Revision of Antifungal Strategies Definitions for Invasive Fungal Infections in Hematological Malignancies

NCT ID: NCT04024995

Last Updated: 2022-10-26

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 513 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-09-01
• Study Completion Date: 2021-12-31

Brief Summary

The primary objective of this study is to evaluate invasive fungal infections (IFI) according to clinicians' opinion vs the opinion of an independent board of experts. The primary output of this study is the evaluation of inter-raters agreement. Secondary objectives are: evaluation of IFI incidence; description of clinical and laboratory features; frequencies of different antifungal treatments; description of outcome; impact on the treatment of underlying hematological malignancy. This is a multicenter, non-interventional observational, prospective study. The duration of the study will be 18 months. The study will recruit all consecutive eligible patients in each participating center, during a period of 6 months until at least 600 patients with acute myeloid leukemia are registered, that represented the highest risk category. Other disease types that fulfill the eligibility criteria in the participating centers during the same period will also be recruited in the study.

The clinical, microbiological, diagnostic and therapeutic procedures operated on these patients will be collected.

An eCRF will be compiled for all patients:

T0: at the start of antifungal treatment, information will be collected regarding hematological malignancy, status of the disease at onset of infection and phase of treatment, last chemotherapy regimen, comorbidities and risk factors; previous IFI, neutropenia, antifungal and antibiotic prophylaxis and the kind of IFI clinicians retain the patient suffer (possible/probable/proven) and the kind of antifungal treatment started (empiric/pre-emptive/target); diagnostic work-up done, positive microbiology and biomarkers, positive radiological findings; antifungal treatment.

T1: at 30-40 days (or before if the patient unfortunately died) a second form must be completed with information regarding any changes in/additional diagnostic work-up done, positive microbiology and biomarkers, positive radiological findings; any changes in antifungal treatment; outcome.

At that time, the local physician must state any revision of his diagnostic classification between the moment in which antifungal treatment was started and the moment of evaluation of the outcome in order to estimate the differences regarding the level of evidence of diagnosis and treatment of IFI during time.

Each case will be examined blinded by 2 different experts, who will review all records based on the existing guidelines, their own experience and the information that was known at the two time points, which may confirm or not the decision of local physician.

The sample size will be driven by the AML patients (approximately 60-70% of the patients). Sample will be described in its clinical and demographic features via descriptive statistics. Quantitative variables will be summarized with the following measures: minimum, maximum, range, mean and standard deviation. Qualitative variables will be represented by frequencies tables.

Detailed Description

Primary objective The primary objective of this study is to evaluate IFI according to clinicians' opinion vs the opinion of an independent board of experts. The independent panel, confirming or not the decision of local physician, will review all cases (blind central review). The primary output of this study is the evaluation of inter-raters agreement.

Secondary objectives:

Evaluation of IFI incidence Description of clinical and laboratory features Frequencies of different antifungal treatments Description of outcome Impact on the treatment of underlying hematological malignancy

Study design This is a multicenter, non-interventional observational, prospective study.

The duration of the study will be 18 months. The schedule for the study will be the following:

Observation and data collection: 6 months Revision board: 6 months Data elaboration and paper: 6 months

Materials and methods The study will recruit all consecutive eligible patients in each participating center, during a period of 6 months until at least 600 AML patients are registered, that represented the highest risk category of patients for IFI. Other disease types that fulfill the eligibility criteria in the participating centers during the same period will also be recruited in the study.

We do not expect that diagnostic work-up would significantly vary among the participating centers. Minimal diagnostic work up must include:

Blood cultures for fungal infection; Chest High Resolution CT-scan; Serum galactomannan; Sinus CT-scan (if indicated); Bronchoalveolar lavage (if indicated);

Centers participating to the study will be selected on the basis of a questionnaire that evaluate their availability to participate to the survey (see Appendix 1).

The clinical, microbiological, diagnostic and therapeutic procedures operated on these patients will be collected.

An electronic CRF will be compiled for all patients at two different time points: T0 and T1.

