Clinical trial NCT04645030: The Value of Ultralow Dosis CT and Ultrasound in the Diagnosing of Pneumonia in the Emergency Department
Official title: The Value of Ultralow Dosis CT and Ultrasound in the Diagnosing of Pneumonia in the Emergency Department
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Respiratory Tract Infections
Keywords: Pneumonia
Ultrasound
Ultra low-dose CT
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
First posted: 2020-11-25
Enrollment: 411
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Adults admitted to the ED will be invited to participate in the study, if the physician, receiving the patient, suspects the patient has an infection (e.g. indication for blood culture) and if the physician suspects community-acquired pneumonia. The physician will base his/her suspicion on clinical symptoms such as cough, increased sputum production, chest tightness, dyspnea and fever \> 38⁰C, and indication for chest x-ray.

Brief summary: Pneumonia is one of the most common infections in the emergency department (ED). Nevertheless, the current diagnostic tools are often slow and inaccurate. Currently, a chest x-ray is the first choice for diagnostic imaging for pneumonia in the ED, but is inaccurate with low sensitivity and specificity, resulting in both over-and underdiagnosing of pneumonia. Alternatively, computer thermography (CT) and high-resolution CT (HR-CT) offers high diagnostic accuracy but involves significantly increased radiation to the patient, and increased costs and examination time. Lately, two alternatives to chest x-ray have emerged:

* The first is lung ultrasound (LUS) which has shown higher sensitivity and specificity for pneumonia than a chest x-ray when performed by experts. However, the diagnostic accuracy of lung ultrasound performed by novice operators in the ED still needs investigation.
* The second alternative to chest x-ray is ultra-low-dose CT (ULD-CT). A ULD-CT is a CT scan where the radiation dose is significantly reduced, while still maintaining acceptable image quality. In effect merging the high diagnostic accuracy of chest CT with the low radiation doses of chest X-ray.

The aim of this study is to investigate the diagnostic accuracy of LUS by novice operators in the ED and the diagnostic accuracy of ULD-CT thorax, in patients suspected of having pneumonia.

Detailed description: Community-acquired pneumonia (CAP) is one of the most common infectious diseases in the emergency department (ED). In Denmark, the incidence of hospitalization is 809 per 100,000 and 30-day mortality is 13%. In 2018, 29.5 per 100.000 people died of pneumonia. An increase from 27.7 per 100,000 in 2017. CAP is usually suspected in patients with dyspnea, cough and fever, without other probable explanations or when other differential diagnosis is less likely. However often patients present with vague and uncharacteristic symptoms such as altered state of consciousness, gastrointestinal symptoms or pain. Likewise is fever not always present in the elderly. The most common CAP pathogens are Streptococcus pneumoniae, Haemophilus influenzae, and gram-negative bacilli. Other notable microbiological pathogens include viruses such as Influenza, COVID-19, parainfluenza and respiratory syncytial virus. Viruses are associated with bacterial co-infections, leading to increase mortality and complications such as admission to the ICU. Normally, when a pulmonary infection is suspected, a chest X-ray is performed. Chest x-rays have a sensitivity of 43,5% (39,4-50,8) and a specificity of 93% (92.1-93.9) for pulmonary opacities compared to CT. A chest x-ray has a sensitivity of 79% for pneumonia. Computed tomography (CT) scan of the thorax has higher diagnostic precision and results improve management but result in a correspondingly increased amount of radiation compared to chest X-ray. An ultra-low-dose CT (ULD-CT) scan of the thorax may be an alternative to CT scan. ULD-CT has a radiation dose of approx. 1.5 times greater than the radiation dose of a chest X-ray and approx. 1.5% of a CT scan. ULD-CT has shown better image quality than chest X-ray, and for acutely admitted patients with dyspnea, it has a clinical effect on both diagnosis and treatment. Like chest X-rays, basic findings on ULD-CT of the thorax can be interpreted by trained clinicians.

Ultrasound is a fast non-invasive diagnostic test, without radiation. LUS has high sensitivity and specificity, with the area under ROC (AUC) of 0.95-0.98 for pneumonia. A meta-study for the use of LUS in the diagnosis of pneumonia in the ED has shown a sensitivity of 92% (87-96%) and a specificity of 94% (87-97%). AUC was calculated at 0.97. The ultrasound operators in the meta-study were all experienced ultrasound operators. Ultrasound is an operator-dependent tool and in children, it has been demonstrated that LUS diagnostic accuracy for pneumonia, is significantly lower when performed by a novice sonographer compared to an advanced sonographer. There are few if any studies that have investigated the diagnostic accuracy of novice LUS operator, in the ED, for pneumonia.

Study goals and objectives The project is divided into two, a ULD-CT study and an LUS study. The study will aim to investigate their diagnostic capabilities in at emergency department setting.

The main objective of the ULD-CT study is to investigate and answer:

* Can ULD-CT be used to diagnose pneumonia in the emergency department?
* How is the agreement between the results from ULD-CT and results from HR-CT
* Is ULDCT more sensitive and specific than standard chest x-ray in the diagnosis of pneumonia?

The investigators hypothesize that ULD-CT can be used in the evaluation of patients with pneumonia and the sensitivity, specificity and area under the curve (AUC ) of ULD-CT is higher than a chest x-ray. The null-hypothesis is that ULD-CT is not an accurate diagnostic tool for pneumonia in the emergency department.

The main objective of the LUS study is to investigate and answer:

* Can LUS be used to diagnose pneumonia in the emergency department, with newly certified LUS operators?
* How is the agreement between the results from LUS and the results from HR-CT
* Is LUS more sensitive and specific than standard chest x-ray in the diagnosis of pneumonia?

The investigators hypothesize that LUS can be used in the evaluation of patients with pneumonia by recently certified operators and the sensitivity, specificity and AUC of LUS is higher than chest x-ray in an emergency department setting. The null-hypothesis is that LUS performed by recently certified operators is not an accurate diagnostic tool for pneumonia in the emergency department.

Eligibility criteria: Inclusion Criteria:

* Admission to an emergency department in the study, with one of following symptoms: dyspnea, cough, expectoration.
* Indication for blood culture
* Indication for chest x-ray OR
* the treating physician suspects a pneumonia diagnosis after the first evaluation of the patient

Exclusion Criteria:

* Patients \< 40 years old due to risk of cancer from the radiation
* 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)
* Patients \< 65 who already participated once due to risk of cancer from the radiation

Primary outcomes:
measure: Diagnostic capabilities of Ultra low-dose computer thermography for pneumonia
timeFrame: Within 24 hours from hospital admission
measure: Title Diagnostic capabilities of lung ultrasound for pneumonia
timeFrame: Within 24 hours from hospital admission
Secondary outcomes:
measure: Diagnostic capabilities of chest x-ray for pneumonia
timeFrame: Within 24 hours from hospital admission
Other outcomes:
measure: CURB-65 score for pneumonia severity
timeFrame: within 4 hours from admission
measure: PSI
timeFrame: within 4 hours from admission
Locations:
city: Aabenraa
country: Denmark
facility: Hospital of Southern Jutland
Study officials:
affiliation: Institute for Regional Sundhedsforskning
name: Christian Backer Mogensen
role: PRINCIPAL_INVESTIGATOR
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