A Randomized Controlled Post-market Study to Assess the Impact of Peripheral Intravenous Catheter Length and Gauge on Catheter Indwell Duration and Haemolysis in Human Participants Using a Bilateral, Cephalic Vein Cannulation Model
Phase: NA
Conditions: Indication for Peripheral Intravenous Catheterisation
Sponsor: Becton, Dickinson and Company

Cover Page 
 
 
Protocol Title: 
A randomized controlled post-market study to assess the impact of 
peripheral intravenous catheter length and gauge on catheter indwell 
duration and haemolysis in human participants using a bilateral, cephalic 
vein cannulation model. 
 
Document Type: 
Clinical Study Protocol 
 
Document Date: 
02-Oct-2020 
 
NCT number: 
NCT04344314 

Protocol Number: BDT-19PIVCAU001 
 
CONFIDENTIAL 
Version: 4.0 
 
Date: 02 Oct 2020 
Page 1 of 60 
 
TITLE PAGE 
Protocol Title:  
A randomized controlled post-market study to assess the impact of peripheral intravenous 
catheter length and gauge on catheter indwell duration and haemolysis in human participants 
using a bilateral, cephalic vein cannulation model.  
 
Protocol Number: BDT-19PIVCAU001 
Version Number: Version 4.0 
 
Study Device: 
BD Nexiva™ (20G x 1); single port 
BD Nexiva™ (20G x 1.75”); single port 
BD Nexiva™ (22G x 1); single port 
BD Nexiva™ (22G x 1.75”); single port 
Study Type: Feasibility 
Short Title: Impact of PIVC Length and Gauge on Catheter Indwell Time. 
 
Sponsor Name: Becton Dickinson Pty Ltd 
Legal Registered Address:  
66 Waterloo Road 
Macquarie Park, NSW 2113 
Australia 
 
Sponsor Contact: 
David Maggs, MD  
david.maggs@bd.com 
Principal Investigator: 
Andrew Bulmer, PhD 
Associate Professor of Pathophysiology 
a.bulmer@griffith.edu.au 
 
Regulatory Agency Identifier Number(s) 
Registered with Australian TGA:  ARTG 243114 
  
Approval Date: 22 May 2020  
Version History 
Version Number 
Date 
Type 
1.0 
11 Mar 2020 
 
 
Original 
2.0 
15 May 2020 
Revision 
3.0 
28 Aug 2020 
Revision 
4.0 
02 Oct 2020 
Revision 

Protocol Number: BDT-19PIVCAU001 
 
CONFIDENTIAL 
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Date: 02 Oct 2020 
Page 2 of 60 
 
 
 
 
SPONSOR PROTOCOL APPROVAL 
 
Signature below indicates approval of the protocol as written. 
Individual or 
function 
Name 
Signature 
Date 
Medical Affairs 
Team Representative 
Vincent Hugo, 
Director, Medical 
Affairs 
This document is 
signed 
electronically in the 
eTMF system 
 
R&D Study Lead 
Christopher Rini 
This document is 
signed 
electronically in the 
eTMF system 
 
Study Statistician 
Didier Morel 
This document is 
signed 
electronically in the 
eTMF system 
 
Regulatory Affairs 
Kim Geisler 
This document is 
signed 
electronically in the 
eTMF system 
 
Project Manager 
Erin White 
This document is 
signed 
electronically in the 
eTMF system 
 
Medical Safety and 
Governance / 
Medical Monitor  
David Maggs, M.D. 
This document is 
signed 
electronically in the 
eTMF system 
 
Legal Team 
Representative  
Elise Masiee    
This document is 
signed 
electronically in the 
eTMF system 
 

Protocol Number: BDT-19PIVCAU001 
 
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PRINCIPAL INVESTIGATOR AGREEMENT PAGE 
Investigator Responsibilities 
 
1. Prior to participation in this study, the Investigator or Institution must sign the Clinical 
Study Agreement (CSA) and obtain written approval from the appropriate Human 
Research Ethics Committee (HREC). 
2. The Investigator must receive BD-sponsored training prior to site activation. The 
Investigator is responsible for ensuring that all Sub-Investigators and clinical staff are 
adequately trained prior to performing any data collection or study-related procedures.   
3. The Principal Investigator shall ensure that the study is conducted in accordance with the 
study protocol, any modifications as requested by the HREC, the signed CSA, the ethical 
principles of the Declaration of Helsinki, Good Clinical Practice (ICH E6) / ISO 14155), 
and applicable national/regional regulations and laws. 
4. If applicable, ensure that written informed consent is obtained from each participant prior 
to the conduct of any study procedure, using the current HREC approved Informed 
Consent Form. 
 
 
I have read and understand the contents of this study protocol. I agree to follow and abide by the 
requirements set forth in this document. I agree to conduct the trial in accordance with 
the study protocol, the signed Clinical Study Agreement, and Good Clinical Practice (GCP) as 
well as applicable TGA guidelines and ISO 14155:2011). I agree to participate in BD-Sponsored 
training prior to performing any data collection or study-related procedures. 
 
 
Agreed to by (Investigator):  
  
_______________________________________________  
Printed Name – Investigator   
  
_______________________________________________  
Signature – Investigator  
 
_______________________________________________  
 Site Number 
 
_______________________________________________  
Date  
 
 
 

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TITLE PAGE ............................................................................................................................................................... 1 
ABBREVIATIONS ...................................................................................................................................................... 8 
1 
PROTOCOL SUMMARY .............................................................................................................................. 9 
1.1 
Synopsis ........................................................................................................................... 9 
1.2 
Schedule of Activities .................................................................................................... 12 
1.3 
Schema ........................................................................................................................... 13 
2 
INTRODUCTION ......................................................................................................................................... 13 
2.1 
Background .................................................................................................................... 13 
2.2 
Rationale......................................................................................................................... 15 
2.3 
Risk/Benefit Assessment ................................................................................................ 15 
2.3.1 
Risk Assessment ..................................................................................................... 15 
2.3.2 
Benefit Assessment ................................................................................................. 18 
2.3.3 
Overall Benefit: Risk Conclusion ........................................................................... 18 
3 
OBJECTIVES AND ENDPOINTS .............................................................................................................. 18 
3.1 
Brief Description of Objectives and Endpoints.............................................................. 18 
3.2 
Hypotheses for Specific Outcomes ................................................................................ 19 
3.2.1 
Indwell time ............................................................................................................ 19 
3.2.2 
Cell free haemoglobin ............................................................................................. 19 
4 
STUDY DESIGN ........................................................................................................................................... 20 
4.1 
Overall Design................................................................................................................ 20 
4.2 
Scientific Rationale for Study Design ............................................................................ 20 
4.2.1 
Participant Input into Design .................................................................................. 21 
4.3 
End of Study Definition ................................................................................................. 21 
5 
STUDY POPULATION ................................................................................................................................ 21 
5.1 
Inclusion Criteria ............................................................................................................ 21 
5.2 
Exclusion Criteria ........................................................................................................... 21 
5.3 
Lifestyle Considerations ................................................................................................. 22 
5.3.1 
Lifestyle restrictions................................................................................................ 22 
5.3.2 
Dietary restrictions .................................................................................................. 22 
5.3.3 
Medication restrictions............................................................................................ 23 

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5.3.4 
Blood donation restrictions ..................................................................................... 23 
5.4 
Screen Failures ............................................................................................................... 23 
6 
STUDY INTERVENTIONS ......................................................................................................................... 23 
6.1 
Study Device .................................................................................................................. 23 
6.2 
Control Device/Standard of Care ................................................................................... 24 
6.3 
Ancillary Devices/Products ............................................................................................ 24 
6.4 
Device Labeling ............................................................................................................. 25 
6.5 
Treatment Allocation and Measures to Minimize Bias .................................................. 25 
6.5.1 
Randomization ........................................................................................................ 25 
6.5.2 
Blinding/Masking ................................................................................................... 26 
7 
STUDY PROCEDURES AND ASSESSMENTS ........................................................................................ 26 
7.1 
Venipuncture-blood collection ....................................................................................... 26 
7.2 
PIVC- Insertion .............................................................................................................. 27 
7.3 
PIVC-blood collection and pressure monitoring ............................................................ 27 
7.4 
Image acquisition of indwelling catheter and cephalic vein .......................................... 27 
7.4.1 
Blood flow velocity................................................................................................. 28 
7.4.2 
Angle of insertion, catheter length in vessel ........................................................... 28 
7.4.3 
Vessel diameter, C/V ratio ...................................................................................... 28 
7.4.4 
Valve, side branch location ..................................................................................... 28 
7.4.5 
Visualization and quantification of intraluminal/intravascular thrombus formation
 
28 
7.5 
Blood analyses................................................................................................................ 28 
7.6 
PIVC-Failure .................................................................................................................. 29 
7.7 
PIVC Removal ............................................................................................................... 29 
7.8 
Extravenous Thrombus Assessment (Post-Removal) .................................................... 29 
7.9 
Video/Audio or Photography ......................................................................................... 29 
7.10 Safety Assessments ........................................................................................................ 30 
7.10.1 Insertion Site Assessment ....................................................................................... 30 
7.10.2 Securement Dressing Assessment........................................................................... 31 
8 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ........................................................................ 31 
8.1 
Discontinuation/Withdrawal .......................................................................................... 31 
8.2 
Lost to Follow-Up .......................................................................................................... 31 
8.3 
Patient replacement ........................................................................................................ 31 

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9 
ADVERSE EVENTS AND DEVICE DEFICIENCIES.............................................................................. 32 
9.1 
Definitions of Events ...................................................................................................... 32 
9.1.1 
Adverse Events (AEs) ............................................................................................. 32 
9.1.2 
Serious Adverse Events (SAEs).............................................................................. 32 
9.1.3 
Adverse Device Effect (ADE) / Serious Adverse Device Effect (SADE) .............. 32 
9.1.4 
Unanticipated (Serious) Adverse Device Effect (UADE/USADE) ........................ 32 
9.2 
Severity of Adverse Events ............................................................................................ 33 
9.3 
Relationship of Adverse Event to Device(s)/Procedure ................................................. 33 
9.4 
Reporting of Events ........................................................................................................ 34 
9.4.1 
Pregnancies ............................................................................................................. 34 
9.5 
Adverse Event (AE) Management ................................................................................. 35 
9.5.1 
Follow-up of Adverse Events (AE) ........................................................................ 35 
9.5.2 
Additional procedures for Assessing & Reporting Serious Adverse Events (SAE)35 
9.6 
Device Deficiencies........................................................................................................ 36 
10 
STATISTICAL METHODS ......................................................................................................................... 37 
10.1 Overview of Study Design ............................................................................................. 37 
10.2 Sample Size Considerations ........................................................................................... 37 
10.3 Analysis Population........................................................................................................ 37 
10.4 General Considerations .................................................................................................. 37 
10.5 Primary Endpoint(s) ....................................................................................................... 38 
10.6 Secondary Endpoint(s) ................................................................................................... 38 
10.7 Tertiary/Exploratory Endpoint(s) ................................................................................... 39 
10.8 Other Analyses ............................................................................................................... 39 
10.9 Interim Analysis ............................................................................................................. 39 
11 
DATA COLLECTION AND RECORD MAINTENANCE ....................................................................... 39 
11.1 Data Management .......................................................................................................... 39 
11.2 Source Documentation ................................................................................................... 40 
11.3 Record Retention ............................................................................................................ 41 
12 
QUALITY CONTROL AND ASSURANCE ............................................................................................... 42 
12.1 Control of Study Products .............................................................................................. 42 
12.2 Monitoring ...................................................................................................................... 42 
12.3 Audits and Inspections ................................................................................................... 43 

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12.4 Protocol Deviations ........................................................................................................ 43 
13 
ADMINISTRATIVE REQUIREMENTS .................................................................................................... 43 
13.1 Investigator and Site Selection ....................................................................................... 43 
13.2 Training .......................................................................................................................... 44 
13.3 Required Documents ...................................................................................................... 44 
13.4 Publication Policy .......................................................................................................... 44 
13.5 Study Registration .......................................................................................................... 45 
13.6 Termination of Study ..................................................................................................... 45 
14 
ETHICAL AND REGULATORY CONSIDERATIONS........................................................................... 45 
14.1 HUMAN RESEARCH ETHICS COMMITTEE  Approval .......................................... 45 
14.1.1 Informed Consent and Confidentiality.................................................................... 46 
14.2 Regulatory Status ........................................................................................................... 46 
14.3 Statement of Compliance ............................................................................................... 47 
15 
REFERENCES .............................................................................................................................................. 48 
16 
LIST OF APPENDICES ............................................................................................................................... 51 
16.1 IFU ................................................................................................................................. 52 
16.2 PIVC cannulation protocol ............................................................................................. 53 
16.3 Quantification of cell-free haemoglobin ........................................................................ 58 
16.4 Participant Instructions ................................................................................................... 59 
 
 
 

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Abbreviations 
ADP 
Adenosine diphosphate 
AE 
Adverse event 
aPTT 
Activated partial thromboplastin time 
BD 
Becton Dickinson and Company 
BMI 
Body Mass Index 
CF 
Color flow 
cfHb 
Cell-free haemoglobin 
CRF 
Case Report Form 
CTU 
Clinical Trials Unit 
C/V 
Catheter:vein 
EDTA 
Ethylenediaminetetraacetic acid 
GCP 
Good Clinical Practice 
HIV 
Human immunodeficiency virus 
HREC 
Human Research Ethics Committee 
IFU 
Instructions For Use  
INS 
Intravenous Nursing Standards 
HREC 
Human Research Ethics Committee 
LLAD 
Luer-LokTM Access Device 
MHz 
Megahertz 
mL 
Milliliter 
mm 
Millimeter 
PI 
Principal Investigator 
PIVC 
Peripheral intravenous catheter 
PT 
Prothrombin 
PWD 
Pulse wave doppler 
RBC 
Red blood cell 
SAE 
Serious Adverse Event 
SOP 
Standard Operating Procedure 
SP 
Sterile path 
TRAP 
Thrombin receptor activating peptide 
WHO 
World Health Organization 
 
 

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1 
PROTOCOL SUMMARY 
 
1.1 
Synopsis 
Protocol Title 
A randomized controlled post-market study to assess the impact of 
peripheral intravenous catheter length and gauge on catheter indwell 
duration and haemolysis in human participants using a bilateral, cephalic 
vein cannulation model 
Short Title 
Impact of PIVC Length and Gauge on Catheter Indwell Time 
Rationale 
Identifying device design factors that increase PIVC indwell time and 
reduce incidence of haemolysis would minimize patient discomfort 
(pain, anxiety due to multiple venipuncture) during the course of 
treatment and reduce associated workload costs (e.g., recollection of 
haemoglobin-free serum samples, PIVC reinsertion, needlestick injuries) 
for healthcare institutions. 
Objectives and Endpoints 
 
Objective(s) 
Endpoint(s) 
Primary 
• Assess patent indwell time 
between PIVCs of different 
length and gauge. 
Primary 
• Catheter indwell time 
Secondary 
• Assess haemolysis occurrence 
based on blood collection 
device, catheter device 
configuration 
 
• Blood draw fill time 
 
• Determine the relationship, if 
any, between catheter blood 
draw patency indwell time and 
presence of intra/extravenous 
thrombi, catheter angle/tip 
location in situ, catheter length 
in vessel, vein depth from skin 
surface, C/V ratio, and vessel 
anatomy 
 
 
 
Secondary 
• Haemolysis: Quantification 
and frequency of occurrence 
 
 
 
• Blood draw fill time 
 
• Incidence of 
o Intravenous thrombus 
(mural, at tip), sheath, vein 
collapse, presence / 
location of a valve relative 
to catheter tip, side 
branches relative to 
catheter tip detected via 
ultrasound 
o Extravenous thrombus 
within catheter hub, 
needleless connector, 

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Protocol Title 
A randomized controlled post-market study to assess the impact of 
peripheral intravenous catheter length and gauge on catheter indwell 
duration and haemolysis in human participants using a bilateral, cephalic 
vein cannulation model 
 
 
 
• Evaluate changes in vessel 
dimensions, PIVC position 
(insertion angle and in situ tip 
position), and hemodynamics 
from baseline throughout 
indwell time 
extension tubing via visual 
observation 
 
• Vessel dimensions, blood 
flow velocity (color and 
PWD), vessel depth from 
skin surface, catheter length 
in vessel, catheter insertion 
angle, in situ tip 
position/length 
Exploratory 
• Assess incidence of 
complications prompting device 
removal  
 
 
 
• Evaluate manual flush 
variability (as applicable) using 
in-line pressure measurements  
 
Exploratory 
• PIVC Complications: 
Frequency of occurrence 
(vein collapse, phlebitis, 
dislodgement, extravasation, 
accidental removal)  
 
• Flush pressure profile and 
duration of flush 
 
Design and Overview 
This is a single-centre, open-label, multi-visit, self-controlled study 
design, in ~40 healthy participants, randomized by gauge of peripheral 
intravenous catheter (PIVC) device into the lower arm cephalic vein of 
both arms.  
The purpose of this feasibility study is to assess impact of catheter 
length and gauge on PIVC indwell time over a multi-day (72 hour) 
period. This study will also evaluate the incidence of haemolysis from 
PIVC using a LLAD and vacutainer tube (2mL, 6mL) blood collection 
method compared to venipuncture from the antecubital fossa.   
The visit schedule is outlined in the section 1.3.  
 
 
 

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Protocol Title 
A randomized controlled post-market study to assess the impact of 
peripheral intravenous catheter length and gauge on catheter indwell 
duration and haemolysis in human participants using a bilateral, cephalic 
vein cannulation model 
Study Device 
Description 
Part Number 
Manufacturer 
BD Nexiva™ (20G x 1); single port 
383516 
BD 
BD Nexiva™ (20G x 1.75”); single port 
383518 
BD 
BD Nexiva™ (22G x 1); single port 
383512 
BD 
BD Nexiva™ (22G x 1.75”); single port 
383513 
BD 
 
Participants 
Recruitment and screening of approximately forty healthy (18-65 years 
old) male or female participants after ethics approval and provision of 
their informed consent to participate. 
Intervention(s)/Procedure(s) After screening and enrollment, participants will be randomized in order 
of their enrollment to either 20 or 22G of the BD NexivaTM PIVC and 
order of placement location (left or right arm first).  The participant will 
have both the 1 inch and 1.75 inch PIVCs inserted on Study Day 1 (Visit 
2), one into each arm. After successful insertion into the lower cephalic 
vein of the selected arm, the site will be regularly accessed (twice daily) 
for phlebotomy and then flushed.  The site will be assessed visually for 
tissue effects, skin reactivity, and pain, and using ultrasound for vessel 
anatomy/dimensions, catheter tip location in the vessel, color, and PWD.  
After catheter removal there will be a final inspection of the insertion 
site and securement dressing, assessing for tissue effect, skin reactivity, 
and pain. 
Investigational Sites 
This study is a single-center study that will be conducted at Griffith 
University Gold Coast Campus, Clinical Trials Unit in Queensland, 
Australia. 
Data Monitoring 
Committee 
Not applicable. 
Regulatory Status 
Registered with Australian TGA:  ARTG 243114 
 
 
 
 

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1.2 
Schedule of Activities 
Procedure 
Screening  
(up to 30 
days 
before 
Day 1) 
Study Visits (Days, Weeks, etc.) 
Notes 
 
 
Index 
Procedure 
(Day 1) 
Day 2 
Day 3 
Day 4 
Follow-up 
Informed consent 
X 
 
 
 
 
 
 
Inclusion and exclusion criteria 
X 
 
 
 
 
 
Recheck clinical status before 
randomization/ study intervention 
Demography 
X 
 
 
 
 
 
 
Physical Exam (including vital signs) 
X 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
Drug Screening (Urine) 
X 
X* 
 
 
 
 
*Testing required prior (up to 48 
hrs) to Day 1 procedures  
Venipunture 
X 
X 
 
 
 
 
 
Platelet Aggregometry 
X 
 
 
 
 
 
 
Blood Glucose / Cholesterol, Lipids 
X 
 
 
 
 
 
Fasted blood samples 
Complete Blood Count 
X 
 
 
 
 
 
 
Ultrasound (cephalic vessels) 
X 
X 
X 
X 
X 
 
 
Randomization 
 
X 
 
 
 
 
 
PIVC Insertion 
 
X 
 
 
 
 
 
Injection Site Assessment  
 
X 
X 
X 
X 
X 
 
PIVC Securement Dressing Assessment 
 
X 
X 
X 
X 
 
 
PIVC Blood Draw/Flush 
 
X 
X 
X 
X 
 
 
Flush Pressure Monitoring 
 
X 
X 
X 
X 
 
 
AE review 
 
=============================→ 
 
SAE review 
 
=============================→ 
 

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1.3 
Schema 
 
 
2 
INTRODUCTION 
Peripheral intravenous catheters (PIVCs) are key tools required for the management of patient 
care worldwide. Indeed, more than 80% of patients admitted to hospital will have a PIVC 
inserted during their stay1 largely due to their widespread application including drug/fluid 
administration, monitor blood pressure, blood transfusion, and blood sampling for analytical 
assays2,3.  Clinical research has reported early PIVC removal and replacement due to multiple, 
and complex failure modes encompassing device placement/maintenance, device design, 
infusate properties, biological response, and patient factors4. Further development efforts to 
identify device and technique factors affecting PIVC function are needed to improve patient 
outcomes and reduce healthcare costs. 
2.1 
Background 
The rate and prevalence of PIVC failure remains unnecessarily high5-7 despite the significant 
advances in PIVC design and a renewed focus on improving clinical techniques.  Multiple 
failure modes (phlebitis, infiltration, occlusion (biological/mechanical/infusate precipitate), 
dislodgement, and infection) have been identified through review of PIVC failure in clinical 
research4. Recently, using a Computational Fluid Dynamic (CFD) research model, Piper et al.8 
identified multiple variables including PIVC dimensions, PIVC in situ position, and infusion 
rate could influence catheter survival. Delineating the complex interactions between clinical 
practice (e.g., infusion rate, PIVC angle of insertion, PIVC tip positioning relative to vessel 
wall, blood collection equipment, site maintenance), device design (e.g., PIVC gauge and 
length, biomaterial), and physiology (e.g., vessel diameter, vasospasm, phlebitis, blood flow 
velocity, RBC fragility) may help to identify the mechanisms that induce thrombosis, 
haemolysis and, subsequently, PIVC failure.   
It has been hypothesized that longer PIVC catheters may extend indwell time based upon 
catheter tip location within the vessel, increased tip distance from insertion site, and reduced 

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probability of accidental dislodgement; however there is limited published data investigating 
the impact of PIVC catheter length on indwell time9,10. Identifying device design factors that 
impact PIVC indwell time and lead to blood damage and/or thrombosis may help to minimize 
patient discomfort (e.g., multiple needlesticks) and reduce associated costs (e.g., recollection 
of haemoglobin-free serum samples, PIVC reinsertion) for healthcare institutions – the 
importance of which should not be underestimated. 
An additional related ongoing concern for healthcare institutions is the prevalence of 
haemolysis (defined as cell membrane leakage or rupture that causes haemoglobin to be 
released into the plasma) in routine blood samples (3.3%) which can impact patient care and 
treatment 11-13. 
Multiple factors may contribute to increased haemolysis during PIVC blood collection.  These 
include: 
• proficiency of the clinician or nurse in phlebotomy techniques 14;  
• prolonged application of a tourniquet which can increase red blood cell (RBC) fragility 
and susceptibility to lysis 15-17;  
• the soft biomaterial from which the PIVCs are made (i.e., silicone or polyurethane) 
which aim to increase indwell time, may collapse (silicone) and increase the negative 
pressure upon the RBC 18,19;  
• the length and gauge of the catheter employed for blood collection 17,20;  
• the lubricant (e.g., polydimethylsiloxane) and solvent used for manufacturing that can 
lead to chemically-induced haemolysis 20;  
• increased suction and turbulence during blood draw through a vacutainer which may 
cause mechanically-induced haemolysis 19,21, although this remains uncertain 22; and  
• the inflammatory status of the patient which can increase the mechanical fragility of 
RBC making them more susceptible to lysis 23.   
The prevalence of haemolysis can lead to erroneous biochemical results including creatine 
kinase, lactate dehydrogenase, potassium, coagulation testing, iron, aspartate aminotransferase 
and alanine aminotransferase thus necessitating a second blood draw and laboratory analysis 
24.  This can present a potential delay in patient care and increase healthcare cost per patient 25.   
The current protocol for drawing blood via venipuncture is inefficient for time-poor nursing 
staff, taking an average of approximately 5-10 minutes 26.  In contrast, the benefits of 
performing blood collection via PIVC is highlighted by the endorsement of the Infusion 
Nurses Society guidelines 27 and include: 1) reduced chance of needle stick injuries for health 
care workers 28; 2) reduced pain, discomfort and anxiety for patients 28,29; and 3) reduced cost 
of care 12,29. Nevertheless, many institutions 30 continue to perform venipuncture for blood 
sampling based on recent studies that indicate increased prevalence of haemolysis via PIVC 
collection 17,19,28,29,31 which itself increases an economical burden for healthcare institutions 25.  
Caution should be used, however, when comparing the effect of blood collection device (i.e., 
venipuncture vs. PIVC) on haemolysis rates.  Wollowitz, Bijur, et al. 17, for example, 
compared PIVC haemolysis rates between PIVCs and butterfly needles in patients from an 

