Individualized Precision Therapy With Ceftobiprole Guided by PK/PD in Geriatric Populations

NCT ID: NCT07127185

Last Updated: 2025-09-23

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 150 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-09-12
• Study Completion Date: 2029-12-31

Brief Summary

Ceftobiprole, a fifth-generation cephalosporin, exhibits potent antibacterial activity against MRSA, penicillin-resistant Streptococcus pneumoniae (PRSP), and certain Gram-negative bacteria (e.g., Pseudomonas aeruginosa). In elderly patients, significant interindividual variability often leads to inappropriate dosing (subtherapeutic or excessive), compromising efficacy or increasing toxicity risks. This prospective, multicenter study will enroll patients aged ≥60 years receiving ceftobiprole. Using LC-MS/MS for therapeutic drug monitoring (TDM), we will measure plasma concentrations and integrate individual characteristics (age, body weight, creatinine clearance, etc.). Population pharmacokinetic (PPK) modeling with Bayesian forecasting will be employed to estimate individual PK parameters and identify covariates influencing variability, thereby establishing a PPK model for ceftobiprole in the elderly.

Based on pathogen-specific MIC values, dosing regimens (dose, frequency) will be dynamically optimized to guide precision therapy. Subsequent TDM data will continuously refine the PPK model, creating a self-optimizing system. This framework lays the groundwork for extending individualized treatment strategies to other antimicrobials in geriatric populations.

Conditions

Ceftobiprole

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Ceftobiprole

Clinical Blood Sampling Protocol for Ceftobiprole in Geriatric Patients: Elderly patients received intravenous ceftobiprole (250 mg or 500 mg) every 12 hours, with infusion durations of 1 h, 1.5 h, or 2 h. After 3 days of antibiotic therapy (steady-state achievement), blood sampling was performed as follows:

Trough Concentration: A 3-mL peripheral blood sample was collected from the antecubital vein pre-dose (before the next scheduled administration) using EDTA-containing Vacutainers®.

Peak Concentration: A blood sample was drawn immediately after completion of the intravenous infusion. All blood specimens were centrifuged at 2500 × g for 10 minutes. Plasma samples were stored at -20°C and analyzed within 1 week of collection via liquid chromatography-tandem mass spectrometry (LC-MS/MS).

LS/MS

Intervention Type: DIAGNOSTIC_TEST

Quantitative determination of ceftobiprole concentrations in plasma and urine was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Interventions

LS/MS

Quantitative determination of ceftobiprole concentrations in plasma and urine was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Aged ≥60 years Scheduled to receive ceftobiprole therapy for >5 days No prior ceftobiprole use within 1 month before enrollment

Exclusion Criteria

• Patients requiring renal replacement therapy (hemodialysis, peritoneal dialysis, or continuous renal replacement therapy [CRRT]) or with renal impairment history (nephrectomy, renal transplantation, solitary kidney, uremia) Obese patients with body mass index (BMI) ≥30 kg/m²

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese PLA General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Wu Jionghui

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

He Jiong Wu

Role: CONTACT

wujionghe1995@163.com

010-876250

Other Identifiers

S2025-448-01

Identifier Type: -

Identifier Source: org_study_id