Clinical trial NCT03771313: Pharmacokinetic and Pharmacodynamic Analysis of Ceftaroline in Children and Adolescents With Cystic Fibrosis
Official title: Pharmacokinetic and Pharmacodynamic Analysis of Ceftaroline in Children and Adolescents With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Cystic Fibrosis
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2018-12-11
Enrollment: 24
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, single center, prospective study
Primary purpose: TREATMENT

Brief 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Ceftaroline Exposure and PK/PD Target Attainment
timeFrame: 12-hour maximum, single visit
Secondary outcomes:
measure: FEV1 Percentage Change Assessment
timeFrame: 12-hour maximum, single visit
measure: Treatment Failures
timeFrame: 12-hour maximum, single visit
measure: Side Effects
timeFrame: 12-hour maximum, single visit
measure: Pulmonary Exacerbations
timeFrame: 12-hour maximum, single visit
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Alexander Vinks, PhD
role: PRINCIPAL_INVESTIGATOR
References: