Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial

Objectives To determine the effect of long term inhaled corticosteroids on lung function, exacerbations, and health status in patients with moderate t o severe chronic obstructive pulmonary disease. Design Double blind, placebo controlled study: Setting Eighteen UK hospitals. Participants 751 men and women aged between 40 and 75 years with mean force d expiratory volume in one second (FEV1) 50% of predicted normal. Interventions Inhaled fluticasone propionate 500 mu g twice daily from a me tered dose inhaler or identical placebo. Main outcome measures Efficacy measures: rate of decline in FEV1 after the bronchodilator and in health status, frequency of exacerbations, respirator y withdrawals. Safety measures: morning serum cortisol concentration, incid ence of adverse events. Results There was no significant difference in the annual rate of decline i n FEV1 (P = 0.16). Mean FEV1 after bronchodilator remained significantly hi gher throughout the study with fluticasone propionate compared vith placebo (P < 0.001). Median exacerbation rate was reduced by 25% from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate (P = 0.026). Healt h status deteriorated by 3.2 units a year on placebo and 2.0 units a year o n fluticasone propionate (P = 0.0043). Withdrawals because of respiratory d isease not related to malignancy were higher in the placebo group (25% v 19 %, P = 0.034). Conclusions Fluticasone propionate 500 mu g twice daily did not affect the rate of decline in FEV1 but did produce a small ina ease in FEV1. Patients on fluticasone propionate had fewer exacerbations and a slower decline in h ealth status. These improvements in clinical outcomes support the use of th is treatment in patients with moderate to severe chronic obstructive pulmon ary disease.