Idebenone in Friedreich ataxia cardiomyopathy-results from a 6-month phase III study (IONIA)

Background Friedreich ataxia (FRDA) is commonly associated with hypertrophic cardiomyopathy, but little is known about its frequency, severity, or treatment. In this 6-month randomized, double-blind, controlled study, we sought to determine whether idebenone improves cardiac measures in FRDA. Methods Seventy pediatric subjects were treated either with idebenone (450/900 mg/d or 1,350/2,250 mg/d) or with placebo. Electrocardiograms (ECGs) were assessed at each visit, and echocardiograms, at baseline and week 24. Results We found ECG abnormalities in 90% of the subjects. On echocardiogram, 81.4% of the total cohort had left ventricular (LV) hypertrophy, as measured by increased LV mass index-Dubois, and the mean ejection fraction (EF) was 56.9%. In linear regression models, longer PR intervals at baseline were marginally associated with longer GAA repeat length (P = .011). Similarly, GAA repeat length did not clearly predict baseline EF (P = .086) and LV mass by M- mode (P = .045). Left ventricular mass index, posterior wall thickness, EF, and ECG parameters were not significantly improved by treatment with idebenone. Some changes in echocardiographic parameters during the treatment phase correlated with baseline status but not with treatment group. Conclusions Idebenone did not decrease LV hypertrophy or improve cardiac function in subjects with FRDA. The present study does not provide evidence of benefit in this cohort over a 6- month treatment period. (Am Heart J 2011; 161: 639- 645. e1.)