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Trial registered on ANZCTR


Registration number
ACTRN12616000315415
Ethics application status
Approved
Date submitted
8/03/2016
Date registered
10/03/2016
Date last updated
7/12/2018
Date data sharing statement initially provided
7/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of alternative dressing and securement options for peripherally inserted central catheters (PICCs) in the prevention of PICC failure and infection. the PISCES Trial
Scientific title
Factorial, superiority, randomised controlled trial testing alternative (1) dressing (chlorhexidine impregnated disc) and (2) securement (integrated securement device) to prevent PICC failure and catheter associated bloodstream infection in cancer patients: the PISCES Trial.
Secondary ID [1] 288604 0
None
Universal Trial Number (UTN)
Trial acronym
The PISCES trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peripherally inserted central catheter (PICC) failure 297746 0
Catheter-associated bloodstream infection (CABSI) 297747 0
Condition category
Condition code
Public Health 297928 297928 0 0
Health service research
Infection 297929 297929 0 0
Studies of infection and infectious agents
Cancer 298116 298116 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants in this study will have peripherally inserted central catheters (PICCs) used in cancer care services departments, including adult and paediatric populations. Consenting patients will have their PICC dressed and secured with one of the following randomly assigned options:
Arm 1 (Control): Securement device (SSD) and simple polyurethane dressing (SP).
Arm 2: Securement device; simple polyurethane dressing and a chlorhexidine impregnated (CHG) disc.
Arm 3: Integrated securement device. Integrated securement devices (ISDs) are simple polyurethane dressings which combine both SP and SD into one product.
Arm 4: Integrated securement device and a chlorhexidine impregnated disc.

Patients will be monitored daily to ensure protocol adherence. The randomly allocated dressing will be applied regularly every 7 days or as clinically indicated until either removal of device or until 8 weeks after device insertion (at which point the allocated dressing/securement will be removed and replaced with standard care).
Intervention code [1] 293997 0
Treatment: Devices
Intervention code [2] 293998 0
Prevention
Comparator / control treatment
Arm 1 (Control): Securement device (SSD) and simple polyurethane dressing (SP).
Control group
Active

Outcomes
Primary outcome [1] 297454 0
Dressing Hypothesis: Catheter-associated bloodstream infection, as defined by CDC NHSN criteria. This will be confirmed by a blinded infectious diseases specialist using de-identified clinical and microbiological data.
Timepoint [1] 297454 0
48 hours after device removal, or patient removal from study (8 week after device insertion).
Primary outcome [2] 297455 0
Securement Hypothesis: Peripherally inserted central catheter (PICC) failure (composite measure of any reason for unplanned PICC removal, including infection, occlusion, dislodgement and venous thrombosis). This outcome will be assessed by a review of patient medical records.
Timepoint [2] 297455 0
At time of PICC removal or patient removal from study (8 week after device insertion).
Secondary outcome [1] 321085 0
Local infection: defined as purulent phlebitis confirmed with a positive (>15cfu) PICC tip culture (without confirmed CABSI).
Timepoint [1] 321085 0
48 hours after device removal, or patient removal from study (8 week after device insertion).
Secondary outcome [2] 321086 0
Occlusion: defined as =>1 lumens cannot be flushed or aspirated.
Timepoint [2] 321086 0
At time of PICC removal or patient removal from study (8 week after device insertion).
Secondary outcome [3] 321087 0
Fracture: Visible split in PICC material with leakage or radiographic evidence of extravasation/infiltration into tissue.
Timepoint [3] 321087 0
At time of PICC removal or patient removal from study (8 week after device insertion).
Secondary outcome [4] 321088 0
Dislogement:
Partial - Change in PICC length from hub to tip, as measured by marking closest to hub, or PICC removal because tip is no longer in superior vena cava (diagnosed by Xray/leakage from site on injection/infusion).
Total - PICC body completely leaves the vein.
Timepoint [4] 321088 0
At time of PICC removal or patient removal from study (8 week after device insertion).
Secondary outcome [5] 321089 0
Venous Thrombosis:
Suspected - Too painful for patient to tolerate
Confirmed - Ultrasound/venographic confirmed thrombosed vessel at the PICC site in a symptomatic patient, or a symptomatic patient with a thrombus/fibrin sheath occluding 1 or more lumen at PICC removal.
Timepoint [5] 321089 0
At time of PICC removal or patient removal from study (8 week after device insertion).
Secondary outcome [6] 321090 0
Patient Safety: Evidence of skin rash, skin tears, blisters, pruritis, local or systemic allergic reactions.
Timepoint [6] 321090 0
At time of PICC removal or patient removal from study (8 week after device insertion).
Secondary outcome [7] 321091 0
Costs: Direct costs to the hospital for the total episode of care, including costs of device and dressing replacement in addition to the costs of treating PICC complications.
Timepoint [7] 321091 0
48 hours after device removal, or patient removal from study (8 week after device insertion).
Secondary outcome [8] 321092 0
Dressing/securement failure: Replacement < 7 days for loose, missing, bloodstained, diaphoresis or secretion soaked dressings.
Timepoint [8] 321092 0
At seven days after each dressing application, until the device is removed or the patient is removed (8 weeks after device insertion).
Secondary outcome [9] 321093 0
PICC dwell time and dressing dwell time: Time in hours/days from insertion/application until device/dressing removal.
Timepoint [9] 321093 0
PICC dwell time: At time of PICC removal.
Dressing dwell time: At time of PICC removal or at time of patient removal from study (8 week after device insertion).
Secondary outcome [10] 321094 0
Device/skin site colonisation: defined as >15 colony forming units (cfu) growth from skin or tip.
Timepoint [10] 321094 0
At the time of dressing change or device removal.
Secondary outcome [11] 321095 0
Patient/parent and staff acceptability: using 0-10 numerical rating scales.
Timepoint [11] 321095 0
At time of PICC removal or patient removal from study (8 week after device insertion).
Secondary outcome [12] 326522 0
Reversible complications: defined as complications related to the PICC which are treated effectively and do not result in device removal. This includes reversible occlusion, device fracture or leakage, partial dislodgement, and local infection.
Timepoint [12] 326522 0
Daily until time of PICC removal or patient removal from study (8 week after device insertion).

