Efficacy and Safety of Nebulized Formoterol as Add-on Therapy in COPD Patients Receiving Maintenance Tiotropium Bromide: Results from a 6-Week, Randomized, Placebo-Controlled, Clinical Trial

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Abstract

Background:

Current guidelines for the treatment of chronic obstructive pulmonary disease (COPD) recommend the use of long-acting bronchodilators in the maintenance management of COPD. Combining bronchodilators that work through different mechanisms is recommended in patients with continuous symptoms.

Objective:

We conducted this study to confirm and further investigate the efficacy and safety of nebulized formoterol as an add-on therapy to maintenance tiotropium in patients with COPD.

Methods:

This randomized, double-blind, placebo-controlled, parallel-group study (NCT00507234) was conducted at 24 US sites from March to October 2007 in 155 patients aged ≥40 years with post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥25% to <65% predicted normal. COPD patients receiving open-label tiotropium bromide 18 μg once daily during a 1- to 2-week run-in period were randomized to receive either formoterol fumarate inhalation solution 20 μg or placebo by nebulization twice daily for 6 weeks while continuing treatment with tiotropium. Outcomes included serial spirometry, inspiratory capacity (IC), baseline dyspnoea index/transition dyspnoea index (BDI/TDI), daily symptom scores, salbutamol (albuterol) use and health status measured by the St George's Respiratory Questionnaire (SGRQ).

Main outcome measures:

The primary efficacy endpoint was standardized absolute FEV1 area under the curve over 3 hours (AUC0-3) at week 6.

Results:

Treatment groups (formoterol plus tiotropium, n = 78; placebo plus tiotropium, n = 77) were comparable at baseline. At 6 weeks, FEV1 AUC0-3 was significantly greater in the formoterol group compared with the placebo group (1.57 vs 1.38 L [p < 0.0001]). Similarly, formoterol plus tiotropium improved other lung function measures, including FEV1, forced vital capacity and post-dose IC at day 1, and maintained efficacy through week 6. Formoterol plus tiotropium decreased rescue albuterol use throughout the study (p < 0.05). Mean TDI, SGRQ and most symptom scores did not differ between the two treatment groups. Overall, 37% of formoterol plus tiotropium recipients experienced adverse events versus 51% of those receiving placebo plus tiotropium.

Conclusions:

The addition of nebulized formoterol to tiotropium in maintenance treatment of COPD provided clinically meaningful, statistically significant and sustained improvements in pulmonary function without additional adverse effects.

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