Eosinophil-guided Reduction of Inhaled Corticosteroids (COPERNICOS)

Chronic Obstructive Pulmonary Disease Trial Network, Denmark

Status and phase: Enrolling; Phase 4

Conditions: Inhaled Corticosteroid; Azithromycin; Pneumonia; COPD; COPD Exacerbation

Treatments: Drug: ICS; Drug: Azithromycin

Study type: Interventional

Funder types: Other

Identifiers

NCT04481555

2020-003014-12 (EudraCT Number)

COPERNICOS_JUJCPR

Details and patient eligibility

About

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.

Full description

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).

Enrollment: 444 estimated patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• COPD (verified by a specialist in respiratory medicine + spirometry)
• GOLD class E anytime within the last 2 years (corresponding to 2 ≥ AECOPD and/or ≥1 AECOPD leading to hospitalization during a 12 months period within the last 2 years) and/or FEV1<30%.
• Treatment for last 4 weeks including LAMA, LABA and ICS
• Informed consent

Exclusion criteria

• Known asthma.
• Male < 40 years.
• Female <40 years, if non-menopausal (had menstruation within the last 12 months) conditioned by a negative urine HCG test
• Severe mental illness which considerably complicates co-operation.
• Language problems that considerably complicate co-operation.
• Current treatment with systemic corticosteroids corresponding to > 5 mg prednisolone per day.
• Systemic antibiotic treatment (if to participate in microbiota sub-study) or systemic corticosteroid treatment within 14 days (also prophylactic Azithromycin).
• Contra-indication to treat with Azithromycin (as listed by the producer).
• Non-bacterial exacerbation per investigator judgement in the last 3 months.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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444 participants in 4 patient groups

Eosinophil_"Control"/Azithro_"Control"

No Intervention group

Description:

1. Azithromycin: patients are given placebo 2. ICS: The patients are given the usual LAMA/LABA/ICS product in the usual dose.

Eosinophil_"Active"/Azithro_"Control":

Experimental group

Description:

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.

Treatment:

Drug: ICS

Eosinophil_"Control"/Azithro_"Active" group

Experimental group

Description:

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

Treatment:

Drug: Azithromycin

Eosinophil_"Active"/Azithro_"Active":

Experimental group

Description:

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):

Treatment:

Drug: Azithromycin

Drug: ICS