Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children
This study will determine the concentrations of the antibiotic meropenem when administered as a 3 hour prolonged infusion in children with cystic fibrosis who are hospitalized with an acute pulmonary exacerbation. Safety and practicality of administering meropenem as a 3 hour infusion will be measured.
Pseudomonas Aeruginosa Infection
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open Label Study to Assess the Population Pharmacokinetics, Safety, and Practicality of Administering Meropenem as a Prolonged Infusion to Cystic Fibrosis Children Admitted With an Acute Pulmonary Exacerbation|
- Meropenem Blood Concentrations [ Time Frame: 8 hours after 3rd meropenem dose ] [ Designated as safety issue: No ]Blood sampling for meropenem concentrations will occur at 4 time points after the third dosage: 3-3.5 hours, 4-5 hours, 5-6 hours, and 7-8 hours.
- Population Pharmacokinetics - Total Body Clearance [ Time Frame: 8 hours after 3rd meropenem dose ] [ Designated as safety issue: No ]Based on meropenem concentrations, the pharmacokinetics of the study population will be analyzed to determine each patient's total body clearance.
- Population Pharmacokinetics - Volume of Distribution [ Time Frame: 8 hours after 3rd meropenem dose ] [ Designated as safety issue: No ]Based on meropenem concentrations, the pharmacokinetics of the study population will be analyzed to determine each patient's volume of distribution.
- Safety [ Time Frame: 14-21 days ] [ Designated as safety issue: Yes ]This will be an intention to treat analysis of all 30 participants receiving meropenem as a 3 hour prolonged infusion. Participants will be monitored for any sign of symptom of adverse events throughout the course of the study. An adverse event will be defined as any pathologic or unintended change in the structure (signs), function (symptoms), or chemistry (laboratory values) of the body associated with the use of the study drug.
- Practicality of 3 Hour Prolonged Infusion [ Time Frame: 14-21 days ] [ Designated as safety issue: No ]This will be an intention to treat analysis of all 30 participants receiving meropenem as a 3 hour prolonged infusion. The Cystic Fibrosis Questionnaire-Revised (CFQ-R) will be utilized to assess patient or parent assessments of the burden of the prolonged infusion treatment. The CFQ-R will be administered at the beginning of the study and then within 7 days after completion of meropenem therapy.
- Meropenem Pharmacodynamics [ Time Frame: 14-21 days ] [ Designated as safety issue: No ]Meropenem exposures defined from the population model for each participant will be analyzed as a function of the isolated pathogens meropenem minimum inhibitory concentration (MIC) to define the exposure of meropenem associated with an absolute and relative percent change in the Forced Expiratory Volume (FEV1).
|Study Start Date:||February 2012|
|Study Completion Date:||January 2014|
|Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Experimental: Meropenem 3 hour prolonged infusion
All 30 participants will receive meropenem as a 3 hour infusion.
meropenem 40mg/kg total body weight will be administered every 8 hours. Each infusion will be infused as a 3 hour infusion.
Other Name: Merrem
This study will be conducted at 7 pediatric hospitals in the United States (Columbia University Medical Center, New York, NY; University of North Carolina, Chapel Hill, NC; St. Christopher's Hospital for Children, Philadelphia, PA, Connecticut Children's Medical Center, Hartford, CT, Riley Hospital for Children, Indianapolis, IN, Nationwide Hospital for Children, Columbus, OH, and Children's Medical Center, Dallas, TX). Cystic Fibrosis children (age 6-17 years) admitted to one of these enrolling sites with an acute exacerbation of his or her pulmonary infection who require antibiotic therapy with meropenem will be eligible. Meropenem will be administered as a 3 hour prolonged infusion and blood concentrations will be measured to determine the population pharmacokinetics in 30 patients, the safety of prolonged infusion meropenem, and the practicality as measured be treatment burden using a questionaire. The population pharmacokinetic model developed will be utilized to determine the optimal dose of meropenem to administer to children with Cystic Fibrosis, and define an exposure response relationship for the drug in this population.
|United States, Connecticut|
|Connecticut Children's Medical Center|
|Hartford, Connecticut, United States, 06106|
|United States, Indiana|
|Riley Hospital for Children|
|Indianapolis, Indiana, United States, 46202|
|United States, New York|
|Columbia University Medical Center Children's Hospital|
|New York, New York, United States, 10032|
|United States, North Carolina|
|University of North Carolina, North Carolina Children's Hospital|
|Chapel Hill, North Carolina, United States, 27514|
|United States, Ohio|
|Nationwide Children's Hospital|
|Colubmus, Ohio, United States, 43205|
|United States, Pennsylvania|
|St. Christopher's Hospital for Children|
|Philadelphia, Pennsylvania, United States, 19134|
|United States, Texas|
|Children's Medical Center|
|Dallas, Texas, United States, 75235|
|Principal Investigator:||Joseph L Kuti, Pharm.D.||Hartford Hospital|