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

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01429259
• Other study ID #: KUTI003498HE
• Status: Completed
• Phase: Phase 4
• First received: September 2, 2011
• Last updated: February 20, 2018
• Start date: February 2012
• Est. completion date: January 2014

Study information

• Verified date: February 2018
• Source: Hartford Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Pneumonia
• Pseudomonas Aeruginosa Infection
• Pseudomonas Infections

Intervention

Drug:
• meropenem
meropenem 40mg/kg total body weight will be administered every 8 hours. Each infusion will be infused as a 3 hour infusion.

Locations

Country	Name	City	State
United States	University of North Carolina, North Carolina Children's Hospital	Chapel Hill	North Carolina
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Medical Center	Dallas	Texas
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Columbia University Medical Center Children's Hospital	New York	New York
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Joseph Kuti	Thrasher Research Fund

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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