RESEARCH Open Access
A comparison of hydrophobic polyurethaneHuman Computer Interaction
and polyurethane peripherally inserted
central catheter: results from a feasibility
randomized controlled trial
Nicole C. Gavin1,2,3,4* , Tricia M. Kleidon2,5,6, Emily Larsen2,6,7, Catherine O’Brien6, Amanda Ullman2,5,7,
Sarah Northfield1, Gabor Mihala2,8,9, Naomi Runnegar10,11, Nicole Marsh2,3,6,7 and Claire M. Rickard2,6,7
Abstract
Background: To evaluate the feasibility of an efficacy trial comparing a hydrophobic polyurethane peripherally
inserted central catheter (PICC) with a standard polyurethane PICC.
Methods: This pilot randomised controlled trial (RCT) was conducted between May 2017 and February 2018. Adult
participants (n = 111) were assigned to hydrophobic polyurethane PICC with proximal valve (intervention) or a
polyurethane PICC with external clamp (standard care). Primary outcome was trial feasibility including PICC failure.
Secondary outcomes were central line-associated bloodstream infection, local infection, occlusion, thrombosis,
fracture and dislodgement, phlebitis, local or systemic allergic reaction, and PICC dwell time.
Results: All feasibility outcomes were achieved, apart from eligibility criteria. In total, 338 patients were screened,
138 were eligible (41%), and of these 111 were randomised (80%). Patients received the allocated PICC in 106 (95%)
insertions. No patients withdrew from the study and there was no missing data. PICC failure was 24% (13/55) in the
intervention group and 22% (12/55) in the standard care group (p = 0.820). PICC failure per 1000 PICC days was 16.3
in the intervention group and 18.4 in the control group (p = 0.755). The average dwell time was 12 days in the
intervention and 8 days in the control group.
Conclusions: This study demonstrates the feasibility of an efficacy trial of PICC materials in an adult population,
once adjustments were made to include not only in-patients, but also patients being discharged to the Hospital in
the Home service.
Trial registration: Australia and New Zealand Clinical Trials Registry ACTRN12616001578493. Prospectively registered
on 16 November 2016. The trial protocol was published a priori (Kleidon et al., Vasc Access 3:15–21, 2017).
Keywords: Feasibility, Hydrophobic polyurethane, Peripherally inserted central catheter (PICC), PICC failure, Pilot
randomised controlled trial, Polyurethane
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* Correspondence: [email protected]
1Cancer Care Services, Royal Brisbane and Women’s Hospital, Butterfield
Street, Herston, Queensland 4029, Australia
2Alliance for Vascular Access Teaching and Research, Menzies Health Institute
Queensland, Griffith University, Nathan, Queensland 4111, Australia
Full list of author information is available at the end of the article
Gavin et al. Trials (2020) 21:787
https://doi.org/10.1186/s13063-020-04699-z
Background
Peripherally inserted central catheters (PICCs) are used
for intravenous (IV) fluids, medications, and blood products and for blood sampling to prevent frequent phlebotomy [1, 2]. PICCs are the most frequently inserted
central venous access device outside of the intensive care
unit [3], and their appropriate use [4, 5] enables treatment in diverse settings, including inpatient, outpatient,
and community-based [2]. Unfortunately, about one
third of PICCs fail prior to completion of treatment [6],
often necessitating removal and replacement [7], due to
mechanical (blockage, dislodgement, vein thrombosis,
rupture) or infective (local or bloodstream infections)
complications [6]. PICC complications reduce patient
satisfaction, prolong hospitalisation, increase healthcare
costs, and risk mortality [8–12].
PICC material and designs have evolved from the first
silicone PICCs with external clamps in the 1970s [13] to
modern materials and characteristics which include the
following: trimmable or un-trimmable catheters, silicone
or polyurethane (power injectable and non-power injectable), and anti-microbial or heparin bonding [14]. PICCs
are available in various sizes (1 to 6 Fr), configured with
single or multiple lumens, open- or closed-ended, with
or without external clamps [14]. Despite this abundance
of choice, there is a paucity of evidence comparing PICC
features. In a recent scoping review [15] of 178 randomised controlled trials (RCTs) in central venous access
devices in the past decade, only five studies compared
PICC materials [16–20] and two PICC types [21, 22].
