|- candidate number||26649|
|- NTR Number||NTR6498|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||6-feb-2017|
|- Secondary IDs||NL60023.058.16 toetsingonline.nl en MEC LUMC|
|- Public Title||Medical study in which the efficacy of anti-arrhythmic drugs on ventricular ectopic heartbeats in children will be examined. |
|- Scientific Title||The efficacy of flEcainide Compared To metOprolol in reducing Premature ventrIcular Complexes. |
An open label cross-over study in pediatric patients.
|- hypothesis||Flecainide is more effective in reducing the amount of PVCs than beta-blocker metoprolol.|
|- Healt Condition(s) or Problem(s) studied||Children, Antiarrhythmic drugs , Left ventricular function|
|- Inclusion criteria||- Age ¡Ý 1 year and < 18 years |
- Structurally normal heart confirmed by echocardiography
- PVCs > 15% on two different 24-hour Holter recording
- With or without asymptomatic VT
|- Exclusion criteria||- Age < 1 year, because of the significant chance of spontaneous resolution of PVCs |
- Structural cardiac defects
- History of cardiac surgery
- Long QT-syndrome
- Catecholaminergic Polymorfic Ventricular Tachycardia (CPVT)
- Verapamil sensitive PVC / Ventricular Tachycardia (VT)
- Patients with mental retardation
|- mec approval received||no|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-mrt-2017|
|- planned closingdate||1-mrt-2021|
|- Target number of participants||49|
|- Interventions||In a pediatric cohort of patients the acute effect of beta-blocker vs flecainide on the amount of PVCs will be tested in an open label cross-over design. After baseline function testing patients will be randomized to first receive an oral dose of metoprolol (1 mg/kg/dose twice daily) and secondly flecainide (2 mg/kg/dose twice daily) or the other way around. Each drug will be administered for at least 5 consecutive days, after which function testing will be repeated. In between a drug free period of at least two weeks will be implemented, to allow complete clearance of the drug.|
|- Primary outcome||The acute effect of flecainide and metoprolol on the reduction of PVCs as measured on Holter registration.|
|- Secondary outcome||The function of the left and right ventricle as measured by echocardiography and cardiac magneticresonance imaging, and NT-pro-BNP levels in the blood.|
|- Timepoints||Holter registration: reduction of % of PVCs, before and after medication testing.|
Echocardiography: measurement of LV/RV function by two dimensional echocardiography and strain imaging, before and after medication testing.
CMR: assessment of ventricular volumes and function, once baseline measurement.
|- Trial web site|
|- CONTACT FOR PUBLIC QUERIES||Drs. MD R.A. Bertels|
|- CONTACT for SCIENTIFIC QUERIES||Drs. MD R.A. Bertels|
|- Sponsor/Initiator ||Leiden University Medical Center (LUMC)|
(Source(s) of Monetary or Material Support)
|Leiden University Medical Center (LUMC)|
|- Brief summary||Rationale: Frequent idiopathic premature ventricular contractions (PVCs) and asymptomatic ventricular tachycardia (VTs) in children are rare, but can lead to left ventricular (LV) dysfunction. PVCs can be reduced by anti-arrhythmic drug therapy and thereby LV function can be restored. In clinical practice beta-blockers are usually the first line of treatment. We hypothesise that flecainide is more effective in reducing the amount of PVCs than metoprolol. |
Objective: To test the acute effect of metoprolol vs flecainide on the reduction of PVCs in a pediatric population. Secondary objectives are to perform a prospective evaluation of the effect of PVCs on LV function, to test the effect of reduction of PVCs by metoprolol or flecainide on LV function and to determine additional risk factors for development of LV-dysfunction.
Study design: In a pediatric cohort of patients the acute effect of metoprolol vs flecainide on the amount of PVCs will be tested in an open label cross-over design. In case of clinical symptoms or subclinical signs of LV dysfunction on echocardiography or cardiac magnetic resonance imaging, the most effective drug will be continued, to evaluate the effect on symptoms or LV dysfunction. The follow-up of these patients will be performed in a prospective observational study.
Study population: Children between 1 year and 18 years of age, a structurally normal heart, more than 15% PVCs on Holter recording and (without) asymptomatic VTs.
Intervention: After baseline function testing patients will be randomized to first receive an oral dose of metoprolol (1 mg/kg/dose twice daily) and secondly flecainide (2 mg/kg/dose twice daily) or the other way around. Each drug will be administered for at least 5 consecutive days, after which function testing will be repeated. In between a drug free period of at least two weeks will be implemented, to allow complete clearance of the drug.
Main study parameters/endpoints: The acute effect of flecainide and metoprolol on the reduction of PVCs as measured on Holter registration.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The burden of the study procedures is limited. Procedures are those routinely performed during regular follow-up in these patients and include physical examination, ECG, echocardiography, Holter registration every 6 months and pro-brain natriuretic peptide measurement once a year. In addition, an exercise test will be performed at the start and after medication testing cardiac magnetic resonance imaging will be performed. The risks of medication testing are limited. Both drugs have been used extensively in the age group in which this study is performed and possible side effects are reversible by discontinuation of the drug. Patients will benefit from the study, as they will learn which medication is most effective in reducing PVCs in each individual case.
|- Main changes (audit trail)|
|- RECORD||6-feb-2017 - 5-aug-2017|