FOVOCIP study: a multicenter randomized trial of fosfomycin versus ciprofloxacin for febrile neutropenia in hematologic patients—efficacy and microbiologic safety
Ainhoa Fernández Moreno,
Lucía Lavín-Alconero,
Paula López de Ugarriza,
Laura Solán Blanco,
Sara Cáceres Hernández,
Juan Miguel Bergua Burgués,
María Izquierdo de Miguel,
Ana Julia González Huerta,
Marta Polo Zarzuela,
Blanca Boluda,
Karem Humala,
Maria Luisa Calabuig,
Maria Luz Amigo,
Marián Cuesta Casas,
María del Mar García-Saiz,
Ana Fernández Verdugo,
Javier Fernández Domínguez,
Teresa Bernal
Affiliations
Ainhoa Fernández Moreno
Hematology Department, University Hospital Central of Asturias
Lucía Lavín-Alconero
Clinical Trials Agency Valdecilla-IDIVAL, Marqués de Valdecilla University Hospital
Paula López de Ugarriza
Hematology Department, University Hospital Central of Asturias
Laura Solán Blanco
Hematology Department, Fundación Jiménez Díaz
Sara Cáceres Hernández
Hematology Department, San Pedro Alcántara Hospital
Juan Miguel Bergua Burgués
Hematology Department, San Pedro Alcántara Hospital
María Izquierdo de Miguel
Hematology Department, San Pedro Alcántara Hospital
Ana Julia González Huerta
Hematology Department, University Hospital Central of Asturias
Marta Polo Zarzuela
Hematology Department, University Clinic Hospital San Carlos
Blanca Boluda
Hematology Department, Instituto de Investigación, University Hospital La Fe
Karem Humala
Hematology Department, University Hospital La Paz
Maria Luisa Calabuig
Hematology Department, University Clinic Hospital of Valencia
Maria Luz Amigo
Hematology Department, University Hospital Morales Messeguer
Marián Cuesta Casas
Hematology Department, University Hospital Carlos Haya
María del Mar García-Saiz
Clinical Trials Agency Valdecilla-IDIVAL, Marqués de Valdecilla University Hospital
Ana Fernández Verdugo
Microbiology Department, University Hospital Central of Asturias
Javier Fernández Domínguez
Clinical Trials Agency Valdecilla-IDIVAL, Marqués de Valdecilla University Hospital
Teresa Bernal
Instituto Universitario de Oncología del Principado de Asturias, C/ Fernando Bongera
Abstract Background Multidrug-resistant Gram-negative bacterial (MRGNB) infections represent a major public health threat. Cancer patients and, among them, hematological patients are most vulnerable to these infections. Gut colonization by MRGNB is a common phenomenon occurring during hospitalization and chemotherapy exposure. In the neutropenic phase that occurs after chemotherapy, MRGNB translocation occurs increasing patient’s mortality. Fluoroquinolone prophylaxis with ciprofloxacin or levofloxacin efficacy is now being questioned due to the increase of incidence in MRGNB. Methods A phase III randomized, controlled, clinical trial, open-label parallel-group with a 1:1 ratio, aimed to demonstrate the non-inferiority of oral fosfomycin versus oral ciprofloxacin for febrile neutropenia prevention in patients with acute leukemia (AL) or hematopoietic cell transplant (HSC) receptors. Weekly surveillance cultures are planned to detect gut colonization. Changes in fecal microbiome at the beginning and end of prophylaxis will also be analyzed. Discussion This trial will provide evidence of the efficacy of an alternative drug to ciprofloxacin for febrile neutropenia prevention in high-risk hematological patients. The battery of planned microbiological studies will allow us to evaluate prospectively the microbiological safety of both pharmacological strategies in terms of the selection of MRGNB occurring in each arm. In addition, valuable information on the way in which each drug changes the fecal microbiome of the patients throughout the treatment will be generated. Trial registration Clinical trials NCT05311254, Registered on 5 April 2022, https://clinicaltrials.gov/ct2/show/NCT05311254?term=FOVOCIP&cntry=ES&draw=2&rank=1 . Protocol version: 3.0, dated 20 May 2022.
