Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children

Phase 4

Completed

• Conditions: Cystic Fibrosis; Pseudomonas Aeruginosa Infection; Pneumonia
• Interventions: Drug: meropenem

• Registration Number: NCT01429259
• Lead Sponsor: Joseph Kuti

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.

Study Timeline

• Study First Submitted: 2011-09-02
• Study First Submitted QC: 2011-09-06
• Study First Posted: 2011-09-07
• Study Start: 2012-02
• Primary Completion: 2014-01
• Study Completion: 2014-01
• Results First Submitted: 2015-03-17
• Results First Submitted QC: 2015-03-26
• Results First Posted: 2015-03-27
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-20
• Last Update Posted: 2018-03-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Meropenem 3 hour prolonged infusion	meropenem	All 30 participants will receive meropenem as a 3 hour infusion.

Primary Outcome Measures

Name	Time	Method
Population Pharmacokinetics - Total Body Clearance	8 hour dosing interval after 3rd meropenem dose	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 Central Compartment	During 8 hour dosing interval after 3rd meropenem dose	Based on meropenem concentrations, the pharmacokinetics of the study population will be analyzed to determine each patient's volume of the central compartment.

Secondary Outcome Measures

Name	Time	Method
Safety	14-21 days	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	14-21 days	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	14-21 days	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).

Trial Locations

Locations (7)

St. Christopher's Hospital for Children; 🇺🇸 Philadelphia, Pennsylvania, United States

Connecticut Children's Medical Center; 🇺🇸 Hartford, Connecticut, United States

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

Children's Medical Center; 🇺🇸 Dallas, Texas, United States

Riley Hospital for Children; 🇺🇸 Indianapolis, Indiana, United States

Columbia University Medical Center Children's Hospital; 🇺🇸 New York, New York, United States

University of North Carolina, North Carolina Children's Hospital; 🇺🇸 Chapel Hill, North Carolina, United States