ECTOPIC trial: The efficacy of flEcainide Compared To metOprolol in reducing Premature ventrIcular contractions. A randomized open label cross-over study in pediatric patients.

BackgroundFrequent premature ventricular contractions (PVCs) in children are usually considered benign. Symptoms and/or left ventricular dysfunction are indications for treatment with anti-arrhythmic drugs (AAD).ObjectiveTo evaluate the efficacy of flecainide versus metoprolol in reducing PVCs in children.MethodsA randomized open label cross-over trial children with a PVC-burden of >15% on Holter; successively treated with metoprolol and flecainide or vice versa, with a drug free interval of at least two weeks. Holter measurements were repeated before and after the start of the AAD.ResultsSixty patients were screened, 19 patients could be included. Median age was 13.9 years (IQR 5.5 years). Mean baseline PVC-burden was 21.7% (N=18, SD±14.0) before the start of flecainide and 21.2% (N=17, SD±11.5) before the start of metoprolol. In a mixed model analysis the estimated mean reduction in PVC-burden was 10.6 percentage-points (95%-CI 5.8–15.3) for flecainide and 2.4 percentage-points (95%-CI -2.7–7.5) for metoprolol, with a significant difference of 8.2 percentage-points (95%-CI of 0.86–15.46, P=0.031). Exploratory analysis revealed that 9/18 patients treated with flecainide and 1/17 patients treated with metoprolol, had a reduction to a PVC-burden below 5%. No discriminating factors between flecainide-responders and non-responders were found; the mean plasma level was not significantly different (0.34 mg/L versus 0.52 mg/L, P=0.277).ConclusionsIn children with frequent PVCs flecainide led to a significant greater reduction of PVC-burden, compared to metoprolol. Flecainide was effective in only a subgroup of patients, which appears to be unrelated to the plasma level. (Dutch Trial Register number 26689).