A recent addition to the market, BioFlo® is a hydrophobic polyurethane PICC with a surface-modifying
macromolecule (Endexo®) that enhances the biocompatibility of medical devices [23]. This durable surface modification occurs during the extrusion moulding
manufacturing process. A small amount of polymer/
macromolecule is added to the polyurethane/carbothane® to provide hydrophobic properties to the PICC
[23, 24]. Earlier unpublished pre-clinical data suggested
the Endexo® technology suppressed procoagulant conformation, reduced platelet adhesion, inhibited platelet
activation in the presence of blood, and reduced bacteria
adhesion and encrustation in the presence of bacteria
[23]; however, no anti-infective claim is made by the
BioFlo® manufacturers [25]. In addition to surface modification, BioFlo® has a direction-specific pressureactivated safety valve situated at the proximal hub of the
PICC, designed to reduce retrograde blood flow into the
PICC during normal venous pressures [25]. This technology demonstrates some effectiveness at reducing
thrombus accumulation in laboratory settings, but its
clinical effectiveness is less established [14].
A recent pilot RCT in paediatric patients [26] compared a polyurethane, power-injected PICC with an
external clamp to a hydrophobic polyurethane PICC
(BioFlo®). Failure was halved in the hydrophobic polyurethane group (8/72; 11%) compared to standard care
(16/74; 22%) (p = 0.087), which when expressed as an incident rate was 12.6 and 7.3 per 1000 PICC days (incident rate ratio 0.58; 95% confidence interval (CI) 0.21–
1.43; p = 0.172). However, this has not been tested in the
adult population. Therefore, the primary aim of our
feasibility RCT was to compare the effectiveness of a
hydrophobic polyurethane PICC with a standard polyurethane PICC to prevent PICC failure. We hypothesised
that conducting an RCT would be feasible.
Methods
Design
This pilot parallel RCT with 1:1 allocation compared a
hydrophobic polyurethane PICC with pressure-activated
proximal valve to a polyurethane PICC with external
clamp.
Study setting
This trial recruited between May 2017 and February
2018 at the Royal Brisbane and Women’s Hospital
(RBWH) in Brisbane, Australia, a large quaternary hospital. During the study, PICCs at this hospital were
inserted in the Department of Medical Imaging, which
provided a specialist diagnostic imaging and radiology
service, supporting the care and treatment of patients.
Patients with a PICC were either be treated in a traditional hospital ward or in the Hospital in the Home
(HITH) service, which allowed patients to receive their
hospital intravenous treatment in their own homes.
Sample
The target sample size was 110 participants, 50 participants per group plus 10% for potential attrition, as determined by pilot trial sample size recommendations
[27]. Patients were consecutively recruited and randomised if they met the inclusion criteria: PICC to be
inserted in the Department of Medical Imaging for fluid
or medication administration, predicted hospital inpatient admission > 24 h, 18 years or older, and provided
informed consent. Due to slow recruitment, the inclusion criteria were expanded to include patients who were
transferred to the HITH service within 24 h of PICC insertion. Patients were excluded if they had a current
bloodstream infection (classified as a positive blood culture within 48 h prior to PICC insertion); had an allergy
to the study product; the PICC was to be inserted
through diseased, burned, or scarred skin; the PICC was
inserted in other departments or units in the hospital;
they could not provide consent without an interpreter;
had a previous enrolment in the study; or had an
Gavin et al. Trials (2020) 21:787 Page 2 of 11
existing central venous access device including pulmonary artery catheters.
Participants were randomised to receive either (1)
standard care—polyurethane, power-injectable PICC
with external clamp (Arrow International, Reading,
Pennsylvania)—or (2) the intervention—hydrophobic
polyurethane PICC with a proximal valve (BioFlo® with
Endexo® and PASV®, AngioDynamics Inc., Queensbury).
Outcomes
Primary outcomes
Feasibility The primary outcome was feasibility of conducting a large, definitive RCT comparing hydrophobic
polyurethane PICC with simple polyurethane to prevent
PICC failure and complications in adults. Feasibility was
assessed as a composite analysis of elements [27–29] of
the following: (i) eligibility (> 70% of screened patients
were eligible), (ii) recruitment (> 70% of eligible patients
agreed to enrol), (iii) retention and attrition (< 15% of
participants are lost to follow-up or withdrew from the
study), (iv) protocol adherence (> 80% of participants received their randomly assigned study product), (v) missing
data (< 10% of endpoint data were missed during data collection), and (vi) patient and healthcare professional satisfaction and acceptability. Patient satisfaction with the
PICC was collected as pain at removal on an 11-point
Likert scale (0 being no pain and 10 being worst imaginable pain). PICC inserters were asked to rate their levels of
satisfaction with insertion equipment (0 being very dissatisfied and 10 being very satisfied) and ease of PICC insertion (0 being very difficult and 10 being very easy) on an
11-point Likert scale. For staff satisfaction and acceptability, nurses were asked to rate their difficulty during PICC
removal on an 11-point Likert scale (0 being no difficulty
and 10 being significant difficulty); and (vii) sample size
estimates for a definitive trial.
PICC failure PICC failure was defined as the following
complications associated with PICC removal: (i) central
line-associated bloodstream infection (CLABSI) [30], (ii)
local infection [30], (iii) device occlusion [31, 32], (iv)
venous thrombosis [33], and (v) PICC fracture or dislodgement [31, 34]. The outcome of device failure was
an objective measure, assigned by clinical staff (not research staff or investigators). The published protocol by
Kleidon and colleagues [35] defines PICC failure in further detail.
Secondary outcomes
In addition to individual complications (CLABSI, local
infection, occlusion, thrombosis, fracture, and dislodgement), secondary outcomes included the following: (i)
phlebitis, defined as any sign of chemical, mechanical, or
infective phlebitis, determined by patient complaint of
pain and nurse examining PICC site; (ii) safety endpoints
(local or systemic allergic reactions); and (iii) PICC dwell
time in days.
Study procedures A research nurse (ReN) screened for
eligible patients. Patients who agreed to participate were
randomised via computer-generated randomisation immediately before PICC insertion via a web-based service
(https://randomisation.griffith.edu.au/) to ensure allocation concealment until study entry. Patients were randomly assigned in a 1:1 ratio with randomly varied block
sizes of two and four. The ReN provided the randomised
study product to the inserting clinician. Data were collected using Research Electronic Data Capture [36].
Demographic and clinical data were collected at recruitment. The ReN visited inpatients twice weekly and the
HITH nurse visited daily until the PICC was removed
due to treatment completion, PICC failure, or until
4 weeks (maximum follow-up). Primary and secondary
outcomes were collected by the ReN from the medical
records, clinical staff, and patient assessment. Outcome
data were collected at 48 h post PICC removal. The infection control physician (adjudicating infection outcomes), radiologist (adjudicating thrombosis outcomes),
and data analyst were blinded to the study allocation. Infection and mortality data were collected at 48 h post
PICC removal. Participants were followed for 4 weeks,
unless the PICC was removed earlier. It was not possible
to blind the PICC inserters, patients, or healthcare professionals caring for the patients enrolled in the study.
PICC procedures Prior to the study, the intervention
PICC was not used in the hospital. Pre-study training for
PICC inserters, inpatient, and HITH staff was provided
by the manufacturer in the month preceding study commencement and for the first month after recruitment of
the first patient. The ReN provided ongoing training and
support for PICC inserters and clinical staff caring for
the PICC.
PICCs were inserted by a registered nurse, radiographer, or medical officer; experience ranged from novice to expert. PICC insertion occurred in either digital
fluoroscopy or the angiography suite. Asepsis was maintained using maximal barrier precautions including use
of 2% chlorhexidine gluconate in 70% isopropyl alcohol
skin preparation (Soluprep; 3M) [37]. Ultrasound was
used for all initial venous assessment and initial vein
puncture. A modified Seldinger technique was used for
the remainder of the PICC insertion. Fluoroscopy was
used to confirm optimal catheter tip placement in the
lower third of the superior vena cava or cavo-atrial junction. When necessary, 10 mL of iodinated contrast and
digital subtraction angiography was used to assist
Gavin et al. Trials (2020) 21:787 Page 3 of 11
accurate tip placement during complicated PICC insertion. Dressing and securement were achieved with a
chlorhexidine impregnated foam disc (Biopatch®; Ethicon, New Jersey), a sterile semi-permeable, adhesive
transparent dressing (IV3000 10 × 12cm; Smith and
Nephew; Hull), and a stabilisation device (StatLock®
PICC Plus Stabilization Device; Bard, Georgia) [37].
