Effects of arformoterol twice daily, tiotropium once daily, and their combination in patients with COPD

Respir Med. 2009 Apr;103(4):516-24. doi: 10.1016/j.rmed.2008.12.014. Epub 2009 Feb 8.


Purpose: Current guidelines support using in combination more than one class of long-acting bronchodilator for COPD patients whose symptoms are not controlled by mono-therapy. This 2-week, multi-center (34 sites), randomized, modified-blind, parallel group study evaluated the efficacy and safety of concomitant treatment with nebulized arformoterol (the formoterol(R,R)-isomer) BID and tiotropium DPI QD.

Methods: COPD patients (mean FEV(1) 1.37L, 45.4% predicted) were randomized to receive mono-therapy (either arformoterol 15microg BID [n=76] or tiotropium 18microg QD [n=80]), or combined therapy (sequential dosing of arformoterol 15microg BID and tiotropium 18microg QD [n=78]). Changes in pulmonary function, dyspnea, and rescue levalbuterol use were evaluated, as were safety outcomes.

Results: Mean FEV(1)AUC(0-24) (the primary endpoint) improved similarly from baseline for arformoterol (0.10L) and tiotropium (0.08L) treatment groups and greater for the combined therapy group (0.22L; all p-values <0.005). Peak FEV(1), peak FVC, 24-h trough FEV(1), and inspiratory capacity also improved similarly for the mono-therapies and greatest for the combined therapy. Dyspnea (mean transition dyspnea index) improved similarly for arformoterol (+2.3) and tiotropium (+1.8) and greatest with combined therapy (+3.1; p-values <0.05). Levalbuterol use decreased for all treatment groups (range -1.8 to -2.5 actuations/day). All treatments had similar frequency of adverse events.

Conclusion: In this study, the combination of nebulized arformoterol 15microg BID plus tiotropium 18microg DPI QD was the most effective in improving pulmonary function and disease symptoms. Mono-therapy improvement with arformoterol or tiotropium was similar. All three treatments were well tolerated.

Trial registration: ClinicalTrials.gov NCT00424528.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Aged
  • Albuterol / administration & dosage
  • Bronchodilator Agents / administration & dosage*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Dyspnea / drug therapy
  • Ethanolamines / administration & dosage*
  • Female
  • Forced Expiratory Volume
  • Formoterol Fumarate
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Scopolamine Derivatives / administration & dosage*
  • Tiotropium Bromide
  • Treatment Outcome
  • Vital Capacity


  • Bronchodilator Agents
  • Ethanolamines
  • Scopolamine Derivatives
  • Albuterol
  • Formoterol Fumarate
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT00424528