PCT-guided Treatment Regarding Antibiotic Use for Acute COPD Exacerbations

COPD Clinical Trial

— PRECISION  

Official title:

Procalcitonin-guided Treatment Regarding Antibiotic Use for Acute COPD Exacerbations: a Prospective Randomised Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05854901
• Other study ID #: NL72662.078.20
• Secondary ID: NL9122
• Status: Recruiting
• Phase: N/A
• Start date: August 10, 2021
• Est. completion date: February 2025

Study information

• Verified date: May 2023
• Source: Erasmus Medical Center
• Contact: Michael L van Schaik, MD/MSc
• Phone: +31615283010
• Email: m.l.vanschaik[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 693
• Est. completion date: February 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• COPD
• COPD Exacerbation
• Pulmonary Disease, Chronic Obstructive

Intervention

Diagnostic Test:
• Procalcitonin
blood test, measuring the concentration of PCT in ug/L

Other:
• Physician's decision
The physician's decided whether the patient will receive antibiotic treatment or not

Locations

Country	Name	City	State
Netherlands	Noordwest hospital group	Alkmaar	Noord-Holland
Netherlands	OLVG	Amsterdam	Noord-Holland
Netherlands	Amphia hospital	Breda	Noord-Brabant
Netherlands	Catharina hospital	Eindhoven	Noord-Brabant
Netherlands	MST Enschede	Enschede	Overijssel
Netherlands	Groene Hart	Gouda	Zuid-Holland
Netherlands	Zuyderland hospital	Heerlen	Limburg
Netherlands	Bravis hospital	Roosendaal	Noord-Brabant
Netherlands	Erasmus MC	Rotterdam	Zuid-Holland
Netherlands	Franciscus Gasthuis & Vlietland	Rotterdam	Zuid-Holland
Netherlands	Isala klinieken	Zwolle	Overijssel

Sponsors (2)

Lead Sponsor	Collaborator
Erasmus Medical Center	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cost-effective analysis	Alongside the clinical trial, an economic evaluation will be performed conform the guidelines of the Health Care Institute Netherlands (17). This evaluation will be conducted from a societal and payer's perspective. When adopting the societal perspective, costs will include 30-day inpatient and outpatient (emergency room, specialist visits) hospital costs, primary care costs (visits to GP and nurse practitioner), medication costs, ambulance costs, productivity costs, informal care costs and travel costs.	30 days
Primary	Treatment failure	Treatment failure is defined as disease-related mortality, need for endotracheal intubation or vasopressors, renal failure (defined as Kidney Disease: Improving Global Outcomes (KDIGO) stage 3 - new renal replacement therapy, tripling of baseline creatinine, or serum creatinine > or = 350 umol/L), lung abcess/empyema, development of pneumonia or rehospitalization within 30 days after inclusion.	30 days
Secondary	Incomplete resolution of the clinical signs and symptoms	Incomplete resolution of the clinical signs and symptoms associated with the AECOPD at day 30 after inclusion of the study (i.e. not reaching the baseline condition prior to the AECOPD) scored using the modified Anthonisen criteria	change between baseline and after 30 days
Secondary	Incomplete resolution of the clinical signs and symptoms	Incomplete resolution of the clinical signs and symptoms associated with the AECOPD at day 30 after inclusion of the study (i.e. not reaching the baseline condition prior to the AECOPD) scored using the modified Anthonisen criteria	day 30
Secondary	Modified Anthonisen criteria	Patients fill in the modified Anthonisen criteria card on day 1 as a baseline measure	baseline
Secondary	Modified Anthonisen criteria	Patients fill in the modified Anthonisen criteria card on day 3	day 3
Secondary	Modified Anthonisen criteria	Patients fill in the modified Anthonisen criteria card on day 1 as a baseline measure	day 5
Secondary	Modified Anthonisen criteria	Patients fill in the modified Anthonisen criteria card on day 1 as a baseline measure	day 10
Secondary	Decision to start antibiotic therapy after an initial opposite decision (after 48 hours)	Decision to start antibiotic therapy after an initial opposite decision (after 48 hours)	30 days
Secondary	Side effects of antibiotic treatment	Side effects of antibiotic treatment, such as gastro-intestinal complaints, allergic reactions	30 days
Secondary	Cumulative antibiotic consumption	The cumulative amount of antibiotic treatment consumed by the patient during follow-up	30 days
Secondary	Cumulative prednisolone consumption	The cumulative amount of prednisolone consumed by the patient during follow-up	30 days
Secondary	Length of hospitalization	Duration of time (in days) of the admission in hospital for the index exacerbation during follow-up	up to 30 days
Secondary	Re-exacerbation	The presence of a new exacerbation, requiring treatment (prednisolone and/or antibiotic treatment) during follow-up	30 days
Secondary	EXACT respiratory questionnaire	PROM symptom score: EXACT - Respiratory symptoms scale	change between baseline and after 30 days
Secondary	EXACT respiratory questionnaire	PROM symptom score: EXACT - Respiratory symptoms scale	baseline
Secondary	EXACT respiratory questionnaire	PROM symptom score: EXACT - Respiratory symptoms scale	day 10
Secondary	EXACT respiratory questionnaire	PROM symptom score: EXACT - Respiratory symptoms scale	day 30
Secondary	CAT	COPD assessment test, quality of life questionnaire	baseline
Secondary	CAT	COPD assessment test, quality of life questionnaire	day 10
Secondary	CAT	COPD assessment test, quality of life questionnaire	day 30
Secondary	CAT	COPD assessment test, quality of life questionnaire	change between baseline and day 30
Secondary	EQ-5D-5L	quality of life questionnaire	baseline
Secondary	EQ-5D-5L	quality of life questionnaire	day 10
Secondary	EQ-5D-5L	quality of life questionnaire	day 30
Secondary	EQ-5D-5L	quality of life questionnaire	change between baseline and day 30
Secondary	iMCQ	Medical consumption questionnaire, measuring the total amount of medical consumption (admission, ER visits, outpatient visits) during follow-up	30 days
Secondary	Non-invasive ventilation after 72 hours of admission	Need for non-invasive ventilation after 72 hours of admission	30 days
Secondary	Time to complete resoluation of symptoms	· Time to complete resolution of symptoms according to daily symptom diaries evaluating the modified Anthonisen criteria	30 days

External Links

•   Netherlands Trial Register registration included in ICTRP