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

Cystic Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03771313
• Other study ID #: Ceftaroline CF PK/PD_2017-2276
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: September 1, 2017
• Est. completion date: July 31, 2025

Study information

• Verified date: October 2023
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: July 31, 2025
• Est. primary completion date: July 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

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.

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	FEV1 Percentage Change Assessment	Assess change in FEV1 percent predicted during ceftaroline treatment	12-hour maximum, single visit
Secondary	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
Secondary	Side Effects	Assess for side effects as documented by providers	12-hour maximum, single visit
Secondary	Pulmonary Exacerbations	Assess for time until next pulmonary exacerbation	12-hour maximum, single visit