Efficacy and Tolerability of Idebenone in Boys With Cardiac Dysfunction Associated With Duchenne Muscular Dystrophy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Tolerability of Idebenone in Boys With Cardiac Dysfunction Associated With Duchenne Muscular Dystrophy (NCT00654784), a randomized phase 2 study. The primary outcome is The Relative Change in Peak Systolic Radial Strain of the Left Ventricle (LV) Inferolateral Wall From Baseline (at Screening) to Week 52, Assessed by Color Doppler Myocardial Imaging (CDMI)..

2. Clinical Question

The trial addressed a cardiac measure in Duchenne muscular dystrophy, a condition for which the registry describes cardiac involvement as including myocardial degeneration, atrophy and fibrosis, with possible progression to dilated cardiomyopathy. The study rationale was that idebenone’s proposed effects on cellular energy production and mitochondrial oxidative damage might slow decline in heart function. That rationale is a hypothesis, not a result of the comparison.

The registry also describes possible interest in muscle strength and respiratory function. Secondary outcomes covered forced vital capacity, forced expiratory volume in 1 second, maximal inspiratory pressure and peak flow; upper-limb strength measures; a timed walking test for ambulant patients; and safety and tolerability. These outcomes are distinct from the primary cardiac endpoint. The registry record does not report posted analysis results for those secondary measures.

The primary comparison is described using group means for relative change, with standard deviations. Those summaries can indicate the observed values and their spread, but they do not alone establish the precision of the between-group comparison. The registry record does not report a confidence interval or a formal inferential result for that comparison.

3. Trial Design

This was a Phase IIa, randomized, placebo-controlled, parallel-group study at a single centre, identified in the official title as the University of Leuven. It was described as double blind in the official title and as quadruple masked in the registry design fields. The registry record does not specify which roles were covered by the quadruple masking designation.

The study compared idebenone, listed at 450 mg/ Day, with placebo in males aged 8 to 16 with Duchenne muscular dystrophy and cardiac dysfunction. The registry reports enrollment of 21. The study status is completed. Its recorded start was 2005-10, and primary completion was 2007-08. Santhera Pharmaceuticals is listed as sponsor.

The primary endpoint was a continuous measure: relative change in peak systolic radial strain in the left-ventricular inferolateral wall from screening baseline to Week 52. The registry describes the reported measure as a mean and its dispersion as standard deviation. At Week 52, primary-endpoint data were available for 18 patients; the record attributes unavailable data to missing data from 2 patients and inability to acquire data from a third patient. The primary efficacy comparison used the LOCF method in the ITT population.

The registry lists idebenone and placebo as drug interventions. It does not report the detailed allocation procedure, the planned sample-size rationale, or a fuller statistical analysis plan. Those design details should not be inferred from the fact that the study was randomized, masked and parallel-group.

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: At Week 52, data from only 18 patients were available for the primary endpoint analysis due to missing data from 2 patients and the inability to acquire data from a 3rd patient. The efficacy comparison for the primary endpoint was conducted using the LOCF method in the ITT population. In addition, the analysis was repeated using the OC dataset.

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 The Relative Change in Peak Systolic Radial Strain of the Left Ventricle (LV) Inferolateral Wall From Baseline (at Screening) to Week 52, Assessed by Color Doppler Myocardial Imaging (CDMI)., measured over baseline and Week 52.

The primary endpoint was relative change in peak systolic radial strain of the left-ventricular inferolateral wall from baseline at screening to Week 52. Color Doppler Myocardial Imaging was used to quantify regional myocardial function. The registry states that measuring this strain characterizes cardiac involvement in participants with Duchenne muscular dystrophy.

The inferolateral wall is relevant to the registry’s description of disease-related cardiac involvement: the process is described as beginning in the posterolateral wall of the left ventricle, with septal involvement appearing at later stages. This makes the regional measure a way to assess a specific aspect of cardiac function rather than a direct measure of every dimension of heart health.

