Clinical trial NCT04481555: Eosinophil-guided Reduction of Inhaled Corticosteroids
Official title: Eosinophil-guided Reduction of Inhaled Corticosteroids
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: COPD
Inhaled Corticosteroid
Azithromycin
COPD Exacerbation
Pneumonia
Lead sponsor: Chronic Obstructive Pulmonary Disease Trial Network, Denmark
Sponsor class: OTHER
First posted: 2020-07-22
Enrollment: 444
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Exacerbations, hospital and death
timeFrame: 365 days
Secondary outcomes:
measure: Days alive, out of hospital
timeFrame: 365 days
measure: Deaths, uncontrolled AECOPD
timeFrame: 365 days
measure: Number of exacerbations
timeFrame: 365 days
measure: Cumulative ICS dose
timeFrame: 365 days
measure: Cumulative OCS dose
timeFrame: 365 days
measure: Change in FEV1
timeFrame: 365 days
measure: Change in blood eosinophils
timeFrame: 365 days
measure: Diabetes mellitus
timeFrame: 365 days
measure: Change in HbA1c
timeFrame: 365 days
measure: Number of antibiotic requiring infections
timeFrame: 365 days
measure: Microbiota, abundance and diversity
timeFrame: 365 days
measure: Microbiota, immunological profile
timeFrame: 365 days
measure: Change in CAT score
timeFrame: 365 days
measure: Change in MRC dyspnoea score
timeFrame: 365 days
measure: Number of non-invasive ventilation (NIV) or intensive care admissions or death
timeFrame: 365 days
measure: Mortality
timeFrame: 365 days
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Hvidovre Hospital
city: Esbjerg
country: Denmark
facility: Sydvestjysk Sygehus Esbjerg
city: Hellerup
country: Denmark
facility: Gentofte Hospital
city: Hillerød
country: Denmark
facility: Nordsjællands Hospital
city: Næstved
country: Denmark
facility: Næstved-Slagelse-Ringsted Sygehus
city: Odense
country: Denmark
facility: Odense University Hospital
city: Roskilde
country: Denmark
facility: Roskilde Sygehus
city: Silkeborg
country: Denmark
facility: Silkeborg Sygehus
Study officials:
References: