Clinical trial NCT04651712: The Effect of a Point-of-care Sputum Specimen Assay at the Emergency Department for Patients Suspected of Pneumonia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pneumonia, Bacterial
Keywords: Emergency department
Antibiotics
Sputum
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
First posted: 2020-12-03
Enrollment: 290
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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)

Primary outcomes:
measure: Antibiotic treatment at 4-hour plan
timeFrame: 4 hours after admission
Secondary outcomes:
measure: Intensive care unit (ICU) treatment
timeFrame: within 60 days from admission to the emergency department
measure: Length of hospital stay
timeFrame: within 60 days from current admission to the emergency department
measure: 30-days mortality
timeFrame: 30 days from the admission to the emergency department
measure: Readmission
timeFrame: within 30 days from the discharge to the hospital
measure: In-hospital mortality
timeFrame: within 60 days from admission to the emergency department
measure: Antibiotic treatment at 48 hour
timeFrame: 48 hours after admission
measure: Antibiotic treatment at discharge from hospital
timeFrame: 24 hours after hospital discharge
measure: Bacterial agents and viruses from the microbiological results
timeFrame: Within the first 7 days from specimen collection
Other outcomes:
measure: CURB-65 score for pneumonia severity
timeFrame: within 4 hours from admission
measure: Pneumonia severity index (PSI)
timeFrame: within 4 hours from admission
measure: Number of clostridium infections
timeFrame: measured 40 days after discharge from the emergency department
measure: Procalcitonin (PCT), Soluble Urokinase Plasminogen Activator Receptor (suPAR), YKL-40 and Krebs von den Lungen (KL-6)
timeFrame: results within 4 hour from admission
measure: 90 days mortality
timeFrame: Within 90 days from admission to emergency department
Locations:
city: Aabenraa
country: Denmark
facility: Hospital of Southern Jutland
Study officials:
affiliation: University Hospital of Southern Denmark
name: Christian Backer Mogensen, MD PhD
role: STUDY_CHAIR
References:
citation: Skjot-Arkil H, Mogensen CB, Lassen AT, Johansen IS, Chen M, Petersen P, Andersen KV, Ellermann-Eriksen S, Moller JM, Ludwig M, Fuglsang-Damgaard D, Nielsen FE, Petersen DB, Jensen US, Rosenvinge FS. Carrier prevalence and risk factors for colonisation of multiresistant bacteria in Danish emergency departments: a cross-sectional survey. BMJ Open. 2019 Jun 27;9(6):e029000. doi: 10.1136/bmjopen-2019-029000.
citation: Sogaard M, Nielsen RB, Schonheyder HC, Norgaard M, Thomsen RW. Nationwide trends in pneumonia hospitalization rates and mortality, Denmark 1997-2011. Respir Med. 2014 Aug;108(8):1214-22. doi: 10.1016/j.rmed.2014.05.004. Epub 2014 May 20.
citation: Welte T, Torres A, Nathwani D. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax. 2012 Jan;67(1):71-9. doi: 10.1136/thx.2009.129502. Epub 2010 Aug 20.
citation: van der Eerden MM, Vlaspolder F, de Graaff CS, Groot T, Bronsveld W, Jansen HM, Boersma WG. Comparison between pathogen directed antibiotic treatment and empirical broad spectrum antibiotic treatment in patients with community acquired pneumonia: a prospective randomised study. Thorax. 2005 Aug;60(8):672-8. doi: 10.1136/thx.2004.030411.
citation: Becerra MB, Becerra BJ, Banta JE, Safdar N. Impact of Clostridium difficile infection among pneumonia and urinary tract infection hospitalizations: an analysis of the Nationwide Inpatient Sample. BMC Infect Dis. 2015 Jul 1;15:254. doi: 10.1186/s12879-015-0925-9.
citation: Ewig S, Schlochtermeier M, Goke N, Niederman MS. Applying sputum as a diagnostic tool in pneumonia: limited yield, minimal impact on treatment decisions. Chest. 2002 May;121(5):1486-92. doi: 10.1378/chest.121.5.1486.
citation: Roson B, Carratala J, Verdaguer R, Dorca J, Manresa F, Gudiol F. Prospective study of the usefulness of sputum Gram stain in the initial approach to community-acquired pneumonia requiring hospitalization. Clin Infect Dis. 2000 Oct;31(4):869-74. doi: 10.1086/318151. Epub 2000 Oct 12.
citation: Hadfield J, Bennett L. Determining best outcomes from community-acquired pneumonia and how to achieve them. Respirology. 2018 Feb;23(2):138-147. doi: 10.1111/resp.13218. Epub 2017 Nov 17.
citation: Skjot-Arkil H, Heltborg A, Lorentzen MH, Cartuliares MB, Hertz MA, Graumann O, Rosenvinge FS, Petersen ERB, Ostergaard C, Laursen CB, Skovsted TA, Posth S, Chen M, Mogensen CB. Improved diagnostics of infectious diseases in emergency departments: a protocol of a multifaceted multicentre diagnostic study. BMJ Open. 2021 Sep 30;11(9):e049606. doi: 10.1136/bmjopen-2021-049606.