Cystic Fibrosis, Pneumonia, Pseudomonas Aeruginosa Infection
Conditions
Keywords
Cystic Fibrosis, Acute Pulmonary Exacerbations, Pseudomonas aeruginosa
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.
Interventions
DRUGmeropenem
meropenem 40mg/kg total body weight will be administered every 8 hours. Each infusion will be infused as a 3 hour infusion.
Sponsors
Thrasher Research Fund
Joseph Kuti
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Meropenem 3 Hour Prolonged Infusion All 30 participants will receive meropenem as a 3 hour infusion.
meropenem: meropenem 40mg/kg total body weight will be administered every 8 hours. Each infusion will be infused as a 3 hour infusion. | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Meropenem 3 Hour Prolonged Infusion |
|---|---|
| Age, Continuous | 12.7 years STANDARD_DEVIATION 2.9 |
| Baseline Forced Expiratory Volume in 1st Second (FEV1) (% predicted) | 58 % predicted STANDARD_DEVIATION 24 |
| Historical Best FEV1 (% predicted) | 71 % predicted STANDARD_DEVIATION 25 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 30 |
| serious Total, serious adverse events | 1 / 30 |
Outcome results
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.
Time frame: 8 hour dosing interval after 3rd meropenem dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Meropenem 3 Hour Prolonged Infusion | Population Pharmacokinetics - Total Body Clearance | 0.36 L/hr/kg | Standard Deviation 0.14 |
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.
Time frame: During 8 hour dosing interval after 3rd meropenem dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Meropenem 3 Hour Prolonged Infusion | Population Pharmacokinetics - Volume of Central Compartment | 0.21 L/kg | Standard Deviation 0.15 |
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).
Time frame: 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.
Time frame: 14-21 days
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.
Time frame: 14-21 days