Clinical trial NCT02088840: Survey of Severe Infections by Gram Negative Bacteria in Patients Submitted to Stem Cell Transplant
Official title: A Prospective, Multicenter Survey of Severe Infections by Gram Negative Bacteria in Patients Submitted to Autologous and Allogeneic Stem Cell Transplant.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Complications of Organ Transplant Stem Cells
Gram-Negative Bacterial Infections
Keywords: SIGNB
severe infections gram negative bacteria
stem cell transplant
Lead sponsor: Gruppo Italiano Trapianto di Midollo Osseo
Sponsor class: OTHER
First posted: 2014-03-17
Enrollment: 2769
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients undergoing autologous or allogeneic Stem Cell Transplant for any underlying disease will be monitored for SIGNB during the engraftment period.

Brief summary: All patients undergoing autologous or allogeneic stem cell transplant (SCT) for any underlying disease will be monitored for severe infections by gram negative bacteria (SIGNB) during the engraftment period. The follow up will be stopped at 4 months from the day of transplant. About 50 transplant centers will be involved in the study.

Detailed description: Severe Infections by Gram Negative Bacteria (SIGNB) remain an important cause of morbidity and mortality in patients submitted to stem cell transplant particularly during engraftment while patients suffer of profound and prolonged neutropenia or during subsequent neutropenia periods related to loss of engraftment or viral infections. Epidemiology of severe infections by gram negative bacteria in stem cell transplant patients has varied in the last decades due to the increasing use of highly immunosuppressive stem cell transplant procedures, and in relation to global epidemiological phenomena involving several populations of immunocompromised patients including those submitted to stem cell transplant.

The epidemiological evolution of severe infections by gram negative bacteria in immunocompromised patients is represented also by the emergence of infections caused by Gram-negative bacilli, in particular enterobacteria, resistant to several antimicrobials. Such pattern of susceptibility to antibacterial agents represents a challenging issue in the currents strategies of the use of antibiotics in prophylaxis or therapy.

Despite an increasing attention to the clinical and therapeutic aspects of infection in stem cell transplant recipients, contrasting data are available on the incidence, microbiologic characteristics and clinical outcome of Severe Infections by Gram Negative Bacteria in this population.

Management of patients submitted to stem cell transplant is frequently complicated by Severe Infections by Gram Negative Bacteria which may represent an obstacle to the transplant procedure. Severe Infections by Gram Negative Bacteria caused by microorganisms resistant to betalactamic antibiotics, which are the golden standard in the empirical antibacterial therapy of febrile neutropenia, represent a challenging problem. A revision of the antibacterial strategies and the consideration of new molecules with different antibacterial mechanism of action should be considered in the light of the emerging epidemiology. Antimicrobial prophylaxis, diagnostic approaches and antimicrobial therapy should be adapted to the infectious risk of the transplant population according to stem cell source, conditioning regimen and also to the infectious history before transplant. A crucial problem in the definition of these strategies is represented by the continuous change in the epidemiological patterns of infections as a result of the modification of risk factors in the transplant population and of the global epidemiology of hospital and community acquired infections. In particular the emergence of antibiotic resistant enterobacteria represents a serious problem which dramatically impacts on the antibacterial prophylaxis and treatments choices.

The Investigator think that a continuous epidemiology survey is required in order to better define proper prevention, diagnostic and treatment approaches. A common problem in the infections control in immunocompromised populations is represented by the lack of epidemiological consciousness in the single centres and its relationship with the local policy in the use of antibacterial drugs. A prospective, multicenter survey of Severe Infections by Gram Negative Bacteria by antibiotic resistant pathogens, in particular enterobacteria, may be a useful tool to evaluate the epidemiological patterns of infections, their impact on the overall survival, and a critical analysis of the use of antibacterial drugs.

The Investigator of this study think that the results of this survey may offer precious indications for the timely update of the prophylaxis, diagnosis and treatment strategies of Severe Infections by Gram Negative Bacteria in patients undergoing a stem cell transplant procedure.

An important aspect of this study is represented by the involvement of both stem cell transplant and microbiology Italian societies, the GITMO Gruppo Italiano per il Trapianto di Midollo Osseo, cellule staminali emopoietiche e terapia cellulare and the AMCLI Associazione Microbiologi Clinici Italiani respectively, as a "joint venture" in the study of the clinical and microbiological aspects of Severe Infections by Gram Negative Bacteria in the autologous and allogeneic stem cell transplant populations. Investigators of both GITMO and AMCLI are involved in the design, writing and monitoring of the study and for each participating transplant center a clinician, responsible for the clinical data, and a microbiologist, responsible for the microbiological data, will be provided.

