Efficacy and safety of a long-acting beta blocker, extended release metoprolol succinate, in hypertensive children

Abstract

Clinical trial data on efficacy, safety, and tolerability of antihypertensive medications in the pediatric ages is emerging but remains limited. Even less data are available on the effects of the beta blocker class of antihypertensive drugs in children. To evaluate the dose range, safety, and blood pressure lowering effect of extended release metoprolol succinate (TOPROL-XL®, TXL). This multicenter clinical trial was a double-blind, placebo-controlled, randomized, parallel group study of children, age 6 to 16 years, with essential hypertension. Following a 2 week screening phase, each subject was randomized to one of a 4-arm treatment phase that lasted 4 weeks. The treatment arms were placebo or TXL (0.2 mg/kg, 1.0 mg/kg, or 2.0 mg/kg approximated by tablet strengths ranging from 12.5 to 200 mg). Data were analyzed using an intent-to-treat approach. Of 204 patients screened, 144 were randomized and 133 (92%) completed the treatment phase. 42% were <12 years, and 50% were < Tanner Stage 3. For the entire sample, mean age was 12.5 ± 2.8 yrs and mean baseline blood pressure (BP) was 132/78 ± 9/9 mmHg. Age, weight, and baseline BP were well balanced across the 4 treatment arms. Compared to placebo, there was a significantly greater reduction in SBP for the TXL 1.0 mg/kg dose and for all active doses combined, and in DBP at the TXL 2.0 mg/kg dose. There were no serious adverse events (AEs) or AEs requiring study drug discontinuation among patients receiving active therapy. Both SBP and DBP were lowered significantly, compared to placebo, following 4 weeks of TXL at doses within the range used in the study. In aggregate, these data indicate that TXL is an effective and well-tolerated treatment of hypertension in children, especially when a beta blocker is considered.