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emergency department whereby confounding factors such as inflammatory status of patients, 
or tip position/angle may have independently contributed to differences in haemolysis rates.  
Moreover, judicious examination of the data reported 17 indicates that haemolysis rates 
differed between PIVC gauges (20G Nexiva™, 13.9% haemolysis; 22G Nexiva™ 25.5% 
haemolysis) thus suggesting that the catheter:vein (C/V) ratio may have also impacted the 
results reported. More recent evidence 28, however, from an alternative population (i.e., 
gastrointestinal surgery patients) indicates PIVC blood collection does not impact haemolysis 
rates or indwell time and is preferable for patients to minimize the pain associated with 
venipuncture.  Collectively, the results from these studies suggest that factors independent of 
blood draw device, including aspiration method (syringe versus vacutainer) may have 
impacted haemolysis rates. 
2.2 
Rationale 
BD Medication Delivery Solutions is investigating a specific PIVC device design factor 
(length) that may extend indwell time and consequently enable successful PIVC based blood 
collection throughout treatment. Identifying device design factors that increase PIVC indwell 
time and reduce incidence of haemolysis would minimize patient discomfort (pain, anxiety 
due to multiple venipuncture) during the course of treatment and reduce associated workload 
costs (e.g., recollection of haemoglobin-free serum samples, PIVC reinsertion, needlestick 
injuries) for healthcare institutions.  
2.3 
Risk/Benefit Assessment 
Before participants choose to volunteer for this study, the possible risks and benefits will be 
explained by a member of the research team. The risks associated with the current study are 
listed below. 
2.3.1 Risk Assessment 
Anticipated risks listed below are based on known risks for study procedures to both the 
participant and HCP, (i.e. venipuncture, cannulation, and flush pressure monitoring). Other 
risks listed below for the study devices as described (listed) in the Nexiva and Diffusics IV 
Catheters (a-EURA). 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
Study Procedures 
Venipuncture 
• Pain 
• Nerve Damage 
• Fainting 
• Bleeding 
• Haematoma 
The risks that are associated with 
taking a small amount of blood are 
minor. A small amount of 
discomfort is possible during blood 
collection; however, this is rare, 
short lived and occasionally cannot 
even be perceived. In accordance 
Infection will be minimized by 
using sterile needles and 
equipment, clean gloves, cleaning 
of participant skin with rubbing 
alcohol around the site, before 
collection.  Bruising is a negligible 
risk and will be followed-up upon 

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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
• Infection at insertion site 
• Exposure to blood to either 
participant or HCP 
• Needle stick injury to either 
participant or HCP 
 
with the collection of blood, there 
is a minor chance of infection at 
the puncture site. There is also a 
minor chance of developing a 
haematoma (bruising) at the site. 
There is also a possibility of 
fainting, light-headedness (due to 
nervous anxiety) after taking 
blood.  
in the days after blood collection 
by the research team. If the 
participant is nervous about blood 
collection, they will be asked about 
this prior to collection so and 
necessary precautions taken (i.e., 
take blood lying down, provide 
water etc.). Participants will be 
asked to inform the team of other 
conditions (e.g. cold/flu, blood 
clotting abnormalities), so that we 
can minimize any risk. 
Cannulation 
• Pain 
• Psychological distress, 
nervousness/anxiety 
• Nerve Damage 
• Fainting 
• Bleeding 
• Haematoma 
• Systemic infection 
(bacteremia) 
• Infiltration 
• Extravasation 
• Thrombophlebitis 
• Thrombosis 
• Local infection/inflammation 
• Swelling/oedema 
• Fever/chills 
• Allergic reaction (adhesive)  
• Exposure to blood to either 
participant or HCP 
• Needle stick injury to either 
participant or HCP 
• Pulmonary embolism 
• Abuse/use of catheter by 
participant 
The risks associated with 
cannulation include: 
thrombophlebitis (blood clot and 
inflammation in/around the vein 
cannulated), infection, 
extravasation and can occur and 
range from 63% in patients 
receiving IV therapy through a 
peripheral intravenous catheter32. 
Blood stream infection is a serious 
but very infrequent complication in 
PIVCs which occurs in 
approximately 0.2% of intravenous 
catheters4. Thrombophlebitis is 
characterized by pain, swelling, 
redness, or palpable venous mass 
beyond the catheter tip. There is a 
minor amount of discomfort 
associated with catheter insertion 
of an indwelling catheter.  
Statistics regarding cannulation 
risks and adverse reactions are 
obtained from a hospital 
environment in patients receiving 
drug/intravenous fluid therapy who 
at risk of clotting/infection etc. The 
size of any thrombus will be 
assessed using sonography, 
recorded, and the participant 
referred to general practitioner for 
Pain, nerve damage, and 
extravasation will be mitigated as 
an experienced nurse (or equivalent 
such as a trained phlebotomist) will 
catheterize the participants 
according to Infusion Therapy 
Standards of Practice guidelines27, 
and under ultrasound guidance. 
Infection will be minimized by 
using an aseptic non-sterile, non-
touch technique (ANTT) approach. 
This includes use of sterile needles 
and equipment, clean gloves, 
cleaning of participant’s skin with 
rubbing alcohol around the site, 
before cannulation.  Bruising is a 
negligible risk and will be 
followed-up upon in the days after 
cannulation by the research team.  
The presence and growth of a 
blood clot can be influenced by 
inter-individual susceptibility to 
clotting/thrombotic risk, in addition 
to the cannula maintenance 
protocol. Risks associated with 
local thrombosis are negligible, 
however, if the clot enlarges (i.e., 
to beyond 5 cm in length) it can 
pose a significant risk to patient 
health47, and if that occurs the 

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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
 
clinical decision. A smaller risk 
exists that any clot may dislodge 
and move into the pulmonary 
circulation, causing a potentially 
serious and life-threatening 
pulmonary embolism. The degree 
of risk is related to the presence of 
peripheral venous thrombosis and 
the size of this thrombus, which 
will be actively monitored in this 
study. A fibrin sheath may also 
form around the PIVC, which if 
dislodged could move to the 
pulmonary circulation. The risk is 
minimal, however, as the duration 
of the study and length of the PIVC 
is short, limiting the size of any 
fibrin sheath over the period of 
investigation. A risk of device 
dislodgement and therefore, 
bleeding exists, if the device 
catches or is intentionally removed. 
A risk also exists of the participant 
using the device to access the 
circulation. 
participant will be referred to local 
health practitioners (i.e. on 
campus), for appropriate clinical 
decision. If the participant is 
nervous about cannulation, they 
will be asked about this prior to 
participating so necessary 
precautions may be taken (i.e., 
provide water etc.). Risk of 
dislodgement will be reduced by 
the use of an adhesive dressing and 
additional bandage over the site to 
prevent catching and inadvertent 
removal of the device. Participants 
will be provided with care 
instructions. A tamper evident 
device will be attached to each 
catheter and the device tested daily 
to assess whether deliberate and 
unauthorized access to the device 
has been made. Unauthorized 
access to the device will result in 
the participant being de-enrolled 
from the study and devices 
removed. 
Flush Pressure Monitoring 
• Electrical shock  
 
 
A real-time, battery-operated data 
logger device is connected to the 
pressure transducer, saline within 
it, and the participant’s body. 
Although the current delivered to 
this device is minimal (i.e., it is 
battery operated), a very small risk 
of electrocution exists from this 
device. 
In order to mitigate these risks, the 
charger for the monitoring device 
will be electrically tested and 
tagged with a safety compliance 
label confirming accordance with 
AUS/NZS 3760 standard as per 
University requirements. Clinically 
approved pressure transducers will 
also be used thus minimizing 
electrical risk to the participant.  
Study Product 
• Pain (more than anticipated 
upon insertion) 
• Blood loss (minimal, no 
intervention required/more 
There is a potential that the 
clinician does not fully reseat after 
breaking system adhesion and the 
To mitigate this from occurring, 
IFU instructs clinicians to push the 
finger grip and tip shield back 
snuggly together prior to accessing 
vessel.  

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Potential Risk of Clinical 
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Summary of Data/Rationale for 
Risk 
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than minimal, intervention 
required) 
• Infection (localized-cellulitis-
abscess 
• Infection (Systemic-Sepsis) 
 
catheter remains over the bevel of 
the needle during insertion. 
If IV components fall off or are not 
tightened properly, could lead to 
leakage of blood or infusate. 
There is always a chance that the 
IV catheter package may be 
compromised. Mishandling of the 
product to the extent that exceeds 
the design intent (e.g., exposure to 
wet surfaces, sharp implements). 
IFU instructs clinicians to carefully 
check that components are 
tightened appropriately and secure. 
In order to mitigate the risk of 
infection(s), IFU instructs 
clinicians to check package 
integrity and not use product if 
package is damaged, opened, or 
expiration date has passed. 
 
 
2.3.2 Benefit Assessment 
There are no direct benefits to the participant for participation in this study.  The findings may 
reveal information that will allow for a better understanding of the effects of catheter 
length/gauge on indwell time and incidence of haemolysis from blood collection, and thus 
may minimize venipuncture and improve medical care for persons with an indwelling PIVC. 
2.3.3 Overall Benefit: Risk Conclusion 
Taking into consideration the measures to minimize risk to participants in this study, the 
potential risks identified in association with the proposed study are justified by the anticipated 
benefits that may be afforded to participants with the need for an indwelling PIVC.  
Furthermore, the BD Nexiva catheter is registered with the Australian Therapeutic Good 
Administration, and in this study, is being used within its approved indication for use.  In 
addition, risks will be minimized through selection of investigators who are qualified and 
skilled in the performance of venipuncture. 
 
3 
OBJECTIVES AND ENDPOINTS 
3.1 
Brief Description of Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary 
 
• 
Assess patent indwell time for PIVCs of 
different length and gauge 
 
• 
Catheter indwell time  

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Secondary 
 
• 
To assess haemolysis occurrence based on 
blood collection device, catheter device 
configuration 
• 
Haemolysis: Quantification and 
frequency of occurrence 
• 
To evaluate blood draw fill time 
• 
Blood draw fill time 
• 
To determine the relationship, if any, 
between catheter blood draw patency 
indwell time and presence of 
intra/extravenous thrombi, catheter 
angle/tip location in situ, catheter length 
in vessel, vein depth from skin surface, 
C/V ratio, and vessel anatomy 
• 
Incidence of: 
o Intravenous thrombus (mural, at 
tip), vein collapse, presence / 
location of a valve relative to 
catheter tip, side branches relative 
to catheter tip detected via 
ultrasound 
• 
To evaluate changes in vessel dimensions, 
PIVC position (insertion angle and in situ 
tip position), and hemodynamics from 
baseline throughout indwell time 
• 
Vessel diameter, blood flow velocity, in 
situ tip position, extravenous thrombus 
within catheter hub, needleless connector, 
extension tubing via visual observation 
Tertiary/Exploratory  
 
• 
To assess incidence of complications 
prompting device removal  
• 
PIVC Complications: Frequency of 
occurrence (vein collapse, phlebitis, 
venous thrombosis, dislodgement, 
extravasation, accidental removal)  
• 
To evaluate manual flush variability (as 
applicable) using in-line pressure 
measurements  
• 
Flush pressure profile and duration of 
flush 
 
3.2 
Hypotheses for Specific Outcomes 
3.2.1 Indwell time 
1) The duration of PIVC indwell time will be greater in duration for longer catheters. 
2) The duration of PIVC indwell time will be greater for catheters of smaller gauge (larger bore). 
3.2.2 Cell free haemoglobin  
1) The cfHb concentrations observed in blood samples (all vacutainers) collected from shorter 
catheters will be greater than that observed in longer catheters over time.  
2) The cfHb observed in blood samples (all vacutainers) collected from catheters with a larger gauge 
(smaller bore) will be greater than blood collected from smaller gauge (larger bore) over time. 
3) The cfHb observed in blood samples (all catheters) collected into greater volume vacutainers will 
be greater than blood collected into smaller volume vacutainers. 
4) The duration of PIVC indwell time will be associated with impairments in other secondary and 
exploratory endpoints 

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4 
STUDY DESIGN 
4.1 
Overall Design 
This is a randomized, single-center, open-label feasibility trial to provide preliminary signals of 
performance to help make decisions about whether to continue with the development of product 
enhancements.  Four variations of the BD Nexiva PIVC (20G x 1, 20G x 1.75, 22G x 1, or 22G x 
1.75) will be placed in the lower cephalic vein of both arms in approximately 40 healthy volunteers; 
20 participants with 20G x 1 inch and 20G x 1.75 inch catheters, and second group of 20 participants 
with 22G x 1inch and 22G x 1.75 inch catheters. PIVC indwell time will be monitored (removal at 72 
hrs or upon inability to flush/aspirate) with blood collected by venipuncture (Day 1 only) and via the 
devices using 2 and 6mL vacutainers throughout the remainder of indwell time. 
After 5 participants have completed their final visit, the in-situ catheter positions will be compared to 
the expected tip position based on the catheter lengths (1 inch versus 1.75 inch for either gauge).  Tip 
position of the longer catheter is expected to reside more horizontally within the vessel. In the event 
catheter tip position differences are not distinct between catheter device lengths study conduct may be 
stopped.  Additionally, this analysis will be used to refine study logistics associated with device 
placement, securement, sonographic measurements, and blood sample acquisition/testing over the 72-
hour study duration. 
Each participant will complete 6 visits: a Screening Visit (V1), followed by 4 Visits (V2-V5) to be 
started within 30 days after screening, and a 24-96 hour follow-up post catheter removal (V6).  
The duration of the study execution is expected to be 5 months. 
4.2 
Scientific Rationale for Study Design 
 
Given that participant variability (e.g., coagulation and platelet function) may impact study endpoints 
(e.g., device indwell time and haemolysis)23, the current study utilizes a simultaneous paired 
experimental design to assess whether differences in device design (i.e., lengths of 1 inch and 1.75 inch) 
impact PIVC indwell time; unpaired analysis will be employed to investigate the effects of catheter 
gauge on PIVC indwell time.  PIVC length was selected for paired analysis as it is hypothesized that 
longer PIVC catheters may extend indwell time based upon catheter tip location within the vessel, 
increased tip distance from insertion site, and reduced probability of accidental dislodgement. Although 
gauge is a factor that may impact indwell time, participant screening is conducted to only enroll those 
with catheter-to-vessel (C/V) ratios no greater than 45%; thus it is anticipated that gauge will have an 
effect less susceptible to participant variability and was selected for the unpaired analysis. As both 
device length and gauge are expected to influence haemolysis17,20 the study design enables evaluation 
of both design features.  
Identification of device design factors that improve PIVC indwell time and decrease incidence of 
haemolysis during PIVC-based blood collection is of clinical significance due to the associated benefits 
for the patient (e.g., uninterrupted medical treatment, and decreased discomfort, pain and anxiety)28,29,33, 
for the health care worker (e.g., reduced chance of needle stick injuries)28, and for the healthcare 
institution (i.e., reduced cost of care)12,29. 

