- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05463406
Procalcitonin and Lung Ultrasonography Guided Antibiotherapy in Emergency Departments (PLUS-IS-LESS)
Procalcitonin and Lung Ultrasonography Based Antibiotherapy in Patients With Lower Respiratory Tract Infection in Swiss Emergency Departments: Pragmatic Stepped-wedge Cluster-randomized Trial
Acute respiratory infections are a common reason of attendance at emergency departments. It is also the main reason of unnecessary antibiotic prescription. Antibiotics save lives, but can also directly harm patients by causing antibiotic-associated adverse events. Antibiotic use is directly related to resistance, which is one of the major threats of our century. In addition, some microorganisms live in and on the human body and promote many aspects of our health. Antibiotic treatment can disturb those microorganisms and therefore have long-lasting negative effects on our health.
Unfortunately, it is difficult to differentiate between viral infections, which usually heal spontaneously, and bacterial pneumonia, which needs antibiotics treatment. This is one of the reasons of this over-prescribing of antibiotics.
This project aims to reduce widespread use of antibiotics in the emergency department through a new diagnostic strategy of bacterial pneumonia. This strategy includes sequential use of well-known techniques: a clinical score, lung ultrasound and finally a biomarker, procalcitonin. The latter tends to be higher in bacterial infections. The combination of these different tests improves the diagnostic process and allows improved use of targeted antibiotics, with the ultimate goal of better patient management.
The study will compare the antibiotic prescription rate and the clinical course of patients managed using this new diagnostic approach with those managed as usual. The project will also evaluate the acceptability and feasibility of this strategy and its cost-effectiveness. These two aspects are essential for a wider implementation of this innovative diagnostic approach and decrease antibiotic resistance.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Background Community-acquired lower respiratory tract infections (LRTI) are one of the most common motivations for emergency department (ED) consultations and stands as the leading cause of inappropriate antibiotic prescription. Besides the side effects, antibiotic overuse alters the microbiome and generates antibiotic resistance. When assessing patients with LRTIs, the challenge for ED physicians is to identify those with community-acquired pneumonia (CAP) of bacterial origin, who will most likely benefit from antibiotics. The low diagnostic accuracy of existing tools, as well as the poor adherence of clinicians to test guidance are leading causes of inappropriate antibiotic use.
Several diagnostic tests can assist in identifying patients with LRTI who require antibiotics. Clinical prediction score can refine the probability of CAP. Lung ultrasound (LUS) has a better diagnostic performance than chest X-ray, the historic reference imaging modality to consolidation in ED. LUS is performed quickly at the bedside without radiation. Procalcitonin (PCT) is a host inflammatory biomarker which tends to be higher in bacterial infections. PCT can be used safely to guide antibiotics use, while its impact on prescription is controversial. None of these tools on its own is sufficient to optimize antibiotic prescription, while a combined approach could better guide clinicians.
Rationale The investigators propose to evaluate the use of a decision support tool to guide antibiotics use in the ED as the summative value of LUS with PCT remains unknown in this setting.
Pragmatic stepped-wedge cluster-randomized controlled clinical trial investigating a new algorithm combining a clinical score, LUS and PCT results (The PLUS algorithm) for the management of LRTIs among adults in EDs. The unit of randomization will be the ED.
Primary safety objective To demonstrate non-inferiority of the intervention in terms of clinical failure by day 28.
Co-primary efficacy objective To show a 15% reduction in the proportion of patients with LRTIs prescribed an antibiotic by day 28 in the intervention group compared with the usual care group.
Secondary objectives
- To compare the quality of life (bothersomeness of CAP-related symptoms) on day 7, day 28 and day 90 between patients in the intervention and control groups.
- To evaluate the acceptability and feasibility of the intervention through the identification of barriers and facilitators in patients and physicians.
- To assess the incremental cost-effectiveness of the intervention as compared to usual care using a within-trial (short-term), and a model-based (long-term) economic evaluation.
