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Eosinophil-guided Reduction of Inhaled Corticosteroids (COPERNICOS)

Primary Purpose

COPD, Inhaled Corticosteroid, Azithromycin

Status
Recruiting
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Azithromycin
ICS
Sponsored by
Chronic Obstructive Pulmonary Disease Trial Network, Denmark
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COPD

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Aarhus University Hospital
  • Hvidovre HospitalRecruiting
  • Sydvestjysk Sygehus EsbjergRecruiting
  • Gentofte HospitalRecruiting
  • Nordsjællands HospitalRecruiting
  • Næstved-Slagelse-Ringsted SygehusRecruiting
  • Odense University Hospital
  • Roskilde SygehusRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

No Intervention

Experimental

Experimental

Experimental

Arm Label

Eosinophil_"Control"/Azithro_"Control"

Eosinophil_"Active"/Azithro_"Control":

Eosinophil_"Control"/Azithro_"Active" group

Eosinophil_"Active"/Azithro_"Active":

Arm Description

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

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.

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

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):

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
July 14, 2020
Last Updated
August 28, 2023
Sponsor
Chronic Obstructive Pulmonary Disease Trial Network, Denmark
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1. Study Identification

Unique Protocol Identification Number
NCT04481555
Brief Title
Eosinophil-guided Reduction of Inhaled Corticosteroids
Acronym
COPERNICOS
Official Title
Eosinophil-guided Reduction of Inhaled Corticosteroids
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 28, 2021 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chronic Obstructive Pulmonary Disease Trial Network, Denmark

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COPD, Inhaled Corticosteroid, Azithromycin, COPD Exacerbation, Pneumonia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
444 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Eosinophil_"Control"/Azithro_"Control"
Arm Type
No Intervention
Arm Description
Azithromycin: patients are given placebo ICS: The patients are given the usual LAMA/LABA/ICS product in the usual dose.
Arm Title
Eosinophil_"Active"/Azithro_"Control":
Arm Type
Experimental
Arm 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.
Arm Title
Eosinophil_"Control"/Azithro_"Active" group
Arm Type
Experimental
Arm 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
Arm Title
Eosinophil_"Active"/Azithro_"Active":
Arm Type
Experimental
Arm Description
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):
Intervention Type
Drug
Intervention Name(s)
Azithromycin
Intervention Description
Prophylactic azithromycin treatment 250 mg three times weekly vs placebo
Intervention Type
Drug
Intervention Name(s)
ICS
Intervention Description
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
Primary Outcome Measure Information:
Title
Days alive
Description
Days alive and out of hospital within 365 days after recruitment
Time Frame
365 days
Title
Exacerbations, hospital
Description
Number of hospitalization-requiring exacerbations within 12 months
Time Frame
365 days
Secondary Outcome Measure Information:
Title
AECOPD tendency
Description
Death or "uncontrolled AECOPD tendency" within 365 days
Time Frame
365 dyas
Title
Number of exacerbations
Description
Number of moderate/severe exacerbation within 12 months
Time Frame
365 days
Title
Cumulative ICS dose
Description
Cumulative dose of ICS within 365 days
Time Frame
365 days
Title
Cumulative OCS dose
Description
Cumulative dose of systemic corticosteroids within 365 days
Time Frame
365 days
Title
Change in FEV1
Description
Change in lung function (ΔFEV1) from baseline
Time Frame
365 days
Title
Change in blood eosinophils
Description
Change in blood eosinophils (eosinophilic trajectories)
Time Frame
365 days
Title
Diabetes mellitus
Description
New diagnosis of diabetes mellitus within 365 days
Time Frame
365 days
Title
Change in HbA1c
Description
Change in HbA1c from baseline to 365 days
Time Frame
365 days
Title
Number of antibiotic requiring infections
Description
Antibiotic-requiring infections within 365 days
Time Frame
365 days
Title
Microbiota
Description
Change in lunge microbiota abundance and diversity
Time Frame
180 days
Title
Change in CAT score
Description
Change in COPD Assessment Test from baseline to final visit
Time Frame
365 days
Title
Change in MRC dyspnoea score
Description
MRC-dyspnea score from < 3 to 3 ≥, fron baseline, 3 ,6 ,9 and 12 months
Time Frame
365 days
Title
Number of non-invasive ventilation (NIV) or intensive care admissions or death
Description
Number of admission-requiring NIV treatment or admissions to intensive care or death within 365 days
Time Frame
365 days
Title
Mortality
Description
Death within 365 days
Time Frame
365 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jens-Ulrik Jensen
Phone
38673057
Ext
45
Email
jens.ulrik.jensen@regionh.dk
Facility Information:
Facility Name
Aarhus University Hospital
City
Aarhus
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elisabeth Bendstrup, MD
Facility Name
Hvidovre Hospital
City
Copenhagen
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Charlotte Ulrik
Facility Name
Sydvestjysk Sygehus Esbjerg
City
Esbjerg
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Torben Jensen
Facility Name
Gentofte Hospital
City
Hellerup
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Rønn
Facility Name
Nordsjællands Hospital
City
Hillerød
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Browatzki
Facility Name
Næstved-Slagelse-Ringsted Sygehus
City
Næstved
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Uffe Bødtger
Facility Name
Odense University Hospital
City
Odense
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sofie L Johansson, MD
Facility Name
Roskilde Sygehus
City
Roskilde
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Meyer

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Eosinophil-guided Reduction of Inhaled Corticosteroids

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