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4.2.1 Participant Input into Design 
Not applicable 
4.3 
End of Study Definition 
A participant is considered to have completed the study if he/she has completed all required phases of 
the study including the last visit or the last scheduled procedure shown in the Schedule of Activities. 
N.B. the number of phases completed can vary depending on the longevity of the devices placed. 
The end of the study is defined as the date of the last visit of the last participant in the study or last 
scheduled procedure shown in the Schedule of Activities for the last participant in the trial globally. 
5 
STUDY POPULATION 
Participants of clinical trials at the Clinical Trials Unit (CTU) based at the Griffith University Gold 
Coast campus are recruited through two primary mechanisms: 1) local advertising via digital and 
paper flyers; and 2) identification of suitable participants in the CTU volunteer registry (database).  
All advertising in the printed and audio-visual medial has prior approval of the Griffith University 
Human Research Ethics Committee (HREC).  The CTU volunteer registry has been maintained since 
2015 and currently contains more than 700 volunteers. 
5.1 
Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
a. Female or Male 
b. 18-65 years of age 
c. Not pregnant at time of recruitment within 48 hrs Day 1 procedures (self-reported) 
d. Normal coagulation results (prothrombin time 13-17 sec; activated partial thromboplastin 
time 27-37 sec) 
e. Normal platelet aggregation results for ADP, TRAP, and collagen induced maximal 
amplitude (>70% amplitude over 6 mins) 
f. Target cephalic veins readily cannulatable  (i.e., ≥ ~2.55 mm to obtain C/V ratio less than 
45% as indicated by standard 52 of the INS guidelines27 
g. Able and willing to provide verbal and written consent 
h. Current Medicare card holder 
 
5.2 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
a. History of pro coagulative state/condition (e.g. previous deep vein thrombosis 
b. Current hypertension (e.g., systolic >139 OR diastolic >89 mmHg) 
c. Currently on any anti-coagulant or platelet inhibitor medication. Use of NSAIDs and 
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d. Hemophilia or any current or history of bleeding disorder or tendency 
e. Presence or report of current blood borne disease/infection (e.g. hepatitis, HIV, leukemia, 
lymphoma) 
f. Difficult vascular access (i.e., vein must be readily palpable and cannulatable – no less 
than ~2.55 mm diameter to maintain ≤45% C/V ratio) as indicated by standard 52 of the 
INS guidelines27 
g. Allergy or sensitivity to chlorhexidine gluconate, isopropyl alcohol, latex, or skin 
adhesives 
h. BMI <18.5 kg/m2 or ≥35 kg/m2 
i. Positive results for the urine drug screen at screening or check-in (including opiates, 
methadone, cocaine, amphetamines) 
j. History or presence of alcoholism (self-reported) or drug abuse within the past 2 years 
k. A current or previous medical, physical, mental/cognitive disorders or anatomical 
conditions that, in the opinion of the investigator, would place the patient at risk, would 
make them unable to perform study procedures or has the potential to confound 
interpretation of the study results. (e.g., musculo-skeletal injury, chronic back pain) 
l. Employed by Becton Dickinson, Teleflex Medical, Smiths Medical or B Braun (conflict of 
interest) 
 
5.3 
Lifestyle Considerations 
5.3.1 Lifestyle restrictions  
During the participant’s commitment in the study the following lifestyle restrictions will apply:  
1) They will not be able to attend work on the days of your participation (Days 1-4 and Visits 2-5 
inclusive), although limited typing, making phone calls may be possible, pending approval of the 
study team.  
2) They will not be able to participate in any sport;  
3) They will not be able to shower away from CTU (sponge bath acceptable-avoiding areas of 
insertion/securement dressings) while catheters are in place 
4) They will not be able to go for a swim; and  
5) They will not be able to undertake any physically vigorous activity.  
This is so that the catheters do not dislodge from the participant’s arm and so that we can minimize the 
chance of the participant bruising and/or getting an infection. 
5.3.2 Dietary restrictions 
The following items will not be consumed for the duration of the study as they impact on the participant’s 
blood clotting capability:  
1) beetroot34;  
2) energy drinks high in taurine content (e.g., Monster, Red Bull, Mother)35; and  
3) alcohol36,37.    

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5.3.3 Medication restrictions 
Some medications may be prohibited (e.g., ibuprofen, high-dose aspirin), while other medications are fine 
(e.g., magnesium): the participant will need to complete a medical history questionnaire where they indicate 
any medications, including over-the-counter medications, that they are currently taking to ascertain 
participant eligibility in the event medications may impact study results; note, if participant meets inclusion 
criteria and no exclusion criteria the use of current medications would not be stopped. Should a participant 
need to take any medications during their time participating in the study, they will be asked to please contact 
a member of the study team. The participant should not take any illegal drugs during involvement in the 
study.  Similar to the dietary restrictions, these medication restrictions apply as they impact on the 
participant’s blood clotting capability. Recreational drugs (i.e., alcohol) will also be prohibited during the 
period of catheterization. 
5.3.4 Blood donation restrictions 
The participant will not be able to donate blood during involvement in the current study.  As we are already 
taking some of the participant’s blood for the current study, the participant may feel fatigued, short-of-breath 
and dizzy due to losing too much blood over a short period of time if they were to also donate blood. 
5.4 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but who do not 
meet the inclusion criteria, or who meet the exclusion criteria. All data collected for screen failures will not 
be reported in the final clinical trial report. 
Individuals who do not meet the criteria for participation in this study (screen failure) may not be rescreened. 
6 
STUDY INTERVENTIONS 
6.1 
Study Device 
The BD Nexiva closed IV catheter systems are intended to be inserted into a patient’s vascular system for 
short term use to sample blood, monitor blood pressure, or administer fluids. These devices may be used for 
any patient population with consideration given to adequacy of vascular anatomy, procedure being 
performed, fluids being infused, and duration of therapy.  
BD Nexiva closed IV catheter systems are over-the-needle, intravascular (IV) catheters. These devices have a 
radiopaque BD Vialon catheter, needle, needle shield, septum, stabilization platform, integrated extension 
tubing, clamp, Luer adapter, and vent plug. The needle and catheter are protected by a needle cover 
The closed system is designed to keep blood contained within the device throughout the insertion process. 
The septum is designed to wipe visible blood from the needle surface as the needle is withdrawn from the 
catheter, further reducing the risk of blood exposure. The needle tip is passively protected when the needle is 
removed, reducing the risk of accidental needlestick injury. 
These devices have BD InstaflashTM Needle Technology, allowing for immediate visualization of blood along 
the catheter. 
Continuous blood return is seen in the extension tubing. The vent plug prevents blood leakage from the 
extension tubing during insertion. Both the stabilization platform and Luer connector are color coded to 

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indicate catheter gauge size (24 GA (0.7 mm) = Yellow, 22 GA (0.9 mm) = Blue, 20 GA (1.1 mm) = Pink, 18 
GA (1.3 mm) = Green). 
See the IFU included in the Appendix (16.1) for full details on the device. 
6.2 
Control Device/Standard of Care 
Not applicable; this is a single-arm study. 
6.3 
Ancillary Devices/Products 
The details of the ancillary devices/products that are critical to the use of the study device and/or execution of 
the protocol (e.g., device/procedure components that are used with the study device) are provided in Table 2 
below. 
Table 1. Ancillary products 
Description 
Manufacturer 
3M™ Tegaderm™ IV Securement Dressing, 
Nexiva or equivalent 
3M 
BD MaxZero™ Needleless Connector 
BD 
BD Vacutainer® Luer-Lok™ Access Device 
BD 
BD Vacutainer® EDTA, 2 mL 
BD 
BD Vacutainer® Citrate, 2.7 mL 
BD 
BD Vacutainer® EDTA, 6 mL 
BD 
BD PosiFlush™ SP Pre-filled Saline Syringe, 
10 mL 
BD 
BD Vacutainer® UltraTouch™ push button 
blood collection set (21G) w/ holder 
BD 
Pressure Transducer, Model TNF-R 
 
Argon Medical 
 
 
Table 2. Ancillary devices-Data Acquisition 
Description 
Manufacturer 
SG-Link Data Logger 
Lord Corporation 
WSDA Base station 
Lord Corporation 

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Pressure Transducer DTX Interface Cable, 
Flying Leads 
Merit Medical 
Custom Graphical User Interface (GUI)  
BD 
Laptop Computer  
• 
7th Generation Intel® Core™ i7-
7820HQ (Quad Core, 2.90Gz, 8MB 
cache  
• 
Intel® Tri-Band Wireless-AC 18265 
WiGig + Wi-Fi + BT4.2 Wireless 
Driver  
• 
512GB Solid State Drive M.2 PCIe)  
• 
32GB (2x16GB) DDR4 Memory 
Dell 
 
The data acquisition system will be utilized to collect in-line fluid pressure measurements during catheter 
flush procedures. The data logger is used to acquire raw pressure data from the transducer and wirelessly 
transmit the data to the base station. The transducer is powered by the data logger via interface cable 
connection between the two components. Calibration of data logger will occur prior to use in the study to 
generate a calibration curve to translate bit values measured by the transducer directly to pressure data. The 
transceiver base station attaches to the computer via USB and provides the communication link between the 
data loggers and LabVIEW GUI software application. The LABVIEW based GUI application is loaded on 
the laptop computer and will be utilized to present the user with functions that allow initialization of data 
acquisition, real-time visualization of pressure data, and downloading data stored on internal memory. 
6.4 
Device Labeling 
All products (Table 1) utilized in the protocol are commercially available in Australia. These products will be 
supplied as labeled by the manufacturer. 
6.5 
Treatment Allocation and Measures to Minimize Bias 
The allocation of participants to a particular intervention (e.g., 20G or 22G) and randomization processes are 
described in the following sub-sections. 
6.5.1 Randomization 
Participants will be randomized using R statistical software*1 (R 3.6.2 or higher).  The generation of the 
randomization list will be conducted by a staff member not involved in data acquisition or analysis.  Each 
randomization number will have a corresponding code (e.g., LA_20G_1.75 – indicating a Nexiva 20G 1.75 
 
 
*1 R Core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria, 
2016. URL https://www.R-project.org/.) 
 

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will be first inserted into the left arm).  The participant will then have the other length PIVC of the same 
gauge inserted into the contralateral arm. 
Intervention kits will be created for each participant using large ziplock bags with all necessary (plus extra) 
consumables inside.  Each kit will be separated via separate ziplock bags into consumables required for the 
right arm and left arm.  Once the kits have been created, the appropriate randomization number will be 
recorded on the outside of each.  Subsequently, the corresponding code will be placed in an envelope and 
sealed with the randomization number written on the outside of the envelope.  These envelopes will be 
produced in duplicate with the second envelope sealed in a locked cabinet in the CTU for the circumstance 
where unblinding is required. Thereafter, the randomization list excluding the corresponding code will be 
given to the postdoctoral research fellow for storage until a randomization number is requested for the study.   
6.5.2 Blinding/Masking 
Due to the concealment of intervention allocation, most staff members, other than the inserter and study 
manager (research assistant), will be blinded to which gauge and length catheter the participant is receiving.  
To avoid bias sonographic data measurements (e.g., vessel diameter, C/V ratio, blood flow velocity) will be 
acquired on a separate day at the end of each working week.  The acquisition of the sonographic 
measurements will be conducted by the sonographer).  All concealed data will be transferred into an excel 
spreadsheet that will be subsequently grouped into 2 groups in a separate excel spreadsheet by a staff member 
not involved in data analysis and is unblinded.  This will allow the researchers to analyze the data without 
having access to information about the allocation 
6.5.2.1 Procedures for Unblinding 
In the unlikely scenario of a SAE, the study manager or post-doctoral research fellow will open the duplicate 
envelope located in the locked cabinet of the CTU that has the randomization number written on the outside 
and contains the corresponding code within.  The information will be provided to any personnel that require 
the information (e.g., the study Medical Doctor) as deemed necessary by the Principal Investigator.  
7 
STUDY PROCEDURES AND ASSESSMENTS 
7.1 
Venipuncture-blood collection 
Blood obtained via venipuncture at screening will be collected into vacutainer tubes (2mL (waste tube), 2mL 
BD Vacutainer® EDTA, 1.8mg/ml–1; 6 x 2.7mL BD Vacutainer® Citrate, 109 mol/m3; Becton Dickinson, 
USA; total volume: 20.2 mL) for assessment of inclusion and exclusion criteria (e.g., platelet aggregation, 
coagulation). During the study, blood will be collected from a prominent antecubital vein of the participant’s 
non-dominant arm using a 21G needle and collection set; Becton Dickinson, USA), and a Luer-Lok™ access 
device and vacutainer tubes (2mL (waste tube), 2mL BD Vacutainer® EDTA, 1.8mg/ml–1; 6mL BD 
Vacutainer® EDTA, 1.8mg/ml–1; Becton Dickinson, USA; Total Volume: 10mL). As per Infusion Therapy 
Standards of Practice guidelines27, the application of a tourniquet will be applied prior to venipuncture but 
will be limited to less than 1 minute.  Once the needle has been inserted and blood has begun to flow into the 
waste vacutainer tube, the tourniquet will be loosened to minimize the incidence of haemolysis. 
 

