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

NCT05059873 | Terminated Phase 4 DMC

• 1 other identifier: Z201100005520029
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (17)

• Requiring or receiving invasive or non-invasive MV during the index hospitalization

  14 days

• Requiring or transferring to ICU during the index hospitalization

  14 days

• Length of index hospitalization longer than 14 days

  14 days

• Death during the index hospitalization or within 30 days after discharge

  30 days after discahrge

• Readmission with acute exacerbations of COPD within 30 days after discharge

  30 days after discahrge

Study Arms (2)

Systemic corticosteroid group

EXPERIMENTAL

Patients will receive Oral prednisone 40mg/day for five consecutive days in addition to standard treatment during emergency admission or hospitalization.

Drug: Prednisone

Control group

PLACEBO COMPARATOR

Participating patients will receive an oral placebo of 40mg/day for five consecutive days in addition to standard treatment.

Drug: Placebo

Interventions

Prednisone DRUG

Oral prednisone 40mg/day for five consecutive days

Systemic corticosteroid group

Placebo DRUG

Oral placebo of 40mg/day for five consecutive days

Control group

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Capital Medical University: lead
• Peking University: collaborator
• Guang'anmen Hospital of China Academy of Chinese Medical Sciences: collaborator
• Xuanwu Hospital, Beijing: collaborator
• Beijing Anzhen Hospital: collaborator
• Beijing Tongren Hospital: collaborator
• Beijing Luhe Hospital: collaborator
• Emergency General Hospital: collaborator
• Beijing Jishuitan Hospital: collaborator
• Beijing Jingmei Group Hospital: collaborator
• Bejing INFI-SAGACITY TECHNOLOGY CO., LTD: collaborator
• Chinese People's Liberation Army of China General Hospital: collaborator
• Beijing Yanhua Hospital: collaborator
• Peking University Shougang Hospital: collaborator
• The First Hospital of Fangshan District: collaborator
• Liangxiang Hospital: collaborator
• Beijing Huairou Hospital: collaborator

Study Sites (1)

Beijing Chao-Yang Hospital

Beijing, Beijing Municipality, 100020, China

Location

Related Publications (9)

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

  PMID: 32745458 BACKGROUND

• 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.

  PMID: 30955513 BACKGROUND

• 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.

  PMID: 31122894 BACKGROUND

• 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.

  PMID: 9603117 BACKGROUND

• 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.

  PMID: 24507843 BACKGROUND

• 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.

  PMID: 26851799 BACKGROUND

• 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.

  PMID: 34179040 BACKGROUND

• 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.

  PMID: 31385389 BACKGROUND

• Liang L, Lin Y, Feng L, Shao S, Cao S, Rong H, Chu S, Xie W, Cai S, Wang J, Tong Z. Multicentre double-blind randomised controlled trial of systematic corticosteroid therapy in patients with acute exacerbations of chronic obstructive pulmonary disease admitted to hospital with higher eosinophil levels: the ECHO protocol. BMJ Open. 2023 May 29;13(5):e066354. doi: 10.1136/bmjopen-2022-066354.

  PMID: 37247957 DERIVED

Related Links

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

MeSH Terms

Conditions

Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive

Interventions

Prednisone

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Tong Zhaohui, PhD

  Beijing Chao Yang Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Derictor of Beijing Institute of Respiratory Medicine and Vice president of Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

Study Record Dates

• First Submitted: September 18, 2021
• First Posted: September 28, 2021
• Study Start: March 5, 2023
• Primary Completion: April 30, 2024
• Study Completion: May 31, 2024
• Last Updated: August 28, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: After the main results of the ECHO study have been published
• Access Criteria: Supporting information will be available from the corresponding author Zhaohui Tong (Email: tongzhaohuicy@sina.com)

Locations

CN (1)