- To develop an advanced automatic LUS image analysis method using machine learning to assist in LUS diagnosis and risk stratification.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Noémie Boillat Blanco, MD
- Phone Number: +41 21 314 88 30
- Email: noemie.boillat@chuv.ch
Study Contact Backup
- Name: Aurélie Fayet (Mello), PhD
- Phone Number: +41 79 556 45 86
- Email: aurelie.mello@chuv.ch
Study Locations
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AG
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Baden, AG, Switzerland, 5404
- Recruiting
- Cantonal hospital of Baden
-
Contact:
- Markus Schwendinger, MD
- Email: markus.schwendinger@ksb.ch
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Principal Investigator:
- Markus Schwendinger, MD
-
Sub-Investigator:
- Tim Bulaty, MD
-
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BS
-
Basel, BS, Switzerland, 4031
- Recruiting
- University Hospital of Basel
-
Contact:
- Roland Bingisser, MD
- Email: roland.bingisser@usb.ch
-
Principal Investigator:
- Roland Bingisser, MD
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Liestal, BS, Switzerland, 4410
- Recruiting
- Kantonsspital Baselland
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Contact:
- Jörg Leuppi, MD
- Email: Joerg.Leuppi@ksbl.ch
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Principal Investigator:
- Jörg Leuppi, MD
-
Sub-Investigator:
- Nicolas Geigy, MD
-
Sub-Investigator:
- Stephan Steuer, MD
-
-
LU
-
Luzern, LU, Switzerland, 6000
- Recruiting
- Luzerner Kantonsspital
-
Contact:
- Michael Christ, MD
- Email: michael.christ@luks.ch
-
Principal Investigator:
- Michael Christ, MD
-
Sub-Investigator:
- Adriana Sirova, MD
-
-
NE
-
Neuchâtel, NE, Switzerland, 2000
- Recruiting
- Réseau Hospitalier Neuchâtelois
-
Contact:
- Vincent Della Santa, MD
- Email: vincent.dellasanta@rhne.ch
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Principal Investigator:
- Vincent Della Santa, MD
-
-
SG
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Saint Gallen, SG, Switzerland, 9007
- Recruiting
- Cantonal Hospital of St. Gallen
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Contact:
- Werner Albrich, MD
- Email: werner.albrich@kssg.ch
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Principal Investigator:
- Werner Albrich, MD
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Sub-Investigator:
- Dieter von Ow, MD
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VD
-
Lausanne, VD, Switzerland, 1011
- Recruiting
- Centre Hospitalier Universitaire Vaudois (Chuv)
-
Contact:
- Noémie Boillat Blanco, MD
- Phone Number: +41 21 314 88 30
- Email: noemie.boillat@chuv.ch
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Contact:
- Olivier Hugli, MD
- Phone Number: +41 21 314 05 67
- Email: olivier.hugli@chuv.ch
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Principal Investigator:
- Noémie Boillat Blanco, MD
-
Sub-Investigator:
- Olivier Hugli, MD
-
Sub-Investigator:
- Cécile Bessat
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Payerne, VD, Switzerland, 1530
- Recruiting
- Hôpital Intercantonal de la Broye
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Contact:
- Yvan Fournier, MD
- Email: yvan.fournier@hibroye.ch
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Principal Investigator:
- Yvan Fournier, MD
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Rennaz, VD, Switzerland, 1847
- Recruiting
- Hôpital Riviera-Chablais
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Contact:
- Magali-Noëlle Pfeil, MD
- Email: magalinoelle.pfeil@hopitalrivierachablais.ch
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Principal Investigator:
- Magali-Noëlle Pfeil, MD
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Sub-Investigator:
- Dominique Schwab, MD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Signed informed consent
- Patients aged 18 years or more
- Acute LRTI (acute illness, less than 21 days, with at least one lower respiratory tract symptom, i.e. cough, sputum, dyspnea, chest pain and no alternative explanation)
At least one of the following clinical criteria:
- Focal abnormal auscultation (decreased breath sounds, crackles, bronchial breath sounds)
- Fever (documented temperature ≥ 38°C in the last 24 hours, including self-measured temperature ≥ 38°C)
- Tachypnea (respiratory rate ≥ 22/minute)
- Tachycardia (heart rate ≥ 100/minute)
Exclusion Criteria:
- Previous receipt of a quinolone, macrolide or ceftriaxone or, of more than one dose of any other antibiotic within 72h prior to enrolment (excepted prophylactic antibiotics or antibiotics given for urinary tract infection)
- Previous hospital stay in the last 14 days
- Cystic fibrosis
- Severe COPD (≥GOLD 3 or if not available, as a proxy: exacerbation treated with antibiotics during the last 6 months)
- Severe immunodeficiency (drug-induced neutropenia with <500 neutrophils/mm3, HIV infection with CD4<200 cells/mm3, solid organ or bone marrow transplant recipient, prednisone ≥ 20mg/day for >28 days)