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7.2 
PIVC- Insertion 
Sonographic assessment and surface description of underlying anatomical features will be completed for 
lower arm cephalic veins on both arms to guide catheter insertion.   
 
Figure 1. Vessel surface description based on ultrasound imaging. V, valve; T, termination; B, bifurcation; 1, 
insertion; dotted-line, vein path; arrow, direction of insertion. 
Next, a PIVC will be inserted according to the Instructions For Use into the lower cephalic vein of one arm in 
accordance with a previously established standard operating procedure (see Appendix 16.2) of the participant 
by a trained phlebotomist or nurse using commercially approved devices with sonographic guidance. After 
successful cannulation a BD MaxZero™ needleless connector will be attached to the extension and flushed 
with 3-5 mL saline (0.9%, BD PosiFlush™; 306575; Becton Dickinson, USA), and site stabilized using a 
Tegaderm IVTM securement dressing27. 
7.3 
PIVC-blood collection and pressure monitoring 
A Luer-Lok™ access device, connected to the needless connector, and vacutainer tubes (2mL (waste tube), 
2mL BD Vacutainer® EDTA, 1.8mg/ml–1, REF 367841; 6mL BD Vacutainer® EDTA, 1.8mg/ml–1, REF 
367873; Becton Dickinson, USA; total volume: 10mL) will be utilized to collect blood and ascertain blood 
quality (haemolysis; see Appendix 16.3 for methodology). Prior to blood collection a pressure transducer 
(DTXPlus TNF-R, Cat. no. 682021; Argon Medical, USA) and flush syringe will then be connected to the 
needless connector and zeroed against venous blood pressure.  The catheter will be flushed while collecting 
pressure data in real-time with a custom-designed LabVIEW© routine. Thereafter, the extension set will be 
clamped and pressure transducer/flushing syringe disconnected from needleless connector.  
7.4 
Image acquisition of indwelling catheter and cephalic vein 
The insertion loci will be assessed prior to, and immediately after, insertion of the PIVC using clinically 
approved ultrasound  with a wide-band, high frequency linear array probe from which all B-Mode, color-flow 
(CF), and pulse wave doppler (PWD) images will be acquired.  At each visit prior to flushing and blood 
collection the following images will be recorded: a) three cross-sectional, B-mode images with the indwelling 
PIVC in view; b) three cross-sectional, B-mode images proximal to the PIVC tip; c) three longitudinal, B-
mode images encompassing close to the insertion point of the PIVC to beyond the PIVC tip; and d) a 15 s 
longitudinal, PWD-CF duplex cine loop with the sample volume set ~1cm proximal to the PIVC tip. The 
sampling frequency for all images will be chosen high enough to avoid frequency aliasing. Coded harmonic 
imaging will be utilized for all images to improve visual clarity via enhancement of near-field resolution. 

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7.4.1 Blood flow velocity  
A 15 s longitudinal, PWD-CF duplex scan positioned 1 cm past the tip of the PIVC will be utilized for the 
measurement of blood flow velocity. The PWD sample volume will be positioned at the center of the vein 
with the axial dimension set to between the upper and lower boundaries of the vessel diameter during data 
acquisition.  Due to variations in echogenicity between participants, the gain will not be kept constant for 
PWD and CF image acquisitions.  The velocity spectrum boundary will be traced and the velocities in the 
area underneath utilized for subsequent calculations (i.e. maximum and mean velocity of 5 seconds of data). 
7.4.2 Angle of insertion, catheter length in vessel 
Calculation of the angle of insertion, and catheter length in vessel will be achieved via assessment of the 
three longitudinal, B-mode scans to be taken where the probe is positioned in-line with the superior surface of 
the PIVC tip. These measurements (superior and inferior angles) will be taken with the internal calculations 
of the clinically approved ultrasound.  The data will be reported as the average of the values taken from the 
three images. 
7.4.3 Vessel diameter, C/V ratio 
Calculation of the vessel diameter, and C/V ratio will be achieved via assessment of the three cross-sectional, 
B-mode scans to be taken with the indwelling tip PIVC in view. The vessel diameter and catheter diameter 
will be calculated from the horizontal axis using the internal calculations of the clinically approved 
ultrasound.  The data will be reported as the average of the values taken from the three images. 
7.4.4 Valve, side branch location 
Identification of a valve/s and/or a side branch vessel will be achieved via assessment of the longitudinal, B-
mode scans with the indwelling PIVC in view.  The number of valves and side branches that are within 1 cm 
proximal to the PIVC tip will be recorded and reported. Valves and side branches great than 1 cm from the 
PIVC tip have not been shown to influence blood flow around the catheter and will not be recorded. 
7.4.5 Visualization and quantification of intraluminal/intravascular thrombus formation  
Visualization and quantification of thrombi will be assessed using three longitudinal, B-mode scans taken 
where the probe was positioned in-line with the superior surface of the PIVC tip.  Intraluminal and/or 
intravascular thrombus will be recorded as a ‘positive’ event if the brightness intensity and position of an 
echogenic mass is maintained throughout three individual scans.  The length of the thrombus will subsequently 
be measured in millimeters.  If the thrombus is greater than 5 cm (i.e., 50 mm) in length, the participant will be 
sent to the medical doctor for assessment of appropriate treatment and the participant’s involvement will be 
terminated (see section 2.3.1). The three-image confirmation approach will be incorporated into the analysis in 
order to eliminate the potential for false-positives. This is done because wall shadowing, harmonic distortion 
and operator movement can all contribute to variations (e.g., brightness) in the appearance of the image 38. 
7.5 
Blood analyses 
A lipid panel, liver function test, blood glucose test, and complete blood count, including white blood cell 
differentials, will be acquired from blood samples anticoagulated with EDTA during screening for 
assessment of inclusion and exclusion criteria.   An automated biochemistry analyzer (AU480, Beckman 
Coulter, USA) will be employed for the lipid panel, liver function test, and blood glucose test. An automated 
haematology analyzer (Beckman Coulter DxH 500™; Beckman Coulter, USA) will be used for the complete 

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blood count. The devices will be operated and maintained in accordance with the manufacturer’s standard 
operating procedure. Blood clotting function and platelet aggregation will be assessed from blood samples 
anticoagulated with Citrate during screening for assessment of inclusion and exclusion criteria.  The activated 
partial thromboplastin time (aPTT), prothrombin time (PT) will be quantified from the average of duplicate 
measurements, using an automated haemostasis analyser (Diagnostica Stago, STA-R Evolution; Diagnostica 
Stago, France).  The ADP-induced, and Collagen-induced platelet aggregation will be assessed from the 
average of duplicate measurements, using an impedance aggregometer (Chrono-Log Corporation, USA). The 
measurements will be performed in accordance with the manufacturer’s standard operating procedures. 
If blood test results are not normal, a member of the study team will inform the participant. If the Principal 
Investigator (PI) believes the results may place the participant at increased risk during the study, the 
participant will not be able to continue in the study. A member of the study team will provide the participant 
with the relevant test results, if the participant would like to discuss them with his/her healthcare practitioner. 
7.6 
PIVC-Failure 
The definition of PIVC failure in the current study will be defined as: 1) an inability to flush or collect blood 
through the PIVC or 2) removal of the PIVC based on medical doctor’s assessment of an AE.  A device 
rescue decision tree will be utilized to identify if the PIVC has failed. 
7.7 
PIVC Removal 
Upon completion of the protocol or if the PIVC fails, the device and attached dressing will be removed and 
disposed of according to the Instructions For Use in biohazard bins and incinerated as per Griffith University 
waste management protocol.  Initially, the dressing will be detached from the participant’s skin from distal to 
proximal direction.  Once the dressing has been detached the PIVC, needless connector and dressing will be 
removed (proximal to distal) together from the participant’s arm and later assessed for extravenous thrombus 
(see section 7.8).  Upon removal, a cotton ball will be immediately placed over the insertion site to stem 
bleeding.  Once bleeding has stopped, the arm and insertion site will be wiped clean with a ethanol wipe, a 
fresh cotton ball placed over the insertion site and taped down with 3M Transpore™ tape. 
7.8 
Extravenous Thrombus Assessment (Post-Removal) 
To assess extravenous thrombus in the removed PIVC and needless connector, a camera will be utilized to 
take digital photographs of the hub of the PIVC (internal surface), the PIVC (external surface), needless 
connector (internal surface) and material ejected from the catheter tip.  For each site (e.g., the hub of the 
PIVC), the presence or absence of an extravenous thrombus will be recorded.   
7.9 
Video/Audio or Photography 
To assist the sponsor BD in best capturing and evaluating all the study results, a technician may photograph 
or video procedures conducted throughout the study.  The technician will concentrate only on the procedure, 
but it is possible that the participant’s face may be filmed. Participants are given the right to refuse consent 
for video/photography, per the informed consent document, and may participate in the study if consent for 
video/photography is refused. 
The recording belongs to BD and will be handled with the same confidentiality as all other information 
obtained from the participant during this research study.  Recorded material will be labeled only with the ID 

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number that was assigned during the study.  The participant’s identity will not be revealed by any use of the 
video recording/photography. 
7.10 Safety Assessments 
7.10.1 Insertion Site Assessment 
Participants will be provided instructions to take care of the catheters while they are away from Clinical 
Trials Unit (see Appendix 16.4).  These include, but are not limited to, instructions on how to take care of 
the device while at home and instructions on how to look out for health-related complications.  
Additionally, the document provides instructions on what to do and who to contact if the participant does 
experience any health-related complications while at home with the indwelling PIVCs. Additionally, a 
nurse will complete visual inspection of the insertion sites including assessment of redness, swelling or any 
signs of infection or other complications prior to each blood draw. This assessment will be done according 
to the Infusion Therapy Standards of Practice guidelines27 using the Visual Infusion Phlebitis Scale.  
Where the site assessment indicates a score of ≥ 4 (Table 4), the participant will be referred to the study 
medical doctor for medical decision. If an adverse event is suspected by the nurse, the patient will be 
referred to an on-site clinician for assessment and/or clinical decision. 
Table 3. Visual infusion phlebitis scale 
Score 
Observation 
0 
PIVC insertion site appears healthy 
1 
One of the following is evident: 
Slight pain near PIVC insertion site OR slight redness near PIVC insertion site 
2 
Two of the following are evident: 
• Pain at PIVC insertion site 
• Erythema 
• Swelling 
3 
All of the following signs are evident: 
• Pain along path of catheter 
• Induration (hardening of the tissue) at PIVC site 
4 
All of the following signs are evident and extensive: 
• Pain along path of catheter 
• Erythema (redness) 
• Induration (hardening) at PIVC site 
• Palpable venous cord 
5 
All of the following signs are evident and extensive: 
• Pain along path of catheter 
• Erythema (redness) 
• Induration (hardening) at PIVC site 
• Palpable venous cord 
• Pyrexia (fever) 
Adapted from ‘A battle in vein infusion: phlebitis’ 39 
 

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7.10.2 Securement Dressing Assessment 
A nurse will complete visual inspection of the securement dressing, including the entire infusion system, 
prior to each blood draw.  This assessment will be done according to the Infusion Therapy Standards of 
Practice guidelines27 and the securement dressing changed if the dressing integrity becomes damp, loosened, 
visibly soiled, or if moisture or blood are present under the dressing.  If the dressing integrity is 
compromised, a photo will be taken for observational records and as it is not considered an endpoint of the 
current study, the data will not be assessed. 
8 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
8.1 
Discontinuation/Withdrawal 
• A participant may withdraw from the study at any time at his/her own request or may be withdrawn at any 
time at the discretion of the investigator or sponsor for safety, behavioral, compliance, or administrative 
reasons. This is expected to be uncommon. 
• At the time of discontinuing from the study, any indwelling catheters will be safely removed and disposed of 
in accordance with the Instructions For Use as per standard protocol without any data collected.  
Additionally, the sites of insertion will be assessed for signs of infection and extravasation.  The participant 
will be followed-up within 96 hours for participant safety and to ensure no adverse events have occurred 
following removal of indwelling catheters. 
• If the participant withdraws consent for disclosure of future information, the sponsor may retain and continue 
to use any data collected before such a withdrawal of consent. 
• If a participant withdraws from the study, he/she may request destruction of any samples taken and not tested, 
and the investigator must document this in the site study records. 
 
8.2 
Lost to Follow-Up 
A participant will be considered lost to follow-up and summarily withdrawn if he or she fails to return for 
consecutive study visits post PIVC insertion (Visits 2 through 5). 
The following actions must be taken if a participant fails to return for/complete a required study visit: 
• The site must attempt to contact the participant and attempt to schedule catheter removal and follow-up as 
designated by Visits 5 and 6 procedures. 
• These contact attempts should be documented in the participant’s study record. 
• Should the participant continue to be unreachable, he/she will be considered to have withdrawn from the 
study. 
• Participants lost to follow-up after Visit 1 but successfully contacted prior to PIVC placement may be 
allowed to continue with Visits 2 through 6 at PI discretion. 
 
