Febrile NeutropeniaPhase 3FOVOCIPNCT05311254
A Trial of Fosfomycin vs Ciprofloxacin for Febrile Neutropenia
A Phase 3 study testing Fosfomycin Calcium in people with Febrile Neutropenia, run by Fundación para la Investigación Biosanitaria del Principado de Asturias at 1 site in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Febrile Neutropenia
- What is being tested?
- Fosfomycin Calcium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- 1 siteSpain
- Study dates
- 14 Mar 2022to 14 Mar 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 17Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Instituto de Investigación Sanitaria del Principado de Asturias
Oviedo, Principality of Asturias, 33011
Teresa Bernal del Castillo, MD PHD, +34 985108000 ext. 37613, bernalmaria@uniovi.es
Javier Fernandez Domínguez, PHD, javifdom@gmail.com
About this study
Official title: A Multicenter Randomized Trial of Fosfomycin vs Ciprofloxacin for Febrile Neutropenia in Hematological Patients: Efficacy and Microbiological Safety
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.
Read the 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
- Conditions
- Febrile Neutropenia
- Being tested
- Fosfomycin Calcium
- Medical subject headings
- Febrile Neutropenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fosfomycin CalciumDrug
Oral fosfomycin, three times daily, starting from the first day of induction chemotherapy or conditioning until absolute neutrophil count >0,5x109/L.
| Study group | Role | What they receive |
|---|---|---|
| Fosfomycin | Experimental | Drug: Fosfomycin: oral capsules containing 700 mg of calcium fosfomycin, equivalent to 500 mg of active drug. Receives: Drug: Fosfomycin Calcium |
| Ciprofloxacin | Active comparator | Oral ciprofloxacin, tablets containing 500 mg of active drug. Receives: Drug: Fosfomycin Calcium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Febrile neutropenia of infectious origin
Febrile neutropenia that requires antibacterial treatment.
Measured: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Secondary outcomes (7)
Documented infections
Rate and type of documented infections
Measured: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Use of broad spectrum antibiotics
Index of days of antibiotics per hospitalization days. Antibiotics will be classified according the Watch/Reserve classification
Measured: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Overall survival
Measured: Time from the day of randomization to the date of death, whatever the cause of death, up to 12 weeks.
Drug related adverse events
Incidence of Adverse Events (AE), severity and type of AEs.
Measured: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Evolution of resistome
Rate of patients colonized by multidrug resistant bacteria as determined by metagenomic sequencing
Measured: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Microbiome evolution
Changes in the gut microbiome produced under both prophylactic strategies during the study period.
Measured: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Microbiological safety
Rate of patients colonized by multidrug resistant bacteria as determined by surveillance cultures
Measured: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2022
- Study start14 Mar 2022
- Primary completion14 Mar 2024 (estimated)
- Study completion14 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Febrile NeutropeniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicenter, randomized, prospective, open-label
- Masking
- None (open label)
- Enrolment
- 156 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundación para la Investigación Biosanitaria del Principado de Asturias
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto de Investigación Marqués de Valdecilla, Instituto de Salud Carlos III
- Responsible party
- Principal investigator, Teresa Bernal del Castillo, Fundación para la Investigación Biosanitaria del Principado de Asturias
- Investigators
- Teresa Bernal, MD PHD, Principal investigator, Hospital Universitario Central Asturias
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05311254
- Sponsor's protocol ID
- FOVOCIP
- Other IDs
- 2021-000354-25
- Acronym
- FOVOCIP
- Status last verified
- Sep 2023
- First submitted
- 9 Mar 2022
- Last updated
- 14 Sep 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Moreno AF, Lopez de Ugarriza P, Gonzalez Huerta AJ, Pascual BB, Caceres S, Blanco LS, Calabuig ML, Zarzuela MP, Rodriguez-Veiga R, Montesinos P, Fernandez Verdugo AM, Gonzalez-Barbera EM, Izquierdo M, Medel-Plaza M, Colomina J, Olave MT, Humala K, Lopez L, Labrador J, Seral C, Amigo ML, de Toro M, Carrascoso GR, Megias G, Blazquez R, Antuna M, Lumbreras P, Dominguez JF, Bernal T. Fosfomycin versus ciprofloxacin for febrile neutropenia prophylaxis in high-risk haematological patients (FOVOCIP): a phase 3, open-label, multicentre, randomised, non-inferiority trial. Lancet Reg Health Eur. 2026 May 7;66:101698. doi: 10.1016/j.lanepe.2026.101698. eCollection 2026 Jul.
PubMed 42164340Moreno AF, Lavin-Alconero L, de Ugarriza PL, Blanco LS, Hernandez SC, Burgues JMB, de Miguel MI, Huerta AJG, Zarzuela MP, Boluda B, Humala K, Calabuig ML, Amigo ML, Casas MC, Del Mar Garcia-Saiz M, Verdugo AF, Dominguez JF, Bernal T. FOVOCIP study: a multicenter randomized trial of fosfomycin versus ciprofloxacin for febrile neutropenia in hematologic patients-efficacy and microbiologic safety. Trials. 2023 Oct 27;24(1):694. doi: 10.1186/s13063-023-07702-5.
PubMed 37891616
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Randomized Trial of Fosfomycin vs Ciprofloxacin for Febrile Neutropenia in Hematological Patients: Efficacy and Microbiological Safety
- ClinicalTrials.gov ID
- NCT05311254
- Acronym / sponsor ID
- FOVOCIP / FOVOCIP
- Conditions
- Febrile Neutropenia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 156 participants (estimated)
- Lead sponsor
- Fundación para la Investigación Biosanitaria del Principado de AsturiasUniversity, hospital or other
- Collaborators
- Instituto de Investigación Marqués de Valdecilla, Instituto de Salud Carlos III
- Study start
- 14 Mar 2022 (actual)
- Primary completion
- 14 Mar 2024 (estimated)
- Study completion
- 14 Mar 2024 (estimated)
- First posted
- 5 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Multicenter, randomized, prospective, open-label
| Arm | Type | Receives |
|---|---|---|
| Fosfomycin | Experimental | Drug: Fosfomycin CalciumDrug: Fosfomycin: oral capsules containing 700 mg of calcium fosfomycin, equivalent to 500 mg of active drug. |
| Ciprofloxacin | Active comparator | Drug: Fosfomycin CalciumOral ciprofloxacin, tablets containing 500 mg of active drug. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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) of 0 to 3.
- Adequate organ function defined as:
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fosfomycin CalciumOral fosfomycin, three times daily, starting from the first day of induction chemotherapy or conditioning until absolute neutrophil count >0,5x109/L. | Drug | Ciprofloxacin, Fosfomycin |
Primary outcome
Febrile neutropenia of infectious origin
Time frame: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Febrile neutropenia that requires antibacterial treatment.
7 secondary outcomes
Documented infections
Time frame: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Use of broad spectrum antibiotics
Time frame: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Overall survival
Time frame: Time from the day of randomization to the date of death, whatever the cause of death, up to 12 weeks.
Drug related adverse events
Time frame: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Evolution of resistome
Time frame: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Microbiome evolution
Time frame: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Microbiological safety
Time frame: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2023.
- Derived from this study: PubMed 42164340Moreno AF, Lopez de Ugarriza P, Gonzalez Huerta AJ, Pascual BB, Caceres S, Blanco LS, Calabuig ML, Zarzuela MP, Rodriguez-Veiga R, Montesinos P, Fernandez Verdugo AM, Gonzalez-Barbera EM, Izquierdo M, Medel-Plaza M, Colomina J, Olave MT, Humala K, Lopez L, Labrador J, Seral C, Amigo ML, de Toro M, Carrascoso GR, Megias G, Blazquez R, Antuna M, Lumbreras P, Dominguez JF, Bernal T. Fosfomycin versus ciprofloxacin for febrile neutropenia prophylaxis in high-risk haematological patients (FOVOCIP): a phase 3, open-label, multicentre, randomised, non-inferiority trial. Lancet Reg Health Eur. 2026 May 7;66:101698. doi: 10.1016/j.lanepe.2026.101698. eCollection 2026 Jul.
- Derived from this study: PubMed 37891616Moreno AF, Lavin-Alconero L, de Ugarriza PL, Blanco LS, Hernandez SC, Burgues JMB, de Miguel MI, Huerta AJG, Zarzuela MP, Boluda B, Humala K, Calabuig ML, Amigo ML, Casas MC, Del Mar Garcia-Saiz M, Verdugo AF, Dominguez JF, Bernal T. FOVOCIP study: a multicenter randomized trial of fosfomycin versus ciprofloxacin for febrile neutropenia in hematologic patients-efficacy and microbiologic safety. Trials. 2023 Oct 27;24(1):694. doi: 10.1186/s13063-023-07702-5.
- Individual participant dataSharing planned: No
Related trials for Febrile Neutropenia
RecruitingPhase 4
Adjustment of Antibiotic Dosage in Pediatric Oncology Patients With Febrile Neutropenia and Augmented Renal Clearance
Febrile Neutropenia
Not yet recruiting
Diagnostic Accuracy, Clinical Utility and Implementation of Point-of-Care Absolute Neutrophil Count in Suspected Neutropenic Fever (DUCATIS) - Diagnostic Accuracy (S1)
Suspected Neutropenic Fever, Confirmed Neutropenic Fever
RecruitingObservational study
Mecapegfilgrastim for Prevention of Chemotherapy-Induced Neutropenia in Advanced Breast Cancer
Breast Cancer, Chemotherapy-induced Neutropenia
Not yet recruiting
Impact of a Telemonitoring Device on the Occurever at Home in Children at Risk of Chemotherapy-Induced Neutropenia
Oncopediatrics, Febrile Neutropenia
Not yet recruitingPhase 2
Restrictive Versus Standard Antibiotic Treatment During CAR-T Therapy
Large B-Cell Lymphoma (LBCL), Multiple Myeloma (MM)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Teresa Bernal, MD PHD principal investigator
Hospital Universitario Central Asturias
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fosfomycin Calcium in people with Febrile Neutropenia, run by Fundación para la Investigación Biosanitaria del Principado de Asturias at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Teresa Bernal, MD PHD (+34 985108000 ext. 37613, bernalmaria@uniovi.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Febrile neutropenia of infectious origin (time frame: Immediately after the intervention until febrile neutropenia develops, neutrophil count >0,5x109/L up to 60 days maximum). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05311254, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2023.