NOBICS - NOvel BIomarker In Invasive CandidiasiS/Candida Sepsis (NOBICS)
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ClinicalTrials.gov Identifier: NCT02801682 |
Recruitment Status :
Completed
First Posted : June 16, 2016
Last Update Posted : September 22, 2021
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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.
Condition or disease |
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Invasive Candidiasis |
Study Type : | Observational |
Actual Enrollment : | 200 participants |
Observational Model: | Cohort |
Time Perspective: | Prospective |
Official Title: | NOBICS - NOvel BIomarker In Invasive CandidiasiS/Candida Sepsis |
Actual Study Start Date : | June 2016 |
Actual Primary Completion Date : | August 2021 |
Actual Study Completion Date : | August 2021 |

Group/Cohort |
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Healthy Controls |
Invasive Candidiasis |
Bacterial Sepsis (Bacteremia) |
ICU patients without infectious disease |
- Biomarkers indicating or excluding invasive Candidiasis [ Time Frame: through study completion, an average of 2 years ]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)
- Risk factors for Invasive Candidiasis [ Time Frame: through study completion, an average of 2 years ]Risk factors as described in previous literature, e.g. Eggimann, Lancet Infect Dis 2003; 3: 685-702

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Sampling Method: | Non-Probability Sample |
- Healthy subjects
- Patients with invasive candidiasis/Candida sepsis
- Patients with sepsis and bacteremia
- ICU Patients without infectious disease
ad 1:
Inclusion Criteria:
-subjects without any evidence of current or chronic infectious diseases
Exclusion Criteria:
- Clinical or radiological or laboratory evidence of current infectious disease (temperature >38°C, elevated CRP >5mg/dl, leukocytosis >11400, elevated neutrophiles)
- antifungal therapy within 8 weeks prior to inclusion
- immunosuppressive therapy (e.g. glucocorticoids, methotrexate, azathioprin, etc)
- active haematooncological diseases
- HIV positivity
ad 2:
Inclusion criteria:
-Patients with invasive Candidias/Candida sepsis as defined in recent EORTC/MSG definitions.
Exclusion criteria:
- glucocorticoid treatment with prednisone equivalent of ≥20mg/d
- inherited neutrophil deficiency
- absolute neutrophil count of ≤500cells/mm3
- antifungal therapy within 8 weeks prior to inclusion
- immunosuppressive therapy (glucocorticoids with prednisone equivalent of ≥20mg/d, methotrexate, azathioprin etc)
- active hematooncological disease
- HIV positivity
ad 3:
Inclusion criteria:
-ICU patients with sepsis and proven bacteremia (Staph. aureus or E. coli)
Exclusion criteria:
- Antifungal therapy within 8 weeks prior to inclusion
- immunosuppressive therapy (glucocorticoids with prednisone equivalent of ≥20mg/d, methotrexate, azathioprin etc)
- active hematooncological disease HIV positivity
ad 4:
Inclusion criteria:
-ICU patients without invasive candidiasis as defined above, without bacteremia and without clinical and laboratory markers of infection(e.g. intubated and mechanically ventilated patients with stroke or CPR)
Exclusion criteria:
- Clinical or radiological or laboratory evidence of current infectious disease (temperature >38°C, elevated CRP >5mg/dl, leukocytosis >11400, elevated neutrophiles)
- antifungal therapy within 8 weeks prior to inclusion
- immunosuppressive therapy (e.g. glucocorticoids, methotrexate, azathioprin, etc)
- active haematooncological diseases
- HIV positivity

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02801682
Austria | |
Medical University of Graz | |
Graz, Stmk, Austria, 8036 |
Principal Investigator: | Robert Krause, MD | Section of Infectious Diseases and Tropical Medicine, Dpt of Internal Medicine, Medical University of Graz |
Responsible Party: | Robert Krause, MD, Univ.Prof.Dr., Medical University of Graz |
ClinicalTrials.gov Identifier: | NCT02801682 |
Other Study ID Numbers: |
KLI 561-B31 |
First Posted: | June 16, 2016 Key Record Dates |
Last Update Posted: | September 22, 2021 |
Last Verified: | September 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Candidiasis Candidiasis, Invasive Infections |
Mycoses Bacterial Infections and Mycoses Invasive Fungal Infections |