8.3 
Patient replacement 
Any participants lost to the current study (withdrawn or lost to follow-up) will be replaced through normal screening 
processes and allocated to the incomplete experimental group to ensure at least 20 participant completers for each 
catheter gauge. Replacement participants will be started in the same order as drop-out/withdrawal; drop-outs will not 
be considered eligible for readmission due to potential effects of prior catheter placement on subsequent study 
outcomes. 
 

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9 
ADVERSE EVENTS AND DEVICE DEFICIENCIES 
9.1 
Definitions of Events 
9.1.1 Adverse Events (AEs) 
An AE is defined as any untoward medical occurrence, unintended disease or injury, or untoward clinical 
signs (including abnormal laboratory findings) in participants, users or other persons, whether or not related 
to study device [ISO14155:2011(E)]. 
Pre-existing conditions should be considered as part of the participant’s medical history and should not be 
reported as an AE unless there is a substantial increase in severity or frequency of the condition, which has 
not been attributed to natural history. Exacerbation of an existing condition should be reported as an AE if the 
event meets the protocol definition of an AE. 
9.1.2 Serious Adverse Events (SAEs) 
A serious adverse event is defined by ISO 14155 and/or 21 CFR 803.3 as an adverse event that:  
a. led to death;  
b. led to serious deterioration in health that resulted in life-threatening illness or injury, resulted in 
permanent impairment;  
c. required inpatient hospitalization/prolonged hospitalization, or resulted in medical/surgical intervention to 
prevent life-threatening illness/injury or permanent impairment; or  
d. led to fetal distress, fetal death, or a congenital abnormality or birth defect. 
 
9.1.3 Adverse Device Effect (ADE) / Serious Adverse Device Effect (SADE) 
An adverse device effect is defined as any adverse event that is considered to be related to the use of an 
investigational medical device. This definition includes any event resulting from insufficiencies or 
inadequacies in the instructions for use, deployment, implantation, or operation or any malfunction of the 
investigational device (study device) and includes any event that is a result of a user error. 
A serious adverse device effect (SADE) is defined as an ADE that has resulted in any of the consequences 
characteristic of an SAE. 
9.1.4 Unanticipated (Serious) Adverse Device Effect (UADE/USADE) 
An unanticipated (serious) adverse device effect (UADE/USADE) is any (serious) adverse device effect on 
health or safety or any life-threatening problem or death caused by, or associated with, a study device, which 
by its nature, incidence, severity, or outcome has not been identified in the current instructions for use and/or 
current version of the risk analysis report, or any other unanticipated serious problem associated with a 
device that relates to the rights, safety or welfare of participants. 
UADEs/USADEs will be reported to all applicable regulatory authorities as per the respective regulatory 
authority guidelines.  
9.2 
Severity of Adverse Events 
Each AE shall be assessed for its severity, or the intensity of an event, experienced by the participant 
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Severity Rating 
Description 
Mild 
Event, signs, or symptoms that do not interfere with the participant’s daily activity, are 
usually considered self-limiting, can be treated with non-prescription type medications, 
and do not require medical intervention 
Moderate 
Event may interfere or cause low level inconvenience with the participant’s daily activity. 
Requires medical intervention and/or treatment; however, unlikely to require 
hospitalization or be considered potentially life-threatening in nature 
Severe 
Event may cause significant discomfort to the participant and/or interferes with the 
participant’s daily activity. Requires medical intervention and/or treatment to preclude a 
permanent impairment; may be life threatening and/or require hospitalization 
 
 
9.3 
Relationship of Adverse Event to Device(s)/Procedure 
Each AE will be assessed for its relationship to the study device or procedure according to the following 
guidelines. 
A.  Assess each AE for its relationship to the device or procedure. 
 
• Device Related: This category should be restricted to AEs directly attributable to the study device 
used. 
 
• Procedure:  A procedure includes any study-related activity performed. 
 
B.  The following categories shall be used for assigning the certainty of the relatedness. 
 
Relatedness 
Description 
Not Related 
Event is independent of study intervention and/or evidence exists that the event is 
related to another etiology. There must be an alternative etiology documented by the 
clinician. 
Unlikely Related 
Event in which the temporal relationship to study intervention makes a causal 
relationship improbable (e.g., the event did not occur within a reasonable time of the 
study device use) and in which underlying disease provides plausible explanations 
(e.g., the participant’s clinical condition other concomitant treatments). 
Likely Related 
Event in which there is evidence to suggest a causal relationship and the influence of 
other factors is less likely. The event occurs within a reasonable time after use of the 
study device and is less likely to be attributed to concurrent disease. 
Related 
Event in which there is clear evidence to suggest a causal relationship and other 
possible contributing factors can be ruled out. The event occurs in a plausible time 
relationship to use of the study device and cannot be explained by concurrent disease. 
 
 
9.4 
Reporting of Events 
In this study, AE collection will be limited to those occurring in the arm in which the study device is inserted, 
as well as any other undesirable clinical event judged to be related or possibly related to the  study device, or 

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a study procedure regardless of anatomical region an event that, in the opinion of the investigator warrants 
reporting. 
 
The Investigator must report any AEs which are serious, unanticipated/unexpected and probably or possibly 
related to the study product or procedures to the reviewing HREC in accordance with the relevant HREC 
reporting requirements.  
The Investigator may also have additional responsibilities for AE reporting to their governing Health 
Authority which they are responsible for identifying and fulfilling. 
For all adverse events collected, all sections of the appropriate Case Report Form (CRF) must be completed. 
All SAEs, SADEs, and/or UADEs/USADEs must be reported to the Sponsor within one (1) working day of 
the site/investigator becoming aware of the event.   
 
De-identified copies of all requested relevant documentation should be submitted to the Sponsor within 72 
hours of knowledge, as appropriate. 
The Sponsor will provide results of any evaluation of an unanticipated/unexpected adverse product effect to 
appropriate Regulatory/Health Authorities and to all Investigators within the respective reporting timelines, 
after the Sponsor is notified of the event. The PI will assume responsibility for submitting reports of 
evaluation results to their relevant HREC. The PI must notify the Sponsor in writing the report has been 
submitted to HREC and must retain evidence of their compliance with this requirement. 
BD will comply with all other Sponsor safety reporting requirements and timelines for other entities  and 
local health authorities in other countries where this study or other studies with the same product are being 
conducted, in compliance with study procedures and applicable local regulatory requirements and BD 
Standard Operating Procedures. 
9.4.1 Pregnancies 
Investigators must instruct participants to inform them immediately if they become pregnant during the trial.  
In case of a pregnancy during the participation in the trial, the participant will be immediately considered for 
premature discontinuation. 
The pregnancy will be registered on the CRF protocol deviation form. In addition, the Pregnancy Form 
(which is independent of the CRF) will be completed with all the available information within the same time 
frame and following the same routing as for a SAE, described previously.  
All pregnancies discovered by the Investigator after the termination of the trial but which were initiated 
during the participation in the trial will be reported to BD as occurring during the trial. 
9.5 
Adverse Event (AE) Management 
Collection of adverse events will begin after the participant has signed the Consent Form through the end of 
the participants participation in the study. 
The participant will be questioned in an open-ended manner regarding any new or worsening undesirable 
signs or symptoms they may have experienced since starting the study. Signs and symptoms must be 

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comprehensively documented on the appropriate source documentation. All related signs and symptoms 
should be grouped under one diagnosis if possible. 
Each sign, symptom, disease or illness reported must be evaluated by the Investigator or designee to 
determine if it meets the definition of an AE.  
Any worsening or undesirable signs or symptoms of the PIVC insertion sites that results in the withdrawal of 
the participants from the study or, in the opinion of the Investigator or designate, warrants medical attention 
or medication will be considered AEs that will be subjected to the same criteria as all other AEs. Overall 
medical coverage for study participants will be provided by Griffith University affiliated general practitioners 
(GP), e.g. GPs at Griffith University Health Clinic and emergency physicians at the Gold Coast University 
Hospital. 
If an AE or SAE occurs around the PIVC insertion site, it may be needed to take photographs of the site only. 
Only the Principal Investigator, Sub-investigator, study staff and Sponsor will have access to the de-identified 
photographs for review and assessment. 
9.5.1 Follow-up of Adverse Events (AE) 
Adverse events that are ongoing at the time of the participant’s scheduled completion visit will be followed 
until resolution of the event means of the investigational site contacting the participant via telephone or by 
any other means considered appropriate. The Investigator will communicate with the sponsor Medical 
Monitor (via telephone and/or email) as to the need for further follow-up. In the case of discrepancies, the 
Investigator’s judgement will prevail. All communications with the participant and medical monitor will be 
documented appropriately.  
The clinical course of any serious adverse event will be followed according to accepted standards of medical 
practice until the event resolves, stabilizes, or in the opinion of the Investigator, is no longer considered 
clinically significant as it relates to the study product and/or study procedures.  
 
9.5.2 Additional procedures for Assessing & Reporting Serious Adverse Events (SAE) 
SAE criteria are specified in Section 9.1. All SAEs must also be assessed by the Investigator and Sponsor 
Medical Monitor to determine whether an SAE is expected or unexpected. An adverse event will be 
considered unexpected or unanticipated if the nature, severity or frequency of the event is not consistent with 
the risk information previously described in the protocol, Informed Consent, Information for Use (IFU) or 
Investigator’s Brochure.  
All adverse events, regardless of the Investigator’s opinion of expectedness or relationship to the study 
product, must be reported to the Sponsor and Safety vendor, in case sponsor should consider outsourcing any 
safety management or reporting tasks, within 24 hours. The Investigator or designee must report the event by 
telephone or email to the Study Monitor. In addition, the Investigator must notify the local Field Assurance 
team within 24 hours of the receipt of the information about any device-related (unlikely related, likely 
related, related) AEs and SAEs by sending the completed AE/SAE form to the following email address: 
complaints.australia@bd.com  
        
 
 
 

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Medical questions about study safety issues and serious adverse events can be directed to the Sponsor 
Medical Monitor. 
 
David Maggs, MD 
VP, Medical Affairs, BDTI, Medical 
Affairs 
Office: +1- 919-597-6255 
Mobile: +1-858-344-1339 
e-mail: David.Maggs@bd.com 
 
9.6 
Device Deficiencies 
The Investigator will record a device deficiency if a device used in the study procedure failed to meet its 
performance specifications whether due to mechanical failure, malfunction, or defect.  Device deficiencies 
also include use errors and inadequate labeling.  This applies to: devices used to treat the participant, or 
devices in which the package was opened, but the device was not used for treatment, or devices with which 
treatment was attempted, but the device did not remain through the entire study procedure/period. 
All mechanical failures, malfunctions, missing components, and defects of the study devices must be 
promptly reported to the Sponsor within 24 hours; notification by email (complaints.australia@bd.com) with 
copy to Sponsor Study Monitor and Sponsor local representative. Information required: Product Code; 
Batch/Lot; Date of event; Did the event occur before, during or after use; Description of the event; Did an 
adverse event occur. In all events, the device(s) in question should be returned to the Sponsor as instructed by 
the Sponsor monitor or sponsor appointed local representative, for analysis. If it is not possible to return the 
device(s), the reason it could not be returned as well as its final disposition should be documented.   
If the device deficiency was associated with an AE, the reporting provisions for AEs, ADEs, SAEs, SADEs 
and UADEs/USADEs apply. 
Reported deficiencies will be investigated and reported under 21 CFR part 803 Medical Device Reporting by 
the Sponsor if necessary.  The site may be contacted to provide additional information to allow the Sponsor 
to conduct a thorough investigation. 
It is the responsibility of the Investigator to notify the responsible HREC of such device deficiencies in 
accordance with the HREC reporting requirements. 
10 STATISTICAL METHODS 
10.1 Overview of Study Design 
This is a single-centre, open-label, multi-visit, self-controlled study design, in ~40 healthy participants, 
randomized by cannula gauge of peripheral intravenous catheter (PIVC) device into the lower arm cephalic 
vein of both arms. 
More details about the statistical methods used for primary, secondary and exploratory objectives will be 
provided in a separate Statistical Analysis Plan (SAP).  This SAP will include mock tables and figures 
whenever possible.   

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10.2 Sample Size Considerations 
There is limited published data investigating the impact of PIVC catheter length on indwell time; a single 
article was found in the literature comparing catheter survival between a BD PIVC catheter (20 gauge; 4.78 
cm/1.88 inch length) and midline catheter (POWERWAND™, 19.5 gauge; 6 cm/2.3 inch length)9.   The 
indwell time results for this research were utilized to calculate a sample size estimate. As this an exploratory 
study no statistical justification for sample size is required; however, an estimate was compiled to provide an 
initial assessment of potential sample requirements. Based on the available dataset, a sample size of ~20 
participants per PIVC gauge would be required given median failure times of catheter lengths at 1 and 3 days 
(Figure 2) 
 
Figure 2. Details of estimation of sample size calculation. 
 
