Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease

Am J Respir Crit Care Med. 2009 Oct 15;180(8):741-50. doi: 10.1164/rccm.200904-0492OC. Epub 2009 Jul 30.


Rationale: Budesonide/formoterol and tiotropium are commonly used maintenance treatments for patients with chronic obstructive pulmonary disease. Combining these medications may provide additional benefits.

Objectives: To assess the efficacy and tolerability of budesonide/formoterol added to tiotropium in patients eligible for inhaled corticosteroid/long-acting beta(2)-agonist combination therapy.

Methods: In this 12-week, randomized, double-blind, parallel-group, multicenter study, after a 2-week run-in, 660 subjects (75% male; mean age, 62 yr; FEV(1), 1.1 L; 38% predicted normal), 40 years of age or older, received tiotropium (18 microg once daily) plus either budesonide/formoterol (320/9 microg) (n = 329) or placebo (n = 331) twice daily.

Measurements and main results: Clinic predose (primary outcome) and postdose FEV(1), predose and postdose forced vital capacity and inspiratory capacity, and health status were measured. Other outcomes included daily measurements taken at home (pre- and postdose morning FEV(1) and peak expiratory flow, morning symptoms and activities, and morning reliever use), severe exacerbations, and tolerability. Over the treatment period, budesonide/formoterol plus tiotropium significantly increased predose FEV(1) by 6% (65 ml) and postdose by 11% (123 and 131 ml at 5 and 60 min postdose, respectively) versus tiotropium alone (both P < 0.001). Other outcomes all significantly improved with budesonide/formoterol plus tiotropium versus tiotropium alone. The number of severe exacerbations decreased by 62% (rate ratio, 0.38; 95% confidence interval, 0.25-0.57; P < 0.001). Both treatments were well tolerated.

Conclusions: In patients with chronic obstructive pulmonary disease, budesonide/formoterol added to tiotropium versus tiotropium alone provides rapid and sustained improvements in lung function, health status, morning symptoms and activities, and reduces severe exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT00496470).

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / administration & dosage*
  • Adrenal Cortex Hormones / adverse effects
  • Adrenergic beta-Agonists / administration & dosage*
  • Adrenergic beta-Agonists / adverse effects
  • Adult
  • Aged
  • Aged, 80 and over
  • Budesonide / administration & dosage*
  • Budesonide / adverse effects
  • Double-Blind Method
  • Drug Therapy, Combination
  • Ethanolamines / administration & dosage*
  • Ethanolamines / adverse effects
  • Female
  • Forced Expiratory Volume
  • Formoterol Fumarate
  • Humans
  • Male
  • Middle Aged
  • Muscarinic Antagonists / therapeutic use*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Quality of Life
  • Scopolamine Derivatives / therapeutic use*
  • Tiotropium Bromide


  • Adrenal Cortex Hormones
  • Adrenergic beta-Agonists
  • Ethanolamines
  • Muscarinic Antagonists
  • Scopolamine Derivatives
  • Budesonide
  • Formoterol Fumarate
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT00496470