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

COPD Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05059873
• Other study ID #: Z201100005520029
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: March 5, 2023
• Est. completion date: March 31, 2024

Study information

• Verified date: March 2023
• Source: Capital Medical University
• Contact: Rong Hengmo, PhD
• Phone: +8615810271669
• Email: ronghengmo[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 456
• Est. completion date: March 31, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Prednisone
Oral prednisone 40mg/day for five consecutive days
• Placebo
Oral placebo of 40mg/day for five consecutive days

Locations

Country	Name	City	State
n/a

Sponsors (14)

Lead Sponsor

Collaborator

Capital Medical University

Beijing Anzhen Hospital, Beijing Jingmei Group Hospital, Beijing Jishuitan Hospital, Beijing Luhe Hospital, Beijing Shijingshan Hospital, Beijing Tongren Hospital, Beijing Yanhua Hospital, Bejing INFI-SAGACITY TECHNOLOGY CO., LTD, Chinese People's Liberation Army of China General Hospital, Emergency General Hospital, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Peking University, Xuanwu Hospital, Beijing

References & Publications (8)

Bafadhel M, Greening NJ, Harvey-Dunstan TC, Williams JE, Morgan MD, Brightling CE, Hussain SF, Pavord ID, Singh SJ, Steiner MC. Blood Eosinophils and Outcomes in Severe Hospitalized Exacerbations of COPD. Chest. 2016 Aug;150(2):320-8. doi: 10.1016/j.chest.2016.01.026. Epub 2016 Feb 3. — View Citation

Cui Y, Zhan Z, Zeng Z, Huang K, Liang C, Mao X, Zhang Y, Ren X, Yang T, Chen Y. Blood Eosinophils and Clinical Outcomes in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Propensity Score Matching Analysis of Real-World Data in China. Front Med (Lausanne). 2021 Jun 9;8:653777. doi: 10.3389/fmed.2021.653777. eCollection 2021. — View Citation

Duffy SP, Criner GJ. Chronic Obstructive Pulmonary Disease: Evaluation and Management. Med Clin North Am. 2019 May;103(3):453-461. doi: 10.1016/j.mcna.2018.12.005. Epub 2019 Mar 14. — View Citation

Ko FWS, Chan KP, Ngai J, Ng SS, Yip WH, Ip A, Chan TO, Hui DSC. Blood eosinophil count as a predictor of hospital length of stay in COPD exacerbations. Respirology. 2020 Mar;25(3):259-266. doi: 10.1111/resp.13660. Epub 2019 Aug 6. — View Citation

Labaki WW, Rosenberg SR. Chronic Obstructive Pulmonary Disease. Ann Intern Med. 2020 Aug 4;173(3):ITC17-ITC32. doi: 10.7326/AITC202008040. — View Citation

Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998 May;157(5 Pt 1):1418-22. doi: 10.1164/ajrccm.157.5.9709032. — View Citation

Sivapalan P, Lapperre TS, Janner J, Laub RR, Moberg M, Bech CS, Eklof J, Holm FS, Armbruster K, Sivapalan P, Mosbech C, Ali AKM, Seersholm N, Wilcke JT, Brondum E, Sonne TP, Ronholt F, Andreassen HF, Ulrik CS, Vestbo J, Jensen JS. Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation (CORTICO-COP): a multicentre, randomised, controlled, open-label, non-inferiority trial. Lancet Respir Med. 2019 Aug;7(8):699-709. doi: 10.1016/S2213-2600(19)30176-6. Epub 2019 May 20. — View Citation

Wedzicha JA, Singh R, Mackay AJ. Acute COPD exacerbations. Clin Chest Med. 2014 Mar;35(1):157-63. doi: 10.1016/j.ccm.2013.11.001. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Requiring or receiving invasive or non-invasive MV during the index hospitalization	Collect during index hospitalization.	14 days
Secondary	Requiring or transferring to ICU during the index hospitalization	Collect during index hospitalization.	14 days
Secondary	Length of index hospitalization longer than 14 days	Collect during index hospitalization.	14 days
Secondary	Death during the index hospitalization or within 30 days after discharge	Collect during index hospitalization and 30-day follow-up.	30 days after discahrge
Secondary	Readmission with acute exacerbations of COPD within 30 days after discharge	Collect during index hospitalization and 30-day follow-up.	30 days after discahrge
Secondary	All-cause mortality within 90 days after discharge	Collect during 90-day follow-up.	90 days after discahrge
Secondary	Readmission rates of AECOPD at 60-day and 90-day follow-ups	Collect during 90-day follow-up.	90 days after discahrge
Secondary	Time to readmission of AECOPD within 90 days after discharge	Collect during 90-day follow-up.	90 days after discharge
Secondary	Severer infection or development of pneumonia during hospitalization	Collect during index hospitalization.	14 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Length of hospital stay during hospitalization	Collect during huopitalization	14 days

External Links

•   Chinese expert consensus on the diagnosis and treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) (updated version in 2017)