Eligibility
Key inclusion criteria
1. Cancer patient (haematological malignancy or solid tumour)
2. PICC scheduled/expected use >24 hours
3. Informed written consent

To ensure generalisability, PICCs inserted after-hours will also be studied if the following additional inclusion criteria are met:
4. <24 hours since PICC insertion
5. The treating clinician agree it is safe to replace the initial dressing/securement.
Minimum age
No limit
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Other CVC insertion (not PICC)
2. Current bloodstream infection (<48 hours)
3. PICC inserted through burned or diseased skin
4. Known allergy to any study product
5. Non-English speaking patients without interpreter
6, CHG disc/dressing already in place.

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)
Research nurses (RNs) will screen patients 5 days per week (Monday to Friday) and liaise heavily with the staff responsible for inserting the majority of PICCs (medical imaging, intensive care, nurse PICC inserters). All eligible patients (or their representative) will be approached for written informed consent by the RN. If this is given, the staff member will log on to a web-based, independent randomisation service customised for the trial and be advised of group allocation. Allocation is fully concealed until the patient is randomised.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated. Randomisation will be stratified by (i) hospital site, (ii) cancer type (haematological malignancy or solid tumour), (iii) inpatient/outpatient, and (iii) first/subsequent PICC . Randomisation will be in a 1:1:1:1 ratio between the four study groups. Block randomisation will be used with random variation in block size.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Factorial
Other design features
Participants will be allocated to:
1. Standard care (no intervention): SP+SD (no CHG disc)
2. One intervention: a. SP+SD+CHG disc; or b. ISD (no CHG disc)
3. Both interventions: ISD+CHG disc.

Blinded microbiologist and infectious diseases physicians will assign infectious outcomes (including Primary Outcome (1) catheter-associated bloodstream infection).
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
To test the dressing hypothesis: Baseline CABSI is 8% for SP with no CHG disc, and we predict this incidence in the combined no-CHG disc groups. We hypothesise incidence in the combined CHG disc groups of 4% based on the RR of 0.52 previously associated with CHG-discs. An inequality test of two proportions calculated that 602 patients/group were needed to detect reduced CABSI from 8% to 4% with 90% power (p=0.05, 1-sided, PASS) (602 CHG disc; 602 no CHG disc).

To test the securement hypothesis: We anticipate PICC failure of 26% in the SD groups, based on the RSVP Trial (funded APP1008428), and a pilot PISCES Trial. We hypothesise 19% failure in the combined ISD groups i.e. RR=0.73. This was the mid-point between RR=0.84 associated with ISD vs SP+Sutures in PICCs, and the pooled RR=0.63 seen in our pilot trials. Conservatively, we expect a smaller effect size than our pilot trials. An inequality test of two proportions calculated a sample of 608 patients/group (608 ISD; 608 SD) is needed to compare 26% and 19% PICC failure with 90% power (p=0.05, 1-sided, PASS).
As this trial has a factorial design, we will use the comparison that needs the larger sample, thus 608 per group plus 2% for potential attrition, so 620/group, and split these so that each of the 4 study groups will have 310 devices. Thus the total trial will be 1240 devices, which can test both hypotheses.

