Eosinophil-guided Reduction of Inhaled Corticosteroids

NCT ID: NCT04481555

Last Updated: 2025-03-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 444 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-28
• Study Completion Date: 2026-12-31

Brief Summary

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.

Detailed 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).

Conditions

COPD; Inhaled Corticosteroid; Azithromycin; COPD Exacerbation; Pneumonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Eosinophil_"Control"/Azithro_"Control"

1. Azithromycin: patients are given placebo

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Eosinophil_"Active"/Azithro_"Control":

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.

Group Type: EXPERIMENTAL

ICS

Intervention Type: DRUG

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

Eosinophil_"Control"/Azithro_"Active" group

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

Group Type: EXPERIMENTAL

Azithromycin

Intervention Type: DRUG

Prophylactic azithromycin treatment 250 mg three times weekly vs placebo

Eosinophil_"Active"/Azithro_"Active":

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):

Group Type: EXPERIMENTAL

Azithromycin

Intervention Type: DRUG

Prophylactic azithromycin treatment 250 mg three times weekly vs placebo

ICS

Intervention Type: DRUG

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

Interventions

Azithromycin

Prophylactic azithromycin treatment 250 mg three times weekly vs placebo

Intervention Type: DRUG

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) vs continued LABA/LAMA/ICS treatment

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chronic Obstructive Pulmonary Disease Trial Network, Denmark

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Aarhus University Hospital

Aarhus, , Denmark

Site Status: RECRUITING

Hvidovre Hospital

Copenhagen, , Denmark

Site Status: RECRUITING

Sydvestjysk Sygehus Esbjerg

Esbjerg, , Denmark

Site Status: RECRUITING

Gentofte Hospital

Hellerup, , Denmark

Site Status: RECRUITING

Nordsjællands Hospital

Hillerød, , Denmark

Site Status: RECRUITING

Næstved-Slagelse-Ringsted Sygehus

Næstved, , Denmark

Site Status: RECRUITING

Odense University Hospital

Odense, , Denmark

Site Status: RECRUITING

Roskilde Sygehus

Roskilde, , Denmark

Site Status: RECRUITING

Silkeborg Sygehus

Silkeborg, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Jens-Ulrik Jensen

Role: CONTACT

jens.ulrik.jensen@regionh.dk

38673057 ext. 45

Facility Contacts

Charlotte Ulrik

Role: primary

Torben Jensen

Role: primary

Christian Rønn

Role: primary

Andrea Browatzki

Role: primary

Uffe Bødtger

Role: primary

S

Role: primary

Christian Meyer

Role: primary

References

Ronn C, Bonnesen B, Alispahic IA, Tonnesen LL, Kjaergaard JL, Moberg M, Ulrik CS, Harboe ZB, Browatzki A, Jensen TT, Meyer CN, Bodtger U, Bendstrup E, Johansson SL, Kaiser DU, Hyldgaard C, Vestbo J, Sivapalan P, Jensen JS. Study protocol: COPD-eosinophil-guided reduction of inhaled corticosteroids (COPERNICOS) : A randomized, double-blinded, multicenter, four-arm intervention clinical trial on eosinophil-guided time-updated person-specific reduction of inhaled corticosteroid therapy and prophylactic low dose Azithromycin therapy in patients with severe or very severe chronic obstructive pulmonary disease (COPD). Trials. 2025 Sep 2;26(1):335. doi: 10.1186/s13063-025-09032-0.

Reference Type: DERIVED

PMID: 40898355 (View on PubMed)

Other Identifiers

2020-003014-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

COPERNICOS_JUJCPR

Identifier Type: -

Identifier Source: org_study_id