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Trial registered on ANZCTR


Registration number
ACTRN12619000393156
Ethics application status
Approved
Date submitted
18/01/2019
Date registered
12/03/2019
Date last updated
1/08/2019
Date data sharing statement initially provided
12/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Normal saline versus heparin flushes in paediatric oncology: a pilot randomised controlled trial
Scientific title
Normal saline versus heparin flushes in paediatric oncology to prevent occlusion: a pilot randomised controlled trial
Secondary ID [1] 296771 0
Nil known
Universal Trial Number (UTN)
U1111-1224-9276
Trial acronym
POSH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Central venous access device complications 310666 0
Children's cancer 311615 0
Condition category
Condition code
Cancer 309369 309369 0 0
Children's - Leukaemia & Lymphoma
Cancer 310240 310240 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
0.9% Sodium Chloride locking (10mL 0.9% Sodium chloride pulsatile flush and catheter lock)
Volume will be determined as per hospital protocol, appropriate to the volume of the catheter, administered intravenously

Current policy is: When CVADs (including PICCs, tunnelled catheters and totally implanted venous port device) are accessed daily, a 10mL pulsatile flush of 0.9% sodium chloride is administered after each use. When CVADs (including PICCs, tunnelled catheters and totally implanted venous port device) are not likely to be used for > 24 hours and up to 1 week, 1-2mLs (volume of catheter dependent) 10U/mL heparin sodium is instilled in the catheter to ensure patency. This is repeated weekly or after use whichever comes sooner. When totally implanted venous port device will not be used for > 1 week, up to 6-8 weeks, 2 mLs of 100u/mL heparin lock is administered to ensure patency.
Intervention code [1] 313080 0
Treatment: Other
Intervention code [2] 313690 0
Prevention
Comparator / control treatment
Heparinised saline locking (10mL 0.9% Sodium chloride pulsatile flush and catheter lock - 50units/mL PICC or tunneled CVAD or 100units/mL totally implanted CVAD) as per current practice and policy. Volume will be determined as per hospital protocol, appropriate to the volume of the catheter. Administered intravenously.

Current policy is: When CVADs (including PICCs, tunnelled catheters and totally implanted venous port device) are accessed daily, a 10mL pulsatile flush of 0.9% sodium chloride is administered after each use. When CVADs (including PICCs, tunnelled catheters and totally implanted venous port device) are not likely to be used for > 24 hours and up to 1 week, 1-2mLs (volume of catheter dependent) 10U/mL heparin sodium is instilled in the catheter to ensure patency. This is repeated weekly or after use whichever comes sooner. When totally implanted venous port device will not be used for > 1 week, up to 6-8 weeks, 2 mLs of 100u/mL heparin lock is administered to ensure patency.
Control group
Active

Outcomes
Primary outcome [1] 308325 0
Study feasibility: The feasibility outcome will be determined based on the following criteria:
a. Eligibility: % of screened patients meeting all inclusion and no exclusion criteria;
b. Recruitment: % of eligible patients providing informed consent;
c. Retention: % of recruited patients lost to follow up or withdrawing consent;
d. Protocol fidelity: % of randomised patients receiving their allocated intervention;
e. Missing data: % of total data unable to be collected by study staff;
f. Patient and staff acceptability with the study intervention and control: % of patient/parents and staff scoring greater than or equal to 7 on an 11point numeric rating scale at study completion.
Timepoint [1] 308325 0
End of trial
Primary outcome [2] 308326 0
Occlusive events
As assessed by clinicians and researchers, as per the Catheter Injection and Aspiration (CINAS) classification system described proportionally and per 1,000 catheter days.
Timepoint [2] 308326 0
Until study completion (Patients will be enrolled in the study for up to four weeks, or up until admission to PICU/ regional or other healthcare facility, or until removal of the device)
Secondary outcome [1] 354613 0
Fracture: Visible split in CVAD material with leakage or radiographic evidence of extravasation/infiltration into tissue, in a CVAD during or following flushing or infusion (as opposed to accidental fracture).
Timepoint [1] 354613 0
Until study completion (Patients will be enrolled in the study for up to four weeks, or up until admission to PICU/ regional or other healthcare facility, or until removal of the device)
Secondary outcome [2] 354614 0
Venous thrombosis: suspected: too painful for the patient to tolerate device remaining insitu, or Confirmed Ultrasound/venographic, confirmed by blinded Radiologist, thrombosed vessel within which the CVAD is placed in a symptomatic patient, or a patient with a thrombus/fibrin sheath occluding 1 lumen on visual inspection at CVAD removal.
Timepoint [2] 354614 0
Until study completion (Patients will be enrolled in the study for up to four weeks, or up until admission to PICU/ regional or other healthcare facility, or until removal of the device)
Secondary outcome [3] 354615 0
Central venous access device -associated bloodstream infection (CABSI): A laboratory confirmed BSI that is not secondary to an infection at another body site (excludes Mucosal Barrier Injury LCBSI), with CVAD in place for >2 calendar days on the day of the BSI (day of CVAD placement being Day 1) and the CVAD was in place on the date of the event or the day before, when all elements of LCBSI, were first present together (see CDC NHSN for full criteria) confirmed by a blinded infectious disease specialist using de-identified clinical and microbiological data
Timepoint [3] 354615 0
Until study completion (Patients will be enrolled in the study for up to four weeks, or up until admission to PICU/ regional or other healthcare facility, or until removal of the device)
Secondary outcome [4] 354616 0
Medication error: As determined by the completion of a Riskman (clinical incident form). Frequency of when incorrect strength or amount of heparin is instilled, resulting in either overdosing, under-dosing, or omission of heparin, resulting in accessing the CVAD again to correct the error or an adverse event such as bleeding or need for protamine reversal.
Timepoint [4] 354616 0
Until study completion (Patients will be enrolled in the study for up to four weeks, or up until admission to PICU/ regional or other healthcare facility, or until removal of the device)
Secondary outcome [5] 354617 0
Healthcare costs: Estimate of direct product costs, healthcare resource utilisation (including additional equipment, staff time) and failure-associated resource usage.

These data will be collected using a combination of individual patient assessment, Medicare data and study-specific questionnaires.
Timepoint [5] 354617 0
At CVAD failure, completion of treatment, or study completion (which ever is soonest).

Eligibility
Key inclusion criteria
• Ages 0 – 18years
• Have a central venous access device in situ;
• Diagnosed with an oncological or malignant haematological condition
• Informed consent to participate
Minimum age
0 Years
Maximum age
18 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• End of life pathway
• Pre-existing coagulopathic condition not related to current diagnosis or treatment such as (but not limited to): Haemophilia A & B or other factor deficiency; Idiopathic Thrombocytopenic Purpura (ITP); Von Willibrand’s disease
• Coagulation disorders related to current diagnosis or treatment e.g. Disseminated Intravascular Coagulopathy (DIC)
• Current treatment with PEG-Asparaginase
• Allergy to heparin
• Admission to Paediatric Intensive Care Unit (PICU)
• Admission to regional hospital or alternative healthcare facility
• Previous study participation


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)
Participants will be randomised to treatment allocation by the research nurse using a secure web-based central randomisation service provided by Griffith University (https://www151.griffith.edu.au/).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The allocation sequence will be computer generated in a ratio of 1:1, stratified per CVAD device (PICC, tunnelled cuffed CVAD, totally implanted CVAD), using a randomly variable permuted block size (2, 4) to avoid allocation prediction.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety
Statistical methods / analysis
Feasibility outcomes will be reported descriptively. All randomised patients will be analysed on an Intention to Treat (ITT) basis. The CVAD is the unit of measurement. For this pilot trial, we will test the feasibility of the statistical analysis that will be used in the definitive trial. Prior to analysis, data cleaning of outlying observations will be undertaken, and a random 5% sample of source data re-entered and checked. All attempts will be made to collect the primary endpoint. Missing data will not be imputed. Comparability of groups at baseline will be assessed using clinically significant differences. Frequency and Incidence Rate Ratio (with 95% confidence intervals) of device occlusion will summarise the impact of the intervention. Secondary endpoints will be compared between groups using clinically significant differences. P values of <0.05 will be considered 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)
QLD
Recruitment hospital [1] 12621 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 25042 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 301349 0
Charities/Societies/Foundations
Name [1] 301349 0
Children's Hospital Foundation
Address [1] 301349 0
494 Stanley St, South Brisbane QLD 4101
Country [1] 301349 0
Australia
Primary sponsor type
Hospital
Name
Queensland Children's Hopsital
Address
Formerly Lady Cilento Children's Hospital
501 Stanley St, South Brisbane QLD 4101
Country
Australia
Secondary sponsor category [1] 301020 0
University
Name [1] 301020 0
Griffith University
Address [1] 301020 0
170 Kessels Rd, Nathan QLD 4111
Country [1] 301020 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302093 0
Children's Health Queensland Hospital and Health Service Human Research Ethics Committee
Ethics committee address [1] 302093 0
Human Research Ethics Committee
Centre for Children’s Health Research
Lady Cilento Children’s Hospital Precinct
Level 7, 62 Graham Street
South Brisbane QLD 4101
Ethics committee country [1] 302093 0
Australia
Date submitted for ethics approval [1] 302093 0
23/11/2018
Approval date [1] 302093 0
23/01/2019
Ethics approval number [1] 302093 0

Summary
Brief summary
This study aims to evaluate the feasibility and safety of normal saline, compared to heparinised saline, for the prevention of occlusions (blockages) in central venous access devices (CVADs) in a paediatric oncology population.

Who is it for?
You or your child may be eligible to join this study if you/they are aged 0-18 years, have been diagnosed with an oncological or malignant haematological condition, and have a central venous access device (CVAD) in situ. CVADs are flexible tubes inserted in the chest, neck or upper arm veins, which enable the administration of anti-cancer drugs, collection of blood tests, and delivery of supportive therapies.

Study details
Participants in this study will be randomly allocated (by chance) into one of two groups. Participants in one group will have their CVAD locked with 0.9% Sodium Chloride, whilst participants in the other group will have theirs locked with heparinised saline. Duration of study enrollment will be capped at four weeks.

All participants will be monitored throughout their enrolment in the study to determine any CVAD blockages (known as occlusions), or other adverse events such as venous thrombosis and infection. We hope to determine whether a larger efficacy trial of these CVAD locking techniques is feasible and safe.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89082 0
Ms Rachel Edwards
Address 89082 0
Level 12b
Queensland Children's Hospital, 501 Stanley Street
South Brisbane, QLD, 4101
Country 89082 0
Australia
Phone 89082 0
+61 7 3068 1756
Fax 89082 0
Email 89082 0
rachel.edwards@health.qld.gov.au
Contact person for public queries
Name 89083 0
Ms Rachel Edwards
Address 89083 0
Level 12b
Queensland Children's Hospital, 501 Stanley Street
South Brisbane, QLD, 4101
Country 89083 0
Australia
Phone 89083 0
+61 7 3068 1756
Fax 89083 0
Email 89083 0
rachel.edwards@health.qld.gov.au
Contact person for scientific queries
Name 89084 0
Ms Rachel Edwards
Address 89084 0
Level 12b
Queensland Children's Hospital, 501 Stanley Street
South Brisbane, QLD, 4101
Country 89084 0
Australia
Phone 89084 0
+61 7 3068 1756
Fax 89084 0
Email 89084 0
rachel.edwards@health.qld.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
Individual patient data is not available
What supporting documents are/will be available?
No other documents available
Summary results
No Results