Post insertion care and maintenance was standardised
with the PICC dressing and needleless connectors
(SmartSite™; BD, Utah) replaced weekly or as required if
soiled or lifting [38]. Inpatients who had continuous infusions had their IV administration sets replaced every
72 h, excluding blood products or chemotherapy, which
were replaced on completion of the infusion. Intermittent infusions were flushed and locked with 0.9% sodium
chloride. Complications were identified and monitored
by the treating team. Occlusion was managed with a
thrombolytic agent (e.g. urokinase). The decision to take
blood cultures and remove PICCs was made by the medical officer treating the patient. HITH patients were visited daily to have their elastomeric device (Infusor™;
Baxter, Illinois) and antibiotic replaced. If HITH patients
required treatment to manage a PICC complication,
such as administration of a thrombolytic agent, they
were re-admitted to the ward.
Statistical analyses
Data were exported to Stata 15 for cleaning and analysis.
Data cleaning of outlying figures and missing and implausible data were undertaken prior to analysis. Missing
data were not imputed. The patient was the unit of
measurement, and all randomly assigned patients were
analysed on an intention-to-treat basis [39]. Descriptive
statistics (frequencies and percentages) were used to ascertain the primary outcome of feasibility for the larger
trial. Incidence rates (per 1000 PICC days) and rate ratios, including 95% confidence intervals, were calculated.
The comparability of groups at baseline was described
across demographic, clinical, and device characteristics.
Kaplan-Meier survival curves (with log-rank tests) were
used to compare PICC failure between study groups
over time. Associations between failure and baseline
characteristics were described by calculating hazard ratios. Multivariable Cox regression was not performed
due to the relatively low number of outcomes. p values
of < 0.05 were considered statistically significant.
Results
Participant and PICC characteristics
The participant and PICC characteristics are described
in Table 1. Over 90% of patients recruited to this study
were medical or surgical patients. Demographic and
PICC insertion characteristics were balanced between
the groups. The PICC inserters were more experienced
at inserting the standard care PICC: in only 1/52 (2%)
PICC insertions had the PICC inserter never inserted a
standard care PICC compared to 16/56 (29%) in the
intervention group, and three quarters of the PICC inserters (39/52; 75%) had inserted more than 11 standard
care PICCs compared to 3/56 (5%) in the intervention
group.
Feasibility outcomes
Apart from eligibility criteria, all feasibility outcomes
were achieved. In total, 338 patients screened, 138 were
eligible (41%), and of these 111 were randomised (80%).
Figure 1 outlines the reasons for unsuccessful achievement of the eligibility criteria. Additionally, Fig. 1 displays the flow of patients through the study confirming
> 80% participants received their randomly assigned
study product. Of the five who did not receive the intervention (106/111 received the allocated treatment, 95%),
four received the standard care PICC. No patients withdrew from the study; therefore, the retention and attrition criteria of < 15% were met. Thirteen (12%) patients
were censored on transfer to another hospital (seven in
the standard care and six in the intervention group).
There was no missing data for the primary outcome.
The research team did not have ethical approval to request clinical information for these patients transferred
to another hospital.
PICC inserter satisfaction with ease of insertion with
the insertion equipment was rated higher in the standard
care group (10.0 in the standard care group and 7.0 in
the intervention) (Table 1). Although the number of insertion attempts was balanced between the groups, there
were more difficult insertions in the intervention group
(20; 36% in the intervention group compared to 13; 24%
in the standard care group). Patient satisfaction and acceptability was collected as pain on PICC removal. Of
the twenty-six patients asked, no one reported pain at
removal (Table 2).
