Eosinopenia in Severe COPD Exacerbation (A-TREC)

January 25, 2024 updated by: Northumbria Healthcare NHS Foundation Trust

Associates of, and Time to Recovery From, Eosinopenia in Severe COPD Exacerbation

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Blood eosinophils are a type of white blood cell that play a role in the immune system including fighting infection. They have numerous roles but are primarily involved in inflammation. They are recruited from the blood into sites of inflammation.

The blood eosinophil count (BEC) can be used as a biomarker to predict whether the addition of inhaled corticosteroid (ICS) to long-acting bronchodilators (LABD) will be beneficial in reducing future COPD exacerbations. This association is based on BEC being measured when patients are clinically stable. Patients with a higher BEC are more likely to gain these benefits where as conversely, patients with a lower BEC are less likely to benefit and the risk of side effects such as pneumonia will likely outweigh any potential benefit. Current national and international COPD guidelines suggest the use of BEC as a biomarker to help inform the decision of whether to commence or withdraw ICS, but do not specify measuring BEC at a time of clinical stability.

Decisions regarding changes to management are often made in the acute setting. Eosinophils transiently drop to very low levels in half of patients who are admitted to hospital with exacerbations of COPD. Measuring BEC during an acute illness risks incorrectly identifying all patients who may benefit from the introduction of an ICS. In the current BEC COPD study, reliance on admission and discharge BEC inappropriately denied ICS to 47% and 33% of patients respectively compared to a confirmed stable-state measure.

There are co-primary aims for this study. Firstly, the investigators wish to determine when BEC will recover to stable state following a hospital admission for exacerbation of COPD. Determining this will inform healthcare professionals of the optimum time to measure BEC for use as a biomarker when making decisions related to management escalation. Based on the results of BEC COPD, it is likely that an increased number of patients will be identified as being above the BEC threshold and therefore likely to benefit from ICS when time is allowed for BEC to recover to stable state. Appropriate introduction of ICS in this patient group will reduce exacerbation and hospital re-admission rates and thus may reduce overall mortality within this high-risk group. This should reduce the burden of COPD on patient's health, quality of life and the NHS.

Eosinopenia during severe exacerbation of COPD is associated with increased in-hospital and one year mortality. Treatment with oral corticosteroids does not fully explain the mechanism behind the development of eosinopenia, with the phenomenon being less common on discharge compared to admission despite inpatient oral corticosteroid treatment. The investigators other co-primary aim is to identify demographic, physiological and clinical factors independently associated with admission eosinopenia in patients with a severe exacerbation of COPD, providing useful mechanistic information regarding the relationship between BEC and short-term mortality.

The hypothesis for this study is that 90% of participants who are admitted to hospital with a severe exacerbation of COPD and eosinopenia will have recovery of their BEC to baseline stable state within 4 weeks. The investigators also hypothesize that there are demographic, physiological and clinical factors independently associated with admission eosinopenia other than prior systemic corticosteroid use.

Study Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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.

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Inclusion criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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
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 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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Indices independently associated with eosinopenia on admission in patients with a severe exacerbation of COPD.
Time Frame: On admission date
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.
Time Frame: 1, 2, 3, 4 and 6 weeks from admission date
1, 2, 3, 4 and 6 weeks from admission date

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Level of agreement between the index admission eosinophil phenotype and prior admissions for exacerbations of COPD since May 2019.
Time Frame: On admission date
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)
Time Frame: On admission date and 4 weeks from admission date
On admission date and 4 weeks from admission date
The proportion of patients whose BEC reaches 100 cell/uL or higher at each visit.
Time Frame: 1, 2, 3, 4 and 6 weeks from admission date
1, 2, 3, 4 and 6 weeks from admission date
The time taken to reach peak BEC after a severe exacerbation of COPD.
Time Frame: 1, 2, 3, 4 and 6 weeks from admission date
1, 2, 3, 4 and 6 weeks from admission date
Exploratory analysis looking for patient and treatment associations with rate of recovery of BEC.
Time Frame: 1, 2, 3, 4 and 6 weeks from admission date
Patient and treatment variables associated with rate of recovery of BEC will be identified using univariate analysis.
1, 2, 3, 4 and 6 weeks from admission date
Comparison of the rate of recovery of BEC in patients who had further exacerbations of COPD within the study period and patients who have not had further exacerbations.
Time Frame: 1, 2, 3, 4 and 6 weeks from admission date
1, 2, 3, 4 and 6 weeks from admission date

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northumbria Healthcare NHS Foundation Trust

Collaborators

GlaxoSmithKline
Newcastle University
Chiesi UK

Investigators

  • Study Chair: Stephen Bourke, MBChB, PhD, Northumbria Healthcare NHS Foundation Trust
  • Principal Investigator: Peter Ireland, MBBS, Northumbria Healthcare NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 22, 2024

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

July 1, 2026

Study Registration Dates

First Submitted

December 15, 2023

First Submitted That Met QC Criteria

January 2, 2024

First Posted (Actual)

January 3, 2024

Study Record Updates

Last Update Posted (Estimated)

January 29, 2024

Last Update Submitted That Met QC Criteria

January 25, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCI65

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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