Clinical trial NCT02492594: Optimized Diagnostics for Improved Therapy Stratification in Invasive Fungal Infections
Official title: Optimized Diagnostics for Improved Therapy Stratification in Invasive Fungal Infections
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Systemic Mycosis
Lead sponsor: St. Anna Kinderkrebsforschung
Sponsor class: OTHER
First posted: 2015-07-08
Enrollment: 244
Sex: ALL
Minimum age (years): 6
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1. Adult Patients between 18-90 years of age with high risk of invasive fungal infections (patients suffering from acute leukaemia and other tumour entities treated with intensive chemotherapy with neutropenic fever
2. Pediatric patients between 0-18 years of age with high risk of invasive fungal infections ((patients suffering from acute leukaemia, patients undergoing allogeneic stem cell transplantation treated with intensive chemotherapy with neutropenic fever.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with fungal DNAmia (as indicator of fungal infection) detected by new methodologies described in the proposal
timeFrame: until the end of antifungal treatment (up to 6 weeks after the onset of febrile neutropenia)
measure: Frequency of individual fungal pathogens during febrile neutropenia in high risk patients
timeFrame: until the end of antifungal treatment (up to 6 weeks after the onset of febrile neutropenia)
measure: Frequency of fungal pathogens resistant to commonly used antifungal agents
timeFrame: until the end of antifungal treatment (up to 6 weeks after the onset of febrile neutropenia)
Secondary outcomes:
measure: Number of lethal fungal infections
timeFrame: until the end of antifungal treatment (up to 6 weeks after the onset of febrile neutropenia)
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna, Department of Internal Medicine I
city: Vienna
country: Austria
facility: Hospital Hietzing
city: Vienna
country: Austria
facility: Hanusch Krankenhaus
city: Vienna
country: Austria
facility: Wilhelminenspital
city: Vienna
country: Austria
facility: St. Anna Children's Hospital
city: Utrecht
country: Netherlands
facility: Princess Máxima Center for pediatric oncology
city: Saint Petersburg
country: Russian Federation
facility: First Saint-Petersburg Pavlov State Medical University
Study officials:
affiliation: St. Anna Kinderkrebsforschung
name: Thomas Lion, Prof MD PhD MSc
role: STUDY_CHAIR
References:
citation: Landlinger C, Preuner S, Baskova L, van Grotel M, Hartwig NG, Dworzak M, Mann G, Attarbaschi A, Kager L, Peters C, Matthes-Martin S, Lawitschka A, van den Heuvel-Eibrink MM, Lion T. Diagnosis of invasive fungal infections by a real-time panfungal PCR assay in immunocompromised pediatric patients. Leukemia. 2010 Dec;24(12):2032-8. doi: 10.1038/leu.2010.209. Epub 2010 Sep 30.