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

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

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.

Study Overview

• Status: Completed
• Conditions: Invasive Aspergillosis
• Intervention / Treatment: Other: Registry

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).

• Study Type: Observational
• Enrollment (Actual): 203

Contacts and Locations

• Study Contact: Name: Dorothee Arenz, Dr.; Phone Number: +49 221 478 32786; Email: dorothee.arenz@uk-koeln.de
• Study Contact Backup: Name: Susann Bloßfeld; Phone Number: +49 221 478 85523; Email: susann.blossfeld@uk-koeln.de

Study Locations

• Germany
  • NRW
    • Cologne, NRW, Germany, 50931
      • University Hospital of Cologne
• Netherlands
  • Nijmegen, Netherlands, 6500
    • Radboud University Nijmegen Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Cases will be recruited worldwide.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Invasive Aspergillosis	Other: Registry; There is no intervention.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital of Cologne
• Collaborators: Radboud University Medical Center
• Investigators: Principal Investigator: Oliver A. Cornely, Prof., University Hospital of Cologne, Germany; Principal Investigator: Paul E. Verweij, Prof., Radboud University Nijmegen Medical Center, The Netherlands

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): April 30, 2022
• Study Completion (Actual): October 25, 2022

Study Registration Dates

• First Submitted: May 9, 2017
• First Submitted That Met QC Criteria: July 13, 2017
• First Posted (Actual): July 18, 2017

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 11, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Invasive Aspergillosis; Azole resistance; Patient registry; Aspergillus fumigatus; Efficacy of antifungal therapy
• Additional Relevant MeSH Terms: Infections; Neoplasms; Neoplasms by Site; Hematologic Diseases; Bacterial Infections and Mycoses; Mycoses; Hematologic Neoplasms; Aspergillosis
• Other Study ID Numbers: 17-024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared with unauthorized persons. Anonymized data will only be exchanged between study coordinators and the analysis team.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No