The endpoint is reported as a continuous measure of relative change, summarized by a mean and standard deviation. The idebenone group’s reported mean was 104.4, with standard deviation 92.0; the placebo group’s reported mean was 28.9, with standard deviation 40.7. The unit is listed as “% change in peak systolic.” These are group summaries, not a confidence interval or a formal test of the between-group comparison.

The registry record does not provide a confidence interval or a posted inferential analysis for the endpoint. The size and meaning of a change in this imaging measure should therefore be kept distinct from conclusions about overall cardiac status or clinical benefit.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the mean describe?

For a continuous outcome, the mean is the arithmetic average of the observations included in the summary. Here, the endpoint is relative change in peak systolic radial strain, and the registry reports a mean for each treatment group. A mean is useful for describing the group’s central value, but it does not describe every participant’s result and can be influenced by unusually high or low observations.

The standard deviation describes how dispersed observations are around their group mean. It is not the uncertainty interval for the mean or for a treatment contrast. In this record, the reported standard deviations are 92.0 for idebenone and 40.7 for placebo. The relatively large spread is important when reading the means: participants’ measurements varied, so the mean alone does not convey how consistently individual observations followed the group summary.

How would a confidence interval help?

General statistical explanation: a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. For a treatment comparison, an interval around the estimated contrast would show a range of values compatible with the data and analysis, and would help readers judge precision. A narrow interval indicates more precision than a wide interval, but neither the interval nor its interpretation automatically establishes clinical importance.

The registry record does not report a confidence interval for the primary comparison. It also does not report a formal p-value for that comparison. The two group means and their standard deviations should therefore be treated as descriptive summaries, not as a substitute for an inferential analysis.

What does ITT with LOCF mean?

The record says the primary efficacy comparison used the ITT population and the LOCF method. In general, an intention-to-treat approach analyzes participants according to their randomized group, rather than restricting the comparison to those who completed all measurements. The registry does not give further details about how the ITT population was defined for this analysis.

LOCF means last observation carried forward: when a later outcome is unavailable, an earlier observed value is carried forward for the analysis. This method can retain participants with missing later measurements, but it relies on the assumption that carrying the earlier value forward is an acceptable representation of the later outcome. If an outcome changes over time, that assumption may not be appropriate. LOCF does not recover an unobserved measurement; it substitutes an earlier one under a specified rule.

The record reports Week 52 primary-endpoint data for 18 patients and says data were missing for 2 patients, while data could not be acquired for a third patient. It does not report missingness reasons beyond those statements, the last observation carried forward for each case, or sensitivity analyses using alternative assumptions. The impact of missing data on the comparison therefore cannot be fully assessed from the registry record.

Why distinguish the descriptive values from an adjusted comparison?

General statistical explanation: a between-group estimate directly summarizes the contrast of interest and may account for design features or covariates if the analysis specifies them. Separate group means are not necessarily the same as an adjusted treatment estimate. The posted results give group means and standard deviations, but no adjusted estimate or model description for the primary comparison. No recalculated two-arm comparison is reported because the registry’s analysis information does not support one.

The record’s discrepancy indicator is false. That does not create an inferential result where none is posted: the sponsor’s analysis is not contradicted by a recalculation, but the registry record still lacks a reported formal comparison and uncertainty interval.

What should be made of sample-size planning?

General statistical explanation: sample-size planning estimates how many participants might be needed to detect an effect under chosen assumptions about the effect size, variability, significance level, allocation and statistical method. A planning illustration based on an observed effect is not the same as the original trial’s design rationale and is not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. The registry record does not report the trial’s own sample-size justification. No planning count should be interpreted as the number enrolled or as evidence that the trial had a particular probability of detecting an effect.

Why does variability matter?

General statistical explanation: when observations vary substantially, the group mean may be estimated less precisely, all else being equal. In some settings, data may also be more dispersed than a statistical model assumes; over-dispersion can make standard errors too small if it is not handled appropriately. The registry does not report a model for the primary endpoint or an assessment of distributional assumptions, so the relevance of any particular model adjustment cannot be determined. The reported standard deviations nevertheless remind readers that the endpoint values were not tightly clustered around the means.

