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Trial registered on ANZCTR


Registration number
ACTRN12609000069257
Ethics application status
Approved
Date submitted
6/01/2009
Date registered
28/01/2009
Date last updated
4/07/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Optimising cefepime dosing in intensive care: the pharmacokinetics of extended (prolonged) infusions.
Scientific title
In intensive care patients with sepsis, are extended (prolonged) infusions of cefepime, compared to conventional intermittent dosing, more effective in achieving and maintaining plasma concentrations above pharmacodynamic breakpoints?
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
intensive care sepsis 4173 0
Condition category
Condition code
Infection 4382 4382 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
extended (prolonged) intravenous infusion of cefepime 1g over 6 hours every 12 hours for first 3 days of therapy
Intervention code [1] 3892 0
Treatment: Drugs
Comparator / control treatment
2 comparator arms.
1. cefepime at 1g infused intravenously over 5 minutes every 12 hours for first 3 days of therapy
2. 2g infused intravenously over 5 minutes every 12 hours for first 3 days of therapy
Control group
Active

Outcomes
Primary outcome [1] 5260 0
percentage of dosing interval above pharmacodynamic breakpoint during the first 12 hours of treatment determined via limited sampling of cefepime concentrations to facilitate pharmacokinetic modelling
Timepoint [1] 5260 0
At 12 hours from start of treatment
Primary outcome [2] 5261 0
percentage of dosing interval above pharmacodynamic breakpoint from 48 to 60 hours of treatment determined via limited sampling of cefepime concentrations to facilitate pharmacokinetic modelling
Timepoint [2] 5261 0
At 72 hours from the start of treatment
Primary outcome [3] 5262 0
limited sampling of cefepime concentrations along with pharmacokinetic modelling will be used to determine the full pharmacokinetic profile for cefepime in intensive care patients with sepsis
Timepoint [3] 5262 0
Limited sampling will occur on days 1 and 3 at time = 0, 5 minutes, 30 minutes, 3 hours, 6 hours, 8 hours 10 hours and 12 hours after the start of the cefepime infusion. Pharmacokinetic modelling will be completed at the end of the first 3 days of treatment (ie 72 hours after the first dose of cefepime).
Secondary outcome [1] 8867 0
Feasibility of administration of extended (prolonged) infusions of cefepime in the medical / surgical intensive care setting by the monitoring by health care professionals of the success in administering the infusions and survey by the researchers of the intravenous lines and other infusions administered during the study period.
Timepoint [1] 8867 0
Daily during the 3 day study period
Secondary outcome [2] 8868 0
daily monitoring during the study period by health care professionsals of significant clinical outcomes (duration of mechnical ventilation, length of intensive care unit and hospital stay) , and any possible relation to the use of extended (prolonged) infusions of cefepime which may be used to inform the design of future studies of extended infusions
Timepoint [2] 8868 0
hospital discharge

Eligibility
Key inclusion criteria
An adult intensive care patient who: Has been prescribed cefepime according to The Alfred Intensive Care Unit (ICU) Antibiotic Guidelines (ie. after 7 days of hospital admission and requiring empiric or directed anti-microbial treatment); Is likely to remain in ICU for at least three days from enrolment; Has an arterial line already in situ for blood sampling.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any documented allergy or adverse reaction to cefepime or other cephalosporin antibiotic or significant / serious adverse reaction to other beta-lactam or monobactam antibiotics which would normally preclude the prescribing of cefepime according to the Alfred ICU Antibiotic Guidelines.
2. Moderate to severe renal impairment (calculated estimated glomular filtration ratre (eGRF) <30mL/min at enrolment) or need for continous renal replacement therapy or intermittent heamodialysis.
3. Patients with significant burns (ie. greater than 15% body surface area)
4. Patients with extracorporeal circuits (eg. extracorporeal membranous oxygenation, ventricular assist devices)
5. All transplant patients including solid organ and bone marrow transplants
6. Pregnancy
7. Inclusion in other study protocols which preclude enrolment in this study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sequentially numbered sealed envelopes will be prepared and used to randomise patients at enrolment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer generated randomisation table prepared by a statistician will be used.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
2/02/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 4351 0
Hospital
Name [1] 4351 0
The Alfred Research Trusts
Country [1] 4351 0
Australia
Funding source category [2] 4352 0
Self funded/Unfunded
Name [2] 4352 0
Pharmacy Department
Country [2] 4352 0
Australia
Primary sponsor type
Hospital
Name
The Alfred
Address
Commercial Rd
Melbourne, Victoria, 3004
Country
Australia
Secondary sponsor category [1] 3919 0
None
Name [1] 3919 0
Address [1] 3919 0
Country [1] 3919 0
Other collaborator category [1] 525 0
University
Name [1] 525 0
Monash University
Address [1] 525 0
381 Royal Pde
Parkville, Victoria, 3052
Country [1] 525 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6407 0
The Alfred Hospital Ethics Committee
Ethics committee address [1] 6407 0
The Alfred
Commercial Rd
Melbourne, Victoria, 3004
Ethics committee country [1] 6407 0
Australia
Date submitted for ethics approval [1] 6407 0
Approval date [1] 6407 0
12/12/2008
Ethics approval number [1] 6407 0
328/08

Summary
Brief summary
Cefepime is a broad spectrum antibiotic used as part of the Alfred Intensive Care Unit (ICU) antibiotic guidelines at a dose of 1g every 12 hours in combination with other agents, higher doses are used (eg 2g every 12 hours) in many international centres. Conventional administration is via short infusion over a few minutes. However the antibacterial effect is dependent on adequate drug concentrations being maintained over most of the period between doses. Extended infusions have been shown in computer modelling to achieve this for cefepime. Clinically, extended infusions have been shown in intensive care patients to be more effective for other antibiotics of similar class to cefepime.
This study will be a randomised controlled trial in intensive care patients which aims to compare the pharmacokinetic profile (blood concentrations of the drug over time) of conventional administration of cefepime over a few minutes at the dose of 1g every 12 hours (the dose routinely used in The Alfred ICU) and the higher dose of 2g every 12 hours against an extended infusion of 1g given over 6 hours every 12 hours.
Cefepime blood concentration will be obtained from analysis of blood samples taken at predetermined time points over two 12 hour periods on Day 1 and Day 3 (steady state) of therapy. This will allow determination of the pharmacokinetic profile of cefepime in intensive care patients for each of the three dosing regimens. Comparison of these profiles will provide evidence of any advantage of extended infusions in intensive care patients leading to larger scale clinical investigations of this administration method.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35074 0
Address 35074 0
Country 35074 0
Phone 35074 0
Fax 35074 0
Email 35074 0
Contact person for public queries
Name 12421 0
Ms Bianca Levkovich
Address 12421 0
Pharmacy Department
The Alfred
Commercial Rd
Melbourne, Victoria, 3004
Country 12421 0
Australia
Phone 12421 0
+61 3 9076 2061
Fax 12421 0
Email 12421 0
[email protected]
Contact person for scientific queries
Name 3349 0
Ms Bianca Levkovich
Address 3349 0
Pharmacy Department
The Alfred
Commercial Rd
Melbourne, Victoria, 3004
Country 3349 0
Australia
Phone 3349 0
+61 3 9076 2061
Fax 3349 0
Email 3349 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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