The general objectives of this study are to prospectively evaluate the epidemiology of Severe Infections by Gram Negative Bacteria by antibiotic resistant pathogens in autologous and allogeneic stem cell transplant patients during the engraftment period.

All consecutive patients submitted to autologous or allogeneic stem cell transplant for any underlying disease in about 50 Italian transplant centers will be prospectively monitored for severe infections by gram negative bacteria during the engraftment period. The follow up will be stopped at 4 months from the day of transplant. Risk factors, incidence and prognostic factors of Severe Infections by Gram Negative Bacteria will be evaluated in the overall population and in subpopulations according to different transplant characteristics. Data on in vitro susceptibility patterns of the microorganisms and on the antibacterials used in prophylaxis and therapy will be collected.

Descriptive analyses will be performed for all Severe Infections by Gram Negative Bacteria cases occurring among patients enrolled in this study.

The study will be conducted in accordance with the ethical principles derived from the Declaration of Helsinki, the CGP and regulations.

In this study the investigators will use the E-CRF in apposite web site. Data will be collected in E-CRF (electronic case report form) for the registration of clinical data through a special web portal dedicated to the study.

Investigators are responsible for the preparation and storage of clinical data concerning the clinical trial in accordance with ICH guidelines for good clinical practice. Access to clinical data should be reserved exclusively to authorized personnel. Investigators will have to verify and ensure the strict confidentiality of records that could identify patients in compliance with standards on privacy and personal data in accordance with Italian legislation. On data collection forms (and related documentation) patients should be uniquely identified by date of birth and the code of enrolment. The full name of the patient will never be used in any communication and / or correspondence. Will be required direct access to the patient's original medical records for verification and monitoring of clinical data. The investigators are obliged to inform patients that their medical records could be verified, without breach of confidentiality of personal data. Investigators will have to allow monitoring of clinical data related to the study, the revisions IRB / IEC and inspections by regulatory authorities in accordance with Italian legislation, providing direct access to the medical records of patients.

The national coordination of the study is carried out by the Office of Clinical Trials GITMO. The Office of Clinical Trials GITMO will act as the Data Management Center and quality control, providing for data management and administrative support throughout the course of the study.

Eligibility criteria: Inclusion Criteria:

All consecutive patients submitted to autologous or allogeneic SCT at the Centers participating to the survey Signed written informed consent according to IGH/EU/GCP and national local laws.

Without age limit

Exclusion Criteria:

