NCT04481555

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
444

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Jun 2021

Longer than P75 for phase_4

Geographic Reach
1 country

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 14, 2020

Completed
8 days until next milestone

First Posted

Study publicly available on registry

July 22, 2020

Completed
11 months until next milestone

Study Start

First participant enrolled

June 28, 2021

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 27, 2024

Completed
12 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 19, 2025

Completed
Last Updated

January 28, 2026

Status Verified

January 1, 2026

Enrollment Period

3.4 years

First QC Date

July 14, 2020

Last Update Submit

January 27, 2026

Conditions

COPDInhaled CorticosteroidAzithromycinCOPD ExacerbationPneumonia

Outcome Measures

Primary Outcomes (1)

  • Exacerbations, hospital and death

    Number of hospitalization-requiring exacerbations within 12 months and/or death within 365 days

    365 days

Secondary Outcomes (16)

  • Days alive, out of hospital

    365 days

  • Deaths, uncontrolled AECOPD

    365 days

  • Number of exacerbations

    365 days

  • Cumulative ICS dose

    365 days

  • Cumulative OCS dose

    365 days

  • +11 more secondary outcomes

Study Arms (4)

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.

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

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):

Drug: AzithromycinDrug: ICS

Interventions

AzithromycinDRUG

Prophylactic azithromycin treatment 250 mg three times weekly vs placebo

Eosinophil_"Active"/Azithro_"Active":Eosinophil_"Control"/Azithro_"Active" group
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

Eosinophil_"Active"/Azithro_"Active":Eosinophil_"Active"/Azithro_"Control":

Eligibility Criteria

Age40 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Aarhus University Hospital

Aarhus, Denmark

Location

Hvidovre Hospital

Copenhagen, Denmark

Location

Sydvestjysk Sygehus Esbjerg

Esbjerg, Denmark

Location

Gentofte Hospital

Hellerup, Denmark

Location

Nordsjællands Hospital

Hillerød, Denmark

Location

Næstved-Slagelse-Ringsted Sygehus

Næstved, Denmark

Location

Odense University Hospital

Odense, Denmark

Location

Roskilde Sygehus

Roskilde, Denmark

Location

Silkeborg Sygehus

Silkeborg, Denmark

Location

Related Publications (1)

  • 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.

    PMID: 40898355DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic ObstructivePneumonia

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Lung Diseases, ObstructiveLung DiseasesRespiratory Tract DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsRespiratory Tract InfectionsInfections

Intervention Hierarchy (Ancestors)

ErythromycinMacrolidesPolyketidesLactonesOrganic Chemicals

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 14, 2020

First Posted

July 22, 2020

Study Start

June 28, 2021

Primary Completion

November 27, 2024

Study Completion

November 19, 2025

Last Updated

January 28, 2026

Record last verified: 2026-01

Locations

DK(9)