Add-on salmeterol compared to double dose fluticasone in pediatric asthma: A double-blind, randomized trial (VIAPAED)

Abstract

Rationale: In asthmatic children whose symptoms are uncontrolled on standard doses of inhaled corticosteroids (ICS), guidelines recommend to either increase the ICS dose or to add further controller medication, e.g. a long acting ß2-agonist (LABA). The aim of this study was to compare the efficacy and safety of doubling the dose of ICS (fluticasone proprionate FP 200 mg twice daily) with adding a long-acting beta-2 agonist to the ICS (SFC, salmeterol 50 μg/ FP 100 μg twice daily) in children with uncontrolled asthma. Methods: Children between 4 and 16 years of age were eligible for this multicenter, randomized, double blind, double dummy, parallel-group study. During a 14-day run-in phase, all children inhaled FP 100 μg b.i.d.Patientswith persistent symptoms on≥7 of 14 days were randomized to 8 weeks treatment with a Diskus® containing either SFC 50 μg/ 100 μg b.i.d. or FP 200 μg b.i.d.. The primary endpoint was the mean change in morning (a.m.) PEF from baseline. The initial statistical hypothesis of non-inferiority of SFC vs. FP was confirmed in an adaptive interim analysis, so that the study was terminated prematurely. Results: 441 patients from 39 centers entered the run-in phase, and 64% of these were randomized to treatment (N=138 to SFC and N=145 to FP). After 8 weeks, patients on SFC had significantly better results for primary and secondary endpoints: The mean increase in morning PEF was 30.4±34.1 L/min in the SFC group and 16.7±35.8 L/min in the fluticasone group, and the mean (95% CI) improvement from baseline a.m. PEF in the ITT group was significantly larger after SFC (+8.6 L/min, CI: [1.3; ∞]). Patients in the SFC group experienced 8.7% (CI: [1.2;16.3]) more days without asthma symptoms and 8.0% (CI: [0.6;15.3]) more days without salbutamol than patients receiving FP. Good asthma control was achieved for a longer period in the SFC (3.4±2.7 weeks) group than in the FP group (2.7±2.7, P=0.02). Both treatments were generally well tolerated. Asthma exacerbations were recorded in 3 and 6 and SAEs in 2 and 1 patients from the SFC and FP groups, respectively. Conclusions: In children with persistent asthma inadequately controlled on low dose ICS alone, adding a long acting beta-2-agonist to ICS in a single inhaler was more effective than doubling the ICS dose.These results support recommendations of adding LABA to low-dose ICS as the preferred controller option for children older than 4 years with symptomatic asthma. © 2009 Wiley-Liss, Inc.