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A Trial of Fosfomycin vs Ciprofloxacin for Febrile Neutropenia (FOVOCIP)

Primary Purpose

Febrile Neutropenia

Status

Recruiting

Phase

Phase 3

Locations

Spain

Study Type

Interventional

Intervention

Fosfomycin Calcium

About this trial

This is an interventional prevention trial for Febrile Neutropenia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects who are able to understand study procedures, comply with them, and provide written informed consent before any study-specific procedure.
Adult subjects ≥ 18 years of age with acute leukemia diagnosis who are going to receive their first intensive chemotherapy cycle or adult subjects ≥ 18 years of age who are candidates to receive a first stem cell transplant.
Expected neutropenia 100x109/L lasting at least seven days. In case of expected neutropenia range 100-500x109/L lasting seven days or more, at least one of the following risk factors for infection must be present:
1. Performance status (Eastern Cooperative Oncology Group, ECOG) ≥2.
2. Expected mucositis grade 3-4.
3. Age ≥65 years.
4. Comorbidity Index (HCTI) ≥3.
5. Serum albumin< 35 g/L.
6. Total dose of etoposide > 500 mg/m2
7. Total dose of cytarabine > 1 g/m2
8. Active or refractory neoplasia at the moment of stem cell transplant.
Performance status (Eastern Cooperative Oncology Group, ECOG) of 0 to 3.
Adequate organ function defined as:
Liver: bilirubin, alkaline phosphatase, or SGOT < 3 times the upper normal limit (unless it is attributable to tumor activity).
Renal : creatinine ≤ 250 μmol/l (2.5 mg/dL) (unless it is attributable to AML activity).
Life expectancy higher than 3 months.
Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and men with female partners of child-bearing potential must agree to practice 2 highly effective contraceptive measures of birth control and must agree not to become pregnant or father a child while receiving any study therapy and for at least 3 months after completing treatment.

Exclusion Criteria:

Hypersensitivity to fluoroquinolones or fosfomycin.
Treatment with broad spectrum antimicrobial therapy within 4 weeks of first study treatment.
Prior Intensive chemotherapy or stem cell transplant. Treatment with hydroxyurea or corticosteroids used to control white blood cell counts are permitted.
Fever of infectious origin or documented infection within 4 weeks of first study treatment.
Presence of any severe psychiatric disease or physical condition that, according to the physicians criteria, contraindicates the inclusion of the patient into the clinical trial.
Subjects that have participated previously in this study

Sites / Locations

Instituto de Investigación Sanitaria del Principado de AsturiasRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Fosfomycin

Ciprofloxacin

Arm Description

Drug: Fosfomycin: oral capsules containing 700 mg of calcium fosfomycin, equivalent to 500 mg of active drug.

Oral ciprofloxacin, tablets containing 500 mg of active drug.

Outcomes

Primary Outcome Measures

Febrile neutropenia of infectious origin

Febrile neutropenia that requires antibacterial treatment.

Secondary Outcome Measures

Documented infections

Rate and type of documented infections

Use of broad spectrum antibiotics

Index of days of antibiotics per hospitalization days. Antibiotics will be classified according the Watch/Reserve classification

Overall survival

Drug related adverse events

Incidence of Adverse Events (AE), severity and type of AEs.

Evolution of resistome

Rate of patients colonized by multidrug resistant bacteria as determined by metagenomic sequencing

Microbiome evolution

Changes in the gut microbiome produced under both prophylactic strategies during the study period.

Microbiological safety

Rate of patients colonized by multidrug resistant bacteria as determined by surveillance cultures

Full Information

NCT ID

NCT05311254

First Posted

March 9, 2022

Last Updated

September 12, 2023

Sponsor

Fundación para la Investigación Biosanitaria del Principado de Asturias

Collaborators

Instituto de Investigación Marqués de Valdecilla, Instituto de Salud Carlos III

1. Study Identification

Unique Protocol Identification Number

NCT05311254

Brief Title

A Trial of Fosfomycin vs Ciprofloxacin for Febrile Neutropenia

Acronym

FOVOCIP

Official Title

A Multicenter Randomized Trial of Fosfomycin vs Ciprofloxacin for Febrile Neutropenia in Hematological Patients: Efficacy and Microbiological Safety

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 14, 2022 (Actual)

Primary Completion Date

March 14, 2024 (Anticipated)

Study Completion Date

March 14, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Fundación para la Investigación Biosanitaria del Principado de Asturias

Collaborators

Instituto de Investigación Marqués de Valdecilla, Instituto de Salud Carlos III

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

Brief Summary

Randomized phase 3 trial to compare efficacy and safety of oral fosfomycin versus ciprofloxacin to prevent febrile neutropenia in patients with acute leukemia or recipients of hematopoietic stem cell transplant.

