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Trial registered on ANZCTR


Registration number
ACTRN12614001175662
Ethics application status
Approved
Date submitted
29/10/2014
Date registered
7/11/2014
Date last updated
12/12/2018
Date data sharing statement initially provided
12/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Bactericidal External ventricular drainS in paTients with Traumatic Brain Injury
Scientific title
In patients with traumatic brain injury, does insertion of antibiotic-impregnated external ventricular drains compared with standard drains reduce the incidence of catheter-associated central nervous system infections
Secondary ID [1] 285174 0
Nil known
Universal Trial Number (UTN)
U1111-1160-3614
Trial acronym
BEST TBI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Traumatic brain injury 292768 0
Ventriculitis 292769 0
Condition category
Condition code
Injuries and Accidents 293058 293058 0 0
Other injuries and accidents
Infection 293059 293059 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
An external ventricular drain (EVD) can be inserted by a neurosurgeon into the fluid-filled ventricles within the brain for the management of hydrocephalus and intracranial hypertension, and for intracranial pressure monitoring in traumatic brain injury. After the hydrocephalus or intracranial hypertension has resolved (usually within 2 weeks) the EVD can be removed or replaced. Timing of EVD removal is determined by the treating neurosurgical and intensive care teams.

Currently there are both standard, and antibiotic- (rifampicin and clindamycin) impregnated (Bactisealâ„¢) catheters in use, without clear evidence of benefit. This trial will compare antibiotic-impregnated EVDs to standard silicon EVDs.
Intervention code [1] 290028 0
Treatment: Devices
Comparator / control treatment
Standard silicon external ventricular drains
Control group
Active

Outcomes
Primary outcome [1] 292928 0
Cumulative incidence of central nervous system infections.

This will be assessed by combined clinical and laboratory analysis of cerebrospinal fluid (CSF), using standard Center for Disease Control criteria to define CSF infection.
Timepoint [1] 292928 0
At primary hospital discharge
Secondary outcome [1] 309967 0
Rates of complications: cerebrospinal fluid leaks around external ventricular drain (EVD)/Infections of EVD wound.

This composite outcome will be assessed from the participant hospital record and recorded for each patient. Laboratory confirmation of wound infection will be undertaken as clinically indicated.
Timepoint [1] 309967 0
At primary hospital discharge
Secondary outcome [2] 309968 0
ICU and hospital lengths of stay
Timepoint [2] 309968 0
At primary hospital discharge
Secondary outcome [3] 309969 0
Indications for external ventricular drain (EVD) insertion.

This will be assessed by the neurosurgeon at the time of hospital presentation, and recorded at the time of surgery for EVD insertion.
Timepoint [3] 309969 0
At time of external ventricular drain insertion.
Secondary outcome [4] 309970 0
Days alive and free from external ventricular drain (EVD) at Day 30 post-injury.

Time and date of EVD removal will be recorded in patient hospital records, from which this outcome will be assessed. Patients who die with their EVD in situ will be recorded as having 0 days alive and free from EVD. Patients who survive and have their EVDs removed early will have more days alive and free from EVD than those who have their EVD removed later.
Timepoint [4] 309970 0
At day 30 post-injury
Secondary outcome [5] 309971 0
Cumulative incidence of cerebrospinal fluid (CSF) shunt insertion.

Patients who have persistent or recurrent hydrocephalus after external ventricular drain (EVD) removal may require a more permanent CSF shunt to be surgically inserted.

This outcome will be assessed from the patient hospital records and operation reports.
Timepoint [5] 309971 0
At two-weeks following removal of EVD.
Secondary outcome [6] 309973 0
Extended Glasgow Outcome Scale
Timepoint [6] 309973 0
At 6 months post-injury

Eligibility
Key inclusion criteria
1. Aged at least 16 years old
2. Traumatic brain injury requiring external ventricular drain insertion
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known or suspected CSF infection at time of EVD insertion
2. Any other indication for ongoing antibiotics at the time of EVD insertion
3. Prior EVD insertion (last 30 days)
4. Sepsis, ventriculitis, meningitis, skin infection at implantation site.
5. Allergy to Rifampicin and Clindamycin
6. Multiple EVDs required con-currently

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)
Eligible patients will be enrolled in the operating theatre prior to external ventricular drain (EVD) insertion. Sealed, sequentially numbered, opaque randomization envelopes will be placed in the operating theatre and will be opened by the neurosurgeon while the patient is being prepared for the procedure. The scrub nurses will then provide the EVD as per the randomly allocated treatment arm for the surgeon to insert. In rare cases EVD insertion may occur in the intensive care unit (ICU), in which case the next envelope will be opened and treatment allocation identified prior to transfer of appropriate equipment to the ICU.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated randomisation schedule, 1:1 allocation, stratified by site.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The baseline incidence of ventriculitis is estimated to be 9%. Our sample size is based on an absolute decrease of 8%, to 1%. This effect size would be highly clinically relevant (number needed to treat [NNT] to prevent one case of ventriculitis = 13). This relative decrease is equivalent to or less than observed in previous trials. With a type 1 error of 0.05 and type II error of 0.2 (power 80%), the required number is 140 patients per group, or 280 patients in total.

