Pharmacokinetic and Pharmacodynamic Analysis of Ceftaroline in Children and Adolescents With Cystic Fibrosis

Cincinnati Children's Hospital Medical Center

Status and phase: Completed; Phase 4

Conditions: Cystic Fibrosis

Treatments: Drug: Ceftaroline

Study type: Interventional

Funder types: Other

Identifiers

NCT03771313

Ceftaroline CF PK/PD_2017-2276

Details and patient eligibility

About

This is an open-label, single center, prospective study of patients with a diagnosis of cystic fibrosis (CF) and a history of methicillin-resistant Staphylococcus aureus (MRSA), also known as oxacillin-resistant Staphylococcus aureus (ORSA), being treated with intravenous ceftaroline. Patients will have intravenous ceftaroline dosed according to current recommendations based upon its approved usage in pediatric patients for community acquired pneumonia. The investigators will analyze pharmacokinetic (PK) and pharmacodynamic (PD) data using serum concentrations of ceftaroline measured at various time-points following infusion of ceftaroline to develop PK/PD guided dosing strategies of ceftaroline in pediatric CF patients that would be tailored to account for bacterial susceptibility and disease progression.

Full description

This is an open-label, single center, prospective study of patients with a diagnosis of cystic fibrosis (CF) and a history of methicillin-resistant Staphylococcus aureus (MRSA), also known as oxacillin-resistant Staphylococcus aureus (ORSA), being treated with intravenous ceftaroline. Patients will have intravenous ceftaroline dosed according to current recommendations based upon its approved usage in pediatric patients for community acquired pneumonia. The investigators will analyze pharmacokinetic (PK) and pharmacodynamic (PD) data using serum concentrations of ceftaroline measured at various time-points following infusion of ceftaroline to develop PK/PD guided dosing strategies of ceftaroline in pediatric CF patients that would be tailored to account for bacterial susceptibility and disease progression and determine if current dosing regimes used are appropriate for this patient population.

Blood samples will be collected prior to infusion of ceftaroline and at approximately 1 hour (+/- 10 minutes), 1.5 hours (+/- 10 minutes), 3 hours (+/- 30 minutes), and 6 hours (+/- 30 minutes) after initiation of infusion. The blood samples (0.5 to 1 ml) will be collected through intravenous access, venipuncture, or capillary blood puncture. Samples will be centrifuged at 1500g at 4°C for 15 minutes within 15 minutes of collection. Serum will be separated into two aliquots of a minimum of 0.2 mL and stored at -70°C until analysis. Determination of serum ceftaroline concentrations will be measured using high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection.

Key clinical data (PK/PD) that will be collected includes age, sex, genotype, growth parameters, airway microbiology, sweat chloride values, pulmonary function test (FEV1), concomitant medications, and comorbid disorders (i.e.: CF related diabetes, CF liver disease, short gut, renal dysfunction, pulmonary hypertension, coagulopathy).

Enrollment: 8 patients

Sex: All

Ages: 2 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Cystic Fibrosis diagnosis on accepted Cystic Fibrosis Foundation guidelines
• Inpatient
• Decision by treating physician to use intravenous ceftaroline

Exclusion criteria

• less than 2 years old
• 22 years of age or older
• less than 15 kg weight
• Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 5 fold upper limit of normal
• Gamma-glutamyltransferase (GGT) > 3 fold above upper limit of normal
• Total bilirubin > 2 mg/dL
• Platelets < 50,000
• Patients without documented CF
• Non-English speaking patients/families

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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8 participants in 1 patient group

PK/PD

Other group

Description:

Open-label prospective study with participants receiving treating physician-approved intravenous ceftaroline, dosed according to current recommendations. Blood samples collected at baseline, 1 hour, 1.5 hours, 3 hours, and 6 hours after infusion.

Treatment:

Drug: Ceftaroline