COPERNICOS: Eosinophil-guided Reduction of Inhaled Corticosteroids

Sponsor

Chronic Obstructive Pulmonary Disease Trial Network, Denmark (Other)

Overall Status

Recruiting

CT.gov ID

NCT04481555

Collaborator

(none)

444

Enrollment

Locations

Arms

54.1

Anticipated Duration (Months)

55.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COPD Inhaled Corticosteroid Azithromycin COPD Exacerbation Pneumonia	Drug: Azithromycin Drug: ICS	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

444 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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 (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Eosinophil-guided Reduction of Inhaled Corticosteroids

Actual Study Start Date :

Jun 28, 2021

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Eosinophil_"Control"/Azithro_"Control" Azithromycin: patients are given placebo ICS: The patients are given the usual LAMA/LABA/ICS product in the usual dose.
Experimental: 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.	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
Experimental: 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	Drug: Azithromycin Prophylactic azithromycin treatment 250 mg three times weekly vs placebo
Experimental: Eosinophil_"Active"/Azithro_"Active": Azithromycin: 250 mg azithromycin three times weekly. 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 Prophylactic azithromycin treatment 250 mg three times weekly vs placebo 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

Outcome Measures

Primary Outcome Measures

Days alive [365 days]
Days alive and out of hospital within 365 days after recruitment
Exacerbations, hospital [365 days]
Number of hospitalization-requiring exacerbations within 12 months

Secondary Outcome Measures

AECOPD tendency [365 dyas]
Death or "uncontrolled AECOPD tendency" within 365 days
Number of exacerbations [365 days]
Number of moderate/severe exacerbation within 12 months
Cumulative ICS dose [365 days]
Cumulative dose of ICS within 365 days
Cumulative OCS dose [365 days]
Cumulative dose of systemic corticosteroids within 365 days
Change in FEV1 [365 days]
Change in lung function (ΔFEV1) from baseline
Change in blood eosinophils [365 days]
Change in blood eosinophils (eosinophilic trajectories)
Diabetes mellitus [365 days]
New diagnosis of diabetes mellitus within 365 days
Change in HbA1c [365 days]
Change in HbA1c from baseline to 365 days
Number of antibiotic requiring infections [365 days]
Antibiotic-requiring infections within 365 days
Microbiota [180 days]
Change in lunge microbiota abundance and diversity
Change in CAT score [365 days]
Change in COPD Assessment Test from baseline to final visit
Change in MRC dyspnoea score [365 days]
MRC-dyspnea score from < 3 to 3 ≥, fron baseline, 3 ,6 ,9 and 12 months
Number of non-invasive ventilation (NIV) or intensive care admissions or death [365 days]
Number of admission-requiring NIV treatment or admissions to intensive care or death within 365 days
Mortality [365 days]
Death within 365 days

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

COPD (verified by a specialist in respiratory medicine + spirometry)
GOLD risk class C/D 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%.
Must receive at least during last 4 weeks: 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 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.

Contacts and Locations

Locations

	Site	City	Country
1	Aarhus University Hospital	Aarhus	Denmark
2	Hvidovre Hospital	Copenhagen	Denmark
3	Sydvestjysk Sygehus Esbjerg	Esbjerg	Denmark
4	Gentofte Hospital	Hellerup	Denmark
5	Nordsjællands Hospital	Hillerød	Denmark
6	Næstved-Slagelse-Ringsted Sygehus	Næstved	Denmark
7	Odense University Hospital	Odense	Denmark
8	Roskilde Sygehus	Roskilde	Denmark

Sponsors and Collaborators

Chronic Obstructive Pulmonary Disease Trial Network, Denmark

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Chronic Obstructive Pulmonary Disease Trial Network, Denmark

ClinicalTrials.gov Identifier:

NCT04481555

Other Study ID Numbers:

COPERNICOS_JUJCPR
2020-003014-12

First Posted:

Jul 22, 2020

Last Update Posted:

Jul 22, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Respiratory Aspiration

Azithromycin

Study Results

No Results Posted as of Jul 22, 2022