Clinical Implications of Azole-Resistant Aspergillosis in Hematological Malignancy

Invasive Aspergillosis Clinical Trial

— CLARITY  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03221075
• Other study ID #: 17-024
• Status: Completed
• Start date: March 1, 2017
• Est. completion date: October 25, 2022

Study information

• Verified date: May 2023
• Source: University Hospital of Cologne
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 203
• Est. completion date: October 25, 2022
• Est. primary completion date: April 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Aspergillosis
• Hematologic Neoplasms
• Invasive Aspergillosis

Intervention

Other:
• Registry
There is no intervention.

Locations

Country	Name	City	State
Germany	University Hospital of Cologne	Cologne	NRW
Netherlands	Radboud University Nijmegen Medical Center	Nijmegen

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital of Cologne	Radboud University Medical Center

Countries where clinical trial is conducted

Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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