PharmacokineticsCEFTO-EVDNCT04178629
Ceftobiprole's Cerebrospinal Fluid Penetration in Patients With External Ventricular Derivation (CEFTO-EVD)
An observational study of Pharmacokinetics and Cerebral Ventriculitis, run by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia at 1 site in Italy.
Trial summary
The Cerebrospinal fluid penetration of ceftobiprole has been studied in an animal model of meningitidis. Ceftobiprole is bactericidal, well tolerated and it has anti-biofilm activity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pharmacokinetics, Cerebral Ventriculitis, Cephalosporins
- How many people
- 15 participants
- Where
- 1 siteItaly
- Study dates
- 2 Jul 2019to 1 Nov 2020
- Phase
- Observational
- 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
Study population: Patient admitted in Intensive Care Unit or Neurosurgical Unit of Hospital "Spedali Civili di Brescia" (BS, Italy), according to Inclusion and Exclusion Criteria, with an EVD and concomitant Ceftobiprole therapy. When ceftobiprole will be administered i.v. for the first time, patients will be enrolled in the study.
Who may be able to join
- Age>18
- Patients with External Ventricular Derivation (EVD)
- Patients who receive ceftobiprole for any infection where Ceftobiprole could be used, as judged by an expert infectivologist
- Patients or their relatives/parents who consent to study participation
Who cannot join
- Patients with end-stage renal insufficiency
- Patients with a BMI>30
- Pregnancy
- Moribund patients
- Allergy to cephalosporine or ceftobiprole
- Refusal to participate in the study
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Spedali Civili di Brescia
Brescia, 25123
Simone Piva, +393332564230 ext. +393332564230, simone.piva@unibs.it
Fabio Turla, +393332564230, fabioturla2@gmail.com
About this study
Official title: Characterization of Ceftobiprole's Cerebrospinal Fluid Penetration in Patients With External Ventricular Derivation
The Cerebrospinal fluid penetration of ceftobiprole has been studied in an animal model of meningitidis. Ceftobiprole is bactericidal, well tolerated and it has anti-biofilm activity. Altogether, these pharmacodynamics and pharmacokinetic properties of ceftobiprole are suitable for its use in case of External Ventricular Derivation(EVD)-related ventriculitis. Nowadays there are no human studies on the penetration and efficacy of ceftobiprole in the CSF. The study aims to evaluate characteristics of the CSF penetration of Ceftobiprole after intravenous administration in patients with EVD, that need for a concomitant infection this therapy (prescribed by an Infectious Diseases doctor).
Read the detailed description
According with Inclusion and Exclusion criteria, patients with an EVD and concomitant ceftobiprole therapy will be enrolled in the study.
In particular, ceftobiprole will be prescribed by an expert infectivologist, in accordance with the MHRA guidelines.
Once the patients will be enrolled, Ceftobiprole will be administered by 2 hr i.v. infusion at the following dosage:
- normal renal function: 500mg every 8 hr
- mild renal impairment (50-80mL/min): 500mg every 8 hours
- moderate (30-49mL/min): 500mg every 12 hours
- severe (<30mL/min): 250mg every 12 hours.
The following blood and CSF sample will be drowned only during the third dose of antibiotic therapy. Blood Samples (1 mL each) will be obtained at the following time points: before and at the end of infusion of ceftobiprole, then 0.5, 1, 2, 2.5, 3 and 4 hr after drug administration (total of 8 samples), using a single venous or arterial line cannulation. CSF samples: 0.5ml will be drawned from implanted EVD with a sterile field at the same blood sample time-point, and at 6, 8 and 10 hr after the end of drug administration (11 samples total).
CSF and blood will be spin-down at 3000 rpm for 10 minutes and then stored at -80°C.
Samples will be sent all in once by courier to Laboratory of Clinical Pharmacology and Pharmacogenetics, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin (Italy) in order to determine the serum and CSF concentration.
