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

October 25, 2022 updated by: LIVIO PAGANO, Sorveglianza Epidemiologica Infezioni Fungine Emopatie Maligne

Revision of Antifungal Strategies Definitions for Invasive Fungal Infections (Proven/Probable/Possible) in Patients With Hematological Malignancies (REDEFI-SEIFEM)

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.

Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment (Actual)

513

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Bologna, Italy
        • Azienda Ospedaliera Universitaria S. Orsola Malpighi
      • Brescia, Italy
        • ASST-Spedali Civili
      • Firenze, Italy
        • AOUC Carreggi
      • Napoli, Italy
        • AOU Policlinico Federico II
      • Perugia, Italy
        • Azienda Ospedaliera di Perugia
      • Rome, Italy
        • Azienda Ospedaliera San Camillo Forlanini
      • Rome, Italy
        • Fondazione Policlinico A. Gemelli IRCCS
      • Rome, Italy
        • Istituto Nazionale Tumori Regina Elena IFO
      • Torino, Italy
        • Ospedale Infantile Regina Margherita
      • Udine, Italy
        • Azienda Sanitaria Universitaria Integrata di Udine
      • Varese, Italy
        • Osp. di Circolo-Fondazione Macchi
      • Verona, Italy
        • AOUI Verona
      • Verona, Italy
        • Ospedale Donna Bambino
      • Vicenza, Italy
        • Ospedale San Bortolo- AULSS 8 Berica

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of diagnosis Agreement in proven/probable/possible IFI in real life using EORTC/MSG Criteria
Time Frame: 30 days
Rate of diagnosis agreement in proven/probable/possible IFI between local physician in real life and indipendent board of experts according to EORTC/MSG Criteria
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of incidence of invasive fungal infections
Time Frame: 6 months
Evaluation of incidence of IFI among hematological patients
6 months
Attributable and all-cause mortality of patients with invasive fungal infections
Time Frame: 30 days
Description of attributable and all-cause mortality of hematological patients with IFI
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sorveglianza Epidemiologica Infezioni Fungine Emopatie Maligne

Investigators

  • Principal Investigator: Livio Pagano, Fondazione Policlinico Universitario A. Gemelli IRCCS-UCSC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2019

Primary Completion (Actual)

September 30, 2021

Study Completion (Actual)

December 31, 2021

Study Registration Dates

First Submitted

February 26, 2019

First Submitted That Met QC Criteria

July 17, 2019

First Posted (Actual)

July 18, 2019

Study Record Updates

Last Update Posted (Actual)

October 26, 2022

Last Update Submitted That Met QC Criteria

October 25, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • REDEFI-SEIFEM

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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