PICC failure
In total, 25 out of 110 patients (23%) experienced PICC
failure: of these, two patients (one in each group) had
completed their treatment and 23 had not. Presented as
absolute numbers, 13/55 (24%) PICCs failed in the intervention group and 12/55 (22%) in the standard care
group (p = 0.820). The risk ratio was 1.08 (0.54–2.16),
and the risk difference was 1.8% (– 13.8–17.5). PICC failure per 1000 PICC days was 16.3 (95% CI 9.5–28.1) in
the intervention group and 18.4 (95% CI 10.5–32.5) in
the control group (p = 0.755). Failure was most commonly due to dislodgement, followed by occlusion. See
Tables 2 and 3, also Fig. 2. The average dwell time was
12 days in the intervention and 8 days in the control
group (Table 3). During the study, six adverse events
Gavin et al. Trials (2020) 21:787 Page 4 of 11
Table 1 Participant and insertion characteristics at insertion
n Intervention Control Total
Group sizea 111 56 (50) 55 (50) 111 (100)
Female gender 111 28 (50) 29 (53) 57 (51)
Age (years)b 111 59 (15) 62 (16) 61 (16)
Body mass indexb 111 28 (10) 31 (16) 30 (13)
Comorbidities 111
None 2 (4) 1 (2) 3 (3)
One 7 (12) 8 (15) 15 (14)
Two 9 (16) 5 (9) 14 (13)
Three 7 (12) 6 (11) 13 (12)
Four or more 31 (55) 35 (64) 66 (59)
History ofc
Clot 109 17 (30) 17 (32) 34 (31)
Antithrombotic therapy 108 46 (84) 48 (91) 94 (87)
Diagnosis at admission 111
Surgical 39 (70) 35 (64) 74 (67)
Medical 12 (21) 15 (27) 27 (24)
Other 5 (9) 5 (9) 10 (9)
Infection at time of recruitment 111 38 (68) 31 (56) 69 (62)
Wound at time of recruitment 111 35 (62) 27 (49) 62 (56)
Side of insertion: non-dominant arm 110 33 (60) 35 (64) 68 (62)
PICC placement: 110
Basilic 46 (84) 40 (73) 86 (78)
Brachial 8 (15) 12 (22) 20 (18)
Other 1 (2) 3 (5) 4 (4)
Catheter size: 110
5 Fr 54 (98) 53 (96) 107 (97)
4 Fr 1 (2) 2 (4) 3 (3)
Lumens 110
Two 54 (98) 53 (96) 107 (97)
One 1 (2) 2 (4) 3 (3)
Difficult insertion 111 20 (36) 13 (24) 33 (30)
Number of attempts 110
One (first time success) 40 (71) 42 (78) 82 (75)
Two 9 (16) 6 (11) 15 (14)
Three or more 7 (12) 6 (11) 13 (12)
Inserted by 110
Radiographer 27 (49) 26 (47) 53 (48)
Nurse 21 (38) 21 (38) 42 (38)
Doctor 7 (13) 8 (15) 15 (14)
Ease of insertiond,e 108 7.5 (5.0–9.0) 10.0 (7.0–10.0) 8.0 (5.0–10.0)
Satisfaction with insertion kitd,e 108 7.0 (3.0–8.0) 10.0 (10.0–10.0) 9.0 (7.0–10.0)
PICC inserter level of experience 108
No history of insertion 16 (29) 1 (2) 17 (16)
One to ten devices inserted 37 (66) 12 (23) 49 (45)
Gavin et al. Trials (2020) 21:787 Page 5 of 11
Table 1 Participant and insertion characteristics at insertion (Continued)
n Intervention Control Total
11 or more devices inserted 3 (5) 39 (75) 42 (39)
Frequencies and column percentages shown unless noted otherwise
n number of non-missing observations
aRow percentages shown
bMean (standard deviation)
cMultiple responses possible per participant
dMedian (25–75th percentiles) shown
eOn a 0 to 10 scale, 0 = worst and 10 = best
Fig. 1 CONSORT 2010 flow diagram
Gavin et al. Trials (2020) 21:787 Page 6 of 11
Table 2 End points
n Intervention Control
Group sizea 111 56 (50) 55 (50)
Reason for study completion 110
Removed 41 (75) 42 (76)
Patient transferred 6 (11) 7 (13)
4 weeks completed 7 (13) 5 (9)
Patient deceased 1 (2) 1 (2)
Reason for removalb 83
tx completed, no device complications 27 (66) 29 (69)
tx incomplete, device complications 12 (29) 11 (26)
tx completed, device complications 1 (2) 1 (2)
Transferred, no device complications 1 (2) 1 (2)
Complications (resulting in failure)c
Any complication 110 13 (24) 12 (22)
PICC-associated BSI, suspected 25 6 (46) 5 (42)
Dislodgement, full 25 4 (31) 7 (58)
Occlusion 25 3 (23) 1 (8)
Skin reaction 25 1 (8) 0 (0)
Fracture 25 0 (0) 0 (0)
Suspected thrombus 25 0 (0) 0 (0)
Complications (during tx)c
Any complication 110 25 (45) 20 (36)
Occlusion 45 15 (60) 11 (55)
PICC-associated BSI, suspected 45 8 (32) 3 (15)
Dislodgement, partial 45 7 (28) 4 (20)
PICC-associated thrombosis, suspected 45 1 (4) 1 (5)
Other 45 4 (16) 3 (15)
Serious adverse eventsc
Any type 110 5 (9) 6 (11)
Positive blood culture 11 3 (60) 3 (50)
Unplanned admission to ICU 11 2 (40) 2 (33)
Death 11 1 (20) 2 (33)
Infection (baseline or during tx)c
Any type 110 45 (82) 37 (67)
Wound 82 14 (31) 12 (32)
Urinary 82 8 (18) 9 (24)
Bone 82 4 (9) 7 (19)
Faecal/gastrointestinal 82 7 (16) 3 (8)
Respiratory 82 5 (11) 4 (11)
Skin/cellulitis 82 7 (16) 1 (3)
Other 82 11 (24) 13 (35)
Unknown 82 4 (9) 5 (14)
Confirmed BSI classifications (count)c
LCBI (common commensal) 110 3 (5) 0 (0)
CLABSI 110 0 (0) 2 (4)
Gavin et al. Trials (2020) 21:787 Page 7 of 11
were recorded: one skin reaction (in the intervention
group), four patients were transferred to the intensive
care unit (two in each group), and three patients died
(one in the intervention and two in the standard care
group). In all cases, the patients’ deterioration was not
related to the PICC.
