A Phase 4 interventional study of Azithromycin and ICS in COPD, Inhaled Corticosteroid and Azithromycin, sponsored by Chronic Obstructive Pulmonary Disease Trial Network, Denmark. Completed at 9 sites in Denmark. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2026-01-28.
Sponsored by Chronic Obstructive Pulmonary Disease Trial Network, Denmark · Phase 4, Interventional, and Treatment
Clinical trial on eosinophil-guided time-updated person-specific reduction of inhaled corticosteroid (ICS) therapy and prophylactic azithromycin therapy in patients with severe or very severe chronic obstructive pulmonary disease (COPD) receiving long-acting b-agonist (LABA) / long-acting muscarinic receptor antagonists (LAMA) / ICS treatment.
Inhaled corticosteroid (ICS) treatment is recommended by Global Initiative for Obstructive Lung Disease (GOLD) for patients with frequent and/or servere exacerbations and blood eosinophils > 0.3 x 10\^9 cells/L and in those with ≥ 0,1 x 109 cells blood-eosinophils and recurrent exacerbations while on bronchodilators. ICS treatment, however, is associated with side effects such as diabetes, osteoporosis and pneumonia which is costly for both patients and society. By studying the effects of a personalized, eoseosinophil-guided approach to direct ICS in COPD patients with frequent AECOPDs through a randomized clinical trial this study will examine the possibilities of reducing ICS overtreatment and thus ICS-related adverse events.
Long term ICS treatment is known for affecting the bacterial load in stable COPD patients. Azithromycin exerts multiple effects on the structure and composition of the lower airway microbiota and has anti-inflammatory effects. This study will, moreover, investigate whether an oral low-dose prophylactic treatment with Azithromycin 250 mg three times weekly can reduce the number of moderate-severe AECOPD and improves time alive and out of hospital.
This study is a randomized, double-blinded, multicentre, four-arm intervention clinical trial and is conducted based on the principles of good clinical practise (GCP).
Exclusion Criteria:
1. Azithromycin: patients are given placebo 2. ICS: The patients are given the usual LAMA/LABA/ICS product in the usual dose.
a. Azithromycin: placebo b. ICS: All patients will receive LABA/LAMA medication. The ICS medication will be switched on/off according to the most recent blood eosinophil count (at inclusion + every 3 months): i. If blood eosinophil ≥ 300 cells/μL, ICS in usual dose next 3 months. Blood eosinophils are measured every 3 months. ii. If blood eosinophil \<300 cells/μL, ICS is discontinued.
Drug: ICS
Azithromycin: 250 mg azithromycin three times weekly. b. ICS: The patients are given the usual LAMA/LABA/ICS product in the usual dose, where the medical treatment for severe COPD is unchanged throughout the entire project period
Drug: Azithromycin
1. Azithromycin: 250 mg azithromycin three times weekly. 2. ICS: All patients will receive LABA/LAMA medication. The ICS medication will be switched on/off according to the most recent blood eosinophil count (at inclusion + every 3 months):
Drug: Azithromycin · Drug: ICS
Prophylactic azithromycin treatment 250 mg three times weekly vs placebo
All patients will receive LABA/LAMA medication. The ICS medication will be switched on/off according to the most recent blood eosinophil count (at inclusion + every 3 months) vs continued LABA/LAMA/ICS treatment
Exacerbations, hospital and death
Number of hospitalization-requiring exacerbations within 12 months and/or death within 365 days
Time frame: 365 days
Days alive, out of hospital
Days alive and out of hospital within 365 days after recruitment
Time frame: 365 days
Deaths, uncontrolled AECOPD
Death or uncontrolled AECOPD tendency within 365 days
Time frame: 365 days
Number of exacerbations
Number of moderate/severe exacerbation within 365 days
Time frame: 365 days
Cumulative ICS dose
Cumulative dose of inhaled corticosteroids within 365 days
Time frame: 365 days
Cumulative OCS dose
Cumulative dose of systemic corticosteroids within 365 days
Time frame: 365 days
Change in FEV1
Change in lung function (ΔFEV1) from baseline to 365 days
Time frame: 365 days
Change in blood eosinophils
Change in blood eosinophils from baseline to 365 days (eosinophilic trajectories)
Time frame: 365 days
Diabetes mellitus
New diagnosis of diabetes mellitus within 365 days
Time frame: 365 days
Change in HbA1c
Change in HbA1c from baseline to 365 days
Time frame: 365 days
Number of antibiotic requiring infections
Antibiotic-requiring infections within 365 days
Time frame: 365 days
Microbiota, abundance and diversity
Difference in respiratory microbiota abundance and diversity from baseline to 12 months between treatment arms
Time frame: 365 days
Microbiota, immunological profile
Difference in immunological profile including cytokines and chemokines in the upper airways from baseline to 12 months between treatment arms
Time frame: 365 days
Change in CAT score
Change in COPD-related quality of life (Based on COPD Assessment Test - CAT) from baseline to 365 days
Time frame: 365 days
Change in MRC dyspnoea score
Number who progress to MRC -dyspnea score from \< 3 to ≥3 anytime during follow-up (assessed every 3 months).
Time frame: 365 days
Number of non-invasive ventilation (NIV) or intensive care admissions or death
Number of admission requiring non-invasive ventilation (NIV) treatment or admissions to intensive care within 365 days
Time frame: 365 days
Mortality
Mortality within 365 days
Time frame: 365 days
Plan to share: Undecided
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Pulmonary Disease, Chronic Obstructive→
Chronic Obstructive Pulmonary Disease Trial Network, Denmark