NOBICS - NOvel BIomarker In Invasive CandidiasiS/Candida Sepsis

NCT02801682 | Completed

• 1 other identifier: KLI 561-B31
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Invasive Candida infections are serious complications in immunocompromised patients including those undergoing treatment for cancer but occur also in patients treated in ICUs. Survival rate of invasive candidiasis is associated with early initiation of antifungal therapy (15% mortality rate for candidemic patients with antifungal therapy on day 0 related to the culture date of the first blood sample positive for yeasts compared to 41% for patients who received antifungal therapy on day 3). Up to date, no laboratory method or clinical decision rule is available for correct anticipation of invasive candidiasis which would avoid delays in appropriate antifungal therapy initiation. In clinical practice culture based methods (e.g. blood cultures) miss up to 50% of invasive candidiasis cases. Preemptive antifungal therapy is therefore often initiated in critically ill patients after Candida has been isolated from various non-sterile patient samples even without any sufficient evidence for invasive candidiasis. The disadvantages of this approach include over- and undertreatment of patients (up to 50% of candidemia cases are missed, and on the other hand 89% patients are treated unnecessarily), increased selective pressure for the development of antifungal resistance, potential risk of adverse drug reactions, and increased costs (expenses for antifungal therapy account for half of the antimicrobial medication budget in tertiary care hospitals). In addition, no survival benefit could be demonstrated by this strategy in ICU patients. The aim of this study is to identify biological markers to anticipate or support the diagnosis of invasive candidiasis in ICU patients, to overcome current deficiencies in detection of invasive candidiasis and consequently to differentiate between Candida spp. colonization and invasive Candida infection. The investigators intend to examine time dependent courses of potential host and pathogen derived biomarkers as well as innate or acquired predispositions for invasive candidiasis; e.g. automated (1→3) ß- D- Glucan tests, DNA in serum blood samples, pathogen recognition receptors and serum markers like interleukin (IL)-1, IL-2, IL-6, IL-10, IL-12, IL-17A, IL-17F, IL-22, IL-23, Tryptophan, Kynurenine, composition of indigenous microbiota of gastrointestinal and lower respiratory tract and skin, and risk factors for invasive candidiasis like underlying diseases and treatments. The study should contribute to improved assessment of ICU patients at risk for invasive candidiasis and to improved diagnosis of invasive candidiasis in ICU patients. In clinical practice the reliable differentiation between infection and colonization will allow more targeted antifungal therapy leading to enhanced antifungal treatment initiation on the one hand (in cases of true invasive candidiasis) and to reduction of unnecessary antifungal treatments and treatment costs on the other hand.

Conditions

Invasive Candidiasis

Outcome Measures

Primary Outcomes (1)

• Biomarkers indicating or excluding invasive Candidiasis

  Automated (1→3) ß- D- Glucan tests (pg/ml) DNA in serum blood samples (quantity and sequences) pathogen recognition receptors (% of cells as assessed by FACS analysis) serum markers like IL-1, IL-2, IL-6, IL-10, IL-12, IL-17A, IL-17F, IL-22, IL-23, Tryptophan, Kynurenine (quantity) composition of indigenous microbiota of gastrointestinal and lower respiratory tract and skin (comparison of detection rates and abundances of different classes or genera)

  through study completion, an average of 2 years

Secondary Outcomes (1)

• Risk factors for Invasive Candidiasis

  through study completion, an average of 2 years

Study Arms (4)

Healthy Controls

Invasive Candidiasis

Bacterial Sepsis (Bacteremia)

ICU patients without infectious disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

1. Healthy subjects 2. Patients with invasive candidiasis/Candida sepsis 3. Patients with sepsis and bacteremia 4. ICU Patients without infectious disease

You may qualify if:

• subjects without any evidence of current or chronic infectious diseases

You may not qualify if:

• Clinical or radiological or laboratory evidence of current infectious disease (temperature \>38°C, elevated CRP \>5mg/dl, leukocytosis \>11400, elevated neutrophiles)
• immunosuppressive therapy (e.g. glucocorticoids, methotrexate, azathioprin, etc)
• active haematooncological diseases
• HIV positivity
• ad 2:
• Patients with invasive Candidias/Candida sepsis as defined in recent EORTC/MSG definitions.
• glucocorticoid treatment with prednisone equivalent of ≥20mg/d
• inherited neutrophil deficiency
• absolute neutrophil count of ≤500cells/mm3
• immunosuppressive therapy (glucocorticoids with prednisone equivalent of ≥20mg/d, methotrexate, azathioprin etc)
• active hematooncological disease
• HIV positivity
• ad 3:
• ICU patients with sepsis and proven bacteremia (Staph. aureus or E. coli)
• immunosuppressive therapy (glucocorticoids with prednisone equivalent of ≥20mg/d, methotrexate, azathioprin etc)

Sponsors & Collaborators

• Medical University of Graz: lead
• Medical University Innsbruck: collaborator

Study Sites (1)

Medical University of Graz

Graz, Stmk, 8036, Austria

Location

MeSH Terms

Conditions

Candidiasis, Invasive

Condition Hierarchy (Ancestors)

Candidiasis; Mycoses; Bacterial Infections and Mycoses; Infections; Invasive Fungal Infections

Study Officials

• Robert Krause, MD

  Section of Infectious Diseases and Tropical Medicine, Dpt of Internal Medicine, Medical University of Graz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Univ.Prof.Dr.

Study Record Dates

• First Submitted: June 9, 2016
• First Posted: June 16, 2016
• Study Start: June 1, 2016
• Primary Completion: August 1, 2021
• Study Completion: August 1, 2021
• Last Updated: September 22, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)