Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000238077
Ethics application status
Approved
Date submitted
17/03/2010
Date registered
22/03/2010
Date last updated
11/10/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Pilot randomised controlled trial of continuous beta-lactam infusion compared with intermittent dosing in critically ill patients
Scientific title
In critically ill patients with severe sepsis how does continuous beta-lactam infusion compared with intermittent beta-lactam dosing effect pharmacodynamics and clinical response to treatment? A pilot randomised controlled trial.
Secondary ID [1] 1524 0
None
Universal Trial Number (UTN)
Trial acronym
BLING pilot RCT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe sepsis 256738 0
Condition category
Condition code
Infection 256893 256893 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Continuous infusion over 24 hours of one of the following beta-lactam antibiotics: ticarcillin/clavulanate, piperacillin/tazobactam or meropenem; antibiotic choice, dose and duration of treatment are clinician chosen
Intervention code [1] 255956 0
Treatment: Drugs
Comparator / control treatment
Intermittent bolus dosing over 30 minutes of one of the following beta-lactam antibiotics: ticarcillin/clavulanate, piperacillin/tazobactam or meropenem; antibiotic choice, dose and duration of treatment are clinician chosen
Control group
Active

Outcomes
Primary outcome [1] 257938 0
Pilot study primary outcome: Plasma antibiotic concentration above the Minimum Inhibitory Concentration (MIC) for three samples taken on Days 3 and 4 (dichotomous variable: Yes/No)
Timepoint [1] 257938 0
Day 3 and 4 post randomisation
Secondary outcome [1] 263446 0
Clinical response defined as:
1) Resolution - disappearance of all signs and symptoms related to the infection
2) Improvement - a marked or moderate reduction in the severity and/or number of signs and symptoms of infection
3) Failure - insufficient lessening of the signs and symptoms of infection to qualify as improvement, including death or indeterminate (no evaluation possible, for any reason); determined by the clinician
Timepoint [1] 263446 0
1) Each day the study drug was administered
2) The last day of intravenous study drug administration
3) A test of cure date (7-14 days after completion of the intravenous study drug)
Secondary outcome [2] 263447 0
Time to clinical resolution (measured in days)
Timepoint [2] 263447 0
1) Date of the infectious episode
2) First identified date of clinical resolution
(For patients, who don't achieve clinical cure, the time to clinical resolution will be arbitrarily set at 28 days)
Secondary outcome [3] 263448 0
Time to resolution of inflammatory markers (measured in days)
Timepoint [3] 263448 0
1) Date of randomisation
2) First identified occasion in which C-reactive protein (CRP) is less than 100 mg/l
(For patients where the CRP remains above 100mg/l, the time to clinical resolution will be arbitrarily set at 28 days)
Secondary outcome [4] 263449 0
Mortality
Timepoint [4] 263449 0
1) Intensive Care Unit (ICU) discharge
2) Hospital discharge

Eligibility
Key inclusion criteria
1) Confirmed or suspected infection with new organ dysfunction
2) Commencement within the previous 24 hours or planned commencement of ticarcillin/clavulanate, piperacillin/tazobactam or meropenem
3) Expected or actual ICU stay greater than 48 hours
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Allergy or potential allergy to study medications
2) Receiving palliative or supportive treatment only at the time of screening
3) Receiving contrinuous renal replacement therapy
4) No central venous catheter access with 3 or more lumens
5) Receipt of the study drug of interest for > 24 hours prior to enrolment
6) Discharge from the ICU within 48 hours

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)
1) Daily screening of eligible ICU patients
2) Consent obtained from participant/surrogate decision maker
3) Randomisation group determined by sealed envelope method
4) Unblinded researcher/pharmacist prepares concealed study medications, i.e. bolus and continuous infusions (with active medication administered via only one route)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified allocation by institution and computerised sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
14/04/2010
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 2615 0
0811
Recruitment postcode(s) [2] 2614 0
2148
Recruitment postcode(s) [3] 2613 0
3084
Recruitment postcode(s) [4] 2611 0
4029
Recruitment postcode(s) [5] 2612 0
6004
Recruitment outside Australia
Country [1] 2462 0
Hong Kong
State/province [1] 2462 0

Funding & Sponsors
Funding source category [1] 256586 0
Charities/Societies/Foundations
Name [1] 256586 0
Intensive Care Foundation
Country [1] 256586 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Beta-Lactam Infusion Group
Address
c/o Professor Jeffrey Lipman
Department of Intensive Care Medicine
Royal Brisbane and Women's Hospital
Herston QLD 4029
Country
Australia
Secondary sponsor category [1] 255881 0
None
Name [1] 255881 0
Address [1] 255881 0
Country [1] 255881 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258617 0
Royal Brisbane and Women's Hospital Human Research Ethics Committee
Ethics committee address [1] 258617 0
Office of the Human Research Ethics Committee
Royal Brisbane and Women's Hospital
Butterfield Street
Herston QLD 4029
Ethics committee country [1] 258617 0
Australia
Date submitted for ethics approval [1] 258617 0
27/10/2009
Approval date [1] 258617 0
16/12/2009
Ethics approval number [1] 258617 0
HREC/09/QRBW/319

Summary
Brief summary
The purpose of this pilot randomised controlled trial is to establish the fundamental elements (feasibility, adequacy of blinding, pharmacodynamic effect and separation of endpoints) required to proceed with a large multi-centre randomised controlled trial of beta-lactam antibiotics delivered by continuous infusion compared to standard bolus dosing in critically ill patients. We hypothesise that continuous infusion will more consistently achieve pharmacodynamic endpoints than standard bolus dosing, resulting in improved clinical outcomes.
Trial website
Trial related presentations / publications
Dulhunty JM et al. Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial. Clinical Infectious Diseases 2012, in press.
Public notes

Contacts
Principal investigator
Name 30796 0
Address 30796 0
Country 30796 0
Phone 30796 0
Fax 30796 0
Email 30796 0
Contact person for public queries
Name 14043 0
Dr Joel Dulhunty
Address 14043 0
Department of Intensive Care Medicine
Royal Brisbane and Women's Hospital
Herston QLD 4029
Country 14043 0
Australia
Phone 14043 0
+61 7 3636 4114
Fax 14043 0
+61 7 3636 3542
Email 14043 0
Joel_Dulhunty@health.qld.gov.au
Contact person for scientific queries
Name 4971 0
Dr Joel Dulhunty
Address 4971 0
Department of Intensive Care Medicine
Royal Brisbane and Women's Hospital
Herston QLD 4029
Country 4971 0
Australia
Phone 4971 0
+61 7 3636 4114
Fax 4971 0
+61 7 3636 3542
Email 4971 0
Joel_Dulhunty@health.qld.gov.au

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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