T0: at the start of antifungal treatment (study entry), information will be collected regarding:

Hematological malignancy, status of the disease at onset of infection and phase of treatment, last chemotherapy regimen, comorbidities and risk factors (previous allogeneic stem cell transplantation); Previous IFI, neutropenia, antifungal and antibiotic prophylaxis: the local physicians must define the kind of IFI they retain the patient suffer (possible/probable/proven) and the kind of antifungal treatment started (empiric/pre-emptive/target); Diagnostic work-up done, positive microbiology and biomarkers, positive radiological findings; Antifungal treatment.

T1: at 30-40 days (or before if the patient unfortunately died) a second form must be completed with information regarding:

any changes in/additional diagnostic work-up done, positive microbiology and biomarkers, positive radiological findings; any changes in antifungal treatment; outcome. At that time, the local physician must state any revision of his diagnostic classification between the moment in which antifungal treatment was started and the moment of evaluation of the outcome (30 days) in order to estimate the differences regarding the level of evidence of diagnosis and treatment of IFI during time.

Independent central review board The experts (each case will be examined blinded by 2 different experts). The experts will review all records based on the existing guidelines, their own experience and based on the information that was known at the two time points, which may confirm or not the decision of local physician.

Statistical considerations Sample size dimension The sample size will be driven by the AML patients (approximately 60-70% of the patients): Statistical analysis Sample will be described in its clinical and demographic features via descriptive statistics. Quantitative variables will be summarized with the following measures: minimum, maximum, range, mean and standard deviation. Qualitative variables will be represented by frequencies tables (absolute and percentage) The primary object of the study will be achieved evaluating Fleiss' Kappa. Secondary objectives will be using descriptive statistics techniques (already described above) recruit all eligible patients during a period of 6 months until at least 600 AML patients are recruited.

Conditions

Invasive Fungal Infections

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• All patients with hematologic malignancies at any stage of the disease (acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma, myelodysplastic syndromes, chronic lymphocytic leukemia, high and low grade non Hodgkin lymphoma, chronic myeloprolipherative disorders, Hodgkin lymphoma);
• Only inpatients will be eligible;
• Patient that start IV antifungal treatment (irrespective of previous prophylaxis);
• Informed consent signed.

Exclusion Criteria

• Patients with previous or undergoing allogeneic or autologous transplant will be excluded from the study, due to different clinical profiles and risk factors;
• Patients treated, after prophylaxis with oral antifungals
• Patients treated in outpatient clinic or Day hospital

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sorveglianza Epidemiologica Infezioni Fungine Emopatie Maligne

OTHER

Sponsor Role: lead

Responsible Party

LIVIO PAGANO

Associate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Livio Pagano

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico Universitario A. Gemelli IRCCS-UCSC

Locations

Azienda Ospedaliera Universitaria S. Orsola Malpighi

Bologna, , Italy

ASST-Spedali Civili

Brescia, , Italy

AOUC Carreggi

Florence, , Italy

AOU Policlinico Federico II

Napoli, , Italy

Azienda Ospedaliera di Perugia

Perugia, , Italy

Azienda Ospedaliera San Camillo Forlanini

Rome, , Italy

Fondazione Policlinico A. Gemelli IRCCS

Rome, , Italy

Istituto Nazionale Tumori Regina Elena IFO

Rome, , Italy

Ospedale Infantile Regina Margherita

Torino, , Italy

Azienda Sanitaria Universitaria Integrata di Udine

Udine, , Italy

Osp. di Circolo-Fondazione Macchi

Varese, , Italy

AOUI Verona

Verona, , Italy

Ospedale Donna Bambino

Verona, , Italy

Ospedale San Bortolo- AULSS 8 Berica

Vicenza, , Italy

Countries

Italy

References

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Facchinelli D, Marchesini G, Nadali G, Pagano L. Invasive Fungal Infections in Patients with Chronic Lymphoproliferative Disorders in the Era of Target Drugs. Mediterr J Hematol Infect Dis. 2018 Nov 1;10(1):e2018063. doi: 10.4084/MJHID.2018.063. eCollection 2018.

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Other Identifiers

REDEFI-SEIFEM

Identifier Type: -

Identifier Source: org_study_id