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Trial registered on ANZCTR


Registration number
ACTRN12619000022167
Ethics application status
Approved
Date submitted
17/12/2018
Date registered
9/01/2019
Date last updated
3/10/2024
Date data sharing statement initially provided
9/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparing peripherally inserted central catheter (PICC) materials to prevent infections and blood clots: a randomized controlled trial
Scientific title
Randomised controlled trial in adults and children of anti-thrombogenic PICCs, and antiseptic PICCs, in comparison to polyurethane PICCs (standard care), to prevent PICC failure and complications.
Secondary ID [1] 296895 0
Nil known
Universal Trial Number (UTN)
U1111-1225-6916
Trial acronym
PICNIC
Linked study record
Nil

Health condition
Health condition(s) or problem(s) studied:
Blood clots 310845 0
Hospital-acquired infection 310865 0
Condition category
Condition code
Infection 309518 309518 0 0
Studies of infection and infectious agents
Anaesthesiology 309519 309519 0 0
Other anaesthesiology
Cardiovascular 309535 309535 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
At time of PICCs are indicated for insertion (as identified by screening of PICC insertion theatre and medical imaging lists), patients will be randomised to receive either:
Arm 1) Anti-thrombogenic PICC (size decided by clinician due to vascular size and treatment requirements) BioFlo PICC with PASV (by Angiodynamics®)
Arm 2) Anti-microbial (chlorhexidine gluconate [CHG]) PICC (size decided by clinician due to vascular size and treatment requirements) Arrowg+ard Blue Advance PICC (by Teleflex®).

The allocated PICCs will be provided by the research nurses to the PICC inserter (i.e. physician or nurse; not research staff) immediately prior to PICC inserting procedure. The research nurse will then assess the appropriate PICC has been placed within 24 hours of insertion. The PICCs will remain insitu for the entire treatment duration, as clinically indicated (i.e. the discretion of the clinician).

The haematology substudy will evaluate the same intervention products and patients.
Intervention code [1] 313171 0
Treatment: Devices
Comparator / control treatment
Standard care: Polyurethane PICC (size decided by clinician due to vascular size and treatment requirements) Bard PowerPICC*
*In instances where the hospital does not use this product, an equivalent Polyurethane PICC may be used provided it is uncoated, has an external clamp, and is pressure injectable. Any variances from the Bard PowerPICC will be collected.
Control group
Active