Patients who did not sign written informed consent

Primary outcomes:
measure: incidence of each type of Severe Infections by Gram Negative Bacteria
timeFrame: 4 months by stem cell transplant
Secondary outcomes:
measure: incidence particularly of Severe Infections by Gram Negative Bacteria
timeFrame: 4 months by stem cell transplant
measure: risk factors
timeFrame: 4 month by stem cell transplant
measure: prognostic factors
timeFrame: 4 month by stem cell transplant
measure: overall mortality for SIGNB
timeFrame: 3 months from the Severe Infections by Gram Negative Bacteria
measure: overall survival for SIGNB from transplant
timeFrame: 4 months from transplant
measure: susceptibility pattern to antimicrobials of microorganisms
timeFrame: 4 month by stem cell transplant
measure: antibacterial strategies
timeFrame: 4 month by stem cell transplant
measure: local strategy
timeFrame: 4 month by stem cell transplant
Other outcomes:
Locations:
city: Candiolo
country: Italy
facility: FPO Irccs
state: Torino
city: Alessandria
country: Italy
facility: Azienda Ospedaliera SS Antonio e Biagio
city: Ancona
country: Italy
facility: Clinica di Ematologia - Università Politecnica delle Marche
city: Ascoli Piceno
country: Italy
facility: Ospedale Mazzoni
city: Bari
country: Italy
facility: Policlinico di Bari-Ematologia con trapianti
city: Bergamo
country: Italy
facility: Divisione di Ematologia - Ospedali Papa Giovanni XXIII
city: Bologna
country: Italy
facility: Ospedale San Orsola
city: Brescia
country: Italy
facility: AO Spedali Civili di Brescia- USD - TMO Adulti
city: Brescia
country: Italy
facility: Spedali Civili
city: Cagliari
country: Italy
facility: Ospedale Binaghi
city: Catania
country: Italy
facility: Ospedale Ferrarotto - Ematologia
city: Civitanova Marche
country: Italy
facility: Ospedale Civile USL 8
city: Cuneo
country: Italy
facility: S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle
city: Firenze
country: Italy
facility: Cattedra di Ematologia - Azienda Ospedaliera di Careggi
city: Foggia
country: Italy
facility: Ematologia e Centro Trapianti Midollo Osseo - Ospedale IRCCS Casa Sollievo della Sofferenza
city: Genova
country: Italy
facility: AOU IRCCS San Martino - IST
city: Genova
country: Italy
facility: Ospedale Gaslini
city: Milano
country: Italy
facility: Divisione di Ematologia - Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: IEO
city: Milano
country: Italy
facility: Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Napoli
country: Italy
facility: A.O.U. Policlinico Federico II
city: Napoli
country: Italy
facility: INT IRCCS Fondazione Pascale
city: Novara
country: Italy
facility: Ospedale Maggiore della Carità
city: Palermo
country: Italy
facility: AO Ospedali Riuniti Villa Sofia - Cervello
city: Palermo
country: Italy
facility: Dipartimento Oncologico La Maddalena
city: Parma
country: Italy
facility: CTMO Università
city: Pavia
country: Italy
facility: Fondazione IRCCS San Matteo
city: Pavia
country: Italy
facility: Dipartimento di Ematologia - IRCCS Policlinico S. Matteo - Università di Pavia
city: Perugia
country: Italy
facility: Dip. Medicina Clinica e Sperimentale
city: Pescara
country: Italy
facility: Dip. di Ematologia - Unità di Terapia Intensiva Ematologica per il Trapianto Emopoietico - Ospedale Civile di Pescara
city: Piacenza
country: Italy
facility: Ospedale G. Da Saliceto di Piacenza
city: Reggio Calabria
country: Italy
facility: Centro Unico Regionale Trapianti di Midollo Osseo - Ospedale Bianchi-Melacino-Morelli
city: Rimini
country: Italy
facility: Ospedale Infermi
city: Rionero in Vulture
country: Italy
facility: Irccs Crob
city: Roma
country: Italy
facility: A.O. San Camillo
city: Roma
country: Italy
facility: Campus biomedico
city: Roma
country: Italy
facility: Cattedra di Ematologia - Policlinico
city: Roma
country: Italy
facility: Divisione di Ematologia - Istituto di Semeiotica Medica - Policlinico A. Gemelli
city: Roma
country: Italy
facility: Istituto Regina Elena IFO
city: Roma
country: Italy
facility: Ospedale Bambin Gesù
city: Roma
country: Italy
facility: Ospedale San Giovanni
city: Roma
country: Italy
facility: Ospedale Sant'Andrea
city: Roma
country: Italy
facility: Ospedale Santo Eugenio
city: Roma
country: Italy
facility: Policlinico Universitario Tor Vergata
city: Rozzano (MI)
country: Italy
facility: Dipartimento di Oncologia Medica ed Ematologia - Istituto Clinico Humanitas
city: Taranto
country: Italy
facility: Ospedale Moscati
city: Torino
country: Italy
facility: Azienda ospedaliera Città della Salute e della Scienza
city: Torino
country: Italy
facility: Centro Trapianti Metropolitano
city: Torino
country: Italy
facility: Ospedale Gonzaga
city: Treviso
country: Italy
facility: UOC Ematologia
city: Udine
country: Italy
facility: A.O. Santa Maria della Misericordia
city: Verona
country: Italy
facility: Policlinico GB Rossi
city: Vicenza
country: Italy
facility: Ospedale S. Bortolo-Divisione Ematologia
Study officials:
affiliation: Policlinico Umberto I - Rome
name: Corrado Girmenia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Girmenia C, Bertaina A, Piciocchi A, Perruccio K, Algarotti A, Busca A, Cattaneo C, Raiola AM, Guidi S, Iori AP, Candoni A, Irrera G, Milone G, Marcacci G, Scime R, Musso M, Cudillo L, Sica S, Castagna L, Corradini P, Marchesi F, Pastore D, Alessandrino EP, Annaloro C, Ciceri F, Santarone S, Nassi L, Farina C, Viscoli C, Rossolini GM, Bonifazi F, Rambaldi A; Gruppo Italiano Trapianto di Midollo Osseo (GITMO) and Associazione Microbiologi Clinici Italiani (AMCLI). Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia After Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey. Clin Infect Dis. 2017 Nov 13;65(11):1884-1896. doi: 10.1093/cid/cix690.