Improved Diagnostics, Treatment and Follow-up of Acute Exacerbation of Chronic Obstructive Pulmonary Disease (COPEXNOR)

Improved Diagnostics, Treatment and Follow-up of Acute Exacerbation of Chronic Obstructive Pulmonary Disease (COPEXNOR)

Chronic obstructive pulmonary disease (COPD) is a chronic and often progressive pulmonary disease, where inflammation and recurrent infections are key pathophysiological contibutors in disease progression. Acute exacerbations of COPD (AECOPD) are often treated with antibiotics, even though only about 50% are caused by bacteria, and the evidence for benefit of empiric antibiotic treatment in AECOPD is conflicting. Microbiological sampling is often insufficient in the setting of AECOPD, and there is a lack of biomarkers distinguishing AECOPD caused by bacteria from those not caused by bacteria, leaving the clinician with few tools to guide the use of antibiotics. Overuse of antibiotics is the main driver of antimicrobial resistance (AMR), a major global public health threat, and obtaining the correct microbiological diagnose is important in guiding treatment of AECOPD.

COPEXNOR seeks to examine which samples give the highest microbiological yield in AECOPD, comparing induced sputum to nasopharyngeal swabs. We will also compare conventional microbiological diagnostics to modern rapid molecular microbiological tests, to evaluate if faster microbiological diagnosis improves antibiotic stewardship. The study aims to define the microbiological etiology causing AECOPD in the Norwegian COPD-population, and examine the lung microbiome over time. COPEXNOR will explore biomarkers in sputum and blood that can be useful for differentiating patients who will benefit from antibiotic treatment from patients who will not.

Study Overview

• Status: Not yet recruiting
• Conditions: Respiratory Tract Infections; Pneumonia; Chronic Obstructive Pulmonary Disease Exacerbation
• Intervention / Treatment: Device: Rapid diagnostics

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lars Heggelund, MD, PhD; Phone Number: +47 48285882; Email: lars.heggelund@vestreviken.no
• Study Contact Backup: Name: Karl Erik Müller, MD, PhD; Phone Number: +47 97501475; Email: kamull@vestreviken.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years

• Admitted to the emergency room with a tentative diagnosis of AECOPD, and at least two of the following criteria, more than the daily variation,

  • Increased dyspnea
  • Increased cough
  • Increased sputum production
  • Need for change in medication due to AECOPD
• Signed informed consent. Among patients with temporal or permanent reduced ability to consent, close relatives and/or family members must be asked and may approve or reject participation on behalf of the patient. In cases where close relatives/family members are not available, study personnel may include patients according to conscious judgment.
• Patients will be informed about the study and included by dedicated and approved study personnel (study nurses or study doctors), not by the treating health personnel.

Exclusion Criteria:

• Pulmonary embolism, segmental or larger
• Refractory septic shock (meeting the Sepsis-3 definition of septic shock, and requiring vasopressors ≥ 0.5 mcg/kg/min noradrenaline or equivalent dose of other vasopressor(s)
• Glasgow Coma Scale score 3
• Patients not eligible for lower airways sampling within the first 24 hours of admission
• Palliative situation with life expectancy < 1 week

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard diagnostics; Standard microbiological diagnostics, with nasopharyngeal swab and induced sputum or endotracheal aspirate for real-time polymerase chain reaction (PCR) and culture, blood cultures and urinary antigen tests
Experimental: Rapid diagnostics; In addition to standard diagnostics, induced sputum or endotracheal aspirate analyzed with multiplex PCR (FilmArray).	Device: Rapid diagnostics; Sputum sampes will in addition to standard diagnostics be investigated using a rapid diagnostic plattform (FilmArray)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improve microbiological sampling strategies in AECOPD.	Proportion of AECOPD with a microbiologically verified diagnosis from sputum versus nasopharyngeal swab.	Within months to a year after study completion.
Improve microbiological diagnostic workflow for faster initiation of adequate antibiotic therapy.	Time to targeted antimicrobial therapy in hours.	Within months to a year after study completion.
Reduce the use of unnecessary broad antimicrobial therapy.	Proportion of patients with AECOPD who receive targeted antimicrobial therapy.	Within months to a year after study completion.
Increase knowledge of the microbiological etiology in AECOPD.	Microbiological etiology in AECOPD.	Within months to a year after study completion.
Increased understanding of the lung microbiome over time.	Identify differences in lung microbiome over time, both in AECOPD and stabile state.	2-5 years after study completion
Biomarkers at protein level	Identifying biomarkers in blood and sputum that can help differentiate between bacterial and non-bacterial AECOPD	2-5 years after study completion
Protein markers of the iron metabolism	Identifying dynamics in iron metabolism in light of etiology.	2-5 years after study completion
Biomarkers at the transcriptional level	Identifying different transcriptomic profiles in different causes of AECOPD	2-5 years after study completion
Biomarkers for predicting outcome	Identifying biomarkers that can predict outcome in AECOPD.	2-5 years after study completion

Collaborators and Investigators

• Sponsor: Vestre Viken Hospital Trust
• Investigators: Principal Investigator: Lars Heggelund, MD, PhD, Medical department, Drammen hospital, Vestre Viken. Department of clinical science, faculty of medicine, University of Bergen.; Study Director: Karl Erik Müller, MD, PhD, Medical department, Drammen hospital, Vestre Viken. Department of clinical science, faculty of medicine, University of Bergen.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: October 23, 2023
• First Submitted That Met QC Criteria: October 23, 2023
• First Posted (Actual): October 30, 2023

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Diseases; Disease Attributes; Chronic Disease; Disease Progression; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections
• Other Study ID Numbers: DS-INF-COPEXNOR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Research data is likely to be made avaliable upon reasonable request. It has to be anonymized due to national regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No