An Algorithm to Decide on Antibiotic Prescription in Lower Respiratory Tract Infection in Primary Care (UltraPro)

Procalcitonin and Lung Ultrasonography Point-of-care Testing to Decide on Antibiotic Prescription in Patients With Lower Respiratory Tract Infection at Primary Care Level: Pragmatic Cluster Randomized Trial

The study is randomized clustered pragmatic trial whose objective is to decrease unnecessary antibiotic prescription in adult patients with lower respiratory tract infection managed at primary care level in Switzerland, using a simple algorithm based on 2 point of care test results

Study Overview

• Status: Completed
• Conditions: Lower Resp Tract Infection
• Intervention / Treatment: Diagnostic test: UltraPro; Diagnostic test: Blood sampling; Diagnostic test: Naso-pharyngeal swab and sputum culture; Diagnostic test: Procalcitonin

Detailed Description

The study will have two distinct phases:

The first phase will test the feasibility of the intervention (UltraPro) along a pilot study. Following the setup of a lung ultrasound training curriculum for general practitioners, the practicality of the whole UltraPro algorithm will be evaluated at primary care level.

The second phase will be a pragmatic randomized three-arm intervention study using an algorithm based on the results of procalcitonin and lung ultrasound to manage patients with lower respiratory tract infections at primary care level. The procalcitonin-ultrasound algorithm will be compared to procalcitonin-guided management alone and usual care.

• Study Type: Interventional
• Enrollment (Actual): 469
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Vaud
    • Lausanne, Vaud, Switzerland, 1025
      • Centre Hospitalier Universitaire Vaudois

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

All patients presenting to a participating GP's office for a consultation for an acute respiratory infection (ARI) will be screened for inclusion in the study

Inclusion Criteria:

• Informed Consent as documented by signature (Informed Consent Form)
• Patients aged 18 years or more
• No antibiotics prescribed for the current episode
• Acute cough of up to 21 days duration and at least one of the following symptom or sign:
• History of fever for more than 4 days
• dyspnoea
• tachypnoea (≥ 22 cycles per minutes)
• abnormal focal finding during auscultation

Exclusion Criteria:

