[Show abstract][Hide abstract] ABSTRACT: Intravenous (IV) amiodarone has proven efficacy in adults. However, its use in children is based on limited retrospective data.
A double-blind, randomized, multicenter, dose-response study of the safety and efficacy of IV amiodarone was conducted in 61 children (30 days to 14.9 years; median, 1.6 years). Children with incessant tachyarrhythmias (supraventricular arrhythmias [n=26], junctional ectopic tachycardia [JET, n=31], or ventricular arrhythmias [n=4]) were randomized to 1 of 3 dosing regimens (low, medium, or high: load plus 47-hour maintenance) with up to 5 open-label rescue doses. The primary efficacy end point was time to success. Of 229 patients screened, 61 were enrolled during 13 months by 27 of 48 centers in 7 countries. Median time to success was significantly related to dose (28.2, 2.6, and 2.1 hours for the low-, medium-, and high-dose groups, respectively; P=0.028). There was no significant association with dose for any arrhythmia subgroup, including JET, but the subgroups were too small for an accurate assessment. Adverse events (AEs) were common (87%), leading to withdrawal of 10 patients. There were 5 deaths in the 30-day follow-up period (2 possibly related to the study drug). Dose-related AEs included hypotension (36%), vomiting (20%), bradycardia (20%), atrioventricular block (15%) and nausea (10%).
In children, the overall efficacy of IV amiodarone, as measured by time to success, was dose related but not significantly for any arrhythmia subgroup. AEs were common and appeared to be dose related. Although efficacious for critically ill patients, the dose-related risks of IV amiodarone should be taken into account when treating children with incessant arrhythmias. Prospective, placebo-controlled trials would be helpful in assessing antiarrhythmic drug efficacy in children, because their results may differ from retrospective series and adult studies.
[Show abstract][Hide abstract] ABSTRACT: Antihypertensive medications are used extensively in children despite a paucity of randomized, placebo-controlled trials. This study was among the first randomized, controlled pediatric antihypertensive medication trials, in which the combination drug bisoprolol fumarate/hydrochlorothiazide (B/HT) was compared with placebo. The study comprised a 2-week single-blind placebo screening period, a 6-week double-blind dose titration period, a 4-week double-blind dose maintenance period, and a 2-week double-blind dose-tapering period. One hundred and forty subjects were enrolled to achieve 94 randomized subjects treated either with B/HT ( n=62) or placebo ( n=32). B/HT induced significant reductions compared with placebo for average sitting systolic blood pressure (SiSBP) (9.3 vs. 4.9 mmHg, P<0.05) and sitting diastolic blood pressure (SiDBP) (7.2 vs. 2.7 mmHg, P<0.05). The placebo-subtracted BP reductions were greater in younger children and those with more-severe baseline hypertension. The percentage of subjects with BP less than the 90th percentile at study completion was 45% for B/HT and 34% for placebo ( P=NS). Although the study demonstrated that B/HT reduced BP safely compared with placebo, the large placebo effect and failure of most subjects to achieve target BP control make it uncertain whether B/HT is appropriate first-line therapy for pediatric hypertension, particularly in adolescents with mild-to-moderate BP elevation.
No preview · Article · May 2002 · Pediatric Nephrology
[Show abstract][Hide abstract] ABSTRACT: Objectives: Although antihypertensive medications are used extensively in children, usage guidelines are based primarily on results from
adult studies. To investigate patterns of BP response to drug therapy in hypertensive children, we reviewed data from a recent
pediatric trial of the combination drug bisoprolol/hydrochlorothiazide (B/HT).