Pharmacokinetic Study of Extended Infusion Meropenem in Adult Cystic Fibrosis Patients
Information source: St. Michael's Hospital, Toronto
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cystic Fibrosis Pulmonary Exacerbation
Intervention: Meropenem Infusion (Drug)
Phase: N/A
Status: Terminated
Sponsored by: St. Michael's Hospital, Toronto Official(s) and/or principal investigator(s):
Daniel Cortes, Principal Investigator, Affiliation: St. Michael's Hospital, Toronto
Summary
Meropenem is an intravenous antibiotic commonly used to treat acute exacerbation of
respiratory infections in cystic fibrosis. The research study aims to determine if a
different method of infusing the drug over 3 hours or longer, instead of the traditional
half-hour will improve target attainment of drug concentrations and bactericidal activity. A
secondary aim is to assess if the pharmacokinetics of meropenem is different during active
infection compared to non-infective stage. Twelve patients admitted with acute respiratory
infection and who requires meropenem will be enrolled into the study. Meropenem blood
concentrations collected over 8 hours will be measured after half-hour and 3-hour infusions
on different days. A pharmacokinetic modelling and Monte Carlo simulation program will use
the data to assess and predict the optimal method of dosing. When patients return for a
follow-up clinic visit, a single dose of meropenem will be administered and blood
concentrations will be measured to determine the pharmacokinetics during non-infective
stage.
Clinical Details
Official title: Pharmacokinetic Study of Extended Infusion Meropenem in Adult Cystic Fibrosis Patient With Exacerbation of Pulmonary Infection
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label
Primary outcome: Pharmacokinetic profile of extended infusion meropenem in Cystic Fibrosis
Detailed description:
Meropenem plays a crucial role in the treatment of pulmonary exacerbations in cystic
fibrosis patients, because it has activity against both P. aeruginosa and B. cepacia, two of
the most problematic pathogens that are encountered in this disease. These organisms cause
chronic endobronchitis with frequent exacerbations which lead to significant morbidity and
premature mortality. Treatment options for pulmonary exacerbations are limited due to the
high rates of resistance with currently available antibiotics and lack of development of new
effective antibiotics. Therefore optimization of the dosing of meropenem, by use of extended
infusion strategy, is one method to allow us to maximize the efficacy of this drug.
Meropenem is a beta-lactam type antibiotic with time-dependent bactericidal activity and
hence it is suitable for extended infusion dosing. The key rationale for extended infusion
of beta-lactam antibiotics is to allow for optimization of pharmacodynamic target attainment
of time above the minimal inhibitory concentrations (T>MIC) to maximize bactericidal killing
and optimize clinical outcomes. The use of this infusion strategy has been studied in
non-cystic fibrosis patients treated primarily with piperacillin-tazobactam or meropenem for
P. aeruginosa infections. The application of this strategy in cystic fibrosis patients has
not been well studied, and there is no data for the treatment of B. cepacia infections. Also
the pharmacokinetic characteristics of meropenem in adult cystic fibrosis patients with
pulmonary exacerbation have not been previously studied. It is unclear whether or not the
pharmacokinetic profile of meropenem in patients without exacerbation can be accurately
extrapolated to those patients with exacerbation. The first phase of this study will,
therefore, describe the pharmacokinetic profile of meropenem and the distribution of MICs
for P. aeruginosa and B. cepacia in a population of adult cystic fibrosis patients with
pulmonary exacerbation. The data will be used to determine an optimal extended infusion
dosing strategy specifically for our patients with cystic fibrosis. The second phase of our
study will provide additional data on the pharmacokinetics of meropenem in patients without
active infection.
Significance of study:
This study will provide new information regarding the pharmacokinetics of meropenem in a
population of cystic fibrosis patients with pulmonary exacerbation. This will allow us to
apply Monte Carlo simulation to the data set with greater confidence as it directly reflects
our own target population. Optimization of meropenem dosing based on pharmacodynamic profile
and Monte Carlo simulation lays the groundwork for clinical efficacy studies in the future.
Based on results from previous studies, optimization of meropenem dosing has the potential
to produce better patient outcomes, reduce drug utilization and cost and reduce rates of
resistance. These can be examined in future clinical studies.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- ≥18 years old,
- currently experiencing new or exacerbation of active pulmonary infection as evidenced
by increased coughing, sputum production, wheezing, white blood count and/or fever,
- requires meropenem for treatment,
- recent sputum culture positive for P. aeruginosa and/or B. cepacia at a prior visit,
- be able to provide written informed consent.
Exclusion Criteria:
- hypersensitivity and/or intolerance to meropenem,
- history of seizures,
- current use of valproic acid,
- significant psychiatric illness,
- contraindication to insertion of a venous catheter,
- worsening of clinical status requiring admission to intensive care unit (ICU),
- creatinine clearance ≤50 ml/min,
- significant cystic fibrosis-related liver dysfunction characterized by portal
hypertension and cirrhosis
Locations and Contacts
St. Michael's Hospital, Toronto, Ontario M5B 1W8, Canada
Additional Information
Starting date: May 2010
Last updated: May 20, 2015
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