Detailed Description

Multicenter, prospective, randomized, open label phase III trial to assess the efficacy and safety of oral fosfomycin vs. oral ciprofloxacin in the prevention of febrile neutropenia in patients with acute leukemia who are treated with intensive chemotherapy and/or are recipients of a hematopoietic stem cell transplant. Non-inferiority design. 156 patients will be recruited: 78 in each arm

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Febrile Neutropenia

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Multicenter, randomized, prospective, open-label

Masking

None (Open Label)

Allocation

Randomized

Enrollment

156 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Fosfomycin

Arm Type

Experimental

Arm Description

Drug: Fosfomycin: oral capsules containing 700 mg of calcium fosfomycin, equivalent to 500 mg of active drug.

Arm Title

Ciprofloxacin

Arm Type

Active Comparator

Arm Description

Oral ciprofloxacin, tablets containing 500 mg of active drug.

Intervention Type

Drug

Intervention Name(s)

Fosfomycin Calcium

Intervention Description

Oral fosfomycin, three times daily, starting from the first day of induction chemotherapy or conditioning until absolute neutrophil count >0,5x109/L.

Primary Outcome Measure Information:

Title

Febrile neutropenia of infectious origin

Description

Febrile neutropenia that requires antibacterial treatment.

Time Frame

Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum

Secondary Outcome Measure Information:

Title

Documented infections

Description

Rate and type of documented infections

Time Frame

Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum

Title

Use of broad spectrum antibiotics

Description

Index of days of antibiotics per hospitalization days. Antibiotics will be classified according the Watch/Reserve classification

Time Frame

Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum

Title

Overall survival

Time Frame

Time from the day of randomization to the date of death, whatever the cause of death, up to 12 weeks.

Title

Drug related adverse events

Description

Incidence of Adverse Events (AE), severity and type of AEs.

Time Frame

Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum

Title

Evolution of resistome

Description

Rate of patients colonized by multidrug resistant bacteria as determined by metagenomic sequencing

Time Frame

Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum

Title

Microbiome evolution

Description

Changes in the gut microbiome produced under both prophylactic strategies during the study period.

Time Frame

Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum

Title

Microbiological safety

Description

Rate of patients colonized by multidrug resistant bacteria as determined by surveillance cultures

Time Frame

Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects who are able to understand study procedures, comply with them, and provide written informed consent before any study-specific procedure. Adult subjects ≥ 18 years of age with acute leukemia diagnosis who are going to receive their first intensive chemotherapy cycle or adult subjects ≥ 18 years of age who are candidates to receive a first stem cell transplant. Expected neutropenia 100x109/L lasting at least seven days. In case of expected neutropenia range 100-500x109/L lasting seven days or more, at least one of the following risk factors for infection must be present: Performance status (Eastern Cooperative Oncology Group, ECOG) ≥2. Expected mucositis grade 3-4. Age ≥65 years. Comorbidity Index (HCTI) ≥3. Serum albumin< 35 g/L. Total dose of etoposide > 500 mg/m2 Total dose of cytarabine > 1 g/m2 Active or refractory neoplasia at the moment of stem cell transplant. Performance status (Eastern Cooperative Oncology Group, ECOG) of 0 to 3. Adequate organ function defined as: Liver: bilirubin, alkaline phosphatase, or SGOT < 3 times the upper normal limit (unless it is attributable to tumor activity). Renal : creatinine ≤ 250 μmol/l (2.5 mg/dL) (unless it is attributable to AML activity). Life expectancy higher than 3 months. Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and men with female partners of child-bearing potential must agree to practice 2 highly effective contraceptive measures of birth control and must agree not to become pregnant or father a child while receiving any study therapy and for at least 3 months after completing treatment. Exclusion Criteria: Hypersensitivity to fluoroquinolones or fosfomycin. Treatment with broad spectrum antimicrobial therapy within 4 weeks of first study treatment. Prior Intensive chemotherapy or stem cell transplant. Treatment with hydroxyurea or corticosteroids used to control white blood cell counts are permitted. Fever of infectious origin or documented infection within 4 weeks of first study treatment. Presence of any severe psychiatric disease or physical condition that, according to the physicians criteria, contraindicates the inclusion of the patient into the clinical trial. Subjects that have participated previously in this study

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Teresa Bernal, MD PHD

Phone

+34 985108000

Ext

37613

bernalmaria@uniovi.es

First Name & Middle Initial & Last Name or Official Title & Degree

Javier Fernandez Dominguez, BD

Phone

+34985108000

javifdom@gmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Teresa Bernal, MD PHD

Organizational Affiliation

Hospital Universitario Central Asturias

Official's Role

Principal Investigator

Facility Information:

Facility Name

Instituto de Investigación Sanitaria del Principado de Asturias

City

Oviedo

State/Province

Asturias

ZIP/Postal Code

33011

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Teresa Bernal del Castillo, MD PHD

Phone

+34 985108000

Ext

37613

bernalmaria@uniovi.es

First Name & Middle Initial & Last Name & Degree

Javier Fernandez Domínguez, PHD

javifdom@gmail.com

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

A Trial of Fosfomycin vs Ciprofloxacin for Febrile Neutropenia

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