10.3 Analysis Population 
The following populations are defined as: 
 
Population 
Description 
Enrolled  
All participants who sign the ICF 
Evaluable 
All participants who complete the study until either the catheter fails or the 
protocol is completed (i.e., 72 hours) 
 
10.4 General Considerations 
Participants who have withdrawn consent for continuation of the study (i.e., dropouts or non-compliant) will 
be included in the analysis by modern imputation methods for missing data.  In the unforeseen circumstance 
of a protocol violation (e.g., 20G PIVC instead of 22G PIVC; blood was collected into 6mL vacutainer before 
2mL for a specific participant), the data will be analyzed ‘as treated’ – that is, data will be analyzed as the 
participant’s actual received intervention. However, in the unforeseen circumstance of a protocol violation 
whereby a participant receives the wrong intervention (e.g., two different gauge catheters; two 20G catheters 
of the same length), they will be treated as per protocol and thus their data will be excluded from the study. 
10.5 Primary Endpoint(s) 
Comparisons across and between device configurations (i.e., length/gauge) will be made using logrank tests for 
indwell time. The primary endpoint will be evaluated using statistical modeling software (Prism, Release 8.3; 
GraphPad Software Inc., USA) or R (R 3.6.2 or higher). 
 

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10.6 Secondary Endpoint(s) 
Linear mixed-effects models will be used to evaluate the following endpoints over time and determine the 
effect on PIVC indwell time for a given configuration (i.e., length/gauge):  
1) cfHb concentration;  
2) blood draw fill time;  
3) blood flow velocities above or below the catheter  
4) vessel dimensions; and  
5) intravenous thrombus size.  
Underlying normality assumptions will be verified and if not fulfilled non-parametric tests will be used. 
Multivariate analysis (to be defined in the SAP) will be employed to assess the effect of baseline 
characteristics on catheter indwell time and thus identify their power as predictive biomarkers using the 
following the independent variables including, but not limited to:  
1) angle of insertion;  
2) vessel dimension;  
3) presence of side branches and/or intravenous valves;  
4) age;  
5) sex;  
6) height;  
7) weight;  
8) BMI;  
9) medical history questionnaire responses; and 
10) exploratory endpoints.  
A multiple-logistic regression analysis will be employed to assess the effect of baseline characteristics on 
catheter failure over a period of 72 hours and thus identify their power as predictive biomarkers using the 
independent variables including, but not limited to:  
1) angle of insertion;  
2) vessel dimension;  
3) presence of side branches and/or intravenous valves;  
4) age;  
5) sex;  
6) height;  
7) weight;  
8) BMI;  
9) medical history questionnaire responses; and  
10) exploratory endpoints. 
A chi squared analysis will be employed to assess the proportion of individuals in each group (i.e., PIVC 
length and gauge) that have presence of the following at failure/end-of-protocol:  
1) vein collapse;  
2) intravenous thrombus; and  

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3) extravenous thrombus. 
All data will be evaluated using statistical modeling software (Prism, Release 8.3; GraphPad Software Inc., 
USA) or R (R 3.6.2 or higher). P-values ≤0.05 will be considered statistically significant. 
10.7 Tertiary/Exploratory Endpoint(s) 
Exploratory endpoints collected at baseline will be included in the multiple-regression analysis described in 
section 10.6 
10.8 Other Analyses 
Descriptive statistics (number of observations, mean, standard deviation, minimum, maximum and 95% mean 
confidence interval) will be calculated and presented for all quantitative responses (e.g., medical history 
questionnaire responses). Frequency tables with number of observations, percentage of total and 95% 
confidence interval for the percentage (as applicable) will be created for discrete responses. 
10.9 Interim Analysis 
A formal interim analysis is not planned; however, after 5 participants have completed their follow-up visit 
(V6), in-situ catheter positions will be compared to the expected position based on the catheter lengths as 
described in Section 4.1. 
11 DATA COLLECTION AND RECORD MAINTENANCE 
11.1 Data Management  
All participant data relating to the study will be recorded on paper or electronic CRFs.   
The PI or qualified designee is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF.    
All entries to paper CRFs will be made clearly in black or dark blue ink. Corrections will be made using the 
principles of Good Documentation Practice. 
A Data Management Plan (DMP) will be developed that outlines the procedures used for data review, 
database cleaning and issuing/resolving data queries. Procedures for validations and data storage will also be 
contained within the DMP.   
The PI must maintain accurate documentation (source data) that supports the information entered in the CRF. 
The PI must permit study-related monitoring, audits, HREC review, and regulatory agency inspections and 
provide direct access to source data documents. 
Study documentation will be promptly and fully disclosed to the Sponsor by the PI upon request.  The PI 
agrees to promptly take any reasonable steps that are requested by the Sponsor or regulatory authority as a 
result of an audit or inspection to correct deficiencies in the study documentation and CRFs/worksheets.  
The Sponsor or designee is responsible for the data management of this study including quality checking of 
the data. 

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Participant ID will be used to track participant information throughout the study.  Participant personal 
information will be de-identified. 
The transmission of paper CRFs to the sponsor (i.e., Becton Dickinson) will be conducted via scans of the 
CRFs once per week. 
11.2 Source Documentation 
Original or certified copies of all relevant clinical findings, observations, and other activities throughout the 
clinical investigation must be recorded and maintained in the medical study file of each enrolled participant.  
Where there is no prior written or electronic record of data, such as for subjective data (e.g., pain scales, 
questionnaires), these data may be recorded directly on the CRF(s) and the CRF is then considered to be the 
source.  Typical source documents can include the laboratory report, clinician notes, patient record, recorded 
data from automated instruments or other documentation prepared and maintained by the investigator/staff 
which contains a record of all observations and other data pertinent to the investigation on a study participant.  
Electronic data sources included in the database will comprise: 
• A PDF that provides raw cfHb absorbance at three wavelengths obtained from Thermo Scientific 
MultiSkan GO and SkanIT software 
• A scanned document that provides the calculated haemolysis value and whether it is above 200 
mg/dL, obtained from Beckman Coulter AU480 
• A scanned document that provides the blood glucose, lipid and liver function test results and whether 
they are above healthy limits, obtained from Beckman Coulter AU480 
• A scanned document that provides the FBC values and reference ranges obtained from Beckman 
Coulter DxH500 
• A digital photograph (JPEG/TIFF) that provides evidence of an extravenous thrombus (or not) 
• A digital photograph (JPEG/TIFF) that provides visual assessment of haemolysis 
• A digital photograph (JPEG/TIFF) that provides visual assessment of drug test result (dipstick) 
• DICOM/JPEG images and cine loops (video capture) that allow for the measurement of blood flow 
velocity, C/V ratio, and other sonographic raw data (e.g., angle of insertion, presence of side branches 
and/or intravenous valves) 
• A CSV file and MATLAB file that provides raw pressure reading data and the analysis and 
interpretation of the pressure trace 
The PI is required to maintain original source documents at the site.  Should an original source document 
(e.g., an instrument printout, direct entry CRF) need to be forwarded to the Sponsor for data entry, the site 
must retain a clearly designated certified copy.  The Study Monitor will confirm that procedures for copy 
certification have been established at the site prior to transmittal of any original source documents.  
 
All source documents will be held within the Clinical Trial Unit, Griffith University, which has strict access 
provisions/processes.  Additionally, electronic data sources listed in section 11.2 will be printed and included 
in the medical study file; however, the DICOM images and cine loops will not be kept in the medical study 
file.  Subsequently, there will be an electronic file for each participant which will contain all electronic data 
sources (Figure 3). 

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Electronic source documents and data will be securely stored on the Griffith University Research Space and 
will be accessible by only the investigational staff, Griffith University Research support staff, and the 
Sponsor monitor. Additionally, electronic source documents will be backed up onto an external hard drive at 
the end of each day which will be password protected and held securely within the Clinical Trial Unit, 
Griffith University, which has strict access provisions/processes. 
 
Figure 3: Electronic data sources 
11.3 Record Retention 
Records and documents, including PICF, pertaining to the conduct of this study must be retained by the PI for 
15 years after the study completion in line with local regulations or unless institutional policies require a longer 
retention period.  No records may be destroyed during the retention period without the written approval of the 
Sponsor.  No records may be transferred to another location or party without written notification to the 
Sponsor. 
Notice of a transfer shall be given to the Sponsor not later than ten (10) working days after the transfer occurs. 
 

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12 QUALITY CONTROL AND ASSURANCE 
12.1 Control of Study Products 
Investigational study product will be released only for use by PI/Investigational site who has obtained written 
HREC approval (as required) to conduct this study, who has completed all required study documentation, and 
who has been qualified by the Sponsor.  The PI must maintain control over all study product, and ensure the 
study device are used in accordance with this protocol.  Failure to do so may result in the Sponsor suspending 
or terminating the study at the Investigator’s site.  
The Investigator will ensure that study products are only dispensed to participants (or used for specimens) 
properly enrolled in the study. The Investigator must maintain records of receipt, disposition, return and/or 
destruction of all study products. All investigational study products released to the site must be accounted for 
at the unit level prior to study close out, regardless of disposition.  The Sponsor Monitor will regularly review 
all records regarding study product accountability.  
The Sponsor will maintain records that document the shipment, receipt, disposition, return and/or destruction 
of study products. 
12.2 Monitoring 
The Sponsor will designate trained and qualified personnel to monitor the progress of this clinical study in 
accordance with established standard operating procedures and the study-specific Monitoring Plan.   
Prior to study start, a study initiation visit (SIV) will be conducted to review with the PI, Sub-Investigator(s) 
and study staff the provisions and proper conduct of this study. This visit will include a detailed review of 
this protocol, verification that all necessary documents are on file at the investigational site and confirmation 
of HREC approvals.   
During the study, routine monitoring visits (RMVs) will be conducted to assure the site continues to adhere to 
the protocol, the investigator agreement, and regulations regarding conduct of clinical studies.  The Sponsor 
Monitor will confirm that the ICF to be used is the version approved by the HREC, confirm the applicable 
national privacy laws have been followed, verify that all necessary documents are on file at the 
investigational site and confirm that there are provisions to continue and maintain all documents and records 
throughout the study as required by applicable regulations. These monitoring visit will assess continued 
protocol compliance, adequate participant enrollment, accurate data reporting, monitoring of participant 
safety through identification and/or review of any device-related AEs, UADEs, or SAEs, device 
accountability, continued maintenance and calibration of study-specific equipment (if applicable), and 
continued HREC acceptance of the study. 
At the completion of the study, the Sponsor Monitor will conduct a final close-out visit. The purpose of this 
visit may include but is not limited to collecting all outstanding study data documents, confirming that the 
Investigator files are accurate and complete, reviewing the record retention requirements with the PI, 
providing for the return of unused devices to the Sponsor, reviewing records which account for device 
shipments and ensuring that all applicable requirements for closure of the study are met.  

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12.3 Audits and Inspections 
If the study is selected for audit by the Sponsor or if there is an inspection by the appropriate Health 
Authorities, the PI and his team will make themselves available during the visit.  The PI must agree to the 
inspection of all study related records and give the auditor/inspector direct access to source documents for 
verification of data on CRFs/eCRFs.  The participant’s anonymity must be ensured, and data checked during 
the audit must remain confidential. 
As soon as the PI is aware of an upcoming inspection/audit by the Health Authorities, he/she will promptly 
inform the Sponsor.  As agreed with the PI, Sponsor personnel may be present at the site during the 
inspection. 
12.4 Protocol Deviations 
A protocol deviation is defined as an event where the Investigator or site personnel did not conduct the study 
according to the protocol. 
Except when necessary to protect the life or physical well-being of a participant, protocol deviations are not 
permitted.  The Sponsor and the investigational site’s HREC must be notified immediately if an emergency 
situation arises in which the safety of a participant may require immediate intervention different than that 
defined in the protocol.  This must be followed by written confirmation that describes the emergency action 
and outcomes, within five (5) working days from the date of the emergency action in accordance with the 
governing HREC requirement.   
It is the PI responsibility to ensure that there are no deviations from the Protocol.  Except in an emergency, a 
protocol deviation requires Sponsor approval.   
Any and all deviations must be recorded on the appropriate CRF regardless of whether medically justifiable 
or sponsor approved.  Upon evaluation by the Sponsor, actions may be required to prevent additional 
deviations, such as retraining of the site, implementation of additional site procedures, and more frequent 
monitoring.  If these steps fail, more serious measures, up to and including termination of enrollment at the 
site. 
13 ADMINISTRATIVE REQUIREMENTS 
13.1 Investigator and Site Selection 
The PI must be of good standing as an Investigator and knowledgeable in relevant areas of clinical research 
to ensure adherence to the requirements of this protocol, including the protection of human participants.  
Other site personnel must have appropriate research experience and infrastructure to ensure adherence to this 
protocol and enrollment of sufficient numbers of evaluable participants. The curriculum vitae (CV) of the PI, 
Sub-Investigator(s) and Study Coordinator(s) will be maintained in the Sponsor’s files as documentation of 
qualification by training and experience. 
The PI will sign the Investigator Agreement pages of this protocol, agreeing to comply with all applicable 
regulations and the requirements of this study as per the clinical study agreement.  Federal or local databases 
will be searched to ensure that the Investigator(s) and/or the site are not prohibited from engaging in 
sponsored clinical research.  

