic valvuloplasty in elderly patients with severe calcific aortic stenosis. Masking is classified as quadruple.

The primary endpoint was echocardiographic aortic valve area at 6 months, reported as a continuous measure. The mean was 0.64 cm^2 in the EBRT group and 0.72 cm^2 in the control group. The registry reports standard errors but no inferential comparison or confidence interval. The trial status is terminated; the record states that it was halted early due to a funding shortfall and did not reach its enrollment goal.

The registry lists five secondary outcomes, but their analyses are not reported. Safety entries include serious-event and other-event counts, deaths, and selected serious-event terms. Further details on missing data, analysis populations, multiplicity, and the primary statistical method are not reported in the registry record.