Back to resultsAn Algorithm to Decide on Antibiotic Prescription in Lower Respiratory Tract Infection in Primary Care (UltraPro)
Primary Purpose
Lower Resp Tract Infection
Status
Completed
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
UltraPro
Procalcitonin
Blood sampling
Naso-pharyngeal swab and sputum culture
Sponsored by
About this trial
This is an interventional diagnostic trial for Lower Resp Tract Infection focused on measuring pneumonia, procalcitonin, lung ultrasound, point of care testing, antibiotic prescription, respiratory pathogens, host biomarkers
Eligibility Criteria
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
Sites / Locations
- Centre Hospitalier Universitaire Vaudois
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
UltraPro
Procalcitonin
Usual Care
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
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.
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
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.
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.
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.
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.
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.
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
Host biomarkers
Sensitivity and specificity of combinations of host biomarkers to identify patients with clinical failure or with pneumonia
Transcription patterns
Association between SNPs in genes involved in microvascular integrity and poor outcome or clinical failure
Full Information
NCT ID
NCT03191071
First Posted
May 21, 2017
Last Updated
July 16, 2020
Sponsor
Centre Hospitalier Universitaire Vaudois
1. Study Identification
Unique Protocol Identification Number
NCT03191071
Brief Title
An Algorithm to Decide on Antibiotic Prescription in Lower Respiratory Tract Infection in Primary Care
Acronym
UltraPro
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
September 1, 2018 (Actual)
Primary Completion Date
April 10, 2020 (Actual)
Study Completion Date
April 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Centre Hospitalier Universitaire Vaudois
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lower Resp Tract Infection
Keywords
pneumonia, procalcitonin, lung ultrasound, point of care testing, antibiotic prescription, respiratory pathogens, host biomarkers
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Randomized clustered pragmatic trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
469 (Actual)
8. Arms, Groups, and Interventions
Arm Title
UltraPro
Arm Type
Experimental
Arm Description
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.
Arm Title
Procalcitonin
Arm Type
Experimental
Arm Description
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.
Arm Title
Usual Care
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Diagnostic Test
Intervention Name(s)
UltraPro
Intervention Description
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 .
Intervention Type
Diagnostic Test
Intervention Name(s)
Procalcitonin
Intervention Description
Procalcitonin will be measured using a rapid point-of-care test
Intervention Type
Diagnostic Test
Intervention Name(s)
Blood sampling
Intervention Description
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.
Intervention Type
Diagnostic Test
Intervention Name(s)
Naso-pharyngeal swab and sputum culture
Intervention Description
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.
Primary Outcome Measure Information:
Title
Proportion of patients prescribed an antibiotic in each arm
Description
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.
Time Frame
Assessed at day 28 after baseline
Secondary Outcome Measure Information:
Title
Duration of the episode
Description
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
Time Frame
Assessed at day 28 after baseline
Title
Clinical failure
Description
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.
Time Frame
Day 7 after baseline
Title
Number of medical visits
Description
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
Time Frame
Day 7 and Day 28 after baseline
Title
Serious adverse outcome
Description
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.
Time Frame
During the first 28 days following baseline
Title
Duration of algorithm completion
Description
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.
Time Frame
Assessed at baseline (Day 0)
Title
Satisfaction of providers
Description
The overall satisfaction of general practitioners regarding the process of the consultation and its different components will be assessed using a Likert scale.
Time Frame
Assessed at baseline
Title
Satisfaction of patients
Description
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.
Time Frame
Assessed at day 7
Title
Cost / effectiveness ratio
Description
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.
Time Frame
Assessed one month after data collection is complete
Title
Aetiology of LRTIs in primary care
Description
Prevalence of different respiratory pathogens as assessed by realtime multiplex PCR performed on a naso-pharyngeal swab and in sputum
Time Frame
Assessed within the first year after data collection is complete
Title
Host biomarkers
Description
Sensitivity and specificity of combinations of host biomarkers to identify patients with clinical failure or with pneumonia
Time Frame
Assessed within the first year after data collection is complete
Title
Transcription patterns
Description
Association between SNPs in genes involved in microvascular integrity and poor outcome or clinical failure
Time Frame
Assessed within the first year after data collection is complete
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Noémie Boillat, PhD
Organizational Affiliation
Centre Hospitalier Universitaire Vaudois
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Hospitalier Universitaire Vaudois
City
Lausanne
State/Province
Vaud
ZIP/Postal Code
1025
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
Only coded and anonymous data will be made available to protect patients right to privacy
Citations:
PubMed Identifier
34548312
Citation
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.
Results Reference
derived
PubMed Identifier
31387559
Citation
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.
Results Reference
derived
Learn more about this trial
An Algorithm to Decide on Antibiotic Prescription in Lower Respiratory Tract Infection in Primary Care
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