Nebulized formoterol effect on bronchodilation and satisfaction in COPD patients compared to QID ipratropium/albuterol MDI

ABSTRACT

Objective: Bronchodilator maintenance treatment improves pulmonary function and health-related quality of life in COPD patients. Pulmonary function and patient preference/satisfaction were compared before and after treatment with a short-acting ipratropium/albuterol combination and long-acting nebulized formoterol.

Methods: A randomized, open-label, crossover trial was conducted at 16 centers in the US. COPD subjects (n = 109, 52.8% predicted FEV₁) received nebulized formoterol fumarate inhalation solution (Perforomist**, FFIS 20 μg BID) or ipratropium and albuterol combined in a metered-dose inhaler (MDI) (Combivent, IPR-ALB, QID) for 2 weeks. After a 1-week washout, subjects were crossed over to the other treatment. Efficacy was assessed with 6-h pulmonary function tests and the transition dyspnea index (TDI). Treatment satisfaction and preference were assessed after treatment. Post-hoc subgroup analyses were conducted by age, gender and COPD severity.

** Perforomist is a registered trademark name of Dey LP, Napa, CA, USA

† Combivent is a registered trademark of Boehringer Ingelheim, Ridgefield, CT, USA

Main outcome measure: Morning pre-dose FEV₁ (trough) after 2 weeks of treatment.

Results: FFIS significantly increased morning pre-dose FEV₁ relative to IPR-ALB (p = 0.0015). FFIS also improved pre-dose FEV₁ beyond that of IPR-ALB in subjects who were older (≥65 years), male, and with both moderate and severe/very severe COPD. Post-dose efficacy at 6 h was maintained in the FFIS group compared with IPR-ALB (p ≤ 0.0001). Patient satisfaction and the perception of disease control were significantly greater with FFIS in the older, male, and severe subgroups. Severe subjects preferred FFIS to IPR-ALB. Both FFIS and IPR-ALB treatments resulted in clinically meaningful changes in dyspnea, but no significant differences were observed between treatments.

Conclusions: Following a 2-week treatment period, twice-daily nebulized FFIS was significantly more effective in improving lung function than the IPR-ALB combination MDI delivered four times daily. Although the open-label design may limit interpretation of pulmonary function, the crossover design enabled demonstration of greater treatment satisfaction and perception of disease control following nebulized FFIS treatment.

Clinical trial registration: Clinicaltrials.gov NCT00462540

Key words: :

• Albuterol
• Bronchodilators
• COPD
• Formoterol
• Ipratropium
• Nebulizer

Acknowledgments

Declaration of interest: The study was supported by Dey LP. E. R. S., S. B., and G. F. received research grants from Dey as investigators in the study, and E. R. S. has served as an advisor to Dey. L. T., J. M., and K. D-M. were employees of Dey at the time of the study. The authors thank the principal investigators and personnel at these study sites: R. Abrahams, Morgantown, WV; S. Brazinsky, San Diego, CA; T. Bruya, Spokane WA; S. C. Cohen, San Antonio, TX; H. D. Covelli, Coeur d’Alene, ID; P. A. Emrie, Wheat Ridge, CO; D. Erb, Gaffney, SC; G. Feldman, Spartanburg, SC; W. Gilbert, Johnson City, TN; S. H. Kimura, Pensacola, FL; T. G. Moriarty, Panama City, FL; M. J. Noonan, Portland, OR; J. S. Sibille, Sunset, LA; S. Spangenthal, Charlotte, NC; E. R. Sutherland, Denver, CO. The authors also acknowledge Elizabeth Field, Ph.D., Field Advantage Medical Communications, for support in writing the manuscript.

Notes

* Some of these data were presented at the 2008 Annual Meeting of the American College of Chest Physicians (CHEST 2008) in Philadelphia, PA, USA, October 25–30, 2008

** Perforomist is a registered trademark name of Dey LP, Napa, CA, USA

† Combivent is a registered trademark of Boehringer Ingelheim, Ridgefield, CT, USA