Pharmacokinetics of Piperacillin, Given as Continuous Infusion to Patients With Cystic Fibrosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kristina Öbrink-Hansen, University of Aarhus
ClinicalTrials.gov Identifier:
NCT01983787
First received: July 11, 2013
Last updated: November 6, 2015
Last verified: November 2015
  Purpose

At the Department of Infectious Diseases, Aarhus University Hospital, continuous infusion with piperacillin/tazobactam for a period of 2 weeks, has been used for several years in patients with cystic fibrosis, suffering from acute pulmonary exacerbations (APE).

It is an outpatient treatment. To assess the efficacy and quality of the treatment, a blood test every 3rd day is taken to determine the concentration of Piperacillin in blood-plasma.


Condition Phase
Cystic Fibrosis
Phase 4

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Pharmacokinetics of Piperacillin, Given as Continuous Infusion to Patients With Cystic Fibrosis

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • Blood-plasma Concentration of Piperacillin [ Time Frame: Piperacillin plasma-concentration was determined 3-5 times for each patient, during the 2 weeks of piperacillin treatment ] [ Designated as safety issue: No ]

    The free, non-protein bound fraction of plasma piperacillin for each patient was determined using Ultra High Performance Liquid Chromatography. The concentration was compared to the MIC-value (Minimal Inhibitory Concentration) of the pathogen isolated in a sputum sample collected prior to initiation of antibiotic treatment.

    Infusion pumps with 16 g of piperacillin per 24 hours were initially used and five patients had piperacillin plasma-concentrations monitored during this treatment regimen. However, in three of these patients, the piperacillin plasma concentrations were unexpectedly low and dropped to a level below the MIC. This was found to be due to antibiotic crystallization within the infusion pumps as a result of the antibiotic concentration being too high. Consequently, infusion pumps with 12 g of piperacillin per 24 hours were used in stead. The median piperaillin concentrations reported below are derived from all measurements within the two weeks of treatment.



Secondary Outcome Measures:
  • The Time Above the Minimum Inhibitory Concentration (T>MIC) [ Time Frame: Patients will be followed for the duration of treatment, which is approximately 2 weeks. ] [ Designated as safety issue: No ]

    The time, expressed in percentage, for which the plasma concentration of Piperacillin lies above the minimum inhibitory concentration for the pathogen,during the treatment. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T>MIC is reported as 100%. MIC for the pathogen in sputum was not reported in patient 5. Therefore,T>MIC for this patient could not be estimated.

    Patient 1-5 were treated with piperacillin 16g/day. Patient 6-10 were treated with piperacillin 12g/day.


  • MIC of Pathogen Detected in Sputum Sample, Prior to Initiation of Treatment. [ Time Frame: Sputum sample was collected 3 to 7 days before treatment initiation. ] [ Designated as safety issue: No ]
    MIC to piperacillin/tazobactam was obtained by using E-tests (AB Biodisk, Solna, Sweden) on Mueller-Hinton agar plates incubated at 35 ± 2 degrees Celcius with inoculum, incubation time and atmosphere in accordance to the E-test application guide.


Biospecimen Retention:   Samples Without DNA
Whole blood

Enrollment: 10
Study Start Date: July 2013
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Pharmacokinetics Piperacillin
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam, given as continuous infusion for a period of two weeks.

Detailed Description:
Patients with cystic fibrosis (CF) are often colonized with multidrug-resistant microorganisms, which increases the risk of suboptimal dosing of antibiotics as the time above the minimum inhibitory concentration (T>MIC) is suboptimal. Continuous infusion of beta-lactam antibiotics is more likely to optimize T>MIC than intermittent infusion. At the Department of Infectious Diseases, Aarhus University Hospital, continuous infusion with piperacillin/tazobactam for a period of 2 weeks, has been used for several years in patients with CF, suffering from acute pulmonary exacerbations (APE). It is an outpatient treatment, and the patients are given 16 g of piperacillin per 24 hours. To assess the efficacy and quality of the treatment, a blood test every 3rd day will be required to monitor the blood-plasma concentration of piperacillin, as well as C-reactive protein (CRP) and white blood cell count (WBC).
  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with Cystic Fibrosis, suffering from acute pulmonary exacerbations.
Criteria

Inclusion Criteria:

  • Patients with Cystic Fibrosis, suffering from acute pulmonary exacerbations, treated with continuous infusion of Piperacillin/Tazobactam for a period of two weeks.

Exclusion Criteria:

  • Age under 18
  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: NCT01983787

Locations
Denmark
Department of Infectious Diseases, Aarhus University Hospital
Aarhus, Aarhus N, Denmark, 8220
Sponsors and Collaborators
University of Aarhus
Investigators
Study Director: Eskild Petersen, Professor Department of Infectious Diseases, Aarhus University Hospital, Denmark
  More Information

No publications provided

Responsible Party: Kristina Öbrink-Hansen, MD, University of Aarhus
ClinicalTrials.gov Identifier: NCT01983787     History of Changes
Other Study ID Numbers: CF-275-13 
Study First Received: July 11, 2013
Results First Received: June 29, 2015
Last Updated: November 6, 2015
Health Authority: Denmark: Danish Dataprotection Agency

Keywords provided by University of Aarhus:
Cystic Fibrosis
Continuous infusion
Pharmacokinetics

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

ClinicalTrials.gov processed this record on February 10, 2016