Skip to main content
OpenTrials
Completed

NCT Number: NCT04652167

Diagnostic Accuracy of Infection Biomarkers in the Initial Investigation of Patients With Suspected Pneumonia

The aim of this study is to investigate the diagnostic and prognostic value of C-reactive protein (CRP), serum procalcitonin (PCT) and soluble urokinase plasminogen activator receptor (suPAR) in the initial investigation of patients acute hospitalized with suspected community-acquired-pneumonia (CAP)

Completed

Looking for future studies?

Notify Me

Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Hospital of Southern Jutland

Aabenraa, Denmark

About this study

Target pneumonia treatment should be initiated within a few hours, which is why early and accurate diagnosis is extremely important. Uncertain or delayed diagnosis will often lead to an overconsumption of broad-spectrum antibiotics, which contributes to increased development of resistant bacteria and thus threaten the treatment options of the future. Pneumonia diagnosis is primarily made today on the basis of clinical symptoms and findings in the form of cough, vomiting, chest pain, fever, shortness of breath, supplemented with X-ray of the lungs, relevant blood tests and analysis of expectoration. However, X-ray is an imprecise diagnostic tool. The diagnosis of CAP is challenged by nonspecific symptoms, uncertain diagnostic methods and waiting time for test results up to several days.

Therefore, numerous studies have investigated biomarkers that can possibly support the diagnosis of CAP. C-reactive protein (CRP) and serum procalcitonin (PCT) are biomarkers that may distinguish CAP from other causes of acute respiratory infections. The CRP biomarker has been endorsed as a guide for antibiotic treatment by the National Institute for Health and Care Excellence (NICE) and PCT was suggested by the American Infectious Diseases Society of America. Soluble urokinase plasminogen activator receptor (suPAR) has emerged as a potentially novel biomarker for inflammatory diseases including pneumonia. Several studies have highlighted suPAR as a significant prognostic mortality marker and strongly related to disease severity and worse outcome in a variety of conditions. It is also a promising biological marker in the diagnosis of CAP.

The diagnostic value of the optimal biomarkers for the diagnosis of CAP remains controversial. The investigators hypothesize that serum CRP, PTC and suPAR have an impact on diagnosing, prognosis, and treatment of patients with a verified community-acquired-pneumonia. The objectives of the study are:

  • To identify the diagnostic accuracy of CRP, PCT and suPAR in community-acquired pneumonia
  • To identify the prognostic value of CRP, PCT and suPAR in relation to adverse events

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adult patients ≥ 18 years old
  • Patients suspected with pneumonia by the attending physician. The physician will base his/her suspicion on e.g. clinical symptoms such as cough, increased sputum production, chest tightness, dyspnea and fever > 38⁰C, 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)

Treatment and study plan

PCT

Diagnostic Test

Serum PCT concentration is quantified with an automated sandwich immunoassay "ECLIA" (Elecsys®, BRAHMS PCT-analyses) on Cobas e801. Calibration (BRAHMS PCT LIA assay) is performed once per reagent lot and no later than 24 h after Cobas e pack has been registered in the instrument. Quality control is performed after each calibration.

suPAR

Diagnostic Test

Serum suPAR was measured using suPARnostic© Turbilatex assay reagents (validated on Cobas© c111) protocol for Cobas© c702 and c502 applying the Multi-Pack cassettes (Roche Diagnostics, Mannheim, Germany). Calibration is performed at least once a month or in connection to a new batch of TurbiLatex reagents, after calibration a quality control is performed.

Standard care

Diagnostic Test

Standard care is the measurement of CRP (C-reactive protein) will be measured with C - reactive protein (CRP4) immunoturbidimetric assay (Tina-quant®, Roche) on Roche/Hitachi cobas© systems c701/702. Calibration is performed (Tina-quant® C - reactive protein IV) once per reagent lot and after 6 months using the same reagent lot. Quality control is required after calibration and according manufacturing instructions.

Primary outcomes

  1. Diagnostic of community acquired pneumonia

    Time frame: expert assessment within 3 months after patient discharge from the hospital

    The percentage of patients diagnosed with community-acquired pneumonia determined by an expert panel. This outcome measure is a binary variable - verified pneumonia or no pneumonia.

    The expert panel consists of two independent consultants from the emergency department with experience in infection and emergency medicine, who individually will determine whether the patient admitted with suspected community-acquired pneumonia, had the diagnosis. The diagnosis will be based on all available relevant information from the patient medical record within 48 hours from admission including computed tomography. A standardized template will be used. Disagreement will be discussed until a consensus is reached.

    .

Secondary outcomes

  1. Intensive care unit (ICU) treatment

    Time frame: within 60 days from admission to the emergency department

    Transfer to the intensive care unit will be recorded during the current hospitalization as a binary variable (transferred/not-transferred)

  2. Length of hospital stay (LOS

    Time frame: within 60 days from current admission to the emergency department

    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.

  3. 30-days mortality

    Time frame: 30 days from the admission to the emergency department

    Mortality within 30 days from admission to the Emergency Department

  4. 90-days mortality

    Time frame: 90 days from the admission to the emergency department

    Mortality within 90 days from admission to the Emergency Department

  5. Readmission

    Time frame: within 30 days from the discharge to the hospital

    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

  6. In-hospital mortality

    Time frame: within 60 days from admission to the emergency department

    Patient mortality during the current hospitalization. Binary outcome - Died/ Not died

Other outcomes

  1. CURB-65 score for predicting mortality in community-acquired-pneumonia:

    Time frame: within 4 hours from admission

    CURB-65 score consists of: Confusion of new onset, Blood Urea nitrogen greater than 7 mmol/L (19 mg/dL), respiratory rate of 30 breaths per minute or greater, blood pressure less than 90 mmHg systolic or diastolic blood pressure 60 mmHg or less and age 65 or older. The score stratify patients to groups 1 (mild pneumonia), 2 (moderate pneumonia) and 3-5 (severe pneumonia).

  2. Pneumonia severity index (PSI):

    Time frame: within 4 hours from admission

    Risk classes to predict the severity of pneumonia. Scores are given based on demographics, comorbidity, clinical measurements and physical Exam Findings (<70 = Risk Class II, 71-90 = Risk Class III, 91-130 = Risk Class IV, >130 = Risk Class V)

  3. Microbial agents

    Time frame: results within 7 days from sputum sample collection

    Microbial agents (bacteria and viruses) identified in standard culture, PCR and multiplex PCR. Sputum samples are collected within 1 hour from patient admission.

    Descriptive findings in percentage will be registered

  4. Level of markers of lung injury

    Time frame: within 4 hours from admission

    serum surfactant protein D, KL-6 and YKL-40

Sponsors and collaborators

Lead sponsor

University of Southern Denmark

Other

Registry information

Official study title

What is the Diagnostic and Prognostic Accuracy of C-reactive Protein, Serum Procalcitonin and Soluble Urokinase Plasminogen Activator Receptor in the Initial Investigation of Patients With Suspected Community-acquired Pneumonia

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Dec 3, 2020
Registry last updated
Sep 14, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.