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 microg twice daily) with adding a long-acting beta-2 agonist to the ICS (SFC, salmeterol 50 microg/ FP 100 microg 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 microg b.i.d. Patients with persistent symptoms on > or =7 of 14 days were randomized to 8 weeks treatment with a Diskus(R) containing either SFC 50 microg/100 microg b.i.d. or FP 200 microg 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; infinity]). 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.