• Previous prescription of antibiotics for the current episode
• Working diagnosis of acute sinusitis or a non-infective disorder
• Cystic fibrosis
• Previous episode of chronic obstructive pulmonary disease exacerbation treated with antibiotics during the last 6 months
• Known pregnancy
• Severe immunodeficiency (untreated HIV infection with CD4 count < 200 cells/mm3, solid organ transplant receiver, neutropenia, treatment with corticosteroids with dose equivalent to 20 mg prednisone/day for > 28
• Admission of the patient
• GP not available for performing study
• Patient unable to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UltraPro; General practitioners randomly assigned to the UltraPro arm will be responsible to recruit patients fulfilling the inclusion criteria and manage them using the UltraPro algorithm. The UltraPro algorithm combines the result of a procalcitonin point-of-care test with lung ultrasound result to decide on antibiotic prescription. Blood sampling will be performed to identify potential novel biomarkers. Naso-pharyngeal swabs as well as sputum culture will allow for microbiologic identification of aetiological agents.	Diagnostic test: UltraPro; First, procalcitonin will be measured using a rapid point-of-care test. In case of elevated procalcitonin result (≥0.25 µg/L), a lung ultrasound will be performed to look for the presence of a lung infiltrate or consolidation suggesting the presence of community acquired pneumonia. A portable ultrasound machine with a convex probe, that will be provided to the general practitioner by the study, will be used. The lung ultrasound will be done following international evidence-based recommendations for point-of-care lung ultrasound using the basic eight-region sonographic technique and the criteria for positive scan and positive examination for the diagnosis of pneumonia .; Diagnostic test: Blood sampling; A venous blood sample (17.5 mL) will be collected. Whole blood and plasma will be stored at - 80°C. Further analysis will be performed in order to identify novel biomarkers and gene transcription patterns that could predict the necessity of antibiotic prescription or the severity of disease.; Diagnostic test: Naso-pharyngeal swab and sputum culture; A pooled nasal swab will be performed and sputum will be collected. Samples will be stored at -80°C. Further analysis of the naso-pharyngeal swab and cultures of sputum will be performed to identify by molecular techniques pathogens implicated in the clinical presentation.
Experimental: Procalcitonin; General practitioners randomly assigned to the procalcitonin arm will be responsible to recruit patients fulfilling the inclusion criteria and manage them using the procalcitonin algorithm. The procalcitonin point-of-care test will be performed, as described above, to decide on antibiotic prescription. Blood sampling will be performed to identify potential novel biomarkers. Naso-pharyngeal swabs as well as sputum culture will allow for microbiologic identification of aetiological agents.	Diagnostic test: Blood sampling; A venous blood sample (17.5 mL) will be collected. Whole blood and plasma will be stored at - 80°C. Further analysis will be performed in order to identify novel biomarkers and gene transcription patterns that could predict the necessity of antibiotic prescription or the severity of disease.; Diagnostic test: Naso-pharyngeal swab and sputum culture; A pooled nasal swab will be performed and sputum will be collected. Samples will be stored at -80°C. Further analysis of the naso-pharyngeal swab and cultures of sputum will be performed to identify by molecular techniques pathogens implicated in the clinical presentation.; Diagnostic test: Procalcitonin; Procalcitonin will be measured using a rapid point-of-care test
Active Comparator: Usual Care; General practitioners randomly assigned to the usual care arm will be responsible to recruit patients fulfilling the inclusion criteria and will manage and treat these patients as they usually do. Only general practitioners who do not use procalcitonin and lung ultrasonography routinely will be included in the usual care arm. Naso-pharyngeal swabs as well as sputum culture will be performed to allow for microbiologic identification of aetiological agents.	Diagnostic test: Naso-pharyngeal swab and sputum culture; A pooled nasal swab will be performed and sputum will be collected. Samples will be stored at -80°C. Further analysis of the naso-pharyngeal swab and cultures of sputum will be performed to identify by molecular techniques pathogens implicated in the clinical presentation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients prescribed an antibiotic in each arm	For each arm, we will assess the proportion of patient's prescribed an antibiotic following the consultation with the general practitioner. This will be done by recording the prescription decision of the general practitioner.	Assessed at day 28 after baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of the episode	Number of days, within the first 28 days after enrolment, during which the patient's daily activities (work or recreation) were restricted by the lower respiratory tract infection. This will be assessed by telephone follow-up consultations	Assessed at day 28 after baseline
Clinical failure	Presence of symptoms of an ongoing or relapsing lower respiratory tract infection at 28 days after enrolment. This will be assessed by a telephone follow-up consultation.	Day 7 after baseline
Number of medical visits	The incidence of supplementary medical visits for the episode of lower respiratory tract infection within 28 days of enrolment will be assessed by reporting from the general practitioners and telephone follow-up consultations	Day 7 and Day 28 after baseline
Serious adverse outcome	Secondary hospitalisation or death of any cause or disease specific complications (lung abscess, empyema and acute respiratory distress), within 28 days of enrolment. Assessed by serious adverse event reporting, general practitioner reporting and telephone follow-up.	During the first 28 days following baseline
Duration of algorithm completion	Median duration of time spent for the medical consultation, procalcitonin testing, lung ultrasound and total time spent in the practice. These will be assessed by the general practitioner by filling in a case report form at baseline.	Assessed at baseline (Day 0)
Satisfaction of providers	The overall satisfaction of general practitioners regarding the process of the consultation and its different components will be assessed using a Likert scale.	Assessed at baseline
Satisfaction of patients	The overall satisfaction of patients regarding the process of the consultation and of follow-up will be assessed using a Likert scale. These will be assessed by telephone follow-up.	Assessed at day 7
Cost / effectiveness ratio	Cost / effectiveness ratio expressed as the cost required per 1% decrease of the rate of antibiotic prescription during the studio will be assessed using review of the medical records and estimation of the costs of the various process of the diagnostic algorithm based on the Swiss Federal HealthCare Law.	Assessed one month after data collection is complete
Aetiology of LRTIs in primary care	Prevalence of different respiratory pathogens as assessed by realtime multiplex PCR performed on a naso-pharyngeal swab and in sputum	Assessed within the first year after data collection is complete
Host biomarkers	Sensitivity and specificity of combinations of host biomarkers to identify patients with clinical failure or with pneumonia	Assessed within the first year after data collection is complete
Transcription patterns	Association between SNPs in genes involved in microvascular integrity and poor outcome or clinical failure	Assessed within the first year after data collection is complete

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Vaudois
• Investigators: Principal Investigator: Noémie Boillat, PhD, Centre Hospitalier Universitaire Vaudois

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.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Actual): April 10, 2020
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: May 21, 2017
• First Submitted That Met QC Criteria: June 16, 2017
• First Posted (Actual): June 19, 2017

Study Record Updates

• Last Update Posted (Actual): July 17, 2020
• Last Update Submitted That Met QC Criteria: July 16, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: pneumonia; procalcitonin; lung ultrasound; point of care testing; antibiotic prescription; respiratory pathogens; host biomarkers
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Infections; Communicable Diseases; Respiratory Tract Infections
• Other Study ID Numbers: SNF 407240_167133/1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Only coded and anonymous data will be made available to protect patients right to privacy

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No