Corticosteroid Reduction in COPD

Study Overview
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Brief Summary
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This study explores whether patients hospitalized with chronic obstructive pulmonary disease (COPD) exacerbation may have fewer days with prednisolone and with the same treatment effect by controlling the treatment by daily measurements of eosinophils.

Detailed Description
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The most commonly used treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a 5-day treatment with corticosteroids in moderate-high dose. Some patients receive repeated treatments, although it has been shown that corticosteroids only have temporary beneficial effects and no effect in relation to serious incidents or mortality. It has been found that the higher accumulated prednisolone dose disables patients due to serious side effects, including pneumonia, dysregulated diabetes, bone fracture in the context of osteoporosis, mental disorder and adrenal insufficiency etc. However, the extent of the side effects is unknown. Recent research has shown that it is presumably only a small subset of COPD patients who benefit from corticosteroid therapy. This group can be identified by the biomarker blood-eosinophils as already measured on most AECOPD patients during hospitalization. This is a randomized, controlled, multi-center, non-Inferiority trial evaluating the effect of eosinophil guided corticosteroid therapy to patients with AECOPD. The aim of the study is to investigate whether the accumulated dose corticosteroid treatment during admissions for AECOPD can be reduced, including the presumed side effects, while (still) remaining the optimal treatment effect.

Official Title
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The Effect of Reduced Corticosteroid Therapy in Patients With Acute Exacerbation of COPD

Conditions
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COPD, Lung Diseases, Obstructive, Blood Eosinophil Count, Glucocorticoids, Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Prednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients hospitalized with AECOPD Age ≥ 40 years Spirometry-verified COPD (defined as FEV1 / FVC ≤ 70%) Chronic Obstructive Lung Disease (GOLD) class C or D Inclusion within 24 hours after admission Exclusion criteria: Known with a diagnosis of asthma Life expectancy less than 30 days Serious exacerbation requiring invasive ventilation or admission to ICU Allergy to systemic corticosteroids Severe mental illness, which is not controlled by medication People who are detained under the act on the use of coercion in psychiatry Severe language problems or inability to provide written informed consent Pregnancy and lactation Systemic fungal infections

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blood eosinophil guided prednisolone treatment<br>Intravenous Solu-Medrol 80 mg, followed by prednisolone tablet 37.5 mg daily (maximum of 5 days in all) if the eosinophil count in the blood ≥ 0.3 x 10E9/L. Eosinophil count in the blood <0.3 x 10E9/L results in no treatment with prednisolone. If the patient is discharged during the treatment period, given treatment from the last measured eosinophil count the remaining days. | Drug: Prednisolone<br> <br> |
| Active Comparator: Standard of care<br>Intravenous Solu-Medrol 80 mg on the first day followed by 37.5 mg of prednisolone tablets (1 x 25 mg plus 1 x 12.5 mg) daily for 5 days | Drug: Prednisolone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days alive and out of hospital within 14 days after recruitment |  | 14 days from recruitment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment failure (Recurrence of AECOPD resulting in emergency room visits, hospitalization or need to intensify pharmacological treatment within 30 days) |  | 30 days | 
| Change in lung function (ΔFEV1) on day 3, after 1 month and 3 month |  | 90 days | 
| Mortality |  | 360 days | 
| Infection requiring antibiotic treatment within 180 days after the index of AECOPD |  | 180 days | 
| The period between index AECOPD and the next AECOPD exacerbation | Readmission with AECOPD or death Time to readmission with AECOPD or death | 90 days | 
| Cumulative corticosteroid dose at 1 and 3 month follow-up | Proportions of patients using corticosteroids during hospitalization (day 1 to day 5) between treatment arms Mean total cumulative dose from recruitment to 3-month follow-up | 90 days | 
| Hyperglycemia during admission |  | 14 days | 
| Changes in PTH and Vitamin D status between hospitalization and 3-month follow-up |  | 90 days | 
| Change in bone marker levels (Serum P1NP, Serum CTX) |  | 90 days | 
| Dyspepsia or ulcer complications (gastrointestinal bleeding) |  | 90 days | 
| New onset or worsening of diabetes mellitus |  | 30 days | 
| Increase in body mass index between hospitalization, at 30 days and 3-month follow-up |  | 90 days | 
| The impact of COPD (cough, sputum, dysnea, chest tightsenes etc) on health status (COPD Assessment Test) between hospitalization, at 30 days and 3-month follow-up |  | 90 days | 
| Changes in level of dyspnea using the Medical Research Council (MRC) Dyspnoea Scale between hospitalization, at 30 days and 3-month follow-up |  | 90 days | 
| Osteoporotic fractures |  | 360 days |