Efficacy and tolerability of fluticasone propionate nasal drops 400 microgram once daily compared with placebo for the treatment of bilateral polyposis in adults.

BACKGROUND: Chronic eosinophilic rhinosinusitis underlies a range of respiratory disorders including nasal polyposis. Surgical and medical methods are used to control polyps, with topical steroids commonly being used for their anti-inflammatory properties. Fluticasone propionate nasal drops (FPND) is a formulation developed specifically for an effective and well tolerated corticosteroid treatment of nasal polyposis. OBJECTIVES: To assess efficacy and tolerability of FPND in the treatment of bilateral nasal polyposis in adults. METHODS: This multicentre, randomized, parallel-group study compared FPND 400 microgram once daily (o.d.) with placebo for 12 weeks in adult patients with mild to moderate bilateral polyposis. The primary efficacy endpoint was visual assessment of polyp size by the physician at monthly clinic visits. Nasal blockage, rhinitis, peak nasal inspiratory flow (PNIF), olfactory function and requirement for polypectomy were also assessed at visits. The patients kept diary card records of symptoms, PNIF, and use of rescue antihistamine. Additional safety data were provided by a 12-week open extension, when all patients received FPND 400 microgram o.d. RESULTS: After 12 weeks double-blind treatment with FPND (n = 52) or placebo (n = 52), polyp size was reduced in 27% and 16% of patients, respectively; clinical reduction of nasal blockage significantly favoured FPND over placebo (55% vs 22%; P = 0.002), and clinic PNIF had increased significantly with FPND (by 52 L/min vs -3 L/min for placebo; P < 0.001). Diary card measurements showed significant benefits of FPND vs placebo for daily PNIF, nasal blockage, rhinitis and use of loratadine rescue medication. Both treatments were well tolerated and no serious adverse events occurred during randomized treatment. Epistaxis was more frequent with FPND than placebo but was generally mild and did not result in withdrawals. Mean serum cortisol levels did not change significantly with either treatment. CONCLUSION: This study showed FPND 400 microgram o.d. to be an effective and well tolerated treatment for bilateral nasal polyposis in adults.

Dose-related efficacy and tolerability of fluticasone propionate nasal drops 400 microg once daily and twice daily in the treatment of bilateral nasal polyposis: a placebo-controlled randomized study in adult patients.

BACKGROUND: Topical corticosteroids are the accepted medical adjunct to surgery in patients suffering from nasal polyposis. Fluticasone propionate (FP) is a potent, topically active corticosteroid which has been formulated as nasal drops specifically for the treatment of polyposis. OBJECTIVES: To evaluate dose-related efficacy and tolerability of FP nasal drops (FPND) in the treatment of mild to moderate bilateral polyposis; in a double-blind, placebo-controlled, multicentre international study. METHODS: Adult patients (n = 142) with bilateral nasal polyps were randomized to receive either FPND 400 microg once daily (o.d.), FPND 400 microg twice daily (b.i.d.) or placebo for 12 weeks. The majority then entered a further 12 week open period during which all patients received FPND 400 microg o.d. The primary efficacy endpoint was the physicians' visual assessment of polyp size. Secondary clinical endpoints were nasal blockage and overall rhinitis (0-3 scores), peak nasal inspiratory flow (PNIF), olfactory function tests, and requirement for polypectomy. The patients also kept twice daily records of symptom scores, peak nasal inspiratory flow (PNIF) and use of rescue medication. RESULTS: At the end of the 12 week randomized treatment period, polyp size was reduced significantly by FPND 400 microg b.i.d. as compared with placebo (P = 0.006). Clinical assessments of nasal blockage and overall rhinitis showed significant improvements at several stages of treatment with both doses of FPND. Clinic PNIF was also improved significantly by both doses of FPND in comparison with placebo, and FPND 400 microg b.i.d. was significantly more effective than 400 microg o.d. (P = 0.045). Patient diary card scores supported the clinical assessments. Two patients on placebo required polypectomy and all treatments were well tolerated with a similar incidence of adverse events. CONCLUSION: FPND 400 microg once or twice daily is an effective and well-tolerated treatment for bilateral nasal polyposis.

Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. International COPD Study Group.

BACKGROUND: The efficacy of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) remains controversial because of a lack of placebo-controlled studies. We compared the effect of inhaled fluticasone propionate with placebo in the treatment of patients with COPD. METHODS: We used a randomised, double-blind, placebo-controlled design. We enrolled from 13 European countries, New Zealand, and South Africa, 281 outpatient current or ex-smokers, aged between 50 and 75 years. They had a forced expiratory volume in 1 s (FEV1) of between 35% and 90% of predicted normal values, a ratio of FEV1 to forced vital capacity of 70% or less and bronchodilator reversibility of less than 15%, as well as a history of chronic bronchitis. Patients were randomly assigned fluticasone propionate 500 microg (n=142) or placebo (n=139) twice daily via a metered-dose inhaler for 6 months. The main outcome measures were the number of patients who had at least one exacerbation by the end of treatment, the number and severity of exacerbations, clinic lung function, diary card symptoms and peak expiratory flow and 6 min walking distance. FINDINGS: 51 (37%) patients in the placebo group compared with 45 (32%) in the fluticasone propionate group had had at least one exacerbation by the end of treatment (p=0.449). Significantly more patients had moderate or severe exacerbations in the placebo group than in the fluticasone propionate group (86% vs 60%, p<0.001). Diary-card and clinic morning peak expiratory flows improved significantly in the fluticasone propionate group (p<0.001, p=0.048, respectively), as did clinic FEV1 (p<0.001), forced vital capacity (p<0.001), and mid-expiratory flow (p=0.01). Symptom scores for median daily cough and sputum volume were significantly lower with fluticasone propionate treatment than with placebo (p=0.004 and p=0.016, respectively). At the end of treatment, patients on fluticasone propionate had increased their 6 min walking distance significantly more than those on placebo (p=0.032). Fluticasone propionate was tolerated as well as placebo, with few adverse effects and without a clinically important effect on mean serum cortisol concentration. INTERPRETATION: Fluticasone propionate may be of clinical benefit in patients with COPD over at least 6 months. Inhaled corticosteroids may have an important role in the long-term treatment of COPD.

Fluticasone propionate compared with budesonide: a double-blind trial in asthmatic children using powder devices at a dosage of 400 microg x day(-1).

The aim of this study was to compare fluticasone propionate (FP) with budesonide (BUD) at a dose of 400 microg x day(-1) in the treatment of children with asthma. Two hundred and twenty nine children with mild-to-moderate asthma, currently receiving 200-400 microg x day(-1) of inhaled corticosteroid, were randomized to receive either 400 microg x day(-1) of FP from the Diskhaler (registered trade mark of the Glaxo Group of Companies) or 400 microg x day(-1) of BUD from the Turbuhaler (registered trade mark of Astra Pharmaceuticals Ltd) for 8 weeks, in a parallel-group, double-blind, double-dummy study. Primary efficacy was assessed by measurement of daily peak expiratory flow (PEF). In addition, pulmonary function tests were performed at each clinic visit and a self-administered patient-centred questionnaire was completed by one parent of each patient at the start and end of study treatment. Mean morning PEF increased following treatment both with FP and BUD, but was significantly higher following treatment with FP during Weeks 1-4 (p=0.015) and Weeks 1-8 (p=0.019). Similar results were found for mean evening PEF and percentage predicted morning and evening PEF. Children receiving FP experienced significantly less disruption in their physical activities (i.e. sports, games) because of their asthma compared to children treated with BUD (p=0.03). Mean cortisol levels increased in both groups, but the increase was significantly higher in the FP group at 4 weeks (p=0.022). Serum and urine markers of bone formation and resorption changed very little and showed no consistent pattern of change. Fluticasone propionate at a dosage of 400 microg x day(-1) from the Diskhaler provided a more rapid and greater improvement in lung function in children with mild-to-moderate asthma than BUD 400 microg day(-1) from the Turbuhaler. Both treatments were well-tolerated, with a similar safety profile.