Eosinophil-guided Reduction of Inhaled Corticosteroids

COPD Clinical Trial

— COPERNICOS  

Official title:

Eosinophil-guided Reduction of Inhaled Corticosteroids

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04481555
• Other study ID #: COPERNICOS_JUJCPR
• Secondary ID: 2020-003014-12
• Status: Recruiting
• Phase: Phase 4
• Start date: June 28, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2024
• Source: Chronic Obstructive Pulmonary Disease Trial Network, Denmark
• Contact: Jens-Ulrik Jensen
• Phone: 38673057
• Email: jens.ulrik.jensen[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 antagonists (LAMA) / ICS treatment.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 444
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Azithromycin
• COPD
• COPD Exacerbation
• Inhaled Corticosteroid
• Pneumonia
• Respiratory Aspiration

Intervention

Drug:
• Azithromycin
Prophylactic azithromycin treatment 250 mg three times weekly vs placebo
• 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

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus
Denmark	Hvidovre Hospital	Copenhagen
Denmark	Sydvestjysk Sygehus Esbjerg	Esbjerg
Denmark	Gentofte Hospital	Hellerup
Denmark	Nordsjællands Hospital	Hillerød
Denmark	Næstved-Slagelse-Ringsted Sygehus	Næstved
Denmark	Odense University Hospital	Odense
Denmark	Roskilde Sygehus	Roskilde
Denmark	Silkeborg Sygehus	Silkeborg

Sponsors (1)

Lead Sponsor	Collaborator
Chronic Obstructive Pulmonary Disease Trial Network, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exacerbations, hospital and death	Number of hospitalization-requiring exacerbations within 12 months and/or death within 365 days	365 days
Secondary	Days alive, out of hospital	Days alive and out of hospital within 365 days after recruitment	365 days
Secondary	Deaths, uncontrolled AECOPD	Death or uncontrolled AECOPD tendency within 365 days	365 days
Secondary	Number of exacerbations	Number of moderate/severe exacerbation within 365 days	365 days
Secondary	Cumulative ICS dose	Cumulative dose of inhaled corticosteroids within 365 days	365 days
Secondary	Cumulative OCS dose	Cumulative dose of systemic corticosteroids within 365 days	365 days
Secondary	Change in FEV1	Change in lung function (?FEV1) from baseline to 365 days	365 days
Secondary	Change in blood eosinophils	Change in blood eosinophils from baseline to 365 days (eosinophilic trajectories)	365 days
Secondary	Diabetes mellitus	New diagnosis of diabetes mellitus within 365 days	365 days
Secondary	Change in HbA1c	Change in HbA1c from baseline to 365 days	365 days
Secondary	Number of antibiotic requiring infections	Antibiotic-requiring infections within 365 days	365 days
Secondary	Microbiota, abundance and diversity	Difference in respiratory microbiota abundance and diversity from baseline to 12 months between treatment arms	365 days
Secondary	Microbiota, immunological profile	Difference in immunological profile including cytokines and chemokines in the upper airways from baseline to 12 months between treatment arms	365 days
Secondary	Change in CAT score	Change in COPD-related quality of life (Based on COPD Assessment Test - CAT) from baseline to 365 days	365 days
Secondary	Change in MRC dyspnoea score	Number who progress to MRC -dyspnea score from < 3 to =3 anytime during follow-up (assessed every 3 months).	365 days
Secondary	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	365 days
Secondary	Mortality	Mortality within 365 days	365 days