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

Sponsor

Sorveglianza Epidemiologica Infezioni Fungine Emopatie Maligne (Other)

Overall Status

Recruiting

CT.gov ID

NCT04024995

Collaborator

(none)

800

Enrollment

Locations

Anticipated Duration (Months)

57.1

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Invasive Fungal Infections

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 Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

800 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Sep 1, 2019

Anticipated Primary Completion Date :

Sep 1, 2021

Anticipated Study Completion Date :

Dec 1, 2021

Outcome Measures

Primary Outcome Measures

Rate of diagnosis Agreement in proven/probable/possible IFI in real life using EORTC/MSG Criteria [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

Secondary Outcome Measures

Evaluation of incidence of invasive fungal infections [6 months]
Evaluation of incidence of IFI among hematological patients
Attributable and all-cause mortality of patients with invasive fungal infections [30 days]
Description of attributable and all-cause mortality of hematological patients with IFI

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country
1	Azienda Ospedaliera Universitaria S. Orsola Malpighi	Bologna	Italy
2	ASST-Spedali Civili	Brescia	Italy
3	AOUC Carreggi	Firenze	Italy
4	AOU Policlinico Federico II	Napoli	Italy
5	Azienda Ospedaliera di Perugia	Perugia	Italy
6	Azienda Ospedaliera San Camillo Forlanini	Rome	Italy
7	Fondazione Policlinico A. Gemelli IRCCS	Rome	Italy
8	Istituto Nazionale Tumori Regina Elena IFO	Rome	Italy
9	Ospedale Infantile Regina Margherita	Torino	Italy
10	Azienda Sanitaria Universitaria Integrata di Udine	Udine	Italy
11	Osp. di Circolo-Fondazione Macchi	Varese	Italy
12	AOUI Verona	Verona	Italy
13	Ospedale Donna Bambino	Verona	Italy
14	Ospedale San Bortolo- AULSS 8 Berica	Vicenza	Italy