Eosinopenia in Severe COPD Exacerbation

NCT06188065 | Recruiting

• 1 other identifier: SCI65
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The goals of this observational study are to identify factors independently associated with admission eosinopenia in patients with a severe exacerbation of chronic obstructive pulmonary disease (COPD) and to determine when blood eosinophil count (BEC) will recover to baseline stable state in patients who are admitted to hospital with a severe exacerbation of COPD and associated eosinopenia. The main aims of the study are to:

1. 1.Identify demographic, physiological and clinical factors independently associated with admission eosinopenia in patients with a severe exacerbation of COPD
2. 2.Assess the time to recovery from eosinopenia to stable BEC following a severe exacerbation of COPD

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (2)

• Indices independently associated with eosinopenia on admission in patients with a severe exacerbation of COPD.

  Candidate indices will be identified by both univariate analysis (inclusion of indices related to eosinopenia at the 0.1 threshold) and domain knowledge (inclusion of indices thought likely to be related to eosinopenia even if no association on univariate analysis). Summary indices will also be created to reduce the number of variables (e.g. evidence of bacterial infection will include positive blood culture, sputum culture or antigens). Once candidate indices have been identifed, collinearity will be addressed and then independent associates of eosinopenia will be identified by logistic regression using backwards stepwise elimination.

  On admission date

• The time taken for BEC to recover to stable state following a severe exacerbation of COPD.

  1, 2, 3, 4 and 6 weeks from admission date

Secondary Outcomes (6)

• Level of agreement between the index admission eosinophil phenotype and prior admissions for exacerbations of COPD since May 2019.

  On admission date

• Change from baseline cytokine levels at day 28m stratified by intercurrent exacerbation or other acute illness status, including sub-group analysis (eosinopenic cohort vs non-eosinopenic cohort)

  On admission date and 4 weeks from admission date

• The proportion of patients whose BEC reaches 100 cell/uL or higher at each visit.

  1, 2, 3, 4 and 6 weeks from admission date

• The time taken to reach peak BEC after a severe exacerbation of COPD.

  1, 2, 3, 4 and 6 weeks from admission date

• Exploratory analysis looking for patient and treatment associations with rate of recovery of BEC.

  1, 2, 3, 4 and 6 weeks from admission date

Study Arms (2)

Participants with severe exacerbation of COPD and eosinophils < 0.05 x 10^9/L

Participants to be included in the co-primary outcomes for the time to recovery from eosinopenia analysis as well as the analysis to identify independent factors associated with eosinopenia on admission in patients with a severe exacerbation of COPD. This group of participants will also be included in all secondary outcomes.

Diagnostic Test: Blood eosinophil count

Participants with severe exacerbation of COPD and eosinophils >= 0.05 x 10^9/L

Participants will be included in the co-primary outcome to identify independent factors associated with eosinopenia on admission in patients with a severe exacerbation of COPD. This group of participants will also be included in some of the secondary outcomes.

Diagnostic Test: Blood eosinophil count

Interventions

Blood eosinophil count DIAGNOSTIC_TEST

To determine the time it takes for blood eosinophil count to recover to baseline stable state following severe exacerbation of COPD associated with admission eosinopenia and to explore independent factors associated with admission eosinopenia.

Participants with severe exacerbation of COPD and eosinophils < 0.05 x 10^9/L; Participants with severe exacerbation of COPD and eosinophils >= 0.05 x 10^9/L

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants will be aged 35 years and over. They will have been admitted to hospital with an exacerbation of COPD +/- eosinopenia.

You may qualify if:

• Admitted to hospital with primary clinical diagnosis of exacerbation of COPD\*
• Smoking history of at least 10 pack years
• Airflow obstruction: FEV1/FVC ratio \< 0.7 confirmed on historic or inpatient spirometry
• Capacity to give informed consent to participate

You may not qualify if:

• Parasitic infection, systemic fungal infection (excluding infection limited to nails or skin), eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome or other conditions associated with a high eosinophil count#
• Active malignancy
• Maintenance oral prednisolone or other systemic steroids, anti-interleukin 5 therapy or other medication known to influence eosinophils
• Patients with poor venous access
• Investigator confirmed history of asthma
• Non-COPD related health problems which in the view of the primary investigator may compromise the conduct and completion of the study
• ADDITIONAL CRITERIA FOR THE TIME TO RECOVERY FROM EOSINOPENIA ANALYSIS ONLY
• Eosinopenia on admission
• Uneventful recovery\*
• Eosinopenia on admission who do not receive a further course of systemic corticosteroids or require emergency hospital admission for an acute illness in the six weeks following admission to hospital with a severe exacerbation of COPD.