This study will be analysed on an intention to treat basis. All analyses will be undertaken by the Chief Investigator with the aide of a biostatistician. Baseline comparisons will be performed using chi-square tests for equal proportion, student t-tests for continuous normally distributed variables and Wilcoxon rank sum tests otherwise. The primary outcome will be analysed using a chi-square test with results reported as frequencies and percentages per arm. A two-sided p-value of 0.05 will be considered to be statistically significant.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,WA,VIC
Recruitment hospital [1] 3093 0
The Alfred - Prahran
Recruitment hospital [2] 12711 0
The Canberra Hospital - Garran
Recruitment hospital [3] 12712 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 25136 0
2605 - Garran
Recruitment postcode(s) [2] 25137 0
6000 - Perth

Funding & Sponsors
Funding source category [1] 289785 0
Charities/Societies/Foundations
Name [1] 289785 0
Brain Foundation
Address [1] 289785 0
PO Box 579, Crows Nest, NSW 1585
Country [1] 289785 0
Australia
Primary sponsor type
Hospital
Name
The Alfred, Intensive Care Research
Address
55 Commercial Road, Melbourne, VIC, 3004
Country
Australia
Secondary sponsor category [1] 288475 0
None
Name [1] 288475 0
Address [1] 288475 0
Country [1] 288475 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291522 0
The Alfred Human Ethics Committee
Ethics committee address [1] 291522 0
55 Commercial Road, Melbourne, VIC, 3004
Ethics committee country [1] 291522 0
Australia
Date submitted for ethics approval [1] 291522 0
19/06/2014
Approval date [1] 291522 0
05/08/2014
Ethics approval number [1] 291522 0

Summary
Brief summary
External ventricular drain (EVD) catheters are integral to the management of patients with severe traumatic brain injury (TBI). EVDs are routinely used in the management of severe TBI, and are recommended by international consensus guidelines. These catheters monitor and can help to lower the pressure within the brain that is often raised as a result of the brain injury.
This process is not without risks. The EVD catheter provides a pathway between the brain and the external environment, which can become colonised by bacteria and lead to infection in the brain, called 'meningitis' or 'ventriculitis'. This infection may worsen brain damage, produce seizures, and increase length of stay in the hospital.
One potential way of reducing this risk of EVD-associated infection is to use antibiotic-impregnated catheters. These EVDs release antibiotics over time, with the aim of preventing bacteria from contaminating the drains. Despite previous research it is still unclear if there is benefit to using these drains, which are considerably more expensive than the standard EVDs. The aim of this project is to determine if antibiotic-impregnated EVDs reduce the rates of infection in patients with TBI.
In this study, patients with TBI who are planned for EVD insertion will have a 50:50 chance (like flipping a coin) to receive either a standard or antibiotic-impregnated EVD. After insertion, patients will be monitored until the EVD is removed (generally within 10 days following injury) to see if they develop catheter-associated infection. Results will then be compared to see if there is a difference between each group.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 50718 0
Dr Justin Moore
Address 50718 0
The Alfred
Department of Neurosurgery
55 Commercial Road, Melbourne, VIC, 3004
Country 50718 0
Australia
Phone 50718 0
+61 03 9076 2000
Fax 50718 0
Email 50718 0
justinmurraymoore@gmail.com
Contact person for public queries
Name 50719 0
Ms Shirley Vallance
Address 50719 0
The Alfred
Intensive Care Research
55 Commercial Road, Melbourne, VIC, 3004
Country 50719 0
Australia
Phone 50719 0
+61 03 9076 2000
Fax 50719 0
Email 50719 0
s.vallance@alfred.org.au
Contact person for scientific queries
Name 50720 0
Dr Dashiell Gantner
Address 50720 0
The Alfred
Department of Intensive Care
55 Commercial Road, Melbourne, VIC, 3004
Country 50720 0
Australia
Phone 50720 0
+61 03 9076 2000
Fax 50720 0
Email 50720 0
dashiell.gantner@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No HREC approval for this data sharing
What supporting documents are/will be available?
Study protocol
Attachments/websites
Type [1] 717 0
Study protocol
URL/details/comments [1] 717 0
Summary results
Not applicable