Discussion
This study demonstrates the feasibility of an efficacy trial
of PICC materials in an adult population, once adjustments were made to include patients to be discharged to
the HITH service. No lead-in time with the intervention
PICC was possible outside of the trial; therefore, PICC
inserters were inexperienced with the new device. This
study included a broad selection of medical/surgical patients who required a PICC for treatment in the hospital
and/or as a HITH patient in their own homes. Patients
ranged from being ambulant requiring long-term antibiotics to patients with major surgery, such as pelvic exenterations. To further improve eligibility, future trials
might consider surrogate decision maker and telephone
consent as 21 out of the 338 (6%) patients approached
were too confused to consent. Despite these challenges, it
is important that an adequately powered trial comparing
the effectiveness of hydrophobic PICCs to other PICC
technologies is conducted, as PICC failure remains unacceptably high. Previous systematic reviews have
highlighted that one-third of PICCs fail [6] with comparable incidence seen in our study. Clinicians and policy
makers need to take urgent steps to investigate potential
improvements in PICC outcomes since failure disrupts patient treatment due to delay in insertion of a new PICC
and multiple PICCs can increase patient complications
and decrease the quality of a patient’s experience [8–12].
PICCs are associated with morbid complications, such as
CLABSI and deep vein thrombosis; thus, it is essential researchers generate further evidence to guide clinicians to
select the most appropriate PICC materials to reduce
these potentially fatal adverse events and improve the
overall quality of care provided to patients [14, 40].
This pilot RCT compared a hydrophobic polyurethane
PICC with proximal valve with a power-injectable polyurethane PICC with external clamp to reduce PICC failure and complications in an adult population. This study
followed the same methodology as the paediatric protocol [35] and published study [26] and was reported in
line with the CONSORT guidelines. A quarter of PICCs
failed (25/110; 23%) before treatment completion. The
Table 2 End points (Continued)
n Intervention Control
MBI-LCBI 110 1 (2) 0 (0)
Thrombus, confirmed 110 1 (2) 0 (0)
Pain at removal (0 = worst, 10 = none)d 26 0.0 (0–0) 0.0 (0–0)
Outpatient/HITH tx 110 19 (35) 14 (25)
Frequencies and column percentages shown unless noted otherwise
ICU intensive care unit, PICC peripherally inserted central catheter, BSI bloodstream infection, incl. including, HITH hospital in the home, CLABSI central line
associated bloodstream infection, MBI-LCBI mucosal barrier injury laboratory confirmed bloodstream infection, LCBI laboratory confirmed bloodstream infection,
tx treatment
aRow percentages shown
bDenominator was the number of observations with device removed
cMultiple outcomes per device possible
dMedian (25th/75th percentiles shown)
Table 3 Failure rates and survival analysis
n Intervention (n = 55) Control (n = 55) p value
PICC failure 110 13 (24%) 12 (22%) 0.820a
Dwell time (days)b 110 12 (5–21) 8 (5–15) 0.175c
Device days 110 797 651 –
Incidence rate (per 1000 PICC days)d 16.3 (9.5–28.1) 18.4 (10.5–32.5) 0.755e
Incidence rate ratio 0.89 (0.37–2.12) Reference
hyphen = not calculated
aChi-squared test
bMedian (25–75th percentiles) shown
cWilcoxon rank-sum test
dRate and 95% confidence interval shown
eCox univariable regression
Gavin et al. Trials (2020) 21:787 Page 8 of 11
primary objective of this study was feasibility (rather
than reducing PICC failure); and although the incident
rate ratio of 0.89 favoured the intervention, PICC failure
was not significantly different between the groups (12/
55; 22% in the standard care and 13/55; 24% in the intervention group).
