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

• Sponsor: University Hospital of Cologne (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT03221075
• Collaborator: Radboud University Medical Center (Other)
• Enrollment: 220
• Locations: 2
• Anticipated Duration (Months): 40
• Patients Per Site: 110
• Patients Per Site Per Month: 2.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Invasive Aspergillosis	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 Design

• Study Type: Observational [Patient Registry]
• Anticipated Enrollment: 220 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: CLARITY - Clinical Implications of Azole-Resistant Aspergillosis in Hematological Malignancy
• Actual Study Start Date: Mar 1, 2017
• Anticipated Primary Completion Date: Jun 1, 2020
• Anticipated Study Completion Date: Jul 1, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Treatment response to antifungal therapy in patients with an invasive Aspergillosis caused by an azole resistant pathogen. [Change from diagnosis at day 14, 28, 42 and 84 and throughout study completion]

   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.

Secondary Outcome Measures

1. Overall survival [4 years]

   Final outcome will be compared between the two groups in consideration of the type and state of underlying diseases and risk factors.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital of Cologne	Cologne	NRW	Germany	50931
2	Radboud University Nijmegen Medical Center	Nijmegen		Netherlands	6500

Sponsors and Collaborators

• University Hospital of Cologne
• 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Prof. Dr. Oliver A. Cornely, Prof., University Hospital of Cologne
• ClinicalTrials.gov Identifier: NCT03221075
• Other Study ID Numbers: 17-024
• First Posted: Jul 18, 2017
• Last Update Posted: Oct 30, 2018
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Prof. Dr. Oliver A. Cornely, Prof., University Hospital of Cologne: Invasive Aspergillosis; Azole resistance; Aspergillus fumigatus; Efficacy of antifungal therapy; Patient registry
• Additional relevant MeSH terms: Aspergillosis; Hematologic Neoplasms

Study Results

No Results Posted as of Oct 30, 2018