Sponsors & Collaborators

• Northumbria Healthcare NHS Foundation Trust: lead
• Newcastle University: collaborator
• Chiesi UK: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

Northumbria Healthcare NHS Foundation Trust

North Shields, United Kingdom

RECRUITING

Related Publications (9)

• Bafadhel M, Peterson S, De Blas MA, Calverley PM, Rennard SI, Richter K, Fageras M. Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials. Lancet Respir Med. 2018 Feb;6(2):117-126. doi: 10.1016/S2213-2600(18)30006-7. Epub 2018 Jan 10.

  PMID: 29331313 BACKGROUND

• Singh D, Agusti A, Martinez FJ, Papi A, Pavord ID, Wedzicha JA, Vogelmeier CF, Halpin DMG. Blood Eosinophils and Chronic Obstructive Pulmonary Disease: A Global Initiative for Chronic Obstructive Lung Disease Science Committee 2022 Review. Am J Respir Crit Care Med. 2022 Jul 1;206(1):17-24. doi: 10.1164/rccm.202201-0209PP. No abstract available.

  PMID: 35737975 BACKGROUND

• Suissa S, Ernst P. Precision Medicine Urgency: The Case of Inhaled Corticosteroids in COPD. Chest. 2017 Aug;152(2):227-231. doi: 10.1016/j.chest.2017.05.020. No abstract available.

  PMID: 28797382 BACKGROUND

• Global Strategy for Prevention, Diagnosis and Management of COPD: 2023 Report. Global Initiative for Chronic Obstructive Lung Disease, 2023.

  BACKGROUND

• Steer J, Gibson J, Bourke SC. The DECAF Score: predicting hospital mortality in exacerbations of chronic obstructive pulmonary disease. Thorax. 2012 Nov;67(11):970-6. doi: 10.1136/thoraxjnl-2012-202103. Epub 2012 Aug 15.

  PMID: 22895999 BACKGROUND

• Prasad A, Echevarria C, Steer J, Bourke S C. Blood eosinophil counts during severe exacerbations do not reflect stable state inflammatory phenotype in COPD. European Respiratory Journal 2022 60: 1870.

  BACKGROUND

• Lipson DA, Barnhart F, Brealey N, Brooks J, Criner GJ, Day NC, Dransfield MT, Halpin DMG, Han MK, Jones CE, Kilbride S, Lange P, Lomas DA, Martinez FJ, Singh D, Tabberer M, Wise RA, Pascoe SJ; IMPACT Investigators. Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med. 2018 May 3;378(18):1671-1680. doi: 10.1056/NEJMoa1713901. Epub 2018 Apr 18.

  PMID: 29668352 BACKGROUND

• Lipson DA, Crim C, Criner GJ, Day NC, Dransfield MT, Halpin DMG, Han MK, Jones CE, Kilbride S, Lange P, Lomas DA, Lettis S, Manchester P, Martin N, Midwinter D, Morris A, Pascoe SJ, Singh D, Wise RA, Martinez FJ. Reduction in All-Cause Mortality with Fluticasone Furoate/Umeclidinium/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2020 Jun 15;201(12):1508-1516. doi: 10.1164/rccm.201911-2207OC.

  PMID: 32162970 BACKGROUND

• Echevarria C, Steer J, Prasad A, Quint JK, Bourke SC. Admission blood eosinophil count, inpatient death and death at 1 year in exacerbating patients with COPD. Thorax. 2023 Nov;78(11):1090-1096. doi: 10.1136/thorax-2022-219463. Epub 2023 Jul 24.

  PMID: 37487711 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

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

Study Officials

• Stephen Bourke, MBChB, PhD

  Northumbria Healthcare NHS Foundation Trust

  STUDY CHAIR

• Peter Ireland, MBBS

  Northumbria Healthcare NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephen Bourke, MBChB, PhD

CONTACT

0191 293 4351; stephen.bourke@nhct.nhs.uk

Peter Ireland, MBBS

CONTACT

peter.ireland@northumbria-healthcare.nhs.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2023
• First Posted: January 3, 2024
• Study Start: January 22, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)