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

NCT06105814 | Not Yet Recruiting

• 1 other identifier: DS-INF-COPEXNOR
• Study Type: interventional
• Target: 200
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Chronic Obstructive Pulmonary Disease Exacerbation; Pneumonia; Respiratory Tract Infections

Outcome Measures

Primary Outcomes (9)

• 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

Study Arms (2)

Standard diagnostics

NO INTERVENTION

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

Rapid diagnostics

EXPERIMENTAL

In addition to standard diagnostics, induced sputum or endotracheal aspirate analyzed with multiplex PCR (FilmArray).

Device: Rapid diagnostics

Interventions

Rapid diagnostics DEVICE

Sputum sampes will in addition to standard diagnostics be investigated using a rapid diagnostic plattform (FilmArray)

Rapid diagnostics

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Vestre Viken Hospital Trust: lead

MeSH Terms

Conditions

Pneumonia; Respiratory Tract Infections

Interventions

Rapid Diagnostic Tests

Condition Hierarchy (Ancestors)

Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Point-of-Care Testing; Point-of-Care Systems; Patient Care Management; Health Services Administration

Study Officials

• Lars Heggelund, MD, PhD

  Medical department, Drammen hospital, Vestre Viken. Department of clinical science, faculty of medicine, University of Bergen.

  PRINCIPAL INVESTIGATOR

• Karl Erik Müller, MD, PhD

  Medical department, Drammen hospital, Vestre Viken. Department of clinical science, faculty of medicine, University of Bergen.

  STUDY DIRECTOR

Central Study Contacts

Lars Heggelund, MD, PhD

CONTACT

+47 48285882; lars.heggelund@vestreviken.no

Karl Erik Müller, MD, PhD

CONTACT

+47 97501475; kamull@vestreviken.no

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: COPEXNOR is a prospective, randomized controlled trial with two arms: (1) 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, and (2) in addition to (i), induced sputum or endotracheal aspirate analyzed with multiplex PCR (FilmArray).

Study Record Dates

• First Submitted: October 23, 2023
• First Posted: October 30, 2023
• Study Start: January 1, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2030
• Last Updated: October 30, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share