Clinical trial NCT05854901: PCT-guided Treatment Regarding Antibiotic Use for Acute COPD Exacerbations
Official title: Procalcitonin-guided Treatment Regarding Antibiotic Use for Acute COPD Exacerbations: a Prospective Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: COPD Exacerbation
COPD
Acute Copd Exacerbation
Keywords: Procalcitonin
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2023-05-11
Enrollment: 693
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective randomized clinical multi-center study to evaluate procalcitonin-guided treatment regarding antibiotic use in patients who are admitted because of an acute COPD exacerbation. Patients who are admitted are randomly assigned to either procalcitonin-guided treatment (in which antibiotics are started when the procalcitonin concentration is above 0.25 ng/mL) or usual care in which the treating physician decides whether or not to start with antibiotic treatment. Patients will be stratified for study center.
Primary purpose: DIAGNOSTIC

Brief summary: This study the investigators will examine whether procalcitonin-guided treatment regarding antibiotic therapy is non-inferior to usual care in patients who are admitted because of an acute COPD exacerbation when it comes to treatment failure on day 30.

Detailed description: Chronic obstructive pulmonary disease (COPD) is a prevalent disease, worldwide, and in the Netherlands with approximately 600.000 patients. COPD is currently the 3rd leading cause of death worldwide and is also a leading cause of disability-adjusted life years. Given the contribution of exacerbations both to loss in quality of life and to health-care costs, it is of paramount importance to improve the current treatment of exacerbations.

Pulmonary physicians are well aware of overuse of antibiotics, but lack the tools to decide which medication to give in the clinical setting. Biomarkers may aid towards a more personalized treatment of acute COPD exacerbations (AECOPD). Procalcitonin (PCT), the precursor of calcitonin, is released in response to a bacterial infection by many tissues within 6-12 hours after the onset of infection, while the concentration is only minimally raised in viral infections, making it a relative specific diagnostic tool for bacterial infection. Several trials have shown a reduction in antibiotic consumption in AECOPD when using a PCT-guided treatment algorithm. Recent systematic reviews concluded that appropriately powered trials are lacking to confirm that clinical outcomes are comparable with usual care.

In this study the investigators will examine whether a PCT-guided treatment regarding antibiotic therapy is non-inferior to usual care in patients who are admitted because of an acute COPD exacerbation when it comes to treatment failure on day 30.

Eligibility criteria: Inclusion Criteria:

* COPD, according to GOLD 2018 definition
* Indication for hospitalization because of acute severe exacerbation of COPD, as defined by GOLD 2018 and modified Anthonisen criteria
* Presence of at least 2 major symptoms of the modified Anthonisen criteria (acute deterioration in sputum volume, sputum purulence and dyspnea) or the presence of 1 major symptom and 1 minor symptom (coughing, wheeze, nasal discharge, sore throat, fever)
* Post-bronchodilator FEV1/FVC \< 0,70 and FEV1% \< 80%pred. within last 5 years
* At least 40 years
* Smokers or ex-smokers with \> 10 packyears
* Written informed consent
* Start of symptoms no more than 7 days before admission

Exclusion Criteria:

* Indication for ICU and or non-invasive ventilation \< 72h of admission
* Pneumonia, radiologically confirmed
* Infection at another site and/or sepsis according to the SIRS criteria (with tachycardia and tachypnea not being caused by the exacerbation)
* COPD before age 40
* Asthma, without presence of COPD.

  * Patients with COPD , with or without a history of asthma (in childhood or as an adolescent) will NOT be excluded/are allowed to participate.
  * Patients with Asthma/COPD overlap syndrome (with current asthma AND COPD) will NOT be excluded/are allowed to participate.
* Clinically relevant heart failure or myocardial ischemia
* Chronic use of immunosuppressants, including prednisolone (a prednisone equivalent of 10mg or less is allowed/is NOT an exclusion criterion)
* Known bronchiectasis as a primary diagnosis
* Colonisation with Pseudomonas spp. or other micro-organisms in recent cultures (last 60 days) not susceptible to amoxicillin-clavulanic acid
* Pregnancy
* Recent exacerbation (last 28 days)

Primary outcomes:
measure: Treatment failure
timeFrame: 30 days
Secondary outcomes:
measure: Incomplete resolution of the clinical signs and symptoms
timeFrame: change between baseline and after 30 days
measure: Incomplete resolution of the clinical signs and symptoms
timeFrame: day 30
measure: Modified Anthonisen criteria
timeFrame: baseline
measure: Modified Anthonisen criteria
timeFrame: day 3
measure: Modified Anthonisen criteria
timeFrame: day 5
measure: Modified Anthonisen criteria
timeFrame: day 10
measure: Decision to start antibiotic therapy after an initial opposite decision (after 48 hours)
timeFrame: 30 days
measure: Side effects of antibiotic treatment
timeFrame: 30 days
measure: Cumulative antibiotic consumption
timeFrame: 30 days
measure: Cumulative prednisolone consumption
timeFrame: 30 days
measure: Length of hospitalization
timeFrame: up to 30 days
measure: Re-exacerbation
timeFrame: 30 days
measure: EXACT respiratory questionnaire
timeFrame: change between baseline and after 30 days
measure: EXACT respiratory questionnaire
timeFrame: baseline
measure: EXACT respiratory questionnaire
timeFrame: day 10
measure: EXACT respiratory questionnaire
timeFrame: day 30
measure: CAT
timeFrame: baseline
measure: CAT
timeFrame: day 10
measure: CAT
timeFrame: day 30
measure: CAT
timeFrame: change between baseline and day 30
measure: EQ-5D-5L
timeFrame: baseline
measure: EQ-5D-5L
timeFrame: day 10
measure: EQ-5D-5L
timeFrame: day 30
measure: EQ-5D-5L
timeFrame: change between baseline and day 30
measure: iMCQ
timeFrame: 30 days
measure: Non-invasive ventilation after 72 hours of admission
timeFrame: 30 days
measure: Time to complete resoluation of symptoms
timeFrame: 30 days
Other outcomes:
measure: Cost-effective analysis
timeFrame: 30 days
Locations:
city: Heerlen
country: Netherlands
facility: Zuyderland hospital
state: Limburg
city: Breda
country: Netherlands
facility: Amphia hospital
state: Noord-Brabant
city: Eindhoven
country: Netherlands
facility: Catharina hospital
state: Noord-Brabant
city: Roosendaal
country: Netherlands
facility: Bravis hospital
state: Noord-Brabant
city: Alkmaar
country: Netherlands
facility: Noordwest hospital group
state: Noord-Holland
city: Amsterdam
country: Netherlands
facility: OLVG
state: Noord-Holland
city: Enschede
country: Netherlands
facility: MST Enschede
state: Overijssel
city: Zwolle
country: Netherlands
facility: Isala klinieken
state: Overijssel
city: Gouda
country: Netherlands
facility: Groene Hart
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis & Vlietland
state: Zuid-Holland
Study officials:
affiliation: Erasmus Medical Center
name: Menno M van der Eerden, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: