Optimized Diagnostics for Improved Therapy Stratification in Invasive Fungal Infections

Study Overview
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Brief Summary
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Invasive fungal infections (IFI) in immunocompromised patients pose a major challenge for diagnostics designed to permit timely onset of appropriate treatment. The aim of the current clinical-diagnostic studies, one in in pediatric and one in adult patients at high risk of IFI, is to test newly developed diagnostic approaches to invasive fungal infections in relation to established procedures. The studies will be performed in a prospective, blinded fashion, and represent a work package within the FUNGITECT grant supported by the European Commission. The studies will focus on analyses of blood-samples from patients with febrile neutropenia during treatment of acute leukaemia and other tumour entities, and patients undergoing allogeneic stem cell transplantation treated with intensive chemotherapy.

Detailed Description
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Samples from immunosuppressed patients with febrile neutropenia (NP - defined as fever ≥ 38.5ºC and <500 ANC) will be taken: at the start of neutropenic fever after 24 hours after 48 hours before the start of antimycotic therapy, if pertinent at the end of antimycotic therapy, if pertinent The results ot analyses by a panfungal PCR screening assay developed at our institution (European patent No 1960536) and methods newly developed during the FUNGITECT project will be compared with conventional methods for fungal diagnostics such as HR (High Resolution)-CT, serological testing, histology and fungal culture. Additionally, genomic approaches will be employed to investigate host- and pathogen-related factors of susceptibility, pathogenicity and antimycotic resistance.

Official Title
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Optimized Diagnostics for Improved Therapy Stratification in Invasive Fungal Infections

Conditions
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Systemic Mycosis

Intervention / Treatment
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* Other: Peripheral blood sampling


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Adult study: Patients between 18-90 years of age with high risk of invasive fungal infections signed informed consent Pediatric study: patients between 0-18 years of age with high risk of invasive fungal infections signed informed consent EXCLUSION CRITERIA Adult study: pregnancy no consent Pediatric study: - no consent

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pediatric patients with febrile neutropenia<br>Peripheral blood sampling - samples from 200 pediatric patients with severe immunosuppression and neutropenic fever will be analyzed | Other: Peripheral blood sampling<br>* Peripheral blood samples will be taken at 3-5 defined timepoints during febrile neutropenia: at the start of neutropenic fever after 24 hours after 48 hours before the start of antimycotic therapy, if pertinent at the end of antimycotic therapy, if pertinent<br>|
| Adult patients with febrile neutropenia<br>Peripheral blood sampling - samples from 200 adult patients with severe immunosuppression and neutropenic fever will be analyzed | Other: Peripheral blood sampling<br>* Peripheral blood samples will be taken at 3-5 defined timepoints during febrile neutropenia: at the start of neutropenic fever after 24 hours after 48 hours before the start of antimycotic therapy, if pertinent at the end of antimycotic therapy, if pertinent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with fungal DNAmia (as indicator of fungal infection) detected by new methodologies described in the proposal | Invasive fungal diseases will be evaluated by developing improved diagnosis: technical validation of individual assays (PCR-based, NGS, and protein-based), validation of biomarkers in clinical specimens (MoAbs, proteinaceous infection markers) and optimized for time and parallel processing of samples by establishing a robust protocol to generate reproducible results, implementation of automated or semi-automated techniques and by use of defined quality control systems. | until the end of antifungal treatment (up to 6 weeks after the onset of febrile neutropenia) | 
| Frequency of individual fungal pathogens during febrile neutropenia in high risk patients | The frequency of invasive fungal disease in the paediatric and adult patient cohorts as well as in each individual patient will be elucidated. | until the end of antifungal treatment (up to 6 weeks after the onset of febrile neutropenia) | 
| Frequency of fungal pathogens resistant to commonly used antifungal agents | Progress and changes in healthcare practices provide opportunities for new and drug-resistant fungal pathogens emerging in hospital settings. | until the end of antifungal treatment (up to 6 weeks after the onset of febrile neutropenia) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of lethal fungal infections | Evaluation of potentially life-threatening fungal infections according to EORTC criteria. | until the end of antifungal treatment (up to 6 weeks after the onset of febrile neutropenia) |