The Effect of a Point-of-care Sputum Specimen Assay at the Emergency Department for Patients Suspected of Pneumonia

Study Overview
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Brief Summary
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Antibiotic resistance has been identified by the WHO as one of the biggest threats to the health of the world population. In Denmark, there has been an increasing focus on optimizing antibiotic consumption in recent years, but despite significant efforts, total consumption has increased in the hospital sector, especially regarding consumption and in the use of broad-spectrum antibiotics. Currently, a pneumonia diagnosis is primarily based on clinical symptoms such as cough, shortness of breath, chest pain, fever and sputum production, combined with X-ray of the lungs, relevant blood tests and microbiological analysis of sputum samples. X-ray is however an imprecise diagnostic tool, and sputum assays responses are available after 2 days. Sputum can be cultivated to determine the bacterial agent. However, the sputum samples are often of poor quality and many patients cannot deliver a sample. A recently published Danish study shows, that only half of the patients at the ED have sputum samples collected for culturing and none of them had the antibiotic treatment adjusted based on the microbiological results of the sputum. This study's hypothesis is that point-of-care-polymerase chain reaction (POC-PCR) is superior to standard care on the prescription of targeted pneumonia treatment.

Detailed Description
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The diagnosis of pneumonia is challenged by nonspecific symptoms, uncertain diagnostic methods, poor prognostic tools and waiting time for test results up to several days. A patient's length of stay in a Danish Emergency Department rarely exceeds 48 hours. Within this period the patient is examined, treated and discharged either home or to another department. Therefore, rapid molecular detection of respiratory pathogens is needed to add value to the management of the diagnostics of pneumonia and could reduce the initial use of antibiotics. Molecular diagnostic tests based on polymerase chain reaction (PCR) assays generate high sensitive analyses in one hour from specimen collection. The Biofire® FilmArray® Pneumonia Panel plus (Biomérieux) can identify 18 bacterial agents including 3 atypical pathogens 9 viruses and 7 antimicrobial resistance genes. This point-of-care (POC) test is promising, as bacterial pathogens often coexist with viruses or are identified with mixed infections. However, the high specificity of molecular diagnostics can challenge the interpretation of clinically significant agents and demands interpretation by highly qualified specialists. Therefore, the POC-PCR combined with advice from a microbiologist has the potential to optimize therapeutic regimens and reduce prescriptions of inappropriate broad-spectrum antibiotics in the initial management of pneumonia. This study aims to investigate how effective the addition of POC-PCR analysis of sputum is to the diagnostic set-up for community-acquired pneumonia on antibiotic prescription at 4 hours after admission without consequent adverse advents to identify the effect of POC-PCR on prescribed antibiotic treatment 48 hours after admission and 24 hours after discharge to investigate the agreement between POC-PCR and sputum culture on microbiological analysis

Official Title
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The Effect of a Point-of-care Sputum Specimen Assay on Antibiotic Treatment of Patients Admitted Acutely With Suspected Pneumonia: A Multicenter Randomized Controlled Trial

Conditions
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Pneumonia, Bacterial

Intervention / Treatment
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* Diagnostic Test: POC-PCR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Emergency department patients suspected of pneumonia by the attending physician and with at least one of the following symptoms: dyspnea, cough, expectoration, chest tightness or fever and indication for chest x-ray Exclusion Criteria: If the attending physician considers that participation will delay a life-saving treatment or patient needs direct transfer to the intensive care unit. Admission within the last 14 days Verified COVID-19 disease within 14 days before admission Pregnant women Severe immunodeficiencies: Primary immunodeficiencies and secondary immunodeficiencies (HIV positive CD4 <200, Patients receiving immunosuppressive treatment (ATC L04A), Corticosteroid treatment (>20 mg/day prednisone or equivalent for >14 days within the last 30 days), Chemotherapy within 30 days)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard care<br>A treating physician must perform a clinical assessment within half an hour of patient arrival. This assessment includes the decision whether the patient is suspected of having pneumonia and if this is the case, a sputum specimen and chest x-ray will be ordered. Patients with suspected pneumonia who can deliver a sputum specimen will be randomly allocated with a 1:1 computer-generated randomization schedule with permuting blocks in relation to optimal therapeutical intervention strategy. All standard care sputum samples will be cultured and analysed according to the sites' standard procedures. Under standard care, the treating physician alone decides on the optimal therapeutical intervention. | |
| Active Comparator: POC-PCR analysis supplied with a recommended action list developed by a microbiologist<br>Along with standard analyses, the specimens will be analysed with POC-PCR and the treating physician will receive an action-list with the results from POC-PCR. | Diagnostic Test: POC-PCR<br>* The result of the POC-PCR will be presented by the study assistant to the treating physician within four hours upon admission. The treating physician will along with the result receive a recommended action list, developed by microbiologists.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibiotic treatment at 4-hour plan | The primary outcome is to determine the effectiveness of POC-PCR sputum analysis on antibiotic prescription, the treatment will either be registered as targeted or non-targeted antibiotic treatment at four hours after admission. This is a binary outcome. | 4 hours after admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensive care unit (ICU) treatment | Transfer to the intensive care unit will be recorded during the current hospitalization as a binary variable (transferred/not-transferred) | within 60 days from admission to the emergency department | 
| Length of hospital stay | Defined as the time (in days) spent in hospital during the current admission. Measured in days from admission to hospital discharge. Discharge date minus admission date. | within 60 days from current admission to the emergency department | 
| 30-days mortality | Mortality within 30 days from admission to the Emergency Department | 30 days from the admission to the emergency department | 
| Readmission | If a subject is admitted over a 30 day period after the current hospitalization discharge measured as a binary outcome Re-admissions/not re-admissions. | within 30 days from the discharge to the hospital | 
| In-hospital mortality | Patient mortality during the current hospitalization. Binary outcome - Died/ Not died | within 60 days from admission to the emergency department | 
| Antibiotic treatment at 48 hour | The treatment will either be registered as targeted or non-targeted antibiotic treatment 48 hours after admission. This is a binary outcome. | 48 hours after admission | 
| Antibiotic treatment at discharge from hospital | The treatment will either be registered as a targeted or non-targeted antibiotic treatment after the patient is discharged from the hospital. This is a binary outcome. | 24 hours after hospital discharge | 
| Bacterial agents and viruses from the microbiological results | The bacterial agents and viruses from the Biofire® FilmArray® Pneumonia Panel plus (Biomérieux) and standard sputum culture for the two microbiological analysis will be presented as descriptive statistics. | Within the first 7 days from specimen collection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Emergency department, Antibiotics, Sputum