Pharmacokinetics of Small Spectrum Beta-lactam Antibiotics (Amoxicillin/Clavulanic Acid and Cefuroxime) in Patients on Intensive Care Units (AMOCEF)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by University Hospital, Ghent
Sponsor:
Information provided by (Responsible Party):
University Hospital, Ghent
ClinicalTrials.gov Identifier:
NCT01581047
First received: February 15, 2012
Last updated: February 1, 2013
Last verified: February 2013
  Purpose

Adequate antibiotic therapy is very important in the treatment of infections. Spectrum and dosing of the antibiotics are two factors of the therapy: the spectrum of an antibiotic can't be changed, but the dosing scheme can be optimized. Recent studies proved that an optimized dosing scheme can improve the efficacy of the treatment. Broad-spectrum antibiotics have unpredictable pharmacokinetics in patients on intensive care units. This is due to the pathophysiologic processes in the patients on intensive care units: increased distribution volume, hypoproteinemia, organ failure… The investigators guess that similar processes influence the pharmacokinetics of small spectrum antibiotics (like amoxicillin and cefuroxime), but data lacks. Because the pharmacokinetics of broad spectrum antibiotics in seriously ill patients are better known, physicians are more confident prescribing these drugs. Studying the pharmacokinetic interactions of small spectrum antibiotics in seriously ill patients, can help to give the physician the confidence to prescribe these small-spectrum antibiotics.

In this study, the investigators will study the pharmacokinetics of amoxicillin/clavulanic acid and cefuroxime, in 60 patients on intensive care. 8 blood samples will be drawn via a central catheter on different moments after one administration of the antibiotic in the steady state phase. All the patients are prescribed the antibiotics for the treatment of their infections: they get the antibiotic therapy anyway. By measuring the concentrations on different moments after one administration, the investigators can reconstruct the pharmacokinetic function.


Condition
Infection

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pharmacokinetics of Small Spectrum Beta-lactam Antibiotics (Amoxicillin/Clavulanic Acid and Cefuroxime) in Patients on Intensive Care Units

Resource links provided by NLM:


Further study details as provided by University Hospital, Ghent:

Primary Outcome Measures:
  • Area under the serum concentration versus time curve (AUC) of Amoxicillin/Clavulanic acid. [ Time Frame: Before and at 15, 30, 45, 60, 120, 240 and 360 minutes after administration ] [ Designated as safety issue: No ]
    The concentrations of the antibiotic in serum samples, drawn at various times after one administration, will be measured. With these data, we can calculate the time above the minimal inhibitory concentration (MIC).

  • Area under the serum concentration versus time curve (AUC) of Cefuroxime. [ Time Frame: Before and at 15, 30, 45, 60, 120, 240 and 480 minutes after administration ] [ Designated as safety issue: No ]
    The concentrations of the antibiotic in serum samples, drawn at various times after one administration, will be measured. With these data, we can calculate the time above the minimal inhibitory concentration (MIC).


Secondary Outcome Measures:
  • Severity of disease classification. [ Time Frame: At date of admission (day 1) and dismissal (up to 3 months). ] [ Designated as safety issue: No ]
    This will be assessed using the Acute Physiology and Chronic Health Evaluation II (APACHE2)-score.

  • Rate of organ failure. [ Time Frame: At date of admission (day 1) and dismissal (up to 3 months). ] [ Designated as safety issue: No ]
    This will be assessed using the Sequential Organ Failure Assessment score (SOFA-score).

  • Concentration serum creatinin [ Time Frame: At day 1. ] [ Designated as safety issue: No ]
  • 24 hour urine creatinine clearance [ Time Frame: At 24 hours ] [ Designated as safety issue: No ]
    Urine will be collected during 24 hours to measure the urine creatinine clearance.

  • Change in fluid balance [ Time Frame: From 0 to 24 hours. ] [ Designated as safety issue: No ]
    Change in fluid balance will be measured.

  • Concentration serum albumin [ Time Frame: At day 1. ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

8 serum samples will be taken per patient.


Estimated Enrollment: 60
Study Start Date: March 2012
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Amoxicillin/Clavulanic Acid
Patients in the intensive care unit, with an infection which will be treated with Amoxicillin/Clavulanic Acid.
Cefuroxime
Patients in the intensive care unit, with an infection which will be treated with Cefuroxime.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients on the intensive care unit, with an infection (which requires amoxicillin/clavulanic acid or cefuroxime).

Criteria

Inclusion Criteria:

  • patients on the intensive care unit, who are treated with amoxicillin/clavulanic acid or cefuroxime for an infection

Exclusion Criteria:

  • informed consent lacking
  • haematocrit < 21 %
  • arterial catheter lacking
  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: NCT01581047

Contacts
Contact: Jan De Waele, MD, PhD Jan.DeWaele@ugent.be

Locations
Belgium
Ghent University Hospital Recruiting
Ghent, Belgium, 9000
Contact: Jan De Waele, MD, PhD       Jan.DeWaele@ugent.be   
Principal Investigator: Jan De Waele, MD, PhD         
Sponsors and Collaborators
University Hospital, Ghent
Investigators
Principal Investigator: Jan De Waele, MD, PhD Ghent University Hospital
  More Information

No publications provided

Responsible Party: University Hospital, Ghent
ClinicalTrials.gov Identifier: NCT01581047     History of Changes
Other Study ID Numbers: 2012/078, 2011-006107-35
Study First Received: February 15, 2012
Last Updated: February 1, 2013
Health Authority: Belgium: Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by University Hospital, Ghent:
amoxicillin
clavulanic acid
cefuroxime
Patients in the intensive care unit, with an infection which requires amoxicillin/clavulanic acid or cefuroxime

Additional relevant MeSH terms:
Infection
Amoxicillin
Cefuroxime
Cefuroxime axetil
Clavulanic Acids
Clavulanic Acid
Beta-Lactams
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 02, 2014