Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000809538
Ethics application status
Approved
Date submitted
9/07/2015
Date registered
5/08/2015
Date last updated
29/09/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Antibiotic disposition in children undergoing heart surgery
Scientific title
Pharmacokinetics of prophylactic antibiotics in children undergoing heart surgery with cardiopulmonary bypass circuitry
Secondary ID [1] 287064 0
NIL Known
Universal Trial Number (UTN)
U1111-1172-0310
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
children with heart disease 295558 0
Cardiac surgery related infection 295619 0
Condition category
Condition code
Infection 295828 295828 0 0
Studies of infection and infectious agents
Cardiovascular 295897 295897 0 0
Other cardiovascular diseases
Surgery 295898 295898 0 0
Other surgery

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Pharmacokinetic analysis of antibiotic disposition in children undergoing cardiac surgery with cardiopulmonary bypass. Antibiotics (cephazolin, vancomycin) are given intravenously during the procedure only. The first dose is at induction of anaesthesia. A second dose is commonly given at the conclusion of cardiopulmonary bypass. They are not continued into the postoperative period. A dosing log will be kept.
Intervention code [1] 292294 0
Not applicable
Comparator / control treatment
This is an observational study of drug disposition in those children given routine prophylactic antibiotics
Control group
Uncontrolled

Outcomes
Primary outcome [1] 295518 0
Characterise antibiotic disposition in children undergoing cardiopulmonary bypass or on extracorporeal circuits.
Blood assays taken after drug administration will be used for a pharmacokinetic population analysis using mixed effects models. Covariate effects (age, size, renal function, surgical type, bypass duration, temperature) will be assessed in order to decrease population parameter variability.
Timepoint [1] 295518 0
Approx 15 blood samples for assay from each individual will be taken over the duration of surgery from anaesthesia induction and into a 12 h postoperative period. Specific time points are not used for this type of analysis, but rather windows of time e.g. early samples assist determination of V; late samples (3 half lives) help determine CL. Samples will be required after interventions (e.g bypass initiation). Optimal design simulation will be used to determine the best windows for sampling
Secondary outcome [1] 316047 0
The use of simulation using computer modelling to predict therapeutic blood concentrations in a typical individual
Timepoint [1] 316047 0
This simulation analysis will be performed once data for primary endpoint analysis is complete. We anticipate 6 months after PK analysis is complete

Eligibility
Key inclusion criteria
children with heart disease presenting for surgery that requires extracorporeal circuits
Minimum age
No limit
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
refusal by parent/caregiver or child for consent
known allergy to antibiotic

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
We will relate given dose to observed drug concentration in the blood, using nonlinear mixed effects models and the computer program NONMEM. Once a structural pharmacokinetic model has been developed, we will consider incorporation of key covariates to better describe variability in observed concentrations following standard dosing in our population. We will assess our model using standard goodness of fit criterion and plots, visual predictive checks and simulation methods. Required numbers required for this population analysis remain uncertain but we anticipate approx. 50 children. This aspect is pharmacokinetics

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/12/2016
Actual
14/08/2017
Date of last participant enrolment
Anticipated
28/02/2018
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
17
Final
Recruitment outside Australia
Country [1] 7027 0
New Zealand
State/province [1] 7027 0
Auckland

Funding & Sponsors
Funding source category [1] 291622 0
Charities/Societies/Foundations
Name [1] 291622 0
Green Lane Research and Education Fund
Country [1] 291622 0
New Zealand
Primary sponsor type
Individual
Name
Brian Anderson
Address
c/o PICU
Starship Hospital
park Road Grafton Auckland 1023
Country
New Zealand
Secondary sponsor category [1] 290294 0
Individual
Name [1] 290294 0
Kirsten Finucane
Address [1] 290294 0
c/o Cardiac Services
Starship Hospital
Park Road, Grafton, Auckland 1023
Country [1] 290294 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293153 0
Health and Disability Ethic Committees
Ethics committee address [1] 293153 0
Ministry of Health
Ethics Department
Freyberg Building
Reception – Ground Floor
20 Aitken Street
Wellington 6011
Ethics committee country [1] 293153 0
New Zealand
Date submitted for ethics approval [1] 293153 0
03/08/2015
Approval date [1] 293153 0
23/09/2015
Ethics approval number [1] 293153 0

Summary
Brief summary
Prophylactic antibiotic choice and dosing during paediatric cardiac surgery using cardiopulmonary bypass remains poorly defined. Cardiac surgery should be associated with an incidence of infection (superficial and deep) < 5%. This target is not reached in many centres. One contributing factor is a lack of understanding of antibiotic pharmacokinetics during support with extracorporeal circuits. Dosing may not achieve desired concentrations in the body. Children undergoing cardiac surgery will receive routine antibiotic prophylaxis. Blood concentrations will be monitored. Population pharmacokinetic modelling will be used to determine a dosing regimen to achieve desired target concentration.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 58682 0
Prof Brian Anderson
Address 58682 0
c/o PICU
Starship Hospital
Park Road
Grafton
Auckland 1023
Country 58682 0
New Zealand
Phone 58682 0
+64 9 3074903
Fax 58682 0
+64 9 3078986
Email 58682 0
[email protected]
Contact person for public queries
Name 58683 0
Prof Brian Anderson
Address 58683 0
c/o PICU
Starship Hospital
Park Road
Grafton
Auckland 1023
Country 58683 0
New Zealand
Phone 58683 0
+64 9 3074903
Fax 58683 0
+64 9 3078986
Email 58683 0
[email protected]
Contact person for scientific queries
Name 58684 0
Prof Brian Anderson
Address 58684 0
c/o PICU
Starship Hospital
Park Road
Grafton
Auckland 1023
Country 58684 0
New Zealand
Phone 58684 0
+64 9 3074903
Fax 58684 0
+64 9 3078986
Email 58684 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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.