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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Ceftaroline

Detailed 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).

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 42229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: PK/PD; 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.	Drug: Ceftaroline; Patients will have intravenous ceftaroline dosed according to current recommendations based upon its approved usage in pediatric patients for community acquired pneumonia. Blood samples will be collected for PK/PD analysis.; Other Names: Ceftaroline fosamil,Teflaro, Zinforo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ceftaroline Exposure and PK/PD Target Attainment	Interpret PK/PD target attainment based on percent time of the free ceftaroline concentration (=PK) above minimum inhibitory concentration (=PD index)	12-hour maximum, single visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 Percentage Change Assessment	Assess change in FEV1 percent predicted during ceftaroline treatment	12-hour maximum, single visit
Treatment Failures	Assess any treatment failures as evidenced by provider documentation (including FEV1 not improving and/or change in antimicrobial drugs)	12-hour maximum, single visit
Side Effects	Assess for side effects as documented by providers	12-hour maximum, single visit
Pulmonary Exacerbations	Assess for time until next pulmonary exacerbation	12-hour maximum, single visit

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Investigators: Principal Investigator: Alexander Vinks, PhD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2017
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): July 31, 2025

Study Registration Dates

• First Submitted: July 11, 2018
• First Submitted That Met QC Criteria: December 7, 2018
• First Posted (Actual): December 11, 2018

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Anti-Infective Agents; Anti-Bacterial Agents; Ceftaroline fosamil
• Other Study ID Numbers: Ceftaroline CF PK/PD_2017-2276

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No