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

• Sponsor: Joseph Kuti (Other)
• Overall Status: Completed
• CT.gov ID: NCT01429259
• Collaborator: Thrasher Research Fund (Other)
• Enrollment: 30
• Locations: 7
• Arm: 1
• Duration (Months): 23
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis; Pneumonia; Pseudomonas Aeruginosa Infection	Drug: meropenem	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

1. 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.

2. 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.

3. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
2	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
3	Columbia University Medical Center Children's Hospital	New York	New York	United States	10032
4	University of North Carolina, North Carolina Children's Hospital	Chapel Hill	North Carolina	United States	27514
5	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
6	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134
7	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joseph Kuti, Associate Director, Center for Anti-Infective Research and Development, Hartford Hospital
• ClinicalTrials.gov Identifier: NCT01429259
• Other Study ID Numbers: KUTI003498HE
• First Posted: Sep 7, 2011
• Last Update Posted: Mar 20, 2018
• Last Verified: Feb 1, 2018

• Keywords provided by Joseph Kuti, Associate Director, Center for Anti-Infective Research and Development, Hartford Hospital: Cystic Fibrosis; Acute Pulmonary Exacerbations; Pseudomonas aeruginosa
• Additional relevant MeSH terms: Pseudomonas Infections; Cystic Fibrosis; Fibrosis; Meropenem

Study Results

Participant Flow

Arm/Group Title	Meropenem 3 Hour Prolonged Infusion
Arm/Group Description	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.
Period Title: Overall Study
STARTED	30
COMPLETED	30
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Meropenem 3 Hour Prolonged Infusion
Arm/Group Description	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.
Overall Participants	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.7 (2.9)
Sex: Female, Male (Count of Participants)
Female	16 53.3%
Male	14 46.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	30 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	30 100%
Baseline Forced Expiratory Volume in 1st Second (FEV1) (% predicted) (% predicted) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [% predicted]	58 (24)
Historical Best FEV1 (% predicted) (% predicted) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [% predicted]	71 (25)

Outcome Measures

1. Primary Outcome

Title	Population Pharmacokinetics - Total Body Clearance
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Meropenem 3 Hour Prolonged Infusion
Arm/Group Description	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.
Measure Participants	30
Mean (Standard Deviation) [L/hr/kg]	0.36 (0.14)

2. Primary Outcome

Title	Population Pharmacokinetics - Volume of Central Compartment
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Meropenem 3 Hour Prolonged Infusion
Arm/Group Description	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.
Measure Participants	30
Mean (Standard Deviation) [L/kg]	0.21 (0.15)

3. Secondary Outcome

Title	Safety
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Practicality of 3 Hour Prolonged Infusion
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Meropenem Pharmacodynamics
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse Events collected from time of consent until completion of the study, which was 7-14 days after completion of meropenem prolonged infusion.
Adverse Event Reporting Description	Laboratory (chemistry, complete blood count, liver function tests, urinalysis) systematically collected at baseline and end of therapy. Other adverse events documented when reported by the participant or on findings during physical examination.
Arm/Group Title	Meropenem 3 Hour Prolonged Infusion
Arm/Group Description	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.
All Cause Mortality
	Meropenem 3 Hour Prolonged Infusion
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Meropenem 3 Hour Prolonged Infusion
	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)
Blood and lymphatic system disorders
Pancytopenia	1/30 (3.3%)	1
Other (Not Including Serious) Adverse Events
	Meropenem 3 Hour Prolonged Infusion
	Affected / at Risk (%)	# Events
Total	7/30 (23.3%)
Blood and lymphatic system disorders
Leukocytosis	1/30 (3.3%)
Thrombocythemia	1/30 (3.3%)
General disorders
Fever	2/30 (6.7%)
Hepatobiliary disorders
Liver Function Test Abnormality	2/30 (6.7%)
Hyperbilirubinemia	1/30 (3.3%)
Immune system disorders
C-Reactive Protein Elevation	3/30 (10%)
Infections and infestations
Clostridium difficile Infection	2/30 (6.7%)
Skin and subcutaneous tissue disorders
Rash	2/30 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.