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

Invasive Fungal Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04024995
• Other study ID #: REDEFI-SEIFEM
• Status: Completed
• Start date: September 1, 2019
• Est. completion date: December 31, 2021

Study information

• Verified date: October 2022
• Source: Sorveglianza Epidemiologica Infezioni Fungine Emopatie Maligne
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 513
• Est. completion date: December 31, 2021
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Hematologic Neoplasms
• Infections
• Invasive Fungal Infections
• Mycoses

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera Universitaria S. Orsola Malpighi	Bologna
Italy	ASST-Spedali Civili	Brescia
Italy	AOUC Carreggi	Firenze
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

Sponsors (1)

Lead Sponsor	Collaborator
Sorveglianza Epidemiologica Infezioni Fungine Emopatie Maligne

Country where clinical trial is conducted

Italy, 

References & Publications (6)

Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, Helfgott D, Holowiecki J, Stockelberg D, Goh YT, Petrini M, Hardalo C, Suresh R, Angulo-Gonzalez D. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007 Jan 25;356(4):348-59. — View Citation

De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Muñoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE; European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008 Jun 15;46(12):1813-21. doi: 10.1086/588660. — View Citation

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. Review. — View Citation

Maccioni F, Vetere S, De Felice C, Al Ansari N, Micozzi A, Gentile G, Foà R, Girmenia C. Pulmonary fungal infections in patients with acute myeloid leukaemia: is it the time to revise the radiological diagnostic criteria? Mycoses. 2016 Jun;59(6):357-64. doi: 10.1111/myc.12480. Epub 2016 Feb 11. — View Citation

Mercier T, Maertens J. Clinical considerations in the early treatment of invasive mould infections and disease. J Antimicrob Chemother. 2017 Mar 1;72(suppl_1):i29-i38. doi: 10.1093/jac/dkx031. — View Citation

Pagano L, Verga L, Busca A, Martino B, Mitra ME, Fanci R, Ballanti S, Picardi M, Castagnola C, Cattaneo C, Nadali G, Nosari A, Candoni A, Caira M, Salutari P, Lessi F, Aversa F, Tumbarello M. Systemic antifungal treatment after posaconazole prophylaxis: results from the SEIFEM 2010-C survey. J Antimicrob Chemother. 2014 Nov;69(11):3142-7. doi: 10.1093/jac/dku227. Epub 2014 Jun 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of diagnosis Agreement in proven/probable/possible IFI in real life using EORTC/MSG Criteria	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	Evaluation of incidence of invasive fungal infections	Evaluation of incidence of IFI among hematological patients	6 months
Secondary	Attributable and all-cause mortality of patients with invasive fungal infections	Description of attributable and all-cause mortality of hematological patients with IFI	30 days