Treatment Efficacy of Systemic Corticosteroids in AECOPD Patients With Higher Blood Eosinophil Levels

Study Overview
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Brief Summary
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Chronic Obstructive Pulmonary Disease (COPD) is one of the top three causes of death worldwide now. Acute exacerbations (AEs) of COPD are a risk factor for lung function deterioration, poor quality of life, longer hospitalization, and increased mortality. To date, COPD is associated with a heavy clinical and socioeconomic burden, of which AEs of COPD account for a significant part of the cost of patients with COPD. Although several retrospective cohort studies and post-hoc analyses from randomized controlled trials (RCTs) showed that AECOPD patients with higher blood eosinophils had a shorter length of hospital stay (LOS), lower doses of corticosteroid use, and better response to systematic corticosteroid treatment than those with lower blood eosinophils, the efficacy of systematic corticosteroids in AECOPD patients with higher blood eosinophils has not been confirmed by RCTs. Therefore, this study aims to evaluate if AECOPD patients admitted to hospitals with higher blood eosinophil levels could benefit from systemic corticosteroid therapy. In this study, all eligible AECOPD participants with peripheral blood eosinophil blood count >2% or > 300 cells/μL will be randomly assigned (1:1) to either a control group or a systemic corticosteroid group. The control group will receive an oral placebo of 40mg/day for five consecutive days in addition to standard treatment during emergency admission or hospitalization. And systemic corticosteroid group will receive oral prednisone 40mg/day for five consecutive days and standard treatment. This study will provide evidence on using peripheral blood eosinophil blood count to guide corticosteroid therapy in AECOPD patients and help the clinician make an individual decision for each patient.

Detailed Description
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Data about individual deidentified participants of this trial will be available from the corresponding author Zhaohui Tong (Email: tongzhaohuicy@sina.com) on reasonable request after the main results of the ECHO study have been published.

Official Title
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A Multicenter Double-blind Randomized Controlled Trial of Systemic Corticosteroid Therapy in AECOPD Patients Admitted to Hospital With Higher Blood Eosinophil Levels

