Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000314224
Ethics application status
Approved
Date submitted
13/01/2017
Date registered
2/03/2018
Date last updated
2/03/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
A comparison of the efficacy of intermittent versus continuous infusions of vancomycin at achieving therapeutic concentrations in an adult Australian critically ill population.
Scientific title
A comparison of the efficacy of intermittent versus continuous infusions of vancomycin at achieving therapeutic concentrations in an adult Australian critically ill population.
Secondary ID [1] 290913 0
nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
sepsis 301633 0
Condition category
Condition code
Infection 301338 301338 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is a before/after study design

The after phase begins after the implementation of a protocol for continuous intravenous infusions of vancomycin. This protocol consists of an intravenous infusion of a 25mg/kg loading dose, based on actual body weight, followed by a continuous infusion of vancomycin with initial dosing rates dictated by a protocol driven daily assessment of renal function using an estimated creatinine clearance. This protocol also involves daily therapeutic drug monitoring.

Creatinine clearance as per Cockcroft-Gault (Column 1) Total dose over 24 hours (Column 2) Infusion rate (Column 3)
Less than 10mL/min
10-21mL/min 750mg 3.8mL/hour
22-39mL/min 1000mg 5 mL/hour
40-57mL/min 1250mg 6.3 mL/hour
58-75mL/min 1500mg 7.5 mL/hour
76-93mL/min 1750mg 8.8 mL/hour
94-111mL/min 2000mg 10 mL/hour
112-129mL/min 2250mg 11.3 mL/hour
130-147mL/min 2500mg 12.5 mL/hour
148-165mL/min 2750mg 13.8 mL/hour
Greater than or equal to 166mL/min 3000mg 15 mL/hour


This data collection takes place over 7 months
Intervention code [1] 296854 0
Treatment: Drugs
Comparator / control treatment
The study is a before/after study design.

The before phase consists of observing standard practice of intravenous vancomycin (intermittent bolus dosing). This dosing varies depending on the patient- but is generally 1-2g every 12 hours.

This data collection takes place over 12 months
Control group
Active

Outcomes
Primary outcome [1] 300743 0
Hours until therapeutic serum vancomycin concentration.

International guidelines define a therapeutic serum vancomycin concentration as measure of 15mg/L or greater for intermittent bolus dosing.

There is no consensus for a therapeutic serum vancomycin concentration when a continuous infusion is utilised, however common practice is greater than 20mg/L and that was what is to be used in this study.
Timepoint [1] 300743 0
During the before phase serum vancomycin concentration monitoring is to occur at the discretion of the treating intensivist, with advice from pharmacy when required.

The protocol used in the after phase directs for daily concentration monitoring, until therapeutic concentrations have been achieved on consecutive days.
Primary outcome [2] 300744 0
The number of vancomycin courses per treatment group that achieved a therapeutic concentration. A vancomycin course that achieves a therapeutic concentration, is defined as follows.
If at any point during treatment with vancomycin a serum concentration is returned greater than 15mg/L for the intermittent dosing group or 20mg/L for the continuous infusion group.
Timepoint [2] 300744 0
While patients are recieving an intravenous infusion of vancomycin daily therapeutic drug monitoring takes place, until the completion of therapy.
Primary outcome [3] 300745 0
Number of serum vancomycin concentrations in therapeutic range per treatment course.

International guidelines define a therapeutic serum vancomycin concentration range as measure of 15-20mg/L or greater for intermittent bolus dosing.

There is no consensus for a therapeutic serum vancomycin concentration when a continuous infusion is utilised, however common practice is greater than 20-25mg/L and that was what is to be used in this study.
Timepoint [3] 300745 0
During the before phase serum vancomycin concentration monitoring is to occur at the discretion of the treating intensivist, with advice from pharmacy when required.

The protocol used in the after phase directs for daily concentration monitoring, until therapeutic concentrations have been achieved on consecutive days.
Secondary outcome [1] 330772 0
Rates of nephrotoxicity.

This will be assessed by using the Cockroft-Gault equation, and comparing the change from start to end of vancomycin treatment course. Additionally the rates of patients requiring renal replacement therapy will also measured
Timepoint [1] 330772 0
Duration of treatment course

Eligibility
Key inclusion criteria
- At least 24 hours of intravenous vancomycin therapy
- At least one serum vancomycin concentration measured
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Non-intravenous vancomycin (ie. oral)
- Breastfeeding patients
- Pregnant patients

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Before-and-After study design
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
114 treatment courses from 101 critically ill patients
Statistical analysis via SPSS
independent t test or Mann Whitney U test depending on distribution of data

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
1/02/2015
Date of last participant enrolment
Anticipated
Actual
30/09/2016
Date of last data collection
Anticipated
Actual
30/09/2016
Sample size
Target
166
Accrual to date
Final
101
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 7303 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 15078 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 295335 0
Hospital
Name [1] 295335 0
Flinders Medical Centre
Country [1] 295335 0
Australia
Primary sponsor type
Individual
Name
Mr Simon Potts
Address
c/o ICCU
Flinders Medical Centre
Flinders Drive
Bedford Park
5042
South Australia
Country
Australia
Secondary sponsor category [1] 294161 0
None
Name [1] 294161 0
Address [1] 294161 0
Country [1] 294161 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296672 0
Southern Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 296672 0
c/o Flinders Medical Centre
Flinders Drive
Bedford Park
SA
5042
Ethics committee country [1] 296672 0
Australia
Date submitted for ethics approval [1] 296672 0
13/01/2016
Approval date [1] 296672 0
17/03/2016
Ethics approval number [1] 296672 0
371.15

Summary
Brief summary
Vancomycin is an intravenous antibiotic used in the treatment of serious infections, commonly seen in the Intensive and Critical Care Unit (ICCU). Unlike many antibiotics, vancomycin requires serum drug concentration monitoring to ensure both efficacy and safety. Traditionally vancomycin is dosed as an intravenous intermittent infusion every 8-12 hours. However, critically ill patients experience greater pharmacokinetic changes which can have a major impact on the dosage of vancomycin required to treat infection. There is emerging evidence to suggest that the administration of vancomycin by a continuous infusion may be more efficacious in achieving therapeutic serum concentrations, doing so promptly, and limiting nephrotoxicity which is a known adverse effect of the drug. The aims of this project are as follows
1. To evaluate the current practice administering vancomycin by intermittent infusion within the ICCU at Flinders Medical Centre (FMC)- phase one/Before
2. To develop and implement a protocol for the administration of vancomycin by continuous infusion- phase two/Implementation
3. By using a Before-and-After study design evaluate the efficacy of a protocol for the administration of vancomycin by continuous infusions, when compared to standard practice within the ICCU at FMC- phase three/After
Data on the current practice of vancomycin dosing via intermittent infusion was commenced in February 2015, this data formed the basis for the Before group. The protocol was developed, using a dosing nomogram derived from a series of published studies identified from a literature review on the topic. This protocol
underwent beta-testing and was implemented into the ICCU in March 2016 with concurrent education sessions. Prospective post-implementation data collection was undertaken, making up the After group.
Trial website
Trial related presentations / publications
Public notes
Data collection started as an audit of current practice, as such ethics approval was not required until the initiation of the After phase

Contacts
Principal investigator
Name 71698 0
Mr Simon Potts
Address 71698 0
C/O ICCU
Flinders Medical Centre
Flinders Drive
Bedford Park
South Australia
5042
Country 71698 0
Australia
Phone 71698 0
+61 8 8204 6807
Fax 71698 0
Email 71698 0
simon.potts@sa.gov.au
Contact person for public queries
Name 71699 0
Simon Potts
Address 71699 0
C/O ICCU
Flinders Medical Centre
Flinders Drive
Bedford Park
South Australia
5042
Country 71699 0
Australia
Phone 71699 0
+61 8 8204 6807
Fax 71699 0
Email 71699 0
simon.potts@sa.gov.au
Contact person for scientific queries
Name 71700 0
Simon Potts
Address 71700 0
C/O ICCU
Flinders Medical Centre
Flinders Drive
Bedford Park
South Australia
5042
Country 71700 0
Australia
Phone 71700 0
+61 8 8204 6807
Fax 71700 0
Email 71700 0
simon.potts@sa.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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