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

• Published in: Pediatric pulmonology 2009-11, Vol.44 (11), p.1132-1142
• Main Authors: Gappa, Monika, Zachgo, Wolfgang, von Berg, Andrea, Kamin, Wolfgang, Stern-Sträter, Catrin, Steinkamp, Gratiana
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones - administration & dosage; Adrenergic beta-Agonists - administration & dosage; Albuterol - administration & dosage; Albuterol - analogs & derivatives; Androstadienes - administration & dosage; asthma; Asthma - drug therapy; asthma control; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Child; Child, Preschool; Chronic obstructive pulmonary disease, asthma; comparison; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; efficacy; Female; Fluticasone; General aspects; Humans; inhaled corticosteroid; long-acting-beta-2-agonist; Male; Medical sciences; Peak Expiratory Flow Rate; Pharmacology. Drug treatments; Pneumology; salmeterol; Salmeterol Xinafoate
• ISSN: 8755-6863; 1099-0496
• DOI: 10.1002/ppul.21120

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 µg 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. Patients with 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. Pediatr Pulmonol. 2