To date, six studies, published in peer reviewed journals and as conference abstracts, have compared the BioFlo® PICC with non-hydrophobic PICCs: one paediatric
pilot RCT [26], one adult RCT [41], one quasiexperimental clinical evaluation [42], and three retrospective cohort studies [43–45]. With the exception of
the paediatric pilot RCT [26], it is difficult to assess the
risk of bias in the other studies published to date as they
are conference abstracts. All but one [41] study demonstrated an improvement in PICC-associated thrombosis
and occlusion with BioFlo®. Musial and Hamad [43] reported in their economic evaluation that despite the reduction in occlusion with BioFlo® PICC, when the
increased cost of BioFlo® was compared to cost savings
from reduced use of the thrombolytic treatment alteplase (Cathflo Activase, Genentec Inc., San Francisco,
CA), there was no economic benefit, but they did not
consider costs of lost treatment time and extended inpatient stay. Currently, there is insufficient clinical data
to definitively demonstrate the potentially beneficial
hydrophobic properties of BioFlo® PICC in clinical practice, thus further large trials have commenced.
Limitations of this study include the length of follow-up
of patients. We followed our patients for up to of 4 weeks
rather than until PICC removal. This might explain why
only four incidences of occlusion resulting in PICC failure
occurred (see Table 2). Another limitation was that only
patients showing clinical symptoms of thrombus were referred for an ultrasound for confirmation. This may explain
the low rate of PICC-associated thrombus in this cohort.
Future studies should consider routine ultrasounds as approximately two-thirds of PICC-associated thrombi are
asymptomatic [46]. Additionally, it was not possible to
blind the PICC inserters, patient or other healthcare professionals. Despite these limitations, intervention fidelity was
strong and the potential for reproducibility in future trials
through the publication of the trial protocol [35] and
reporting of the study and PICC procedures, which allows
for generalisability of the study results.
The results of this study should be interpreted with caution as it reports the results of a pilot RCT that recruited
110 patients. A full-scale adequately powered efficacy trial
is required to test the statistical hypotheses of the efficacy
of a hydrophobic polyurethane PICC with proximal valve
compared to a plain polyurethane PICC with external
clamp to reduce PICC failure and complications. A multicentre trial recruiting adults and children would ensure
these results are generalizable beyond this single centre
and demonstrate external validity and safeguarding internal validity with comparable groups at baseline.
Conclusions
In conclusion, this study demonstrated that it is feasible
to conduct an RCT comparing the efficacy of
Fig. 2 Kaplan-Meier survival curve
Gavin et al. Trials (2020) 21:787 Page 9 of 11
hydrophobic polyurethane PICCs (with pressureactivated proximal valves) with polyurethane PICCs
(with external clamps) in an adult population receiving
treatment at a large quaternary referral hospital and/or
HITH service. It is important that future studies evaluate
cost-effectiveness, including inserter and patient acceptability, to robustly evaluate the impact of different PICC
materials on failure. Additionally, this study demonstrated the importance of providing a sufficient lead-in
time to train PICC inserters before the commencement
of data collection as lack of familiarity with an interventional product could impact study results.
Abbreviations
CLABSI: Central line-associated bloodstream infection; HITH: Hospital in the
Home; PASV®: Pressure-activated safety valve; PICC: Peripherally inserted
central catheter; RBWH: Royal Brisbane and Women’s Hospital;
RCT: Randomised controlled trial; ReN: Research nurse
Acknowledgments
The authors thank the patients at the RBWH for participating in this research
study. We appreciate the support from the nurses, radiographers, and
medical officers in the Department of Medical Imaging and the nurses from
the Vascular Access Surveillance and Education and the participating wards
for their support.
Authors’ contributions
NG contributed to the acquisition, analysis, and interpretation of data and
drafted the first version; TK contributed to the design of the study and the
analysis and interpretation of data; EL contributed to the analysis and
interpretation of data; COB contributed to the acquisition, analysis, and
interpretation of data; AU contributed to the design of the study and the
analysis and interpretation of data; SN contributed to the design of the
study; GM contributed to the analysis and interpretation of data; NR
contributed to the analysis and interpretation of data; NM contributed to the
analysis and interpretation of data; CR contributed to the design of the study
and the analysis and interpretation of data. All authors substantially revised
the publication and have read and approved the submitted version. All
authors agree to be personally accountable for the author’s own
contributions and to ensure that questions related to the accuracy or
integrity of any part of the work, even ones in which the author was not
personally involved, are appropriately investigated, resolved, and the
resolution documented in the literature.
