Ceftobiprole's Cerebrospinal Fluid Penetration in Patients With External Ventricular Derivation (CEFTO-EVD)

Pharmacokinetics Clinical Trial

— CEFTO-EVD  

Official title:

Characterization of Ceftobiprole's Cerebrospinal Fluid Penetration in Patients With External Ventricular Derivation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04178629
• Other study ID #: NP3617
• Status: Recruiting
• Start date: July 2, 2019
• Est. completion date: November 1, 2020

Study information

• Verified date: November 2019
• Source: Azienda Ospedaliera Spedali Civili di Brescia
• Contact: Simone Piva
• Phone: +393332564230
• Email: simone.piva[@]unibs.it
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: November 1, 2020
• Est. primary completion date: November 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Cephalosporins
• Cerebral Ventriculitis
• Cerebrospinal Fluid
• Pharmacokinetics

Locations

Country	Name	City	State
Italy	Spedali Civili di Brescia	Brescia

Sponsors (4)

Lead Sponsor	Collaborator
Azienda Ospedaliera Spedali Civili di Brescia	Università degli Studi di Brescia, University of Pisa, University of Turin, Italy

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	Ceftobiprole's MDR1 role	Evaluate the role of MDR1 polymorphisms in modulating ceftobiprole CSF penetration.	The MDR1 gene will be analyzed on whole blood samples, by real-time PCR, through study completion, an average of 18 months.
Secondary	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)	The measurement is assessed through study completion, an average of 18 months.