COPDPhase 4COPERNICOSNCT04481555
Eosinophil-guided Reduction of Inhaled Corticosteroids
A Phase 4 study testing Azithromycin and ICS in people with COPD and Inhaled Corticosteroid, run by Chronic Obstructive Pulmonary Disease Trial Network, Denmark at 9 sites in Denmark.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- COPD, Inhaled Corticosteroid, Azithromycin
- What is being tested?
- Azithromycin and ICS
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 444 participants
- Where
- 9 sitesDenmark
- Study dates
- 28 Jun 2021to 19 Nov 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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 locations and contacts
9 sites in 1 country.
9 sites in 1 country
Denmark9 sites
Aarhus University Hospital
Aarhus
Hvidovre Hospital
Copenhagen
Sydvestjysk Sygehus Esbjerg
Esbjerg
Gentofte Hospital
Hellerup
Nordsjællands Hospital
Hillerød
Næstved-Slagelse-Ringsted Sygehus
Næstved
Odense University Hospital
Odense
Roskilde Sygehus
Roskilde
Silkeborg Sygehus
Silkeborg
About this study
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.
Read the 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
- Being tested
- Azithromycin, ICS
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
Prophylactic azithromycin treatment 250 mg three times weekly vs placebo
ICSDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Eosinophil_"Control"/Azithro_"Control" | No intervention | 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 | 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. Receives: Drug: ICS |
| Eosinophil_"Control"/Azithro_"Active" group | Experimental | 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 Receives: Drug: Azithromycin |
| Eosinophil_"Active"/Azithro_"Active": | Experimental | 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): Receives: Drug: Azithromycin; Drug: ICS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Exacerbations, hospital and death
Number of hospitalization-requiring exacerbations within 12 months and/or death within 365 days
Measured: 365 days
Secondary outcomes (16)
Days alive, out of hospital
Days alive and out of hospital within 365 days after recruitment
Measured: 365 days
Deaths, uncontrolled AECOPD
Death or uncontrolled AECOPD tendency within 365 days
Measured: 365 days
Number of exacerbations
Number of moderate/severe exacerbation within 365 days
Measured: 365 days
Cumulative ICS dose
Cumulative dose of inhaled corticosteroids within 365 days
Measured: 365 days
Cumulative OCS dose
Cumulative dose of systemic corticosteroids within 365 days
Measured: 365 days
Change in FEV1
Change in lung function (ΔFEV1) from baseline to 365 days
Measured: 365 days
Change in blood eosinophils
Change in blood eosinophils from baseline to 365 days (eosinophilic trajectories)
Measured: 365 days
Diabetes mellitus
New diagnosis of diabetes mellitus within 365 days
Measured: 365 days
Change in HbA1c
Change in HbA1c from baseline to 365 days
Measured: 365 days
Number of antibiotic requiring infections
Antibiotic-requiring infections within 365 days
Measured: 365 days
Microbiota, abundance and diversity
Difference in respiratory microbiota abundance and diversity from baseline to 12 months between treatment arms
Measured: 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
Measured: 365 days
Change in CAT score
Change in COPD-related quality of life (Based on COPD Assessment Test - CAT) from baseline to 365 days
Measured: 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).
Measured: 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
Measured: 365 days
Mortality
Mortality within 365 days
Measured: 365 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2020
- Study start28 Jun 2021
- Primary completion27 Nov 2024
- Study completion19 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COPDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 4-arm facultative designed, randomized controlled, multicenter, parallel group, double-blinded (azithromycin), non-inferiority intervention study in patients with severe and very severe COPD study. Participants will be randomly allocated to one of four treatment groups.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 444 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chronic Obstructive Pulmonary Disease Trial Network, Denmark
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04481555
- Sponsor's protocol ID
- COPERNICOS_JUJCPR
- Other IDs
- 2020-003014-12
- Acronym
- COPERNICOS
- Status last verified
- Jan 2026
- First submitted
- 14 Jul 2020
- Last updated
- 28 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 40898355
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Eosinophil-guided Reduction of Inhaled Corticosteroids
- ClinicalTrials.gov ID
- NCT04481555
- Acronym / sponsor ID
- COPERNICOS / COPERNICOS_JUJCPR
- Conditions
- COPD, Inhaled Corticosteroid, Azithromycin, COPD Exacerbation, Pneumonia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 444 participants (actual)
- Lead sponsor
- Chronic Obstructive Pulmonary Disease Trial Network, DenmarkUniversity, hospital or other
- Study start
- 28 Jun 2021 (actual)
- Primary completion
- 27 Nov 2024 (actual)
- Study completion
- 19 Nov 2025 (actual)
- First posted
- 22 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- 4-arm facultative designed, randomized controlled, multicenter, parallel group, double-blinded (azithromycin), non-inferiority intervention study in patients with severe and very severe COPD study. Participants will be randomly allocated to one of four treatment groups.
| Arm | Type | Receives |
|---|---|---|
| Eosinophil_"Control"/Azithro_"Control" | No intervention | –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 | Drug: ICSa. 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. |
| Eosinophil_"Control"/Azithro_"Active" group | Experimental | Drug: AzithromycinAzithromycin: 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 |
| Eosinophil_"Active"/Azithro_"Active": | Experimental | Drug: Azithromycin, Drug: ICS1. 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): |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzithromycinProphylactic azithromycin treatment 250 mg three times weekly vs placebo | Drug | Eosinophil_"Active"/Azithro_"Active":, Eosinophil_"Control"/Azithro_"Active" group |
| ICSAll 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 | Drug | Eosinophil_"Active"/Azithro_"Active":, Eosinophil_"Active"/Azithro_"Control": |
Primary outcome
Exacerbations, hospital and death
Time frame: 365 days
Number of hospitalization-requiring exacerbations within 12 months and/or death within 365 days
16 secondary outcomes
Days alive, out of hospital
Time frame: 365 days
Deaths, uncontrolled AECOPD
Time frame: 365 days
Number of exacerbations
Time frame: 365 days
Cumulative ICS dose
Time frame: 365 days
Cumulative OCS dose
Time frame: 365 days
Change in FEV1
Time frame: 365 days
Change in blood eosinophils
Time frame: 365 days
Diabetes mellitus
Time frame: 365 days
Change in HbA1c
Time frame: 365 days
Number of antibiotic requiring infections
Time frame: 365 days
Microbiota, abundance and diversity
Time frame: 365 days
Microbiota, immunological profile
Time frame: 365 days
Change in CAT score
Time frame: 365 days
Change in MRC dyspnoea score
Time frame: 365 days
Number of non-invasive ventilation (NIV) or intensive care admissions or death
Time frame: 365 days
Mortality
Time frame: 365 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2026.
- Derived from this study: PubMed 40898355Ronn 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Azithromycin and ICS in people with COPD and Inhaled Corticosteroid, run by Chronic Obstructive Pulmonary Disease Trial Network, Denmark at 9 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Exacerbations, hospital and death (time frame: 365 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04481555, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2026.