Analysis will be by ‘intention to treat’ with the patient, the unit of randomisation and PICCs, the unit of measurement. Pairwise, sequential comparisons will be made for CHG vs. SP, and ISD vs. SD. Baseline group comparisons will be by clinical parameters. Relative incidence rates of PICC failure/100 devices and /1,000 PICC days (95% CIs) will summarise treatment impact, with group differences tested. Kaplan-Meier survival curves (and log rank M-H test) will compare failure rates over time. Secondary endpoints will be compared between groups using parametric/nonparametric techniques. The proportional hazards assumption will be checked, and Cox regression will test the effect of group, patient, device and clinical variables on failure, and assess for an interaction effect. Regression models will allow for stratification factors and clustering by ward (gamma shared frailty). Subgroup analysis (a priori) will test for differences within and between strata. Data will be exported into PASW after cleaning outlying figures, missing and implausible data, with all attempts to collect the primary endpoint. Missing data will be modelled for best- and worst-case outcomes, with multiple imputation considered if data is missing at random. A per-protocol analysis will assess the effect of protocol violations. P-values <0.05 will be statistically 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] 5331 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [2] 5332 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 5333 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 12793 0
4006 - Herston
Recruitment postcode(s) [2] 12794 0
4101 - South Brisbane
Recruitment postcode(s) [3] 12795 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 292970 0
Government body
Name [1] 292970 0
National Health and Medical Research Council
Address [1] 292970 0
GPO Box 1421
Canberra, ACT 2601
Country [1] 292970 0
Australia
Primary sponsor type
University
Name
Griffith University
Address
Nathan Campus
170 Kessels Road,
Nathan QLD, 4111
Country
Australia
Secondary sponsor category [1] 291742 0
None
Name [1] 291742 0
Address [1] 291742 0
Country [1] 291742 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294469 0
Children's Health Queensland Hospital and Health Service Human Research Ethics Committee
Ethics committee address [1] 294469 0
Level 7, Centre for Children's Health Research
Lady Cilento Hospital Precinct
62 Graham Street,
South Brisbane, QLD, 4101
Ethics committee country [1] 294469 0
Australia
Date submitted for ethics approval [1] 294469 0
27/11/2015
Approval date [1] 294469 0
14/01/2016
Ethics approval number [1] 294469 0
HREC/15/QRCH/241
Ethics committee name [2] 294470 0
Griffith University Human Research Ethics Committee
Ethics committee address [2] 294470 0
Human Research Ethics and Integrity
Office for Research
Bray Centre, Nathan Campus
Griffith University
170 Kessels Road
Nathan, QLD, 4111
Ethics committee country [2] 294470 0
Australia
Date submitted for ethics approval [2] 294470 0
29/01/2016
Approval date [2] 294470 0
04/02/2016
Ethics approval number [2] 294470 0
2016/063

Summary
Brief summary
The primary purpose of this study is to evaluate the efficacy of alternative dressing and securement devices in preventing device failure and infection in peripherally inserted central catheters (PICCs) in cancer patients.

You may be eligible to participate in this trial if you are a cancer patient of any age, with a haematological malignancy or solid tumour, and are having a PICC inserted as part of your therapy (which is expected to remain in place for at least 24 hours).

All participants enrolled in this trial will be randomly allocated (by chance) to receive one of four PICC dressing/securement device combinations. These combinations are the standard securement device with a simple polyurethane dressing; the standard securement device with a simple polyurethane dressing and a chlorhexidine impregnated disc; an integrated securement device and simple polyurethane dressing combined into a single device; or an integrated securement device and chlorhexidine impregnated disc. The allocated dressing will be re-applied every 7 days or more frequently if required, until 8 weeks or until the time of device removal if removal is required earlier. Participants will be asked to rate the acceptability of the device and dressing, and the device will be observed closely to examine side effects, device failures and infections. It is hoped that the findings of this trial will provide information on which PICC securement devices and dressings are most effective in preventing PICC failure and infection in cancer patients.
Trial website
http://www.avatargroup.org.au/the-pisces-trial.html
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63798 0
Prof Claire Rickard
Address 63798 0
NHMRC Centre for Research Excellence in Nursing
Griffith University, Nathan Campus
170 Kessels Road
Nathan, QLD, 4111
Country 63798 0
Australia
Phone 63798 0
+61 7 37356460
Fax 63798 0
+61 7 37355431
Email 63798 0
c.rickard@griffith.edu.au
Contact person for public queries
Name 63799 0
Ms Emily Larsen
Address 63799 0
Centre for Clinical Nursing (Research and Development Unit)
Level 2, Building 34
Royal Brisbane and Women's Hospital
Cnr Bowen Bridge Road & Butterfield Street
Herston, QLD, 4029
Country 63799 0
Australia
Phone 63799 0
+61 7 36468725
Fax 63799 0
Email 63799 0
emily.larsen@health.qld.gov.au
Contact person for scientific queries
Name 63800 0
Prof Claire Rickard
Address 63800 0
NHMRC Centre for Research Excellence in Nursing
Griffith University, Nathan Campus
170 Kessels Road
Nathan, QLD, 4111
Country 63800 0
Australia
Phone 63800 0
+61 7 37356460
Fax 63800 0
+61 7 37355431
Email 63800 0
c.rickard@griffith.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No additional data are available, as per HREC approval requirements.
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 659 0
Study protocol
Citation [1] 659 0
Link [1] 659 0
Email [1] 659 0
Other [1] 659 0
Peripherally InSerted CEntral catheter dressing and securement in patients with cancer: the PISCES trial. Protocol for a 2x2 factorial, superiority randomised controlled trial (BMJ Open)
Summary results
No Results