Tiotropium and olodaterol in the prevention of chronic obstructive pulmonary disease exacerbations (DYNAGITO): a double-blind, randomised, parallel-group, active-controlled trial

Lancet Respir Med. 2018 May;6(5):337-344. doi: 10.1016/S2213-2600(18)30102-4. Epub 2018 Apr 5.


Background: Combinations of long-acting bronchodilators are recommended to reduce the rate of chronic obstructive pulmonary disease (COPD) exacerbations. It is unclear whether combining olodaterol, a long-acting beta-agonist, with tiotropium, a long-acting anti-muscarinic, reduces the rate of exacerbations compared with tiotropium alone.

Methods: This 52-week, double-blind, randomised, parallel-group, active-controlled trial randomly assigned (1:1) patients with COPD with a history of exacerbations using a randomised block design to receive tiotropium-olodaterol 5 μg-5 μg or tiotropium 5 μg once daily. Patients using inhaled corticosteroids continued this therapy. Treatment was masked to patients, investigators, and those involved in analysing the data. The primary endpoint was the rate of moderate and severe COPD exacerbations from the first dose of medication until 1 day after last drug administration. The primary analysis included all randomly assigned patients who received any dose of study medication but were not from a site excluded due to on-site protocol violations. The trial is registered with ClinicalTrials.gov, number NCT02296138.

Findings: Overall, 9009 patients were screened from 818 centres in 51 countries. We recruited 7880 patients between Jan 22, 2015 and March 7, 2016 (mean age 66·4 years [SD 8·5], 5626 [71%] were men, mean FEV1 percent predicted 44·5% [SD 27·7]): 3939 received tiotropium-olodaterol and 3941 tiotropium. The rate of moderate and severe exacerbations was lower with tiotropium-olodaterol than tiotropium (rate ratio [RR] 0·93, 99% CI 0·85-1·02; p=0·0498), not meeting the targeted 0·01 significance level. The proportion of patients reporting adverse events was similar between treatments.

Interpretation: Combining tiotropium and olodaterol did not reduce exacerbation rate as much as expected compared with tiotropium alone.

Funding: Boehringer Ingelheim International GmbH.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists / administration & dosage*
  • Adrenergic beta-2 Receptor Agonists / adverse effects
  • Aged
  • Benzoxazines / administration & dosage*
  • Benzoxazines / adverse effects
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Delayed-Action Preparations / administration & dosage
  • Double-Blind Method
  • Drug Combinations
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscarinic Antagonists / administration & dosage*
  • Muscarinic Antagonists / adverse effects
  • Proportional Hazards Models
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Severity of Illness Index
  • Smokers
  • Tiotropium Bromide / administration & dosage*
  • Tiotropium Bromide / adverse effects
  • Treatment Outcome


  • Adrenergic beta-2 Receptor Agonists
  • Benzoxazines
  • Bronchodilator Agents
  • Delayed-Action Preparations
  • Drug Combinations
  • Muscarinic Antagonists
  • tiotropium-olodaterol
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT02296138