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出境医 / 临床实验 / Revision of Antifungal Strategies Definitions for Invasive Fungal Infections in Hematological Malignancies

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

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
Invasive Fungal Infections

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Study Design
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Study Type : Observational [Patient Registry]
Estimated Enrollment : 800 participants
Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration: 30 Days
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 : September 1, 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : December 2021
Arms and Interventions
Outcome Measures
Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Evaluation of incidence of invasive fungal infections [ Time Frame: 6 months ]
    Evaluation of incidence of IFI among hematological patients

  2. 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


Eligibility Criteria
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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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
Contacts and Locations

Contacts
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Contact: Livio Pagano +390630154180 livio.pagano@unicatt.it

Locations
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Italy
Azienda Ospedaliera Universitaria S. Orsola Malpighi Recruiting
Bologna, Italy
Contact: Daniele Zama         
ASST-Spedali Civili Recruiting
Brescia, Italy
Contact: Chiara Cattaneo         
AOUC Carreggi Recruiting
Firenze, Italy
Contact: Rosa Fanci         
AOU Policlinico Federico II Recruiting
Napoli, Italy
Contact: Marco Picardi         
Azienda Ospedaliera di Perugia Recruiting
Perugia, Italy
Contact: Katia Perruccio         
Azienda Ospedaliera San Camillo Forlanini Recruiting
Rome, Italy
Contact: Mariagrazia Garzia         
Fondazione Policlinico A. Gemelli IRCCS Recruiting
Rome, Italy
Contact: Livio Pagano         
Contact: Marianna Criscuolo         
Istituto Nazionale Tumori Regina Elena IFO Recruiting
Rome, Italy
Contact: Francesco Marchesi         
Ospedale Infantile Regina Margherita Recruiting
Torino, Italy
Contact: Francesca Carraro         
Azienda Sanitaria Universitaria Integrata di Udine Recruiting
Udine, Italy
Contact: Anna Candoni         
Osp. di Circolo-Fondazione Macchi Recruiting
Varese, Italy
Contact: Claudia Maria Basilico         
AOUI Verona Recruiting
Verona, Italy
Contact: Gianpaolo Nadali         
Ospedale Donna Bambino Recruiting
Verona, Italy
Contact: Simone Cesaro         
Ospedale San Bortolo- AULSS 8 Berica Recruiting
Vicenza, Italy
Contact: Maria Chiara Tisi         
Sponsors and Collaborators
Sorveglianza Epidemiologica Infezioni Fungine Emopatie Maligne
Investigators
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Principal Investigator: Livio Pagano Fondazione Policlinico Universitario A. Gemelli IRCCS-UCSC
Tracking Information
First Submitted Date February 26, 2019
First Posted Date July 18, 2019
Last Update Posted Date October 23, 2020
Actual Study Start Date September 1, 2019
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 18, 2019)
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
Original Primary Outcome Measures
 (submitted: July 17, 2019)
Diagnosis of 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
Change History
Current Secondary Outcome Measures
 (submitted: July 18, 2019)
  • Evaluation of incidence of invasive fungal infections [ Time Frame: 6 months ]
    Evaluation of incidence of IFI among hematological patients
  • 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
Original Secondary Outcome Measures
 (submitted: July 17, 2019)
  • Evaluation of incidence of invasive fungal infections [ Time Frame: 6 months ]
  • Attributable and all-cause mortality of patients with invasive fungal infections [ Time Frame: 30 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Revision of Antifungal Strategies Definitions for Invasive Fungal Infections in Hematological Malignancies
Official Title Revision of Antifungal Strategies Definitions for Invasive Fungal Infections (Proven/Probable/Possible) in Patients With Hematological Malignancies (REDEFI-SEIFEM)
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.

Study Type Observational [Patient Registry]
Study Design Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration 30 Days
Biospecimen Not Provided
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.
Condition Invasive Fungal Infections
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications *
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: July 17, 2019)
800
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 2021
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
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
Sex/Gender
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers No
Contacts
Contact: Livio Pagano +390630154180 livio.pagano@unicatt.it
Listed Location Countries Italy
Removed Location Countries  
 
Administrative Information
NCT Number NCT04024995
Other Study ID Numbers REDEFI-SEIFEM
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party LIVIO PAGANO, Sorveglianza Epidemiologica Infezioni Fungine Emopatie Maligne
Study Sponsor Sorveglianza Epidemiologica Infezioni Fungine Emopatie Maligne
Collaborators Not Provided
Investigators
Principal Investigator: Livio Pagano Fondazione Policlinico Universitario A. Gemelli IRCCS-UCSC
PRS Account Sorveglianza Epidemiologica Infezioni Fungine Emopatie Maligne
Verification Date October 2020

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