Clinical trial NCT06456151: Invasive Candidiasis in Critical Care
Official title: Invasive Candidiasis in Critical Care
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Invasive Candidiasis
Keywords: invasive candidiasis
biomarkers
candida sepsis
Lead sponsor: University Hospital Ostrava
Sponsor class: OTHER
Collaborators: name: University Hospital, Motol
First posted: 2024-06-13
Enrollment: 100
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with suspected invasive candidasis.

Brief summary: The combination of acute phase marker monitoring and the "T2Candida" assay (name of the test) will represent an acceleration of the identification of the causative agent of mycotic infection, a significant improvement in the specificity and positive predictive value of this strategy in the diagnosis of invasive candidiasis and candidemia in ICU patients, thereby improving the clinical condition of patients and reducing the cost of specific antifungal therapy.

Detailed description: Speed of response in the treatment of sepsis is crucial for the patient. The time from the collection of a positive haemoculture to the identification of the causative agent of sepsis is around 2 days; therefore, physicians in intensive care units deploy combined empiric antibiotic and antifungal therapy immediately when acute phase markers such as procalcitonin, interleukin-6, Presepsin, C-reactive protein are elevated. A new acute phase marker is lipopolysaccharide-binding protein, which, together with Presepsin, appears to be a suitable marker to distinguish invasive candida infections from bacterial infections. But its kinetics needs to be further analyzed.

At the same time, the causative agent of sepsis, G-/G+ bacteria or yeast, must be identified as soon as possible. Haemoculture and culture of the established drain is the gold standard, but the disadvantage is the low sensitivity and the time delay to obtain the result. It is therefore advisable to combine haemoculture with molecular biology-based tests that can identify the causative organism within hours. Conversely, the disadvantage of these tests is that they identify only the most common sepsis pathogens and do not determine susceptibility to antibiotics and antifungals, but the advantage is that with prophylaxis in place, these tests are often positive when haemoculture is negative. The T2Candida test can detect Candida albicans, Candida tropicalis, Candida glabrata, Candida krusei and Candida parapsilosis, which are the more common causative agents of mycotic bloodstream infections.

Eligibility criteria: Inclusion Criteria:

* critically ill patients
* new onset sepsis
* rise in body temperature \>38°C according to The Third Consensus Definitions for Sepsis and Septic Shock
* colonization with Candida spp. from more than 1 non-sterile site
* body temperature \>38 °C despite 5 days of broad-spectrum antibiotic therapy with the presence of at least 1 of the following risk factors: abdominal surgery, secondary peritonitis, pancreatitis, central venous catheter (CVC) insertion, total parenteral nutrition (CPV), dialysis, steroid therapy, immunosuppressive therapy, or liver transplantation
* microbiological test results will be reviewed and categorized based on whether Candida sp. is isolated from at least 2 non-sterile sites (±3 days) and whether there is an alternative microbiological diagnosis.

Exclusion Criteria:

* not signing the informed consent with participation in the study
* administration of antifungal therapy prior to collection of the biological material required for the study

Primary outcomes:
measure: Acute-phase biomarkers dynamics - procalcitonin
timeFrame: 8 days
measure: Acute-phase biomarkers dynamics - interleukin-6
timeFrame: 8 days
measure: Acute-phase biomarkers dynamics - interleukin-10
timeFrame: 8 days
measure: Acute-phase biomarkers dynamics - Presepsin
timeFrame: 8 days
measure: Acute-phase biomarkers dynamics - C-reactive protein
timeFrame: 8 days
measure: Acute-phase biomarkers dynamics - 1,3-β-D-glucan
timeFrame: 8 days
measure: Acute-phase biomarkers dynamics - pentraxin 3
timeFrame: 8 days
measure: T2Candida test
timeFrame: One-time measurement at the enrolment into the study
measure: Lipopolysaccharide binding protein
timeFrame: One-time measurement at the enrolment into the study
Secondary outcomes:
Other outcomes:
Locations:
city: Ostrava
country: Czechia
facility: University Hospital Ostrava
state: Moravian-Silesian Region
city: Prague
country: Czechia
facility: University Hospital Motol
Study officials:
affiliation: University Hospital Ostrava
name: Hana Slepčanová, Mgr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dobias R, Kanova M, Petejova N, Pisti SK, Bocek R, Krejci E, Struzkova H, Cachova M, Tomaskova H, Hamal P, Havlicek V, Raska M. Combined Use of Presepsin and (1,3)-beta-D-glucan as Biomarkers for Diagnosing Candida Sepsis and Monitoring the Effectiveness of Treatment in Critically Ill Patients. J Fungi (Basel). 2022 Mar 17;8(3):308. doi: 10.3390/jof8030308.
citation: Bassetti M, Giacobbe DR, Vena A, Wolff M. Diagnosis and Treatment of Candidemia in the Intensive Care Unit. Semin Respir Crit Care Med. 2019 Aug;40(4):524-539. doi: 10.1055/s-0039-1693704. Epub 2019 Oct 4.