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Trial registered on ANZCTR


Registration number
ACTRN12620001332910p
Ethics application status
Submitted, not yet approved
Date submitted
14/10/2020
Date registered
10/12/2020
Date last updated
10/12/2020
Date data sharing statement initially provided
10/12/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of topical coconut oil on infection rates in extremely premature infants
Scientific title
Can topical coconut oil reduce the incidence of late-onset sepsis in extremely preterm infants - a pragmatic cluster-randomised controlled trial
Secondary ID [1] 302484 0
Nil Known
Universal Trial Number (UTN)
U1111-1259-3282
Trial acronym
The COSI-2 Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Late onset sepsis 319320 0
extremely preterm infants 319321 0
Condition category
Condition code
Infection 317292 317292 0 0
Studies of infection and infectious agents
Reproductive Health and Childbirth 317651 317651 0 0
Childbirth and postnatal care
Reproductive Health and Childbirth 317652 317652 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Topical coconut oil is the intervention

Eligible infants in neonatal units randomised to the study intervention will receive topical coconut oil starting within 24h from birth. Preterm infants’ skin condition deteriorates rapidly in the first days of life therefore commencement of the intervention within 24h of birth is essential.
• Infants <25 w GA will receive 5ml of coconut oil 4x/day for the first week of life, then 5ml 2x/day until transferred to an open cot.
• Infants >25 w GA will receive 5ml 2x/day until transferred to an open cot.
• Once cared for in an open cot, infants will receive topical coconut oil 1x/day until discharge from the tertiary neonatal unit (to minimise undressing and handling of the infant).
Application:
- Use a new sachet for each application.
- The parents should apply the coconut oil to their infant’s skin if they wish, under supervision of the bedside nurse.
- Apply topical coconut oil during routine care to the entire skin (front and back). Do not apply coconut oil to the face, scalp, and sites of vascular access or other devices (e.g. chest drain).
- Use only a few gentle strokes to apply coconut oil. Do not massage. Application should only take 1-2 minutes per side.
- Discard any unused oil in a sachet after opening.

Monitoring
Pharmacy stock reports at intervention sites will be compared to the number of eligible infants and expected number of days of treatment will provide an indication of compliance with coconut oil use.
Further, monitoring of 20% of eligible infants’ medication charts at the intervention sites, where coconut oil will be prescribed and application signed-off, will be conducted to ensure compliance with the study intervention.
Intervention code [1] 318778 0
Prevention
Comparator / control treatment
Routine care is defined as the current best skin care practice at the sites randomised to the control arm.
Control group
Active

Outcomes
Primary outcome [1] 325350 0
Incidence of late onset sepsis
The primary outcome will assessed by the extraction and analysis of of neonatal data reports from the Australia and New Zealand Neonatal Network (ANZNN)
Timepoint [1] 325350 0
At any time before discharge from neonatal unit.
Secondary outcome [1] 387592 0
Survival
All secondary outcomes will assessed by the extraction and analysis of of neonatal data reports from the Australia and New Zealand Neonatal Network (ANZNN)
Timepoint [1] 387592 0
At any time before discharge from neonatal unit.
Secondary outcome [2] 387594 0
Necrotizing enterocolitis
All secondary outcomes will assessed by the extraction and analysis of of neonatal data reports from the Australia and New Zealand Neonatal Network (ANZNN)
Timepoint [2] 387594 0
Until discharge from neonatal unit
Extract of neonatal data reports from the Australia and New Zealand Neonatal Network (ANZNN)
Secondary outcome [3] 387595 0
Time taken to achieve enteral intake of 150 ml/kg/day
All secondary outcomes will assessed by the extraction and analysis of of neonatal data reports from the Australia and New Zealand Neonatal Network (ANZNN)
Timepoint [3] 387595 0
Time taken to achieve enteral intake of 150 ml/kg/day
Extract of neonatal data reports from the Australia and New Zealand Neonatal Network (ANZNN)
Secondary outcome [4] 388799 0
Brain injury: Brain injury is defined as Grade of 3 and 4 grade of intraventricular haemorrhage (on either side of the head) seen on ultrasound according to the system of grading defined ANZNN guidelines, or presence by ultrasound any of the following: periventricular leukomalacia, porencephalic cysts or hydrocephalus requiring neurosurgical intervention.
All secondary outcomes will assessed by the extraction and analysis of of neonatal data reports from the Australia and New Zealand Neonatal Network (ANZNN)
Timepoint [4] 388799 0
At any time before discharge from neonatal unit
Secondary outcome [5] 388800 0
Duration of any mechanical ventilation: Mechanical ventilation is defined as respiratory support provided either by endotracheal tube ventilation, continuous positive airway pressure or humidified high-flow oxygen.
All secondary outcomes will assessed by the extraction and analysis of of neonatal data reports from the Australia and New Zealand Neonatal Network (ANZNN)
Timepoint [5] 388800 0
At any time before discharge from neonatal unit
Secondary outcome [6] 388801 0
Chronic lung disease: Chronic lung disease (also known as bronchopulmonary dysplasia) is defined as receiving any form of respiratory support for a chronic pulmonary disorder on the day the baby reached 36 weeks’ postmenstrual age.
All secondary outcomes will assessed by the extraction and analysis of of neonatal data reports from the Australia and New Zealand Neonatal Network (ANZNN)
Timepoint [6] 388801 0
At any time before discharge from the neonatal unit
Secondary outcome [7] 388802 0
Retinopathy of prematurity: Stage of retinopathy and necessity for treatment with laser surgery, cryotherapy or monoclonal antibody therapy according to local guidelines.
All secondary outcomes will assessed by the extraction and analysis of of neonatal data reports from the Australia and New Zealand Neonatal Network (ANZNN)
Timepoint [7] 388802 0
At any time before discharge from the neonatal unit
Secondary outcome [8] 388803 0
Length of hospital stay: Hospital stay is defined as the number of days from admission to final discharge home.
All secondary outcomes will assessed by the extraction and analysis of of neonatal data reports from the Australia and New Zealand Neonatal Network (ANZNN)
Timepoint [8] 388803 0
At any time before discharge from the neonatal unit

