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Trial registered on ANZCTR


Registration number
ACTRN12618000073202
Ethics application status
Approved
Date submitted
28/11/2017
Date registered
17/01/2018
Date last updated
18/12/2018
Date data sharing statement initially provided
18/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparing two antibiotic regimens for the treatment of late onset sepsis in neonates
Scientific title
Cefazolin as an alternative to vancomycin for late onset sepsis in preterm infants; A randomised controlled pilot trial.
Secondary ID [1] 293468 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Late Onset Sepsis 305660 0
Preterm Birth 305730 0
Condition category
Condition code
Infection 304882 304882 0 0
Studies of infection and infectious agents
Reproductive Health and Childbirth 304946 304946 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The purpose of this study is to determine if it is possible in the trial setting to use an alternative narrow spectrum antibiotic combination (a more targeted approach) for late onset sepsis in premature infants. Treatment with the antibiotics Vancomycin and Gentamicin (standard care) or Cefazolin and Gentamicin (all intravenous administration).


Cefazolin:
Post natal age less than 8 days Weight: less than 2000g Dose: 25 mg/kg/dose Interval: 12 hourly
Post natal age less than 8 days Weight: greater than or equal to 2000g Dose: 50 mg/kg/dose Interval:12 hourly
Post natal age equal to or greater than 8 days Weight: less than 2000g Dose: 25 mg/kg/dose Interval: 8 hourly
Post natal age equal to or greater than 8 days Weight:greater than or equal to 2000g Dose:50 mg/kg/dose Interval: 8 hourly

Gentamicin Dose: 5mg/kg/dose
Intervals
Corrected Gestational Age/Postmenstrual Age
-Less than 30+0 weeks 48 hourly
-From 30+0-34+6 weeks 36 hourly
- From 35+0 weeks 24 hourly
Duration dependant on if sepsis is confirmed. If blood cultures are negative treatment will be for 48 hours. If sepsis confirmed infectious diseases advise will be sought.
All medications are given as per National Neomed guidelines.
Intervention code [1] 299712 0
Treatment: Drugs
Comparator / control treatment
Drugs all intravenous administration.
Vancomycin Dose: 15mg/kg/dose
Interval:
Corrected Gestational Age/Postmenstrual Age
-Less than 30+0 weeks + Postnatal Age 0-2 days 18 hourly
-Less than 30+0 weeks + Postnatal Age 3+ days 12 hourly
-From 30+0-36+6 weeks + Postnatal Age 0-14 days 12 hourly
-From 30+0-36+6 weeks + Postnatal Age 15+ days 8 hourly
-From 37+0-44+6 weeks + Postnatal Age 0-7 days 12 hourly
-From 37+0-44+6 weeks + Postnatal Age 8+ days 8 hourly
-From 45+0 weeks + Postnatal Age 0+ days 6 hourly

Gentamicin Dose: 5mg/kg/dose
Intervals
Corrected Gestational Age/Postmenstrual Age
-Less than 30+0 weeks 48 hourly
-From 30+0-34+6 weeks 36 hourly
- From 35+0 weeks 24 hourly
Duration dependant on if sepsis is confirmed. If blood cultures are negative treatment will be for 48 hours. If sepsis confirmed infectious diseases advise will be sought.
Control group
Active

Outcomes
Primary outcome [1] 304072 0
The primary outcome is treatment failure. This is defined as worsening or not improving clinical status that leads to change of the initial antibiotic treatment within 48 hours as reviewed by the attending Neonatologist for one of the following reasons:
1. Worsening or not improving clinical status >12 hours after antibiotics were started
2. Progression from sepsis to severe sepsis or septic shock
3. Fluid and catecholamine refractory shock
Timepoint [1] 304072 0
Primary Timepoint 1 will be after 48 hours of treatment with antibiotics, to determine if treatment failure has occurred (i.e. whether antibiotics have been changed)
Secondary outcome [1] 340849 0
None
Timepoint [1] 340849 0
NONE

Eligibility
Key inclusion criteria
Signed, written informed consent by a parent or a legal guardian
Infants <29 weeks gestation at birth
Baby starting treatment for an episode of suspected LOS
Postnatal age more than 72 hours and less than term corrected gestational age (at time of suspected LOS).
Minimum age
72 Hours
Maximum age
16 Weeks
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Presence of major congenital malformation(s) or chromosomal abnormalities
Contraindications for either antibiotic regimen

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)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

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)
NSW
Recruitment hospital [1] 9453 0
John Hunter Children's Hospital - New Lambton
Recruitment postcode(s) [1] 18179 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 298092 0
Charities/Societies/Foundations
Name [1] 298092 0
John Hunter Charitable trust
Address [1] 298092 0
Lookout Road, New Lambton Heights, NSW, 2305
Country [1] 298092 0
Australia
Primary sponsor type
Hospital
Name
John Hunter Childrens Hospital
Address
Lookout Road, New Lambton Heights, NSW, 2305
Country
Australia
Secondary sponsor category [1] 297169 0
None
Name [1] 297169 0
Address [1] 297169 0
Country [1] 297169 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299112 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 299112 0
Lookout Road New Lambton Heights, NSW, 2305
Ethics committee country [1] 299112 0
Australia
Date submitted for ethics approval [1] 299112 0
20/09/2017
Approval date [1] 299112 0
20/11/2017
Ethics approval number [1] 299112 0

Summary
Brief summary
About 25% of very preterm infants in the neonatal intensive care unit will develop a suspected infection, or late onset sepsis. Current empirical late onset sepsis treatment regimens usually include vancomycin, however this antibiotic is associated with the development of drug resistance. Antimicrobial resistance threatens the effective prevention and treatment of infections and is a serious threat to public health. Patients with infections caused by drug-resistant bacteria are at increased risk of worse clinical outcomes and consume more health resources.

The aim of this study is to lead to the development of a safe and effective antibiotic regime for late onset sepsis in preterm infants using a randomised controlled trial design. Preterm infants <29 weeks with suspected late onset sepsis will be randomised to receive either a vancomycin or cephazolin containing antibiotic regimen, both of which should appropriately treat common bacterial causes of late onset sepsis. The trial results will potentially lead to reduced vancomycin use in Australasia and subsequently reduce the development of multi drug resistant organisms, and an overall reduction in health care costs.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79330 0
Dr Joanne McIntosh
Address 79330 0
John Hunter Children's Hospital,
Neonatal Intensive Care Unit
Lookout Road New Lambton Heights, NSW, 2305
Country 79330 0
Australia
Phone 79330 0
+61 249855305
Fax 79330 0
Email 79330 0
joanne.mcintosh@hnehalth.nsw.gov.au
Contact person for public queries
Name 79331 0
Dr Joanne McIntosh
Address 79331 0
John Hunter Children's Hospital,
Neonatal Intensive Care Unit
Lookout Road New Lambton Heights, NSW, 2305
Country 79331 0
Australia
Phone 79331 0
+61249855305
Fax 79331 0
Email 79331 0
joanne.mcintosh@hnehalth.nsw.gov.au
Contact person for scientific queries
Name 79332 0
Dr Joanne McIntosh
Address 79332 0
John Hunter Children's Hospital,
Neonatal Intensive Care Unit
Lookout Road New Lambton Heights, NSW, 2305
Country 79332 0
Australia
Phone 79332 0
+61249855305
Fax 79332 0
Email 79332 0
joanne.mcintosh@hnehalth.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Not applicable