A Trial of Fosfomycin vs Ciprofloxacin for Febrile Neutropenia

Febrile Neutropenia Clinical Trial

— FOVOCIP  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05311254
• Other study ID #: FOVOCIP
• Secondary ID: 2021-000354-25
• Status: Recruiting
• Phase: Phase 3
• Start date: March 14, 2022
• Est. completion date: March 14, 2024

Study information

• Verified date: September 2023
• Source: Fundación para la Investigación Biosanitaria del Principado de Asturias
• Contact: Teresa Bernal, MD PHD
• Phone: +34 985108000
• Email: bernalmaria[@]uniovi.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 156
• Est. completion date: March 14, 2024
• Est. primary completion date: March 14, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subjects who are able to understand study procedures, comply with them, and provide written informed consent before any study-specific procedure.

2. 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.

3. 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.

4. Performance status (Eastern Cooperative Oncology Group, ECOG) of 0 to 3.

5. 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).

6. Life expectancy higher than 3 months.

7. 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:

1. Hypersensitivity to fluoroquinolones or fosfomycin.

2. Treatment with broad spectrum antimicrobial therapy within 4 weeks of first study treatment.

3. Prior Intensive chemotherapy or stem cell transplant. Treatment with hydroxyurea or corticosteroids used to control white blood cell counts are permitted.

4. Fever of infectious origin or documented infection within 4 weeks of first study treatment.

5. 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.

6. Subjects that have participated previously in this study

Related Conditions & MeSH terms

• Febrile Neutropenia
• Fever
• Hyperthermia
• Neutropenia

Intervention

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

Locations

Country	Name	City	State
Spain	Instituto de Investigación Sanitaria del Principado de Asturias	Oviedo	Asturias

Sponsors (3)

Lead Sponsor	Collaborator
Fundación para la Investigación Biosanitaria del Principado de Asturias	Instituto de Investigación Marqués de Valdecilla, Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Febrile neutropenia of infectious origin	Febrile neutropenia that requires antibacterial treatment.	Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Secondary	Documented infections	Rate and type of documented infections	Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Secondary	Use of broad spectrum antibiotics	Index of days of antibiotics per hospitalization days. Antibiotics will be classified according the Watch/Reserve classification	Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Secondary	Overall survival		Time from the day of randomization to the date of death, whatever the cause of death, up to 12 weeks.
Secondary	Drug related adverse events	Incidence of Adverse Events (AE), severity and type of AEs.	Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Secondary	Evolution of resistome	Rate of patients colonized by multidrug resistant bacteria as determined by metagenomic sequencing	Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Secondary	Microbiome evolution	Changes in the gut microbiome produced under both prophylactic strategies during the study period.	Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Secondary	Microbiological safety	Rate of patients colonized by multidrug resistant bacteria as determined by surveillance cultures	Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum