We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03309657




Registration number
NCT03309657
Ethics application status
Date submitted
30/07/2017
Date registered
13/10/2017
Date last updated
10/09/2020

Titles & IDs
Public title
Pharmacokinetics of Ceftolozane/Tazobactam in Plasma and Cerebrospinal Fluid
Scientific title
A Prospective Pharmacokinetic Evaluation of the Plasma and Cerebrospinal Fluid Concentrations of a Single Dose Ceftolozane/Tazobactam in Infected Critically Ill Patients With an Indwelling External Ventricular Drain
Secondary ID [1] 0 0
HREC/17/QRBW/117
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pharmacokinetics 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ceftolozane/tazobactam

Experimental: Ceftolozane Tazobactam - Infected patients with external intraventricular drain will receive a single dose of Ceftolozane/ tazobactam (3000mg) over 1 hour and will undergo blood , csf and urine sampling at specific times over an 8 hour period.


Treatment: Drugs: Ceftolozane/tazobactam
This is an observational pharmacokinetic study whereby patients received a single dose of ceftolozane/tazobactam and plasma and cerebrospinal fluid samples were subsequently collected and analyzed to described the pharmacokinetics.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Unbound Ceftolozane Exposure in the Plasma - Unbound Ceftolozane Exposure in the plasma given by the area under the unbound concentration-time curve from time zero to infinity (AUC0-inf).
Timepoint [1] 0 0
Samples collected from 0 to 8 hours post dose at "0, 1, 2,4,6, & 8 h post dose were use estimate area under the curve from time zero to infinity estimated by non-compartmental analysis
Primary outcome [2] 0 0
Unbound Tazobactam Exposure in the Plasma - Unbound Tazobactam Exposure in the plasma given by the area under the unbound concentration-time curve from time zero to infinity (AUC0-inf).
Timepoint [2] 0 0
Samples collected from 0 to 8 hours post dose at "0, 1, 2,4,6, & 8 h post dose were use estimate area under the curve from time zero to infinity estimated by non-compartmental analysis
Primary outcome [3] 0 0
Unbound Ceftolozane Exposure in the CSF - Unbound Ceftolozane Exposure in the CSF given by the area under the unbound concentration-time curve from time zero to infinity (AUC0-inf).
Timepoint [3] 0 0
Samples collected from 0 to 8 hours post dose at "0, 1, 2,4,6, & 8 h post dose were use estimate area under the curve from time zero to infinity estimated by non-compartmental analysis
Primary outcome [4] 0 0
Unbound Tazobactam Exposure in the CSF - Unbound Tazobactam Exposure in the CSF given by the area under the unbound concentration-time curve from time zero to infinity (AUC0-inf).
Timepoint [4] 0 0
Samples collected from 0 to 8 hours post dose at "0, 1, 2,4,6, & 8 h post dose were use estimate area under the curve from time zero to infinity estimated by non-compartmental analysis

Eligibility
Key inclusion criteria
Patients with any infection requiring treatment with ceftolozane/tazobactam and who have
met the following criteria:

- Age >18 years

- The presence of an indwelling external ventricular drain (EVD) or requiring EVD
insertion due to obstructive hydrocephalus/subarachnoid haemorrhage
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known or suspected allergy to penicillins and cephalosporins

- Pregnancy

- Receiving renal replacement therapy

- Glomerular filtration rate less than 10 mL/min

- Receiving piperacillin/tazobactam or having received piperacillin/tazobactam in the
past 7 days before enrolment

Study design
Purpose of the study
Basic Science
Allocation to intervention
N/A
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
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
QLD
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment postcode(s) [1] 0 0
4029 - Brisbane

Funding & Sponsors
Primary sponsor type
Other
Name
Royal Brisbane and Women's Hospital
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The University of Queensland
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Ceftolozane/tazobactam is an emerging newly available antibiotic that has a broad spectrum of
activity, and could be potentially useful in the management of central nervous system
infections. However, data relating to penetration of ceftolozane/ tazobactam into the central
nervous system, where a barrier against drug distribution exists (i.e. blood brain barrier),
is currently limited. In critically ill patients this is all the more challenging as
achieving adequate antibiotic concentrations even in blood is difficult.

The aim of this study is to describe the concentrations achieved in the cerebrospinal fluid
(i.e. bodily fluid found surrounding and inside of the brain) and blood after a single dose
of ceftolozane/tazobactam administered in critically ill patients with an existing external
ventricular drain (i.e. a device used in neurosurgery that relieves elevated intracranial
pressure in the brain). It is planned that this information gained will help develop dosing
strategies that will achieve target concentrations that will successfully treat central
nervous system infections in the future.
Trial website
https://clinicaltrials.gov/show/NCT03309657
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jason A Roberts, PhD BPharm
Address 0 0
Royal Brisbane and Womens Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications