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

This study has been completed.
Sponsor:
Collaborator:
Thrasher Research Fund
Information provided by (Responsible Party):
Joseph Kuti, Hartford Hospital
ClinicalTrials.gov Identifier:
NCT01429259
First received: September 2, 2011
Last updated: March 4, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Cystic Fibrosis
Pneumonia
Pseudomonas Aeruginosa Infection
Drug: meropenem
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Hartford Hospital:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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).


Enrollment: 30
Study Start Date: February 2012
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Merrem

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01429259

Locations
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
Sponsors and Collaborators
Joseph Kuti
Thrasher Research Fund
Investigators
Principal Investigator: Joseph L Kuti, Pharm.D. Hartford Hospital
  More Information

No publications provided

Responsible Party: Joseph Kuti, Associate Director, Center for Anti-Infective Research and Development, Hartford Hospital
ClinicalTrials.gov Identifier: NCT01429259     History of Changes
Other Study ID Numbers: KUTI003498HE
Study First Received: September 2, 2011
Last Updated: March 4, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Hartford Hospital:
Cystic Fibrosis
Acute Pulmonary Exacerbations
Pseudomonas aeruginosa

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pseudomonas Infections
Bacterial Infections
Digestive System Diseases
Genetic Diseases, Inborn
Gram-Negative Bacterial Infections
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases
Meropenem
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014