- Initial admission of the patient in the intensive care unit
- Microbiologically-documented SARS-CoV-2
- Incapacity of discernment
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: The PLUS algorithm
The PLUS clinical management algorithm: EDs having switched to the intervention period (intervention group) will manage their patients using the PLUS algorithm. The PLUS algorithm starts with a validated pneumonia clinical prediction score (score of Van Vugt), followed by LUS. In case of positive results of any of these tests, PCT is measured to identify patients who will most likely benefit from antibiotics. A validated clinical severity score will ensure the safety of the intervention in those with discordant results (LUS consolidation and low PCT). |
Combination of a clinical prediction score and LUS, and if needed PCT measurement
|
Other: Usual care
Usual care: management as usual
|
Management as usual
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety outcome
Time Frame: Day 28
|
Proportion of patients with clinical failure (defined as a composite of any of the following: death or secondary ICU admission or secondary admission to hospital or hospital re-admission after index hospital discharge or complications due to the LRTI [empyema, lung abscess])
|
Day 28
|
Efficacy outcome
Time Frame: Day 28
|
Proportion of patients prescribed an antibiotic in each intervention group between enrolment and day 28
|
Day 28
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Quality of life measured with the community-acquired pneumonia symptom questionnaire
Time Frame: Day 7, Day 28, Day 90
|
Number of points on the community-acquired pneumonia symptom questionnaire as a surrogate marker of quality of life (range 0 to 90; 90 beeing the worse quality of life)
|
Day 7, Day 28, Day 90
|
Hospitalisation
Time Frame: Day 0 to Day 90
|
Duration of hospitalisation
|
Day 0 to Day 90
|
Efficacy endpoint
Time Frame: Day 90
|
Proportion of patients prescribed an antibiotic in each study group between enrolment and day 28 as well as day 90.
|
Day 90
|
Antibiotic side effects and C. difficile infection
Time Frame: Day 0 to Day 28
|
Proportion of patients with antibiotic-related side effects and C. difficile infections in each study group.
|
Day 0 to Day 28
|
Emergency department stay
Time Frame: Day 0 to Day 28
|
Length of stay in the emergency department in each study group.
|
Day 0 to Day 28
|
Qualitative evaluation
Time Frame: Day 90
|
Acceptability and feasibility of the intervention through extensive identification of barriers and facilitators in patients and physicians conducting qualitative semi-structured interviews
|
Day 90
|
Machine learning of Lung ultrasonography (LUS) images and videos
Time Frame: Day 90
|
Diagnostic performance for pneumonia (sensitivity, specificity, AUROC) of artificial intelligence LUS interpretation using expert interpretation as gold standard
|
Day 90
|
Economic evaluation
Time Frame: Day 90
|
Cost of the intervention as compared to usual care
|
Day 90
|
Clinical gestalt
Time Frame: Day 0
|
Diagnostic performance (sensitivity, specificity, AUROC) of the "Clinical gestalt" of the physician in charge of the patient (probability of pneumonia low/intermediate versus high) versus Van Vugt score (1×absence of runny nose+1×breathlessness+1×crackles+1×diminished vesicular breathing+1×raised pulse (>100/min)+1×fever (temperature >37.8°C: probability of pneumonia low/intermediate (score 0-2 ) versus high (score>=3)) to predict LUS-visualized pneumonia
|
Day 0
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
General Publications
- Lhopitallier L, Kronenberg A, Meuwly JY, Locatelli I, Mueller Y, Senn N, D'Acremont V, Boillat-Blanco N. Procalcitonin and lung ultrasonography point-of-care testing to determine antibiotic prescription in patients with lower respiratory tract infection in primary care: pragmatic cluster randomised trial. BMJ. 2021 Sep 21;374:n2132. doi: 10.1136/bmj.n2132.
- Lhopitallier L, Kronenberg A, Meuwly JY, Locatelli I, Dubois J, Marti J, Mueller Y, Senn N, D'Acremont V, Boillat-Blanco N. Procalcitonin and lung ultrasonography point-of-care testing to decide on antibiotic prescription in patients with lower respiratory tract infection in primary care: protocol of a pragmatic cluster randomized trial. BMC Pulm Med. 2019 Aug 6;19(1):143. doi: 10.1186/s12890-019-0898-3.
- Lamping DL, Schroter S, Marquis P, Marrel A, Duprat-Lomon I, Sagnier PP. The community-acquired pneumonia symptom questionnaire: a new, patient-based outcome measure to evaluate symptoms in patients with community-acquired pneumonia. Chest. 2002 Sep;122(3):920-9. doi: 10.1378/chest.122.3.920.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- PLUS-IS-LESS
- SNSF 33IC30_201300 (Other Grant/Funding Number: SNSF)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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