Outcomes
Primary outcome [1] 308469 0
PICC failure: composite primary outcome of non-infective (venous thrombosis, breakage, occlusion) and infective complications (PICC-associated bloodstream infection, local infection) (all defined below) severe enough to cause cessation of PICC function prior to therapy completion. Each of these complications will be assessed via a review of medical records (including pathology results) and patient assessment.
Timepoint [1] 308469 0
At PICC failure, completion of treatment, or 8 weeks after PICC insertion (which ever is soonest).
Secondary outcome [1] 355068 0
PICC-associated bloodstream infection (BSI): A laboratory confirmed BSI where an eligible BSI organism is identified with PICC in place for >2 consecutive calendar days on the day of the BSI (day of PICC placement being Day 1) and the PICC in place on the date of the event or the day before (see CDC Device-associated Module BSI for full criteria), confirmed by a blinded infectious disease specialist, using de-identified data.
Timepoint [1] 355068 0
At PICC failure, completion of treatment, or 8 weeks after PICC insertion (which ever is soonest).
Secondary outcome [2] 355069 0
Local infection: Clinical signs of local venous infection at the PICC insertion site (e.g. purulent drainage), confirmed with a positive (>15cfu) swab or catheter tip, but with negative or no blood culture (see CDC VASC definition for full criteria) confirmed by a blinded infectious disease specialist.
Timepoint [2] 355069 0
At PICC failure, completion of treatment, or 8 weeks after PICC insertion (which ever is soonest).
Secondary outcome [3] 355070 0
Occlusion: Complete: at least 1 lumen cannot be flushed or aspirated, or resolved post thrombolytic dwell, Partial: decreased ability of at least 1 lumen to either infuse blood or fluid and/or withdraw blood or fluid from at least 1 lumen despite the use of thrombolytic.
Timepoint [3] 355070 0
At PICC failure, completion of treatment, or 8 weeks after PICC insertion (which ever is soonest).
Secondary outcome [4] 355071 0
Breakage: Split in PICC material with leakage or radiographic evidence of extravasation/infiltration into tissue, in a PICC flushed to clear thrombosis or occlusion.
Timepoint [4] 355071 0
At PICC failure, completion of treatment, or 8 weeks after PICC insertion (which ever is soonest).
Secondary outcome [5] 355072 0
Venous thrombosis: Ultrasound/venographic/image confirmed thromboses occurring within the same vessel as the PICC location within one week of PICC removal, in a symptomatic patient (pain, swelling,), confirmed by blinded radiologist.
Timepoint [5] 355072 0
At PICC failure, completion of treatment, or 8 weeks after PICC insertion (which ever is soonest).
Secondary outcome [6] 355073 0
All-cause PICC complication during treatment: (as above, but may/may not require PICC removal). A composite of thrombotic and infective PICC-associated complications (thrombotic complication, infective complication, individual complications, and adverse events). Collected via patient assessment, and medical record (including pathology result) review
Timepoint [6] 355073 0
At PICC failure, completion of treatment, or 8 weeks after PICC insertion (which ever is soonest).
Secondary outcome [7] 355074 0
Non-infective complication: composite of venous thrombosis, occlusion and breakage at any stage of PICC dwell. Collected via patient assessment, and medical record (including pathology result) review
Timepoint [7] 355074 0
At PICC failure, completion of treatment, or 8 weeks after PICC insertion (which ever is soonest).
Secondary outcome [8] 355075 0
Infective complication: composite of PICC-associated BSI and local infection at any stage during the PICC dwell. Collected via patient assessment, and medical record (including pathology result) review
Timepoint [8] 355075 0
At PICC failure, completion of treatment, or 8 weeks after PICC insertion (which ever is soonest).
Secondary outcome [9] 355076 0
Adverse events: Any local or systemic allergic reaction (e.g., pruritus), pain, mortality. Collected via patient assessment, and medical record (including pathology result) review
Timepoint [9] 355076 0
At PICC failure, completion of treatment, or 8 weeks after PICC insertion (which ever is soonest).
Secondary outcome [10] 355077 0
PICC dwell time: hours from insertion until removal. Collected via patient assessment, and medical record (including pathology result) review
Timepoint [10] 355077 0
At PICC failure, completion of treatment, or 8 weeks after PICC insertion (which ever is soonest).
Secondary outcome [11] 355078 0
Staff satisfaction: using 0-10 numeric rating scales. Collected at PICC insertion and removal through discussion.
Timepoint [11] 355078 0
Collected at PICC insertion and study end.
Secondary outcome [12] 355079 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 [12] 355079 0
At PICC failure, completion of treatment, or 8 weeks after PICC insertion (which ever is soonest).
Secondary outcome [13] 355080 0
Sub-study: Bacterial colonisation and CHG resistance: PICC tips removed due to suspected infection and a control group of tips; will be cultured using the roll-plating method on blood agar, with quantification of colony forming units, species identification using Vitek-MS (BioMerieux) and susceptibility testing for a standard panel of antibiotics by Vitek 2 automated broth microdilution. In addition, CHG tolerance will be tested by determining minimum inhibitory concentrations (MICs) against organisms isolated from PICC tips using broth microdilution (with an MIC less than or equal to 4 mg/L defining reduced susceptibility to CHG). Genes known to be associated with CHG tolerance (e.g. qacA/B and smr) will be confirmed by PCR. In patients with suspected CASBI and the same species grown in PICC tip cultures, organisms isolated from both blood and tip cultures will have DNA extracted and whole genome sequencing performed on the Illumina MiniSeq platform. Raw reads will be trimmed, checked for quality, assembled and analysed using a custom pipeline to confirm species identification, define in silico multi-locus sequence type (MLST) and detect the presence of any antibiotic resistance genes. Other genes known to be associated with CHG tolerance and biofilm formation will be sought by BLAST against the assembled genomes. To confirm whether PICC tip and blood culture isolates are clonal, core genome differences between blood and PICC tip isolates are being determined by comparing single nucleotide polymorphisms.
Timepoint [13] 355080 0
At diagnosis of PICC-associated infection.
Secondary outcome [14] 355081 0
Substudy: Haematological activation: Composite analysis of comparative clotting times (PT and APTT), platelet activation, aggregation and platelet count. These data will be assessed via blood samples taken at PICC insertion and study end.
Timepoint [14] 355081 0
At PICC insertion and study end (i.e. failure, completion of treatment, or 8 weeks after PICC insertion, which ever is soonest).
Secondary outcome [15] 355136 0
Patient/parent satisfaction using 0-10 numeric rating scales. Collected at PICC removal.
Timepoint [15] 355136 0
At PICC failure, completion of treatment, or 8 weeks after PICC insertion (which ever is soonest).
Secondary outcome [16] 440409 0
Health-related quality of life, measured , as EuroQol Five Dimension multi attribute utility instrument (including EQ-5D-Y for 8-17 year olds)
Timepoint [16] 440409 0
Secondary outcome [17] 440410 0
Health-related quality of life, measured , as EuroQol Five Dimension multi attribute utility instrument (including EQ-5D-Y for 8-17 year olds)
Timepoint [17] 440410 0
At PICC failure, completion of treatment, or 8 weeks after PICC insertion (which ever is soonest)

