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

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

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.

Study Overview

• Status: Completed
• Conditions: Pneumonia; Cystic Fibrosis; Pseudomonas Aeruginosa Infection
• Intervention / Treatment: Drug: meropenem

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center Children's Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina, North Carolina Children's Hospital
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19134
      • St. Christopher's Hospital for Children
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Meropenem 3 hour prolonged infusion; All 30 participants will receive meropenem as a 3 hour infusion.	Drug: meropenem; meropenem 40mg/kg total body weight will be administered every 8 hours. Each infusion will be infused as a 3 hour infusion.; Other Names: Merrem

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	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.	14-21 days
Practicality of 3 Hour Prolonged Infusion	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.	14-21 days
Meropenem Pharmacodynamics	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).	14-21 days

Collaborators and Investigators

• Sponsor: Joseph Kuti
• Collaborators: Thrasher Research Fund
• Investigators: Principal Investigator: Joseph L Kuti, Pharm.D., Hartford Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: September 2, 2011
• First Submitted That Met QC Criteria: September 6, 2011
• First Posted (Estimate): September 7, 2011

Study Record Updates

• Last Update Posted (Actual): March 20, 2018
• Last Update Submitted That Met QC Criteria: February 20, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; Pseudomonas aeruginosa; Acute Pulmonary Exacerbations
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Pseudomonas Infections; Anti-Infective Agents; Anti-Bacterial Agents; Meropenem
• Other Study ID Numbers: KUTI003498HE