PCT-guided Treatment Regarding Antibiotic Use for Acute COPD Exacerbations

Not Applicable

Recruiting

• Conditions: Acute Copd Exacerbation; COPD Exacerbation; COPD
• Interventions: Diagnostic Test: Procalcitonin; Other: Physician's decision

• Registration Number: NCT05854901
• Lead Sponsor: Erasmus Medical Center

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.

Study Timeline

• Study Start: 2021-08-10
• Study First Submitted: 2023-02-14
• Status Verified: 2023-05
• Study First Submitted QC: 2023-05-09
• Last Update Submitted: 2023-05-09
• Study First Posted: 2023-05-11
• Last Update Posted: 2023-05-11
• Primary Completion: 2025-02
• Study Completion: 2025-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 693

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PCT-guided treatment	Procalcitonin	Patients randomized to this arm will only receive antibiotic treatment when the procalcitonin concentration is \> 0.25ug/L.
Usual care	Physician's decision	Patients randomized to this arm will receive antibiotic treatment based on the physician's decision.

Primary Outcome Measures

Name	Time	Method
Treatment failure	30 days	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.

Secondary Outcome Measures

Name	Time	Method
CAT	change between baseline and day 30	COPD assessment test, quality of life questionnaire
EQ-5D-5L	change between baseline and day 30	quality of life questionnaire
Re-exacerbation	30 days	The presence of a new exacerbation, requiring treatment (prednisolone and/or antibiotic treatment) during follow-up
Decision to start antibiotic therapy after an initial opposite decision (after 48 hours)	30 days	Decision to start antibiotic therapy after an initial opposite decision (after 48 hours)
Incomplete resolution of the clinical signs and symptoms	day 30	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
iMCQ	30 days	Medical consumption questionnaire, measuring the total amount of medical consumption (admission, ER visits, outpatient visits) during follow-up
Cumulative antibiotic consumption	30 days	The cumulative amount of antibiotic treatment consumed by the patient during follow-up
Cumulative prednisolone consumption	30 days	The cumulative amount of prednisolone consumed by the patient during follow-up
Length of hospitalization	up to 30 days	Duration of time (in days) of the admission in hospital for the index exacerbation during follow-up
Non-invasive ventilation after 72 hours of admission	30 days	Need for non-invasive ventilation after 72 hours of admission
Time to complete resoluation of symptoms	30 days	· Time to complete resolution of symptoms according to daily symptom diaries evaluating the modified Anthonisen criteria
Modified Anthonisen criteria	day 10	Patients fill in the modified Anthonisen criteria card on day 1 as a baseline measure
Side effects of antibiotic treatment	30 days	Side effects of antibiotic treatment, such as gastro-intestinal complaints, allergic reactions
EXACT respiratory questionnaire	day 30	PROM symptom score: EXACT - Respiratory symptoms scale

Trial Locations

Locations (11)

Bravis hospital; 🇳🇱 Roosendaal, Noord-Brabant, Netherlands

Amphia hospital; 🇳🇱 Breda, Noord-Brabant, Netherlands

Catharina hospital; 🇳🇱 Eindhoven, Noord-Brabant, Netherlands

Zuyderland hospital; 🇳🇱 Heerlen, Limburg, Netherlands

Noordwest hospital group; 🇳🇱 Alkmaar, Noord-Holland, Netherlands

OLVG; 🇳🇱 Amsterdam, Noord-Holland, Netherlands

Isala klinieken; 🇳🇱 Zwolle, Overijssel, Netherlands

MST Enschede; 🇳🇱 Enschede, Overijssel, Netherlands

Groene Hart; 🇳🇱 Gouda, Zuid-Holland, Netherlands

Erasmus MC; 🇳🇱 Rotterdam, Zuid-Holland, Netherlands

Franciscus Gasthuis & Vlietland; 🇳🇱 Rotterdam, Zuid-Holland, Netherlands