Eligibility
Key inclusion criteria
Infants born < 28 weeks gestational age
Minimum age
12 Hours
Maximum age
24 Hours
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Critically ill infants not expected to survive (as certified by consulting physician)
Infants with a primary surgical diagnosis (inability to apply coconut oil to large proportion of skin)

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The allocation of the study invention will not be concealed. Intervention and control groups of infants will be cluster randomised by site. Upon randomisation, participating sites will be stratified by cluster size and incidence of late-onset sepsis. Participating sites will be advised of their allocation to treatment (all eligible infants receive topical coconut oil) or the control arm where infants receive routine skin care accordingly.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participating sites will be cluster randomised by computer generated program, stratified by size of site and incidence of late-onset sepsit
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
The study design is a pragmatic, cluster-randomised, 2-arm, parallel, multicentre trial
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The current incidence of LOS in extremely preterm infants is ~25% . We will recruit 1232 infants <28w GA from 17 sites with average 80 neonates per centre, yielding >80% power to detect a 35% reduction of LOS incidence from 25% to 16.25%, with two-tailed alpha of 0.05 and intraclass correlation (ICC) of 0.008 (PASS 2019 Power Analysis and Sample Size Software (2019). NCSS, LLC. Kaysville, Utah, USA). These calculations also allow for a reduction in incidence of LOS due to anticipated future advances in care, 5% loss to follow-up and 5% non-compliance

Recruitment
Recruitment status
Not yet 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,QLD,SA,TAS,VIC
Recruitment outside Australia
Country [1] 23046 0
New Zealand
State/province [1] 23046 0

Funding & Sponsors
Funding source category [1] 306910 0
Charities/Societies/Foundations
Name [1] 306910 0
Thrasher Research Fund
Address [1] 306910 0
68 S Main St #400, Salt Lake City, UT 84101, United States
Country [1] 306910 0
United States of America
Primary sponsor type
Charities/Societies/Foundations
Name
Telethon Kids Institute
Address
Northern Entrance, Perth Children's Hospital, 15 Hospital Ave, Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 307468 0
None
Name [1] 307468 0
Address [1] 307468 0
Country [1] 307468 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 307060 0
Child and Adolescent Health Services Human Research Ethics Committee
Ethics committee address [1] 307060 0
Office 5E, Perth Children’s Hospital, 15 Hospital Avenue, Nedlands, Western Australia, 6009
Ethics committee country [1] 307060 0
Australia
Date submitted for ethics approval [1] 307060 0
16/11/2020
Approval date [1] 307060 0
Ethics approval number [1] 307060 0

Summary
Brief summary
Late-onset sepsis (bloodstream infection) remains one of the most common complications of extremely early birth (more than 3 months before the due date). Skin condition in preterm infants deteriorates quickly after birth and the majority of bloodstream infections are caused by bacteria that reside on the skin. At present there is no available skin care product with proven benefit on skin condition and rates of infection.
In this new trial, Neonatal Intensive Care Units of the Australia and New Zealand Neonatal Network will be randomly allocated to either using topical coconut oil or their current standard of skin care for all infants born extremely early to determine if coconut oil may reduce the rate of bloodstream infections. The findings of this trial could be readily translated into clinical practice.

Trial website
TBA
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105890 0
A/Prof Tobias Strunk
Address 105890 0
King Edward Memorial Hospital for Women , Neonatal Unit
Child and Adolescent Health Service
374 Bagot Road
Subiaco
Perth WA 6008
Country 105890 0
Australia
Phone 105890 0
+61 8 6458 1260
Fax 105890 0
Email 105890 0
tobias.strunk@health.wa.gov.au
Contact person for public queries
Name 105891 0
A/Prof Tobias Strunk
Address 105891 0
King Edward Memorial Hospital for Women , Neonatal Unit
Child and Adolescent Health Service
374 Bagot Road
Subiaco
Perth WA 6008
Country 105891 0
Australia
Phone 105891 0
+61 8 6458 1260
Fax 105891 0
Email 105891 0
tobias.strunk@health.wa.gov.au
Contact person for scientific queries
Name 105892 0
A/Prof Tobias Strunk
Address 105892 0
King Edward Memorial Hospital for Women , Neonatal Unit
Child and Adolescent Health Service
374 Bagot Road
Subiaco
Perth WA 6008
Country 105892 0
Australia
Phone 105892 0
+61 8 6458 1260
Fax 105892 0
Email 105892 0
tobias.strunk@health.wa.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
Data is sourced from the ANZNN registry and subject to their confidentiality protocols.
What supporting documents are/will be available?
No other documents available
Summary results
No Results