Funding
AngioDynamics (the BioFlo® PICC manufacturer) provided partial funds to
undertake this research with an unrestricted donation to Griffith University
(but not to the study authors). Queensland Health provided in kind support
to fund the remainder of the trial. The funders had no role in the study
design, collection, analysis, or interpretation of the data, writing of the report,
or decision to submit the article for publication.
Availability of data and materials
The datasets generated and/or analysed during the current study are not
publicly available due to our Human Research and Ethics Committee
approval but are available from the corresponding author on reasonable
request.
Ethics approval and consent to participate
The trial was approved by the Children’s Health Queensland Hospital and
Health Service Human Research Ethics Committee (HREC/15/QRCH/164) and
Griffith University Human Research Ethics Committee (Ref No. 2016/077).
Written informed consent was obtained from all participants prior to entry
into the study.
Consent for publication
Not applicable
Competing interests
NG: none; TK: related to the submitted project, TK reports an investigatorinitiated research grant from Angiodynamics. TK reports investigator-initiated
research grants and speaker fees provided to Griffith University from 3M
Medical, Angiodynamics, Baxter, Becton Dickinson, Centurion Medical, Cook
Medical, Medical Specialties Australia, Smiths Medical, and Vygon (unrelated
to the current project); EL: Griffith University has received consultancy payment for an educational lecture from 3M on behalf of EL; an investigatorinitiated research grant from Cardinal Health (formerly Medtronic); and a conference scholarship attendance supported by Angiodynamics (unrelated to
the submitted work) to support EL’s research. EL is a recipient of a Higher
Degree Research Scholarship from the Australian Government Research
Training Program; COB: none; AU: related to the submitted project, AU reports an investigator-initiated research grant from Angiodynamics. AU reports investigator-initiated research grants and speaker fees provided to
Griffith University from 3M Medical, Becton Dickinson and Cardinal Health
(unrelated to the current project). AU is currently supported by an Australian
Government, National Health and Medical Research Council Fellowship, via
Griffith University; SN: related to the submitted project, SN reports an
investigator-initiated research grant from Angiodynamics; GM: related to the
submitted project, GM reports an investigator-initiated research grant from
Angiodynamics. GM is a recipient of a Higher Degree Research Scholarship
from the Australian Government Research Training Program; NR: none; NM:
NM’s previous employer (Griffith University) has received on her behalf:
investigator-initiated research grants and unrestricted educational grants
from Becton Dickinson and Cardinal Health and a consultancy payment provided to Griffith University from Becton Dickinson for clinical feedback related to catheter placement and maintenance (unrelated to the current
project); CM: Griffith University has received unrestricted investigator-initiated
research or educational grants on my behalf from product manufacturers
(BD-Bard; Cardinal Health,). Griffith University has received consultancy payments on my behalf from manufacturers (3M, BBraun, BD-Bard).
Author details
1Cancer Care Services, Royal Brisbane and Women’s Hospital, Butterfield
Street, Herston, Queensland 4029, Australia. 2Alliance for Vascular Access
Teaching and Research, Menzies Health Institute Queensland, Griffith
University, Nathan, Queensland 4111, Australia. 3School of Nursing,
Queensland University of Technology, Kelvin Grove, Queensland 4059,
Australia. 4Institute of Health and Biomendical Institute to Healthcare
Transformation, Queensland University of Technology, Kelvin Grove,
Queensland 4059, Australia. 5Children’s Hospital Queensland, South Brisbane,
Queensland 4101, Australia. 6Nursing and Midwifery Research Centre, Royal
Brisbane and Women’s Hospital, Herston, Queensland 4029, Australia. 7School
of Nursing and Midwifery, Griffith University, Nathan, Queensland 4111,
Australia. 8School of Medicine, Griffith University, Gold Coast, Queensland
4222, Australia. 9Centre for Applied Health Economics, Menzies Health
Institute Queensland, Griffith University, Nathan, Queensland 4111, Australia.
10Infection Management Services, Princess Alexandra Hospital,
Woolloongabba, Queensland 4102, Australia. 11PA-Southside Clinical Unit,
Faculty of Medicine, University of Queensland, Brisbane, Queensland 4102,
Australia.
Received: 13 February 2020 Accepted: 24 August 2020
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