Eligibility
Key inclusion criteria
Require PICC insertion for fluid or medication
Informed consent
Vascular size sufficient to support 4fr PICC or larger
Minimum age
1 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous enrolment in the current study
Current catheter-related bloodstream infection
Thrombosis in vein where PICC is to be inserted
Non-English speaking without an interpreter
Known sensitivity to any of the study products including CHG
Currently enrolled in conflicting study
Added since trial commencement: Admitted for COVID-19, or to a designated COVID-19 unit/facility

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 research nurse (ReN) will screen patients daily (screening Log kept). The study ReN will gain informed consent and perform randomisation. The RN will have the study products in pre-packs and liaise closely with the ordering and inserting clinician. All eligible patients will be approached for written informed consent by the ReN or inserter. If this is given, the staff member uses a centralised web-based randomisation service. Allocation is fully concealed until the patient is randomised.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The ReNs will randomise patients via a central web-based service immediately prior to each PICC insertion to ensure allocation concealment until study entry. Randomisation (patient level) will be a 1:1:1 ratio between groups with randomly varied block sizes (up to 20) and stratification by: (i) hospital and (ii) hypercoagulable state (Adults: high risk of thrombosis as per Michigan Risk Score; Paediatrics; previous thrombosis or active cancer).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Superiority
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The key presentation principle is complete-case intention to treat. All participants who were randomized and have evaluable data for the endpoint under investigation will be analysed in the study arm to which they were randomized.

Per protocol analysis will be performed to test the sensitivity of the results to noncompliance. In per-protocol analyses all participants who were randomized, were treated with the device they were randomized to receive and have evaluable data for the endpoint under investigation will be analyzed. in the study arm to which they were randomized. The number of missing observations for each primary and secondary outcome will be reported by study group. If the proportion of missing observations is non-trivial (>5%), consideration will be given to the possible introduction of compliance and attrition bias. The cause of any missing data will be assessed. Sensitivity analyses to investigate the potential impact of stratification variables and missing data will be undertaken by (i) adjusting regression models for covariables included in stratification and (ii) imputing missing data using multiple imputation methods and re-running regression models if appropriate. Any multiple imputation will occur using chained equation methods.

Continuous data will be summarized descriptively using either mean and standard deviation (SD) or median and interquartile range (IQR), depending on the distribution of the variable of interest. Categorical data will be presented as frequencies and percentages. A significance level of alpha = 0.035 will be used to evaluate statistical significance for the primary outcome.

The number and proportion of device’s which experience the primary outcome PICC failure (fail/not fail) will be calculated per group. Between-group differences (hydrophobic vs standard polyurethane and CHG vs standard polyurethane) will be analyzed using logistic regression with study group as the main effect. The result will be presented as an odds ratio (95% CI); P value. To test the sensitivity of the primary outcome between-group comparisons will be stratified by site in order to investigate the level of variability across sites.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/06/2019
Actual
8/11/2019
Date of last participant enrolment
Anticipated
31/12/2022
Actual
23/12/2022
Date of last data collection
Anticipated
31/12/2022
Actual
12/05/2023
Sample size
Target
1098
Accrual to date
Final
1098
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 12763 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 12764 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [3] 12765 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 25192 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 25193 0
4101 - South Brisbane
Recruitment postcode(s) [3] 25194 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 301466 0
Government body
Name [1] 301466 0
National Health and Medical Research Council (NHMRC)
Country [1] 301466 0
Australia
Primary sponsor type
Government body
Name
NHMRC
Address
Research Committee Secretariat NHMRC
GPO Box 1421
Canberra ACT 2601
Country
Australia
Secondary sponsor category [1] 301157 0
None
Name [1] 301157 0
Nil
Address [1] 301157 0
N/A
Country [1] 301157 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302205 0
Children's Health Queensland Hospital and Health Service HREC
Ethics committee address [1] 302205 0
Level 7, Centre for Children’s Health Research
Queensland Children’s Hospital Precinct
62 Graham Street, South Brisbane QLD 4101
Ethics committee country [1] 302205 0
Australia
Date submitted for ethics approval [1] 302205 0
23/11/2018
Approval date [1] 302205 0
21/01/2019
Ethics approval number [1] 302205 0
HREC/2018/QCHQ/48682 

Summary
Brief summary
Every year, approximately 140,000 Peripherally Inserted Central Catheters (PICCs) are inserted in Australia in both children and adults to provide a route of administration for anti-cancer therapies, nutrition and antimicrobials for acute and chronically ill patients. This is despite 30% of PICCs failing prior to completion of treatment due to: deep vein thrombosis (DVT), occlusion, breakage or catheter-associated bloodstream infection (CABSI) including Staphylococcus aureus BSI (SAB).

The proposed project will test three different Peripherally Inserted Central Catheter materials (two novel catheters and one standard care) to determine efficacy in preventing PICC complication and failure.

The project is to be completed across The Queensland Children’s, Royal Brisbane and Women’s and Princess Alexandra Hospitals. Our investigator group consists of experienced researchers and clinicians from each of these hospitals areas as well as the University of Queensland and Griffith University.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89458 0
Prof Amanda Ullman
Address 89458 0
School of Nursing, Midwifery and Social Work
The University of Queensland
Brisbane QLD 4072 Australia
Country 89458 0
Australia
Phone 89458 0
+61733652068
Fax 89458 0
Email 89458 0
[email protected]
Contact person for public queries
Name 89459 0
Amanda Ullman
Address 89459 0
School of Nursing, Midwifery and Social Work
The University of Queensland
Brisbane QLD 4072 Australia
Country 89459 0
Australia
Phone 89459 0
+61733652068
Fax 89459 0
Email 89459 0
[email protected]
Contact person for scientific queries
Name 89460 0
Amanda Ullman
Address 89460 0
School of Nursing, Midwifery and Social Work
The University of Queensland
Brisbane QLD 4072 Australia
Country 89460 0
Australia
Phone 89460 0
+6173365 2068
Fax 89460 0
Email 89460 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Still in discussions with HREC regarding 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
SourceTitleYear of PublicationDOI
EmbasePeripherally Inserted Central catheter iNnovation to reduce Infections and Clots (the PICNIC trial): A randomised controlled trial protocol.2021https://dx.doi.org/10.1136/bmjopen-2020-042475
N.B. These documents automatically identified may not have been verified by the study sponsor.