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Optimized Diagnostics for Improved Therapy Stratification in Invasive Fungal Infections

Completed
Conditions
Systemic Mycosis
Interventions
Other: Peripheral blood sampling
Registration Number
NCT02492594
Lead Sponsor
St. Anna Kinderkrebsforschung
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
244
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Adult patients with febrile neutropeniaPeripheral blood samplingPeripheral blood sampling - samples from 200 adult patients with severe immunosuppression and neutropenic fever will be analyzed
Pediatric patients with febrile neutropeniaPeripheral blood samplingPeripheral blood sampling - samples from 200 pediatric patients with severe immunosuppression and neutropenic fever will be analyzed
Primary Outcome Measures
NameTimeMethod
Number of patients with fungal DNAmia (as indicator of fungal infection) detected by new methodologies described in the proposaluntil the end of antifungal treatment (up to 6 weeks after the onset of febrile neutropenia)

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.

Frequency of individual fungal pathogens during febrile neutropenia in high risk patientsuntil the end of antifungal treatment (up to 6 weeks after the onset of febrile neutropenia)

The frequency of invasive fungal disease in the paediatric and adult patient cohorts as well as in each individual patient will be elucidated.

Frequency of fungal pathogens resistant to commonly used antifungal agentsuntil the end of antifungal treatment (up to 6 weeks after the onset of febrile neutropenia)

Progress and changes in healthcare practices provide opportunities for new and drug-resistant fungal pathogens emerging in hospital settings.

Secondary Outcome Measures
NameTimeMethod
Number of lethal fungal infectionsuntil the end of antifungal treatment (up to 6 weeks after the onset of febrile neutropenia)

Evaluation of potentially life-threatening fungal infections according to EORTC criteria.

Trial Locations

Locations (7)

Medical University of Vienna, Department of Internal Medicine I

🇦🇹

Vienna, Austria

Hospital Hietzing

🇦🇹

Vienna, Austria

Hanusch Krankenhaus

🇦🇹

Vienna, Austria

Wilhelminenspital

🇦🇹

Vienna, Austria

St. Anna Children's Hospital

🇦🇹

Vienna, Austria

Princess Máxima Center for pediatric oncology

🇳🇱

Utrecht, Netherlands

First Saint-Petersburg Pavlov State Medical University

🇷🇺

Saint Petersburg, Russian Federation

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