INvestigating COPD Outcomes, Genomics and Neutrophilic Inflammation With Tiotropium and Olodaterol

• Status: Completed
• Trial end date: 2019-11-26
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Dundee
• Collaborators: Boehringer Ingelheim; NHS Tayside
• Treatments: Fluticasone; Olodaterol; Tiotropium Bromide; Xhance

Criteria

Inclusion Criteria:

• Male and female patients aged > 40 years

• Current or ex-smokers having at least a 10 pack year smoking history

• A clinical diagnosis of Chronic Obstructive Pulmonary Disease (COPD) made by a physician

• Post-bronchodilator Forced Expiratory Volume 1 (FEV1)/Forced Vital Capacity ratio at screening of <70%

• Moderate to Very Severe COPD (GOLD II-IV) according to consensus guidelines consisting of a post-bronchodilator FEV1 <80% predicted at screening.

• Currently treated with inhaled corticosteroids (with or without long acting bronchodilators) for at least 12 months prior to screening.

• Able to perform all study procedures including spirometry and questionnaires with minimal assistance

• Blood eosinophil count less than 300 eosinophil cells per microlitre on bloods taken at screening.

• Able to produce a sputum sample at the baseline visit (either spontaneously or with nebulised saline induction)

Exclusion Criteria:

• Inability to give informed consent

• Asthma

• Acute Antibiotics within 28 days prior to screening

• Long term macrolide therapy if newly commenced in the past 3 months

• Current use of the following: roflumilast, ritonavir, itraconazole, telithromycin, or ketoconazole (or other strong CYP3A4 inhibitors).

• Systemic Immunosuppressive medication including current oral corticosteroids at a dose >5mg for >28 days.

• Glomerular filtration rate (eGFR) below 30ml/min/1.73m2 or requiring dialysis. This will be determined at screening.

• Use of any investigational drugs within five times of the elimination half-life after the last study dose or within 30 days, whichever is longer.

• Known allergy, intolerance or contraindication to any of the study drugs

• Unstable co-morbidities (cardiovascular disease, active malignancy) which in the opinion of the investigator would make the patient unsuitable to be enrolled in the study

• An exacerbation of COPD occurring during the 28 days prior to screening requiring treatment with either oral corticosteroids or antibiotics.

• An exacerbation requiring treatment with antibiotics or corticosteroids between the screening and randomization visit

• Pregnancy or breast feeding

• Women of child bearing potential who are not practicing an acceptable method of contraception

• Long term oxygen therapy

• Lapp lactase deficiency, glucose-galactose malabsorption or another inherited disorder of galactose metabolism.