Ceftobiprole concentrations (both in plasma/serum and CFS) will be analyzed with EMA validated LC-MS/MS methods.
MDR1 gene polymorphisms will be analyzed with RT-PCR instrument, using commercial genetic probes on the blood samples.
- Keywords
- Ceftobiprole, External Ventricular Derivation, Cerebrospinal fluid penetration, ATP Binding Cassette Transporter, Subfamily B, Member 1, Tissue Distribution
- Medical subject headings
- Cerebral Ventriculitis
What is being measured
The primary outcome is the main question the study is designed to answer.
Ceftobiprole's CSF penetration
Evaluate the Cerebrospinal Fluid penetration of Ceftobiprole in patients with External Ventricular Derivation. Ceftobiprole concentrations (both in plasma/serum and CFS) will be analyzed with EMA fully validated LC-MS/MS methods.
Measured: Blood samples: before infusion, end of infusion, then 30 minutes, 1 hour, 2 hours, 2,5 hours, 3 hours, 4 hours after end of administration; CSF samples: at the same time of blood samples, then at 6 hours, 8 hours and 10 hours after end of administration
Secondary outcomes (2)
Ceftobiprole's MDR1 role
Evaluate the role of MDR1 polymorphisms in modulating ceftobiprole CSF penetration.
Measured: The MDR1 gene will be analyzed on whole blood samples, by real-time PCR, through study completion, an average of 18 months.
Ceftobiprole's efficacy in CSF
In vitro, the efficacy of ceftobiprole against the most common pathogen causing Ventricular Meningitis (MRSA, MRSE, Pseudomonas Aeruginosa and Enterobacteriaceae) will be assessed using the percentage of time during which the free CSF ceftobiprole concentration remains above the minimal inhibitory concentration (MIC)
Measured: The measurement is assessed through study completion, an average of 18 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2019
- Study start2 Jul 2019
- Primary completion1 Nov 2020 (estimated)
- Study completion1 Nov 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PharmacokineticsStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Sponsor type
- University, hospital or other
- Collaborators
- University of Turin, Italy, University of Pisa, Università degli Studi di Brescia
- Responsible party
- Principal investigator, Piva Simone, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Investigators
- Simone Piva, Principal investigator, Università degli Studi di Brescia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04178629
- Sponsor's protocol ID
- NP3617
- Acronym
- CEFTO-EVD
- Status last verified
- Nov 2019
- First submitted
- 15 Oct 2019
- Last updated
- 26 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The database is in RedCap. We could share all data
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of Ceftobiprole's Cerebrospinal Fluid Penetration in Patients With External Ventricular Derivation
- ClinicalTrials.gov ID
- NCT04178629
- Acronym / sponsor ID
- CEFTO-EVD / NP3617
- Keywords
- Ceftobiprole, External Ventricular Derivation, Cerebrospinal fluid penetration, ATP Binding Cassette Transporter, Subfamily B, Member 1, Tissue Distribution
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di BresciaUniversity, hospital or other
- Collaborators
- University of Turin, Italy, University of Pisa, Università degli Studi di Brescia
- Study start
- 2 Jul 2019 (actual)
- Primary completion
- 1 Nov 2020 (estimated)
- Study completion
- 1 Nov 2020 (estimated)
- First posted
- 26 Nov 2019 (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.
The Cerebrospinal fluid penetration of ceftobiprole has been studied in an animal model of meningitidis. Ceftobiprole is bactericidal, well tolerated and it has anti-biofilm activity. Altogether, these pharmacodynamics and pharmacokinetic properties of ceftobiprole are suitable for its use in case of External Ventricular Derivation(EVD)-related ventriculitis. Nowadays there are no human studies on the penetration and efficacy of ceftobiprole in the CSF. The study aims to evaluate characteristics of the CSF penetration of Ceftobiprole after intravenous administration in patients with EVD, that need for a concomitant infection this therapy (prescribed by an Infectious Diseases doctor).
