Clinical trial NCT03221075: Clinical Implications of Azole-Resistant Aspergillosis in Hematological Malignancy
Official title: CLARITY - Clinical Implications of Azole-Resistant Aspergillosis in Hematological Malignancy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Invasive Aspergillosis
Keywords: Invasive Aspergillosis
Azole resistance
Aspergillus fumigatus
Efficacy of antifungal therapy
Patient registry
Lead sponsor: University Hospital of Cologne
Sponsor class: OTHER
Collaborators: name: Radboud University Medical Center
First posted: 2017-07-18
Enrollment: 203
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cases will be recruited worldwide.

Brief summary: In order to determine the efficacy of antifungal therapy in patients with documented azole-resistant invasive Aspergillosis (IA), anonymized clinical information of patients with a hematological malignancy with a culture-positive invasive fungal infection caused by Aspergillus fumigatus are collected in an online registry. Respective fungal isolates are analysed for azole susceptibility and resistance mechanisms. Patients diagnosed with an IA in 2016 and later are included in the study.

Detailed description: For mold-active azoles (e.g. isavuconazole, itraconazole, posaconazole and voriconazole), cross-resistance of Aspergillus spp. is an increasingly recognized problem. The study aims to determine the efficacy of antifungal therapy in patients with documented azole-resistant IA. On the basis of this study, it will be possible to assess the clinical implications of IA caused by azole-resistant versus azole-susceptible Aspergillus spp.

The investigators aim at collecting at least 55 azole-resistant and 130 azole-susceptible cases. Cases diagnosed with an IA by culture from January 1st, 2016 onwards with an underlying hematological malignancy are eligible for inclusion. Culture of azole-resistant cases must be provided for confirmation of the species, sequencing for azole-resistance mutations and determination of MIC using the EUCAST reference method. Isolates obtained from patients with presumed azole-susceptible disease will be analyzed to confirm the wild type phenotype.

Eligible azole-resistant and azole-susceptible IA cases will be documented using the web-based case report form. If there is ≥1 resistant isolate, the patient fulfills the definition of a resistant case. Patient level data will be recorded at the respective study centres in a continuous fashion. Data items to be documented will include: demographic data; type and status of underlying conditions; concurrent immunosuppressive treatment; diagnostic measures (clinical presentation, radiology, microbiology, pathology, organ involvement); medical and surgical treatment (including prior exposure to antifungals); response to treatment (clinical and radiological) at day 14, 42, 84; overall survival at day 14, 42, 84 and at last contact; and cause of death (if applicable).

Eligibility criteria: Inclusion Criteria:

* Adult and pediatric patients diagnosed with an IA in 2016 and later
* Patients with a hematological malignancy
* Evidence of invasive Aspergillosis
* Aspergillus fumigatus culture from clinical material of the patient

Exclusion Criteria:

* Colonization only, without proof of invasive infection
* Non-availability of the azole resistant isolate

Primary outcomes:
measure: Treatment response to antifungal therapy in patients with an invasive Aspergillosis caused by an azole resistant pathogen.
timeFrame: Change from diagnosis at day 14, 28, 42 and 84 and throughout study completion
Secondary outcomes:
measure: Overall survival
timeFrame: 4 years
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: University Hospital of Cologne
state: NRW
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Center
Study officials:
affiliation: University Hospital of Cologne, Germany
name: Oliver A. Cornely, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Nijmegen Medical Center, The Netherlands
name: Paul E. Verweij, Prof.
role: PRINCIPAL_INVESTIGATOR
References: