PCT-guided Treatment Regarding Antibiotic Use for Acute COPD Exacerbations (PRECISION)

May 9, 2023 updated by: Menno M. van der Eerden, Erasmus Medical Center

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

693

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PCT-guided treatment
Patients randomized to this arm will only receive antibiotic treatment when the procalcitonin concentration is > 0.25ug/L.
Diagnostic test: Procalcitonin
blood test, measuring the concentration of PCT in ug/L
Other Names:
  • PCT
Active Comparator: Usual care
Patients randomized to this arm will receive antibiotic treatment based on the physician's decision.
Other: Physician's decision
The physician's decided whether the patient will receive antibiotic treatment or not

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment failure
Time Frame: 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.
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incomplete resolution of the clinical signs and symptoms
Time Frame: change between baseline and after 30 days
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
Incomplete resolution of the clinical signs and symptoms
Time Frame: 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
day 30
Modified Anthonisen criteria
Time Frame: baseline
Patients fill in the modified Anthonisen criteria card on day 1 as a baseline measure
baseline
Modified Anthonisen criteria
Time Frame: day 3
Patients fill in the modified Anthonisen criteria card on day 3
day 3
Modified Anthonisen criteria
Time Frame: day 5
Patients fill in the modified Anthonisen criteria card on day 1 as a baseline measure
day 5
Modified Anthonisen criteria
Time Frame: day 10
Patients fill in the modified Anthonisen criteria card on day 1 as a baseline measure
day 10
Decision to start antibiotic therapy after an initial opposite decision (after 48 hours)
Time Frame: 30 days
Decision to start antibiotic therapy after an initial opposite decision (after 48 hours)
30 days
Side effects of antibiotic treatment
Time Frame: 30 days
Side effects of antibiotic treatment, such as gastro-intestinal complaints, allergic reactions
30 days
Cumulative antibiotic consumption
Time Frame: 30 days
The cumulative amount of antibiotic treatment consumed by the patient during follow-up
30 days
Cumulative prednisolone consumption
Time Frame: 30 days
The cumulative amount of prednisolone consumed by the patient during follow-up
30 days
Length of hospitalization
Time Frame: up to 30 days
Duration of time (in days) of the admission in hospital for the index exacerbation during follow-up
up to 30 days
Re-exacerbation
Time Frame: 30 days
The presence of a new exacerbation, requiring treatment (prednisolone and/or antibiotic treatment) during follow-up
30 days
EXACT respiratory questionnaire
Time Frame: change between baseline and after 30 days
PROM symptom score: EXACT - Respiratory symptoms scale
change between baseline and after 30 days
EXACT respiratory questionnaire
Time Frame: baseline
PROM symptom score: EXACT - Respiratory symptoms scale
baseline
EXACT respiratory questionnaire
Time Frame: day 10
PROM symptom score: EXACT - Respiratory symptoms scale
day 10
EXACT respiratory questionnaire
Time Frame: day 30
PROM symptom score: EXACT - Respiratory symptoms scale
day 30
CAT
Time Frame: baseline
COPD assessment test, quality of life questionnaire
baseline
CAT
Time Frame: day 10
COPD assessment test, quality of life questionnaire
day 10
CAT
Time Frame: day 30
COPD assessment test, quality of life questionnaire
day 30
CAT
Time Frame: change between baseline and day 30
COPD assessment test, quality of life questionnaire
change between baseline and day 30
EQ-5D-5L
Time Frame: baseline
quality of life questionnaire
baseline
EQ-5D-5L
Time Frame: day 10
quality of life questionnaire
day 10
EQ-5D-5L
Time Frame: day 30
quality of life questionnaire
day 30
EQ-5D-5L
Time Frame: change between baseline and day 30
quality of life questionnaire
change between baseline and day 30
iMCQ
Time Frame: 30 days
Medical consumption questionnaire, measuring the total amount of medical consumption (admission, ER visits, outpatient visits) during follow-up
30 days
Non-invasive ventilation after 72 hours of admission
Time Frame: 30 days
Need for non-invasive ventilation after 72 hours of admission
30 days
Time to complete resoluation of symptoms
Time Frame: 30 days
· Time to complete resolution of symptoms according to daily symptom diaries evaluating the modified Anthonisen criteria
30 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cost-effective analysis
Time Frame: 30 days
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Erasmus Medical Center

Collaborators

ZonMw: The Netherlands Organisation for Health Research and Development

Investigators

  • Principal Investigator: Menno M van der Eerden, MD, PhD, Erasmus Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 10, 2021

Primary Completion (Anticipated)

February 1, 2025

Study Completion (Anticipated)

February 1, 2025

Study Registration Dates

First Submitted

February 14, 2023

First Submitted That Met QC Criteria

May 9, 2023

First Posted (Estimate)

May 11, 2023

Study Record Updates

Last Update Posted (Estimate)

May 11, 2023

Last Update Submitted That Met QC Criteria

May 9, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL72662.078.20
  • NL9122 (Registry Identifier: Netherlands Trial Register)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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