Detailed description
According with Inclusion and Exclusion criteria, patients with an EVD and concomitant ceftobiprole therapy will be enrolled in the study.
In particular, ceftobiprole will be prescribed by an expert infectivologist, in accordance with the MHRA guidelines.
Once the patients will be enrolled, Ceftobiprole will be administered by 2 hr i.v. infusion at the following dosage:
- normal renal function: 500mg every 8 hr
- mild renal impairment (50-80mL/min): 500mg every 8 hours
- moderate (30-49mL/min): 500mg every 12 hours
- severe (<30mL/min): 250mg every 12 hours.
The following blood and CSF sample will be drowned only during the third dose of antibiotic therapy. Blood Samples (1 mL each) will be obtained at the following time points: before and at the end of infusion of ceftobiprole, then 0.5, 1, 2, 2.5, 3 and 4 hr after drug administration (total of 8 samples), using a single venous or arterial line cannulation. CSF samples: 0.5ml will be drawned from implanted EVD with a sterile field at the same blood sample time-point, and at 6, 8 and 10 hr after the end of drug administration (11 samples total).
CSF and blood will be spin-down at 3000 rpm for 10 minutes and then stored at -80°C.
Samples will be sent all in once by courier to Laboratory of Clinical Pharmacology and Pharmacogenetics, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin (Italy) in order to determine the serum and CSF concentration.
Ceftobiprole concentrations (both in plasma/serum and CFS) will be analyzed with EMA validated LC-MS/MS methods.
MDR1 gene polymorphisms will be analyzed with RT-PCR instrument, using commercial genetic probes on the blood samples.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patient admitted in Intensive Care Unit or Neurosurgical Unit of Hospital "Spedali Civili di Brescia" (BS, Italy), according to Inclusion and Exclusion Criteria, with an EVD and concomitant Ceftobiprole therapy. When ceftobiprole will be administered i.v. for the first time, patients will be enrolled in the study.
Key inclusion criteria (4 listed)
- Age>18
- Patients with External Ventricular Derivation (EVD)
- Patients who receive ceftobiprole for any infection where Ceftobiprole could be used, as judged by an expert infectivologist
- Patients or their relatives/parents who consent to study participation
Key exclusion criteria (6 listed)
- Patients with end-stage renal insufficiency
- Patients with a BMI>30
- Pregnancy
- Moribund patients
- Allergy to cephalosporine or ceftobiprole
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Ceftobiprole's CSF penetration
Time frame: Blood samples: before infusion, end of infusion, then 30 minutes, 1 hour, 2 hours, 2,5 hours, 3 hours, 4 hours after end of administration; CSF samples: at the same time of blood samples, then at 6 hours, 8 hours and 10 hours after end of administration
Evaluate the Cerebrospinal Fluid penetration of Ceftobiprole in patients with External Ventricular Derivation. Ceftobiprole concentrations (both in plasma/serum and CFS) will be analyzed with EMA fully validated LC-MS/MS methods.
2 secondary outcomes
Ceftobiprole's MDR1 role
Time frame: The MDR1 gene will be analyzed on whole blood samples, by real-time PCR, through study completion, an average of 18 months.
Ceftobiprole's efficacy in CSF
Time frame: The measurement is assessed through study completion, an average of 18 months.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2019.
- Individual participant dataSharing planned: Yes. The database is in RedCap. We could share all data
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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.
Simone Piva principal investigator
Università degli Studi di Brescia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pharmacokinetics and Cerebral Ventriculitis, run by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia at 1 site in Italy.
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 4 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 26 Nov 2019. 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 Italy. 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.
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 Simone Piva (+393332564230, simone.piva@unibs.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ceftobiprole's CSF penetration (time frame: Blood samples: before infusion, end of infusion, then 30 minutes, 1 hour, 2 hours, 2,5 hours, 3 hours, 4 hours after end of administration; CSF samples: at the same time of blood samples, then at 6 hours, 8 hours and 10 hours after end of administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Nov 2019.