INvestigating COPD Outcomes, Genomics and Neutrophilic Inflammation With Tiotropium and Olodaterol
Status:
Completed
Trial end date:
2019-11-26
Target enrollment:
Participant gender:
Summary
This protocol describes a randomised controlled trial to test the hypothesis that 6 months of
treatment with tiotropium and olodaterol will result in a reduction in bacterial load, an
improvement in neutrophilic inflammation and clinical benefits compared with treatment with
inhaled fluticasone furoate and vilanterol in patients with neutrophilic Chronic obstructive
pulmonary disease (COPD).
COPD is the third leading cause of death worldwide and a major cause of morbidity in the UK.
Exacerbations drive disease progression and worsening quality of life and therefore
prevention of exacerbations has been a major goal of treatment.
In recent years, attempts have been made to phenotype COPD patients in order to target
therapies to the correct groups of patients that will benefit. Inhaled corticosteroids (ICS)
are primarily effective for patients with eosinophilic inflammation, while there are few
established therapies for patients with neutrophilic disease. In recent years, all ICS
preparations have been associated with a significant increased risk of pneumonia and this
risk appears to be greatest in patients with non-eosinophilic inflammation. Combined
treatment with long acting beta-agonists (LABA) and long acting muscarinic antagonists (LAMA)
combinations appears to be a safer and more effective alternative for patients with
non-eosinophilic disease. The combination of tiotropium and olodaterol in particular, has
strong preclinical data supporting beneficial effects on neutrophilic inflammation.
The trial is a multi-centre randomised open label controlled parallel group study with two
treatment arms in 80 participants. Moderate to very severe COPD patients and currently
treated with inhaled corticosteroid therapy will be randomised to treatment with either the
combination of tiotropium and olodaterol (LABA/LAMA) or fluticasone furoate and vilanterol
(ICS/LABA). Participants will return at 1 month, 2 months, 3 months and 6 months for sampling
of the lower airway by sputum samples and the upper airway using oropharyngeal and
nasopharyngeal swabs. Sputum will be used to test for airway neutrophilic inflammation.
This study will make an important contribution to understanding "phenotyping" in COPD by
identifying whether the combination of tiotropium and olodaterol improves airway bacterial
load and restores neutrophil function in patients with neutrophilic COPD.