Clinical trial NCT01429259: Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cystic Fibrosis
Pneumonia
Pseudomonas Aeruginosa Infection
Keywords: Cystic Fibrosis
Acute Pulmonary Exacerbations
Pseudomonas aeruginosa
Lead sponsor: Hartford Hospital
Sponsor class: OTHER
Collaborators: name: Thrasher Research Fund
First posted: 2011-09-07
Enrollment: 30
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: This study will be conducted at 7 pediatric hospitals in the United States (Columbia University Medical Center, New York, New York; University of North Carolina, Chapel Hill, North Carolina; St. Christopher's Hospital for Children, Philadelphia, Pennsylvania, Connecticut Children's Medical Center, Hartford, Connecticut, Riley Hospital for Children, Indianapolis, Indiana, Nationwide Hospital for Children, Columbus, Ohio, and Children's Medical Center, Dallas, Texas). 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.

Eligibility criteria: Inclusion Criteria:

* Cystic Fibrosis
* Hospitalized with acute pulmonary exacerbation
* Caused by Pseudomonas aeruginosa or other bacteria against which meropenem would be an appropriate antibiotic treatment

Exclusion Criteria:

* Known allergy to meropenem
* Require less than 3 days of meropenem in the hospital
* Require another systemic Beta-lactam antibiotic to treat a concomitant pathogen
* Known fungal or viral infection
* Females in their 2nd or 3rd trimester of pregnancy
* Moderate to severe renal dysfunction, as defined by a creatinine clearance less than 50 ml/min/1.73m2 (by use of Schwartz method)
* History of solid organ transplantation within previous 6 months
* Active or recent (within 30 days) participation in another antibiotic clinical trial

Primary outcomes:
measure: Population Pharmacokinetics - Total Body Clearance
timeFrame: 8 hour dosing interval after 3rd meropenem dose
measure: Population Pharmacokinetics - Volume of Central Compartment
timeFrame: During 8 hour dosing interval after 3rd meropenem dose
Secondary outcomes:
measure: Safety
timeFrame: 14-21 days
measure: Practicality of 3 Hour Prolonged Infusion
timeFrame: 14-21 days
measure: Meropenem Pharmacodynamics
timeFrame: 14-21 days
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: New York
country: United States
facility: Columbia University Medical Center Children's Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina, North Carolina Children's Hospital
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Dallas
country: United States
facility: Children's Medical Center
state: Texas
Study officials:
affiliation: Hartford Hospital
name: Joseph L Kuti, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pettit RS, Neu N, Cies JJ, Lapin C, Muhlebach MS, Novak KJ, Nguyen ST, Saiman L, Nicolau DP, Kuti JL. Population pharmacokinetics of meropenem administered as a prolonged infusion in children with cystic fibrosis. J Antimicrob Chemother. 2016 Jan;71(1):189-95. doi: 10.1093/jac/dkv289. Epub 2015 Sep 27.