Conditions
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Acute Exacerbation of COPD, Corticosteroid, Morality, Lung Diseases, Obstructive, Blood Eosinophil Count, COPD, Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Prednisone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Within 24 hours of admission; Aged between of 40 and 80 years old; Established clinical history of COPD with spirometry-verified COPD (defined as post-bronchodilator forced expiratory volume in one second (FEV1)/ forced vital capacity (FVC) ≤ 0.70); AECOPD diagnosis in accordance with the GOLD guideline (An acute worsening of respiratory symptoms that result in additional therapy)12; Current or former cigarette smokers (≥10 packs per year); Blood eosinophil count > 2% or >300 cells/μL tested within 24 hours of admission; Signed informed consent. Exclusion Criteria: Admission due to other diseases (pneumonia, pneumothorax, pulmonary interstitial disease, active tuberculosis or bronchiectasis, ect); Regular use of glucocorticoid ≥3 months; Received prednisone ≥ 60 mg in the past three days (or equivalent doses of other corticosteroid); Allergic or intolerant to corticosteroid; Participating in or completed another drug trial within 90 days; Pregnancy or lactation; Severe COPD exacerbation requiring invasive mechanical ventilation (IMV) or transfer to ICU within 24 hours after emergency admission or hospitalization; With complications that may cause eosinophilia; Pulmonary embolism within the past two years; Myocardial infarction, uncontrollable congestive heart failure or arrhythmia within the past four weeks; Comorbidity that may influence the immune system; Malignant tumor; Neuromuscular disease affecting the respiratory system; Systemic fungal infection; Thoracotomy or bronchoscopic lung volume reduction surgery history; Adrenocortical insufficiency history; Diabetes mellitus with poor glycemic control; Uncontrollable severe psychiatric illnesses even with medication, cognitive impairment, and severe language difficulties; ALT ≥ 100U/L or AST ≥ 80U/L; Serum creatinine ≥ 162umol/L; Life expectancy of less than 30 days.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Systemic corticosteroid group<br>Patients will receive Oral prednisone 40mg/day for five consecutive days in addition to standard treatment during emergency admission or hospitalization. | Drug: Prednisone<br>* Oral prednisone 40mg/day for five consecutive days<br>|
| Placebo Comparator: Control group<br>Participating patients will receive an oral placebo of 40mg/day for five consecutive days in addition to standard treatment. | Drug: Placebo<br>* Oral placebo of 40mg/day for five consecutive days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment failure rates | Collect during index hospitalization and within 30 days after discharge. Treatment failure is defined as either one of events: a) requiring or receiving invasive or non-invasive MV during the index hospitalization; b) requiring or transferring to ICU during the index hospitalization; c) length of index hospitalization longer than 14 days; d) death during the index hospitalization or within 30 days after discharge; e) readmission with acute exacerbations of COPD within 30 days after discharge. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Requiring or receiving invasive or non-invasive MV during the index hospitalization | Collect during index hospitalization. | 14 days | 
| Requiring or transferring to ICU during the index hospitalization | Collect during index hospitalization. | 14 days | 
| Length of index hospitalization longer than 14 days | Collect during index hospitalization. | 14 days | 
| Death during the index hospitalization or within 30 days after discharge | Collect during index hospitalization and 30-day follow-up. | 30 days after discahrge | 
| Readmission with acute exacerbations of COPD within 30 days after discharge | Collect during index hospitalization and 30-day follow-up. | 30 days after discahrge | 
| All-cause mortality within 90 days after discharge | Collect during 90-day follow-up. | 90 days after discahrge | 
| Readmission rates of AECOPD at 60-day and 90-day follow-ups | Collect during 90-day follow-up. | 90 days after discahrge | 
| Time to readmission of AECOPD within 90 days after discharge | Collect during 90-day follow-up. | 90 days after discharge | 
| Severer infection or development of pneumonia during hospitalization | Collect during index hospitalization. | 14 days | 
| Changes in the scores of Hospital Anxiety and Depression Scale between index hospitalization and 90-day follow-up | Collect during 90-day follow-up. The minimum and maximum values are 14 and 70, respectively. Higher scores mean a worse outcome. | 90 days | 
| Changes in the scores of St. George's Respiratory Questionnaire between index hospitalization and 90-day follow-up | Collect during 90-day follow-up. The minimum and maximum values are 1 and 80, respectively. Higher scores mean a worse outcome. | 90 days | 
| Changes in the scores of exacerbations of chronic pulmonary disease tool between index hospitalization and 90-day follow-up | Collect during huopitalization and 90-day follow-up. The minimum and maximum values are 14 and 73, respectively. Higher scores mean a worse outcome. | 90 days | 
| Changes in the scores of modified Medical Research Council Dyspnoea Scale between index hospitalization and 90-day follow-up | Collect during huopitalization and 90-day follow-up. The minimum and maximum values are 1 and 5, respectively. Higher scores mean a worse outcome. | 90 days | 
| Changes in the scores of COPD Assessment Test between index hospitalization and 90-day follow-up | Collect during huopitalization and 90-day follow-up. The minimum and maximum values are 0 and 40, respectively. Higher scores mean a worse outcome. | 90 days | 
| Changes in the scores of Transition Dyspnea Index between index hospitalization and 90-day follow-up | Collect during huopitalization and 90-day follow-up. | 90 days | 
| Changes in the scores of COPD Exacerbation Recognition Tool during 90-day follow-up | Collect during 90-day follow-up by patients. | 90 days after discharge | 
| Length of hospital stay during hospitalization | Collect during huopitalization | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment failure rates, Chronic Obstructive Pulmonary Disease, Randomized Controlled Trial, Mortality, Corticosteroid, Acute Exacerbation of Chronic Obstructive Pulmonary Disease