Clinical trial NCT05059873: Treatment Efficacy of Systemic Corticosteroids in AECOPD Patients With Higher Blood Eosinophil Levels
Official title: A Multicenter Double-blind Randomized Controlled Trial of Systemic Corticosteroid Therapy in AECOPD Patients Admitted to Hospital With Higher Blood Eosinophil Levels
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Acute Exacerbation of COPD
Corticosteroid
Morality
Lung Diseases, Obstructive
Blood Eosinophil Count
COPD
Pulmonary Disease, Chronic Obstructive
Keywords: Treatment failure rates
Chronic Obstructive Pulmonary Disease
Randomized Controlled Trial
Mortality
Corticosteroid
Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Lead sponsor: Capital Medical University
Sponsor class: OTHER
Collaborators: name: Peking University
name: Guang'anmen Hospital of China Academy of Chinese Medical Sciences
name: Xuanwu Hospital, Beijing
name: Beijing Anzhen Hospital
name: Beijing Tongren Hospital
name: Beijing Luhe Hospital
name: Emergency General Hospital
name: Beijing Jishuitan Hospital
name: Beijing Jingmei Group Hospital
name: Bejing INFI-SAGACITY TECHNOLOGY CO., LTD
name: Chinese People's Liberation Army of China General Hospital
name: Beijing Yanhua Hospital
name: Peking University Shougang Hospital
name: The First Hospital of Fangshan District
name: Liangxiang Hospital
name: Beijing Huairou Hospital
First posted: 2021-09-28
Enrollment: 11
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Within 24 hours of admission;
2. Aged between of 40 and 80 years old;
3. 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);
4. AECOPD diagnosis in accordance with the GOLD guideline (An acute worsening of respiratory symptoms that result in additional therapy)12;
5. Current or former cigarette smokers (≥10 packs per year);
6. Blood eosinophil count \> 2% or \>300 cells/μL tested within 24 hours of admission;
7. Signed informed consent.

Exclusion Criteria:

1. Admission due to other diseases (pneumonia, pneumothorax, pulmonary interstitial disease, active tuberculosis or bronchiectasis, ect);
2. Regular use of glucocorticoid ≥3 months;
3. Received prednisone ≥ 60 mg in the past three days (or equivalent doses of other corticosteroid);
4. Allergic or intolerant to corticosteroid;
5. Participating in or completed another drug trial within 90 days;
6. Pregnancy or lactation;
7. Severe COPD exacerbation requiring invasive mechanical ventilation (IMV) or transfer to ICU within 24 hours after emergency admission or hospitalization;
8. With complications that may cause eosinophilia;
9. Pulmonary embolism within the past two years;
10. Myocardial infarction, uncontrollable congestive heart failure or arrhythmia within the past four weeks;
11. Comorbidity that may influence the immune system;
12. Malignant tumor;
13. Neuromuscular disease affecting the respiratory system;
14. Systemic fungal infection;
15. Thoracotomy or bronchoscopic lung volume reduction surgery history;
16. Adrenocortical insufficiency history;
17. Diabetes mellitus with poor glycemic control;
18. Uncontrollable severe psychiatric illnesses even with medication, cognitive impairment, and severe language difficulties;
19. ALT ≥ 100U/L or AST ≥ 80U/L;
20. Serum creatinine ≥ 162umol/L;
21. Life expectancy of less than 30 days.

Primary outcomes:
measure: Treatment failure rates
timeFrame: 30 days
Secondary outcomes:
measure: Requiring or receiving invasive or non-invasive MV during the index hospitalization
timeFrame: 14 days
measure: Requiring or transferring to ICU during the index hospitalization
timeFrame: 14 days
measure: Length of index hospitalization longer than 14 days
timeFrame: 14 days
measure: Death during the index hospitalization or within 30 days after discharge
timeFrame: 30 days after discahrge
measure: Readmission with acute exacerbations of COPD within 30 days after discharge
timeFrame: 30 days after discahrge
measure: All-cause mortality within 90 days after discharge
timeFrame: 90 days after discahrge
measure: Readmission rates of AECOPD at 60-day and 90-day follow-ups
timeFrame: 90 days after discahrge
measure: Time to readmission of AECOPD within 90 days after discharge
timeFrame: 90 days after discharge
measure: Severer infection or development of pneumonia during hospitalization
timeFrame: 14 days
measure: Changes in the scores of Hospital Anxiety and Depression Scale between index hospitalization and 90-day follow-up
timeFrame: 90 days
measure: Changes in the scores of St. George's Respiratory Questionnaire between index hospitalization and 90-day follow-up
timeFrame: 90 days
measure: Changes in the scores of exacerbations of chronic pulmonary disease tool between index hospitalization and 90-day follow-up
timeFrame: 90 days
measure: Changes in the scores of modified Medical Research Council Dyspnoea Scale between index hospitalization and 90-day follow-up
timeFrame: 90 days
measure: Changes in the scores of COPD Assessment Test between index hospitalization and 90-day follow-up
timeFrame: 90 days
measure: Changes in the scores of Transition Dyspnea Index between index hospitalization and 90-day follow-up
timeFrame: 90 days
measure: Changes in the scores of COPD Exacerbation Recognition Tool during 90-day follow-up
timeFrame: 90 days after discharge
measure: Length of hospital stay during hospitalization
timeFrame: 14 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital
state: Beijing
Study officials:
affiliation: Beijing Chao Yang Hospital
name: Tong Zhaohui, PhD
role: STUDY_CHAIR
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