Clinical trial NCT06105814: Improved Diagnostics, Treatment and Follow-up of Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Official title: Improved Diagnostics, Treatment and Follow-up of Acute Exacerbation of Chronic Obstructive Pulmonary Disease (COPEXNOR)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease Exacerbation
Pneumonia
Respiratory Tract Infections
Lead sponsor: Vestre Viken Hospital Trust
Sponsor class: OTHER
First posted: 2023-10-30
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: 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

Primary outcomes:
measure: Improve microbiological sampling strategies in AECOPD.
timeFrame: Within months to a year after study completion.
measure: Improve microbiological diagnostic workflow for faster initiation of adequate antibiotic therapy.
timeFrame: Within months to a year after study completion.
measure: Reduce the use of unnecessary broad antimicrobial therapy.
timeFrame: Within months to a year after study completion.
measure: Increase knowledge of the microbiological etiology in AECOPD.
timeFrame: Within months to a year after study completion.
measure: Increased understanding of the lung microbiome over time.
timeFrame: 2-5 years after study completion
measure: Biomarkers at protein level
timeFrame: 2-5 years after study completion
measure: Protein markers of the iron metabolism
timeFrame: 2-5 years after study completion
measure: Biomarkers at the transcriptional level
timeFrame: 2-5 years after study completion
measure: Biomarkers for predicting outcome
timeFrame: 2-5 years after study completion
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Medical department, Drammen hospital, Vestre Viken. Department of clinical science, faculty of medicine, University of Bergen.
name: Lars Heggelund, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical department, Drammen hospital, Vestre Viken. Department of clinical science, faculty of medicine, University of Bergen.
name: Karl Erik Müller, MD, PhD
role: STUDY_DIRECTOR
References: