Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
Please note the ANZCTR will be unattended on Monday the 7th of October for the Labour Day public holiday.
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
Download to PDF
Trial registered on ANZCTR
Registration number
ACTRN12622000499785
Ethics application status
Approved
Date submitted
2/03/2022
Date registered
29/03/2022
Date last updated
6/07/2024
Date data sharing statement initially provided
29/03/2022
Type of registration
Prospectively registered
Titles & IDs
Public title
Preventing adverse events during paediatric cancer treatment: A multi-site hybrid randomised controlled trial of catheter lock solutions (The CLOCK trial)
Query!
Scientific title
Preventing adverse events during paediatric cancer treatment: A multi-site hybrid randomised controlled trial of catheter lock solutions (The CLOCK trial)
Query!
Secondary ID [1]
306380
0
Nil known
Query!
Universal Trial Number (UTN)
U1111-1273-3129
Query!
Trial acronym
The CLOCK trial
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Paediatric Cancer
325522
0
Query!
Central vascular access device (CVAD) related adverse events
325523
0
Query!
Condition category
Condition code
Cancer
322602
322602
0
0
Query!
Any cancer
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Intervention: KiteLock - 4% Tetrasodium-EDTA T-EDTA) Locking volumes will vary depending on the catheter type: 1-2 mL catheter lumen for PICC and tunnelled CVADs based on clinical discretion and 2mL for totally implanted CVADs.
The frequency of allocated lock solution will be administered depending on clinical requirement (i.e. if the CVAD is de-accessed for greater than 6 hours), or during routine CVAD management procedures (e.g., needleless connector changes, totally implanted device needling and flushing, administration set changes) with a maximum of one dose per 24 hours and a minimum of one dose every 8 weeks where the device is not in use. Clinicians (nursing and medical) will be administering the locking solution as per routine patient care, not research/trial staff.
The intervention will be administered from subject recruitment up until catheter removal or for a maximum of 3 months (whichever occurs first).
Intervention fidelity will be promoted through electronic medication ordering sets (where available), participant information cards, and twice-weekly monitoring by research staff.
Query!
Intervention code [1]
322811
0
Prevention
Query!
Comparator / control treatment
Comparator/control treatment: Comparator 1:
Normal Saline (0.9% Sodium Chloride) 10ml for all catheter types.
Comparator/control treatment: Comparator 2: Sodium Heparin 50units/5mL will be used for Peripherally Inserted Central Catheters (PICC) and Tunnelled CVADs, and for totally implanted CVADs either Sodium Heparin 50units/5mL or 100units/mL will be used. The concentration of the solution is determined by the specific guidelines set by the hospitals and their standard operating procedures.
Locking volumes will vary depending on the catheter type: 1-2 mL catheter lumen for PICC and tunnelled CVADs based on clinical discretion and 2mL for totally implanted CVADs.
Query!
Control group
Active
Query!
Outcomes
Primary outcome [1]
330395
0
The primary outcome is a serious CVAD complication. This is defined as a composite of CVAD-associated bloodstream infection (CABSI), CVAD-associated thrombosis or CVAD occlusion during CVAD dwell or at removal.
i CVAD-associated bloodstream infection (BSI): A laboratory confirmed BSI where an eligible BSI organism is identified with CVAD in place for >2 consecutive calendar days on the day of the BSI (day of CVAD placement being Day 1) and the CVAD in place on the date of the event or the day before (see Centers for Disease Control and Prevention Device-associated Module BSI for full criteria), in addition to single positive blood cultures (SPBC) for common commensals where there is clinical intent to treat as CABSI (i.e. commencement of antibiotics). To be assigned by a blinded infectious disease specialist.
ii. CVAD-associated thrombosis: A symptomatic thrombosed CVAD vessel or fibrin sheath occluding lumen diagnosed via ultrasound or venography. ‘Symptomatic’ is defined by pain and/or swelling of the area drained by the veins where the device is placed, an increasing clinically obvious collateral network superficially in the region of the catheter, or occluded CVAD. To be assigned by blinded radiologist.
iii. CVAD occlusion: Complete injection and/or aspiration catheter occlusion of at least 1 CVAD lumen (assessed using the Catheter Injection and Aspiration (CINAS) classification system), requiring administration of thrombolytic agent, and/or visible split in the CVAD structure related to occlusion event
Query!
Assessment method [1]
330395
0
Query!
Timepoint [1]
330395
0
From recruitment until 24 hours following study completion (device removed, patient withdrawn or up to a maximum of 3 months post-enrolment).
Query!
Secondary outcome [1]
406074
0
CABSI: A laboratory-confirmed bloodstream infection ( BSI) where an eligible BSI organism is identified with CVAD in place for >2 consecutive calendar days on the day of the BSI (day of CVAD placement being Day 1) and the CVAD in place on the date of the event or the day before (see Centers for Disease Control and Prevention Device-associated Module BSI for full criteria). This is in addition to single positive blood cultures (SPBC) for common commensals where there is clinical intent to treat as CABSI (i.e. commencement of antibiotics), Reported proportionally and per 1,000 catheter days.
Query!
Assessment method [1]
406074
0
Query!
Timepoint [1]
406074
0
From recruitment until 24 hours following study completion (device removed, patient withdrawn, or up to a maximum of 3 months post-enrolment).
Query!
Secondary outcome [2]
406075
0
Centres of Disease Control and Prevention (CDC)/National Healthcare Safety Network (NHSN) CABSI only: A laboratory confirmed BSI where an eligible BSI organism is identified with CVAD in place for >2 consecutive calendar days on the day of the BSI (day of CVAD placement being Day 1) and the CVAD in place on the date of the event or the day before (see Centers for Disease Control and Prevention Device-associated Module BSI for full criteria); excluding single positive blood cultures (SPBC) for common commensals.
Query!
Assessment method [2]
406075
0
Query!
Timepoint [2]
406075
0
From recruitment until 24 hours following study completion (device removed, patient withdrawn, or up to a maximum of 3 months post-enrolment).
Query!
Secondary outcome [3]
406076
0
CVAD-associated thrombosis: A symptomatic thrombosed CVAD vessel or fibrin sheath occluding lumen diagnosed via ultrasound or venography. ‘Symptomatic’ is defined by pain and/or swelling of the area drained by the veins where the device is placed, an increasing clinically obvious collateral network superficially in the region of the catheter, or occluded CVAD. To be assigned by blinded radiologist and hematologist.
Query!
Assessment method [3]
406076
0
Query!
Timepoint [3]
406076
0
From recruitment until 24 hours following study completion (device removed, patient withdrawn, or up to a maximum of 3 months post-enrolment).
Query!
Secondary outcome [4]
406077
0
CVAD occlusion: Complete injection and/or aspiration catheter occlusion of at least 1 CVAD lumen (assessed using the Catheter Injection and Aspiration (CINAS) classification system), requiring administration of the thrombolytic agent, and/or visible split in the CVAD structure related to occlusion event.
Query!
Assessment method [4]
406077
0
Query!
Timepoint [4]
406077
0
From recruitment until 24 hours following study completion (device removed, patient withdrawn, or up to a maximum of 3 months post-enrolment).
Query!
Secondary outcome [5]
406078
0
CVAD failure: Cessation of CVAD function prior to completion of treatment, resulting CVAD removal and replacement intravenous (IV) access. This will be determined through direct observation, patient self-report or from medical records.
Query!
Assessment method [5]
406078
0
Query!
Timepoint [5]
406078
0
From recruitment until 24 hours following study completion (device removed, patient withdrawn or up to a maximum of 3 months post-enrolment).
Query!
Secondary outcome [6]
406079
0
Adverse events: Infusion reactions (e.g., allergy), accidental administration of lock, thrombocytopenia, hypocalcemia, and mortality. This will be determined through direct observation, participant self-report, and from medical records.
Query!
Assessment method [6]
406079
0
Query!
Timepoint [6]
406079
0
From recruitment until 24 hours following study completion (device removed, patient withdrawn or up to a maximum of 3 months post-enrolment).
Query!
Secondary outcome [7]
406080
0
Health-related quality of life (HR QoL): will be measured using the EQ-5D-Y tool
Query!
Assessment method [7]
406080
0
Query!
Timepoint [7]
406080
0
EQ-5D-Y will be administered by study staff within 48 hours of recruitment and then again at study completion (device removed, patient withdrawn, or up to a maximum of 3 months post-enrolment).
Query!
Secondary outcome [8]
406081
0
Health-related quality of life (HR QoL): will be measured using the Australian Hospital Patient Experience Question Set (AHPEQS)
Query!
Assessment method [8]
406081
0
Query!
Timepoint [8]
406081
0
AHPEQS will be administered by study staff at study completion (device removed, patient withdrawn, or up to a maximum of 3 months post-enrolment).
Query!
Secondary outcome [9]
406082
0
Healthcare costs: Estimate of direct product costs, healthcare resource utilisation, and complication-associated resource use. This will be determined by observing clinical practice for the management of complications, review of medical records, and consolidated via approximation of direct costs (via hospital purchasing departments).
Query!
Assessment method [9]
406082
0
Query!
Timepoint [9]
406082
0
On an individual participant level, healthcare costs will be measured from recruitment until 24 hours following study completion (device removed, patient withdrawn, or up to a maximum of 3 months post-enrolment).
Query!
Secondary outcome [10]
407845
0
Mortality: will be assessed through a review of participants' medical records.
Query!
Assessment method [10]
407845
0
Query!
Timepoint [10]
407845
0
Outcome will be measured at 1 and again at 5 years following study completion (device removed, patient withdrawn, or up to a maximum of 3 months post-enrolment)
Query!
Secondary outcome [11]
408044
0
Serious CVAD complications: will be assessed through a review of the participant's medical record.
Query!
Assessment method [11]
408044
0
Query!
Timepoint [11]
408044
0
Outcome will be measured at 1 and again at 5 years following study completion (device removed, patient withdrawn, or up to a maximum of 3 months post-enrolment)
Query!
Secondary outcome [12]
434138
0
Incidental asymptomatic VTE: An asymptomatic non occlusive filling defect or occluded CVAD vessel diagnosed via ultrasound, CT, MRI or venography, which was performed for other reasons. i.e. not clinical suspicion of thrombosis or occlusion.
Query!
Assessment method [12]
434138
0
Query!
Timepoint [12]
434138
0
From recruitment until 24 hours following study completion (device removed, patient withdrawn or up to a maximum of 3 months post-enrolment).
Query!
Eligibility
Key inclusion criteria
Children (<18 years) with an oncological or malignant haematological condition who have a CVAD in situ (including peripherally inserted central catheters [PICCs], tunnelled (cuffed or non-cuffed) [e.g. Hickman®; Becton Dickinson, US] and totally implanted [e.g. PORT-A-CATH®; Smith Medical, US] will be eligible for inclusion.
Query!
Minimum age
0
Days
Query!
Query!
Maximum age
18
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
- End-of-life pathway/measures at recruitment
- Pre-existing coagulopathic condition not related to current diagnosis or treatment (e.g. Haemophilia A and B or other factor deficiency; Immune Thrombocytopenic Purpura (ITP); Von Willebrand’s disease)
- Known allergy to heparin or T-EDTA
Query!
Study design
Purpose of the study
Prevention
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will be concealed by central randomisation by computer.
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be in a 3:2 ratio between the combined saline: T-EDTA groups, with randomly varied blocks of size 10 or 20 and stratification by: (i) health care facility; (ii) CVAD type (PICC, tunnelled CVAD, totally implanted CVAD) and (iii) duration of dwell since insertion (>= 8 weeks). Within the saline groups, there will be an even allocation to determine whether normal or heparin saline is allocated. The randomisation will be managed by Griffith Randomisation Service, which provides automated centralised randomisation for research studies, overseen by experienced statisticians, researchers, and with the support of Griffith Information Services. An automated 24-hour randomisation service will be available for investigators to use via a web portal.
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Not Applicable
Query!
Type of endpoint/s
Safety/efficacy
Query!
Statistical methods / analysis
Baseline characteristics for each of the groups will be descriptively presented using frequencies and percentages for categorical variables and means and standard deviations (or median and interquartile range if appropriate) for continuous variables. The primary analysis will compare between-group CVAD complications using mixed effects logistic regression with group (T-EDTA/saline) included as the fixed effect and child included as a random effect to account for re-recruitments from some participants. Effect estimates will be presented as both odds ratio and absolute risk difference with corresponding 95% confidence intervals. The key secondary analysis will examine CVAD complications between heparinised and normal saline. Secondary outcomes assessed using an interval scale will be analysed using mixed-effect linear regression models, dichotomous outcomes will be analysed using missed-effects logistic regression models, count outcomes will be analysed using mixed-effects Poisson regression, and time-to-event outcomes will be analysed using Cox proportional hazards regression with robust variance estimators. Sensitivity analyses to investigate the effect of re-recruitment will be conducted. The cause of any missing data will be assessed, and sensitivity analyses to investigate the potential impact of missingness will be undertaken using multiple imputation techniques if appropriate. Analysis will be ‘intention to treat’ with CVADs the unit of measurement. Sub-group analyses of the primary outcome will compare: totally implanted CVAD vs other CVAD; participant age (neonates/infants vs child/adolescent); past CABSI vs no past CABSI; first CVAD vs subsequent CVAD; and newly inserted CVAD vs >1 month dwell. A per-protocol analysis will assess the effect of protocol violations (i.e. administration of non-randomised catheter lock solution). Analyses will be led by CI Ware (supported by statistician RA). A per-protocol analysis will assess the effect of protocol violations (i.e. administration of non-randomised catheter lock solution). For the primary outcome P-values =0.05 will be considered significant.
Query!
Recruitment
Recruitment status
Recruiting
Query!
Date of first participant enrolment
Anticipated
1/06/2022
Query!
Actual
5/09/2022
Query!
Date of last participant enrolment
Anticipated
30/04/2026
Query!
Actual
Query!
Date of last data collection
Anticipated
31/12/2030
Query!
Actual
Query!
Sample size
Target
720
Query!
Accrual to date
167
Query!
Final
Query!
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Query!
Recruitment hospital [1]
21679
0
Queensland Children's Hospital - South Brisbane
Query!
Recruitment hospital [2]
21680
0
Sydney Children's Hospital - Randwick
Query!
Recruitment hospital [3]
21681
0
The Royal Childrens Hospital - Parkville
Query!
Recruitment hospital [4]
21682
0
Gold Coast University Hospital - Southport
Query!
Recruitment hospital [5]
21683
0
Sunshine Coast University Hospital - Birtinya
Query!
Recruitment hospital [6]
23502
0
Monash Children’s Hospital - Clayton
Query!
Recruitment postcode(s) [1]
36726
0
2031 - Randwick
Query!
Recruitment postcode(s) [2]
36727
0
3052 - Parkville
Query!
Recruitment postcode(s) [3]
38910
0
3168 - Clayton
Query!
Recruitment postcode(s) [4]
36722
0
4101 - South Brisbane
Query!
Recruitment postcode(s) [5]
36728
0
4215 - Southport
Query!
Recruitment postcode(s) [6]
36729
0
4575 - Birtinya
Query!
Recruitment outside Australia
Country [1]
24560
0
New Zealand
Query!
State/province [1]
24560
0
Auckland
Query!
Funding & Sponsors
Funding source category [1]
310731
0
Charities/Societies/Foundations
Query!
Name [1]
310731
0
Cancer Council Queensland
Query!
Address [1]
310731
0
553 Gregory Terrace
Fortitude Valley QLD 4006
PO Box 201 Spring Hill QLD 4004
Query!
Country [1]
310731
0
Australia
Query!
Primary sponsor type
University
Query!
Name
University of Queensland
Query!
Address
Cumbrae Stewart Building
72 Research Road
The University of Queensland
ST LUCIA QLD 4072
Query!
Country
Australia
Query!
Secondary sponsor category [1]
312412
0
None
Query!
Name [1]
312412
0
Query!
Address [1]
312412
0
Query!
Country [1]
312412
0
Query!
Ethics approval
Ethics application status
Approved
Query!
Ethics committee name [1]
310307
0
Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee
Query!
Ethics committee address [1]
310307
0
Human Research Ethics Committee Centre for Children’s Health Research Queensland Children’s Hospital Precinct Level 7, 62 Graham Street South Brisbane QLD 4101
Query!
Ethics committee country [1]
310307
0
Australia
Query!
Date submitted for ethics approval [1]
310307
0
17/01/2022
Query!
Approval date [1]
310307
0
25/02/2022
Query!
Ethics approval number [1]
310307
0
HREC/22/QCHQ/81744
Query!
Ethics committee name [2]
310747
0
The University of Queensland Research Ethics and Integiry
Query!
Ethics committee address [2]
310747
0
St Lucia, QLD 4072 Australia
Query!
Ethics committee country [2]
310747
0
Australia
Query!
Date submitted for ethics approval [2]
310747
0
02/03/2022
Query!
Approval date [2]
310747
0
08/03/2022
Query!
Ethics approval number [2]
310747
0
2022/HE000196
Query!
Summary
Brief summary
Across Australia every year, children undergoing treatment for cancer experience more than 250 bloodstream infections, 70 deep vein thromboses, and 300 blockages - all caused from their central line. This central venous access device (CVAD) is vital as it administers treatments such as chemotherapy drugs and supportive therapies including blood transfusions and antibiotics, however we need to do more to prevent harm. When the CVAD is not in use, it is locked it with fluid. This fluid lock is an opportunity to prevent CVAD-associated complications. Therefore, the aim of this study is so compare the safety and effectiveness of the locking solutions KiteLock (Tetrasodium-EDTA (T-EDTA)) and heparinised saline with normal saline, which is routinely used in as part of standard care. Who is it for? You may be eligible for this study if you are aged younger than 18 years, have been diagnosed with an oncological or malignant haematological condition, and have a CVAD in place. Study details Participants will be randomised (i.e. allocated by chance) to receive either the normal saline (10ml of 0.9% sodium chloride), heparinised saline (1-2ml of sodium heparin 10units/ml or 100units/ml depending on the device and standard operating procedures), or KiteLock (1-2ml of 4% T-EDTA) administered into the lumen of the CVAD. The solution will be administered at a frequency based on clinical requirement (i.e. if the CVAD is de-accessed), plus during routine management procedures (e.g. needleless connector changes, totally implanted device needling, line cares) with a maximum of one dose per 24 hours. This will continue until the device is removed, the participant withdraws from the study, for up to a maximum of 3 months post-enrolment. Throughout this study period, participants may be assessed by their treating clinicians for bloodstream infections using blood cultures, for CVAD-associated thrombosis (i.e. blood clots) with ultrasound or venography, for blockages of the CVAD with a test of injection and/or aspiration catheter occlusion, and for CVAD failure requiring removal. Participants will also be monitored for any adverse events, with a research nurse contacting them twice weekly across the study period. A questionnaire assessing health-related quality of life will be given to participants at the trial commencement and completion. Participants will additionally be followed up at 1 and 5 years after study completion (using medical records only) to assess for any serious CVAD complications, and for any cause of death. It is hoped that this study may help to identify the locking solution with the least complications and adverse effects, in order to prevent harm in children with a CVAD undergoing treatment for cancer.
Query!
Trial website
https://nmsw.uq.edu.au/research/paediatric-nursing-and-patient-safety/preventing-adverse-events-during-paediatric-cancer-treatment-multi-site-hybrid-randomised-controlled-trial
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
117202
0
Prof Amanda Ullman
Query!
Address
117202
0
Level 7, Centre for Children's Health Research, 62 Graham St, South Brisbane QLD 4101
Query!
Country
117202
0
Australia
Query!
Phone
117202
0
+61730697238
Query!
Fax
117202
0
Query!
Email
117202
0
a.ullman@uq.edu.au
Query!
Contact person for public queries
Name
117203
0
Amanda Ullman
Query!
Address
117203
0
Level 7, Centre for Children's Health Research, 62 Graham St, South Brisbane QLD 4101
Query!
Country
117203
0
Australia
Query!
Phone
117203
0
+61730697238
Query!
Fax
117203
0
Query!
Email
117203
0
a.ullman@uq.edu.au
Query!
Contact person for scientific queries
Name
117204
0
Amanda Ullman
Query!
Address
117204
0
Level 7, Centre for Children's Health Research, 62 Graham St, South Brisbane QLD 4101
Query!
Country
117204
0
Australia
Query!
Phone
117204
0
+61730697238
Query!
Fax
117204
0
Query!
Email
117204
0
a.ullman@uq.edu.au
Query!
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Query!
No/undecided IPD sharing reason/comment
Data will only be available to the site staff and project manager unless required by legislative or regulatory agencies and the HRECs.
Query!
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.
Download to PDF