Clinical Implications of Azole-Resistant Aspergillosis in Hematological Malignancy

Study Overview
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Brief Summary
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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
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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).

Official Title
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CLARITY - Clinical Implications of Azole-Resistant Aspergillosis in Hematological Malignancy

Conditions
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Invasive Aspergillosis

Intervention / Treatment
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* Other: Registry


Participation Criteria
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Eligibility Criteria
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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
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 |
| --- | --- |
| Invasive Aspergillosis<br> | Other: Registry<br>* There is no intervention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment response to antifungal therapy in patients with an invasive Aspergillosis caused by an azole resistant pathogen. | Analysis of efficacy of antifungal therapy of azole-resistant and azole-susceptible invasive Aspergillosis. Patient receive either complete response, partial response, stable disease, progression of the disease. Treatment response will be assessed by treating physicians. Response will be compared between the two groups. | Change from diagnosis at day 14, 28, 42 and 84 and throughout study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Final outcome will be compared between the two groups in consideration of the type and state of underlying diseases and risk factors. | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Invasive Aspergillosis, Azole resistance, Aspergillus fumigatus, Efficacy of antifungal therapy, Patient registry