Finally, the registry lists three secondary-outcome descriptions, but does not report their analysis results. It also does not report whether or how multiple outcome comparisons were handled. These omissions make it inappropriate to infer a multiplicity strategy or a broader statistical plan beyond the primary-analysis details stated in the record.

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("Idebenone 450 mg/ Day", "Placebo")
n   <- c(11, 7)
m   <- c(104.4, 28.9)
sp  <- c(92, 40.7)
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  Idebenone 450 mg/ Day  11  104.400  92.000  42.594  166.206
CARM  Placebo  7  28.900  40.700  -8.741  66.541

11. Multiplicity, Missing Data and Analysis Populations

Missing primary-endpoint data are explicitly noted. At Week 52, data were available for 18 patients; the record attributes unavailable data to missing data from 2 patients and inability to acquire data from a third patient. The efficacy comparison used LOCF in the ITT population. This specifies how the record says the primary analysis handled missing values, but does not show whether the result would be similar under other assumptions.

The registry record does not report the timing of the missing measurements, reasons for the missing data beyond inability to acquire one patient’s data, or sensitivity analyses. It also does not describe how the ITT population was operationalized. These limits matter because missing outcomes can affect both the group summaries and the estimated comparison, depending on why the measurements are absent and how the analysis treats them.

The registry lists secondary outcomes for respiratory function, skeletal muscle strength and safety and tolerability. It does not report posted results for those secondary outcomes, nor does it report a method for adjusting or interpreting multiple outcome comparisons. The record does not report an interim-analysis plan or a multiplicity strategy. No such procedures should be assumed.

Without a stated multiplicity approach, a reader cannot determine how the study intended to control the chance of false-positive findings across multiple comparisons. The absence of reported secondary analyses also means that the primary endpoint should not be treated as one result among a known set of analyzed outcomes. The registry record supports only the specific primary-analysis description and the listed outcome categories.

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: femur fracture (12.5%), ankle fracture (7.7%).

The registry reports serious adverse events among 1 of 13 participants at risk in the idebenone group and 1 of 8 at risk in the placebo group. It reports other adverse events among 12 of 13 at risk in the idebenone group and 8 of 8 at risk in the placebo group. These are event summaries as recorded; they do not by themselves establish that an event was caused by a study drug.

The listed top serious-event terms are femur fracture at 12.5% and ankle fracture at 7.7%. The record does not report the arm attribution for those terms. Death counts are not reported in the registry record.

Safety comparisons in a trial of this size are descriptive and have limited ability to characterize uncommon events. The figures should be read with their reported at-risk denominators and without treating the difference in observed counts as proof of a difference in risk. The registry lists safety and tolerability as secondary outcomes, assessed by adverse events, blood and urine laboratory measures, and ECG. Detailed findings for those assessments are not reported in the registry record.

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

The posted primary-endpoint summaries show mean relative change of 104.4 in the idebenone group and 28.9 in the placebo group from baseline to Week 52. Their standard deviations are 92.0 and 40.7, respectively. These values describe the observed summaries for a regional imaging measure of cardiac function. They do not, by themselves, quantify the uncertainty of the comparison or establish its clinical importance.

The result does not establish that idebenone improves cardiac function, nor does it establish that the treatment has no effect. The registry record does not report a formal inferential result, confidence interval, or clinical threshold for interpreting the measure. A larger group mean is not sufficient to determine whether a difference is statistically reliable, clinically meaningful, or attributable to the intervention.

The endpoint is specific to peak systolic radial strain in the left-ventricular inferolateral wall. It should not be taken as a complete account of cardiac status, respiratory function, muscle strength, or overall health. Those domains appear in the registry as secondary outcomes, but their results are not reported. The trial’s rationale refers to possible effects on heart function, muscle strength and respiratory function; those rationales are not evidence that those outcomes changed.

Precision is also constrained by the available information. The registry reports Week 52 primary-endpoint data for 18 patients, LOCF in the ITT population, and substantial standard deviations. It does not provide a missing-data sensitivity analysis, the detailed analysis model, or an uncertainty interval. The registry record therefore leaves important questions about robustness and precision unresolved.

This was a completed Phase IIa, single-centre trial with enrollment of 21. Its findings are best understood as a small study’s descriptive primary-endpoint summaries, not as a definitive conclusion about efficacy or safety. The record does not report the study’s sample-size justification or a formal analysis of the primary comparison.

14. Why This Trial Matters Statistically

Statistically, this trial illustrates why a group mean is only one part of an outcome report. The primary endpoint is a continuous imaging measure, and the posted results include means and standard deviations for both randomized groups. The means describe central values; the standard deviations show substantial variability. Neither supplies the uncertainty interval for the between-group comparison.

The missing-data description is also central to interpretation. The primary efficacy comparison used LOCF in the ITT population, while Week 52 endpoint data were available for 18 patients. LOCF is an explicit analysis choice, but its validity depends on assumptions about what missing measurements would have been. Without sensitivity analyses or more detail on missingness, readers cannot assess how dependent the result is on that choice.

The record also shows the distinction between a trial’s stated objective and a posted statistical conclusion. The study set out to assess idebenone against placebo on a cardiac endpoint, but no formal p-value, confidence interval or analysis entry is reported. The descriptive summaries should not be mistaken for a completed inferential account.

Finally, several secondary outcomes are listed, including respiratory function, skeletal muscle strength, walking performance for ambulant patients, and safety measures. Their results and any multiplicity approach are not reported. This limits how much can be concluded across the study’s broader outcome set. The record is therefore useful for identifying the endpoint, analysis population, missing-data method and descriptive results, while also making clear that precision and wider outcome interpretation remain uncertain.

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.

Several trial-specific limitations are apparent from the registry record. The study was conducted at a single centre and enrolled 21 participants. The primary-endpoint analysis had data available for 18 patients at Week 52, with unavailable data attributed to missing data from 2 patients and inability to acquire data from a third patient. The registry reports LOCF in the ITT population but does not describe sensitivity analyses or the details needed to assess the missing-data assumptions.

The primary results are reported as group means and standard deviations. A confidence interval, formal p-value, adjusted estimate and model specification are not reported in the registry record. The standard deviations indicate considerable variation, but there is no reported distributional assessment or analysis that explains how this variability was handled.

The registry lists respiratory, muscle-strength, walking and safety outcomes, but does not report their analysis results. It also does not report a multiplicity approach, a sample-size justification, or an interim-analysis plan. These details cannot be reconstructed from the available record.

The record describes quadruple masking and the official title describes the study as double blind, but it does not identify which roles were masked. Arm descriptions are empty in the registry data. Beyond the listed intervention names and the idebenone dose, further treatment-administration details are not reported in the registry record.

These limitations do not establish that the analysis was invalid; they identify what cannot be evaluated from the registry information. They constrain the assessment of precision, missing-data robustness, safety patterns and the broader relevance of the posted primary-endpoint summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Tolerability of Idebenone in Boys With Cardiac Dysfunction Associated With Duchenne Muscular Dystrophy — NCT00654784.
• Registry record last updated 2011-08-01; status last verified 2011-07.
• Results first posted 2011-07-29.
• 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

NCT00654784 is a completed Phase IIa, randomized, placebo-controlled, parallel-group, single-centre study sponsored by Santhera Pharmaceuticals. It enrolled males aged 8 to 16 with Duchenne muscular dystrophy and cardiac dysfunction and compared idebenone at 450 mg/ Day with placebo. The recorded start was 2005-10, and primary completion was 2007-08.

The primary endpoint was relative change in left-ventricular inferolateral-wall peak systolic radial strain from baseline to Week 52, assessed using Color Doppler Myocardial Imaging. The reported mean values were 104.4 for idebenone and 28.9 for placebo, with standard deviations of 92.0 and 40.7. The primary efficacy comparison used LOCF in the ITT population; Week 52 endpoint data were available for 18 patients.

The registry record does not report a formal inferential result or confidence interval for the primary comparison. Results for the listed secondary outcomes and a detailed statistical analysis plan are also not reported.