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Any site that is deactivated prior to initial enrollment, either by the Sponsor or by the individual site itself, 
may be replaced. 
13.2 Training 
In addition to each Investigator and appropriate site personnel being trained on this protocol and study 
procedures during the Site Initiation Visit, product training will be provided by the Sponsor or designee and 
is required for each Investigator. Additional study staff (e.g., Sub-Investigator(s)) will also require device 
training provided from the Sponsor or proctoring by the PI. All training will be documented and filed at the 
investigational site and with the Sponsor. 
 Additional training requirements for support staff include the following: 
• Advanced Vascular Ultrasound course provided by the Australian Institute of Ultrasound for principal 
investigator, and research assistant 
• Beckman Coulter Access 2 and AU480 equipment advanced training provided by Beckman Coulter 
for post-doctoral research fellow, and research assistant 
• Good documentation practice provided by Compliance Online for principal investigator, post-doctoral 
research fellow, and research assistant  
 
13.3 Required Documents 
An Investigator may not screen or enroll participants until authorized to do so by the 
Sponsor. At a minimum, the following documentation should be received by the Sponsor 
prior to the commencement of study activities: 
• [Fully executed Non-disclosure Agreement (NDA) between PI/site and Sponsor]; 
• [CVs, signed and dated within 2 years of study start for the PI and Sub-Investigator(s)]; 
• [CVs for Study Coordinator(s)]; 
• [Signed CSA by PI/site (or designee)]; 
• [Signed Investigator Agreement Page by PI and Sub-Investigator(s)]; 
• [Signed Investigator Brochure Acknowledgement Page by PI and Sub-Investigator(s)]; 
• [Signed Financial Disclosure Statement by PI and Sub-Investigator(s)]; 
• [Completed and Signed Training Log by PI and Sub-Investigator(s)]; 
• [Study Personnel Identification list]; 
• [Written approval from the HREC of both the protocol and ICF, and any other 
• applicable protocol specific material]; and 
• [HREC Membership List, Assurance of Compliance Form, or equivalent]. 
 
13.4 Publication Policy 
The sponsor believes that results of applicable clinical studies should be published in peer-reviewed literature 
in a timely, accurate, complete and balanced manner, regardless of study outcomes, whenever possible.  As 
such, at the conclusion of this study, an article may be prepared for publication in a reputable scientific 
journal at the sponsor’s discretion.  The Investigational site will not publish any articles or make any 
presentations relating to the services or referring to any data or materials generated from the study, in whole 
or in part, without the prior written consent of BD, except for any disclosure that is necessary to comply will 
applicable law or regulation.  Formal presentation(s) or publication(s) of data collected from this study will 

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be considered as a joint publication by the investigator(s) and the appropriate personnel of the Sponsor. 
Authorship will be based on generally accepted criteria of the ICMJE (International Committee of Medical 
Journal Editors) and determined by mutual agreement. 
The analysis of other pre-specified and non-pre-specified endpoints will be performed by the Sponsor or its 
designee. Such analyses, as well as other proposed investigations or manuscripts will require the approval of 
the Sponsor. 
13.5 Study Registration 
The study will be registered on clinicaltrials.gov 
13.6 Termination of Study 
The Sponsor reserves the right to suspend enrollment or terminate the study at any time for any reason.  The 
Sponsor may suspend enrollment or terminate the study at a specific investigational site for reasons 
including, but not limited to, inadequate data collection, low participant enrollment rate, achievement of the 
total enrollment, conditions imposed by the reviewing HREC and/or non-compliance with this protocol or 
other clinical research requirements. Written notice will be submitted to the PI in advance of such 
termination.  
In the event of study suspension or termination, the Sponsor will send a report outlining the circumstances to 
the HREC, and all Investigators and Regulatory Authorities as required by regulation.  
14 ETHICAL AND REGULATORY CONSIDERATIONS 
14.1 HUMAN RESEARCH ETHICS COMMITTEE Approval 
The initial PICF (Participant Information Consent Form), any subsequent revised written PICF, and any 
written information provided to the participant must receive the relevant Human Research Ethics Committee 
(HREC) approval before it can be used.  The informed consent will adhere to the HREC requirements, 
applicable laws and regulations, and Sponsor requirements. 
The PI or designee must submit the study protocol, Informed Consent Form (if applicable), and all other 
locally required documentation to an appropriate HREC and obtain study-specific written approval (favorable 
opinion) before being allowed to participate in the study. Before commencement of the study, the 
Investigator or designee must provide the Sponsor with written documentation of such approval.  The HREC 
must give written renewal of the original approval at least annually to continue the study. A copy of the 
written renewal must be provided to the Sponsor. 
The HREC will be notified of any amendments to the protocol, as well as possible associated information and 
consent form changes, where applicable, and written approval (favorable opinion) will be obtained prior to 
implementation, as applicable. 
The PI or designee is responsible for fulfilling any conditions of approval imposed by the HREC, such as 
regular safety reporting, study timing, etc. The PI or designee will provide the Sponsor with copies of such 
reports. 

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14.1.1 Informed Consent and Confidentiality 
Prior to any study procedure, the Investigator (or designee) must explain to each participant in layman’s 
terms, the nature of the study, its purpose, expected duration, and the risks and benefits of study participation. 
Also, participant will be informed of uses and disclosures of their medical information for research purposes, 
and their rights to access information about them. All applicable national and local privacy laws will be 
followed in this study. The participants must be informed of their right to withdraw from the study at any 
time and for any reason without sanction, penalty, or loss of benefits to which they are otherwise entitled, and 
that withdrawal from the study will not jeopardize their future medical care. Participants will be informed of 
their right to new information and/or findings relating to the clinical study, and the process by which this 
information is made available. After this explanation, given sufficient time to decide whether to participate, 
before any study procedure is conducted, and before entering the study, the participant must voluntarily 
provide consent in accordance with 21 CFR Parts 50 and 56 and ISO 14155:2011.  
Consent must be documented by the participant’s dated signature on a consent form along with the dated 
signature of the person conducting the consent discussion.  
A copy of the signed and dated consent form should be given to the participant before participation in the 
study. 
Confidentiality 
Participant confidentiality must be strictly held in trust by the Investigator, study staff, and the Sponsor.  
Participant confidentiality and anonymity will be maintained by removal of identifiers from any data or 
documentation submitted to the Sponsor. Participants will only be identified by a unique participant 
identification (e.g., PD001).  A master list that includes the participant identification, full name, address, 
telephone number and email address of all participants will be created and kept separate from study 
documents on the Griffith University Research Drive, of which only Griffith University staff team members 
will have access.  
Any data collected meeting the definition of protected/confidential health information or personal identifying 
information will be collected and maintained using the designated authorisations and following all applicable 
privacy laws.   
The Sponsor-Monitor, authorized representatives of the sponsor, and/or applicable Health Authorities may 
inspect all documents and records required to be maintained by the Investigator.  The Investigator/Site will 
permit access to such records.  
14.2 Regulatory Status 
 
The Sponsor has determined and documented this to be a non-significant risk device study based on 
congruency with 21 CFR 812.3.  This determination is based on the following assessment of the 
investigational device: 
• Is not intended as an implant; 
• Is not purported or represented to be for a use in supporting or sustaining human life; 
• Is not intended for a use of substantial importance in diagnosing, curing, mitigating, or treating 
disease, or otherwise preventing impairment of human health; and, 

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• Does not present a potential for serious risk to the health, safety, or welfare of a participant. 
 
Classification of NSR is documented in the Study Risk Assessment Form. The study device is registered with 
the Australian TGA:  ARTG 243114. 
 
This study is a feasibility study in healthy volunteers.  The study is not a registration study to receive a 
regulatory approval. 
 
14.3 Statement of Compliance 
This clinical investigation will be conducted in compliance with all stipulations of this protocol, the 
conditions of the Human Research Ethics Committee approval(s), the NHMRC National Statement on ethical 
conduct on Human Research (2007); ISO 14155:2011;  GCP and in accordance with the ethical principles of 
the Declaration of Helsinki; and all applicable federal, state and local laws and regulations. 
 
The clinical investigation will not commence at a clinical site until approval (favorable opinion) from the 
relevant HREC has been received. All additional requirements imposed by the HREC(s) will be followed. 
Involvement of the national competent authorities (e.g. by notification, seeking authorisation) will be 
accomplished as required by national laws and regulations. 
 
 
 

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Malinauskas RA. Plasma haemoglobin measurement techniques for the in vitro evaluation of blood damage 
caused by medical devices. Artif Organs. 1997;21(12):1255-1267. 
43. 
Horobin JT, Sabapathy S, Simmonds MJ. Repetitive Supra-Physiological Shear Stress Impairs Red Blood 
Cell Deformability and Induces Hemolysis. Artif Organs. 2017;41(11):1017-1025. 
44. 
Horobin JT, Simmonds MJ, Nandakumar D, et al. Speed Modulation of the HeartWare HVAD to Assess In 
Vitro Hemocompatibility of Pulsatile and Continuous Flow Regimes in a Rotary Blood Pump. Artif Organs. 
2018;42(9):879-890. 
45. 
Pauls JP, Nandakumar D, Horobin J, et al. The Effect of Compliant Inflow Cannulae on the 
Hemocompatibility of Rotary Blood Pump Circuits in an In Vitro Model. Artif Organs. 2017;41(10):E118-
E128. 
46. 
Harboe M. A method for determination of haemoglobin in plasma by near-ultraviolet spectrophotometry. 
Scand J Clin Lab Invest. 1959;11:66-70. 
47. 
Leon L, et al. Clinical Significance of Superfical Vein Thrombosis. Eur J Vasc Endovasc Surg. 2005;29:10-
17. 
 
 
 
 
 
 
 

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16 LIST OF APPENDICES 
16.1  IFU 
 
 
 
 
 
 
 
 
 
 
 
52 
16.2  PIVC-cannulation protocol 
 
 
 
 
 
 
 
 
53 
16.3  Quantification of cell-free haemoglobin 
 
 
 
 
 
 
58 
16.4  Participant Instructions 
 
 
 
 
 
 
 
 
59 
 
 
 

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16.1 IFU

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16.2 PIVC cannulation protocol 
1. Assess the venous anatomy. In particular note and identify the location of nerves, arteries and muscle.  
 
2. Asses the target vein for bifurcation, insertion point and valves. 
3. Mark the target vessel with key pen 
dots. Using a sterile pen 
1. Site of insertion “Mark 1” 
2. Location of the valves “Mark V”  
3. Location of catheter tip termination 
“Mark T”  
When a sterile pen is not used place the 
marking parallel to the identified 
structures. When the skin antisepsis is 
applied the marking will be removed.  
 
 
4. The clinician is to wash their hands prior to opening procedural equipment. No gloves are required at 
this stage. 
 
5. Open the sterile Mutligate basic dressing 
pack layout this as your sterile field. Do 
not touch anything on the field without 
sterile gloves. This is your sterile working 
field. Place the following sterile items on 
the dressing field.  
1. The desired PIVC 
2. Foliodrape protect  
3. The 15cm micro bore extension set 
4. BD IV starter pack  
5. Pro Pax Gauze swabs  
6. A BD 1ml luer-lock syringe 
120cm pull-up sterile non latex probe 
covers  
 
 
 

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6. Empty one sachet of sterilisation fluid 
and wipe area of insertion – allow to dry. 
 
 
7. 
Open and put on gloves without 
touching portions of gloves that will make 
contact with the sterile field.  
 
 
 
 
 
 
 
 
8. Place the sterile field under the 
patients’ arm. Ensure the arm/ hand 
does not come in contact with the 
sterile working field.   
An additional sterile field found in the 
additional insertion pack can be placed 
under the back of the hand. 
 
 
 
 
 
 
 
 

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9. Attach tourniquet making the 
assistant aware to tighten it when 
needed.  
 
 
 
10. Place sterile fenestrated drape around 
the site of insertion- fold to reduce 
fenestration (adhesive is very sticky) 
Clean area again (circular movement) and 
allow to dry. 
 
11. Apply the swab-stick using liberal 
movements. If some solution remains in 
the packaging the assistant can pour this 
over the site of insertion.  
 
 
12. Gently squeeze inner cardboard sterile 
ultrasound cover. Apply gel into the 
ultrasound probe cover.  
 
 
 
 
 
 
 
 
 
 
 

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13. Ask the assistant to drop carefully the 
paediatric probe into the sterile probe 
cover. Tighten membrane to ultrasound 
transducer surface and apply the blue 
elastic bands.  
 
 
 
 
14.  Apply a small amount of ultrasound 
gel on the area for insertion. Apply 
tourniquet if necessary (<0.2cm).   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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15. Ensure the vein is centre of the screen. 
Using the yellow guide on the screen and 
the centre mark on the probe line up the 
PIVC to pierce the skin.  You can orientate 
your probe from Transverse to 
longitudinal. 
 
 
 
16. Insert the PIVC through the skin 
ensuring you are looking at the USG 
image. A white echogenic dot signifies the 
needle tip. Be careful to consider 
shadowing and therefore orientate the 
probe from Transverse to longitudinal.  
Advance the probe mms forward and then 
the PIVC mm (prevents damage) 
 
17. Once you are satisfied that the PIVC is 
well in the vein or in as far as it can go 
advance the catheter off the needle stylet. 
 
 
18. Withdraw the needle from the catheter 
another 1cm. Then distally occlude the 
target vein, then; proximally occlude the 
cannulated vein the intension to stop any 
blood spillage. Remove the needle and 
insert in the sharps bin.  
 
 
  
 
 

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16.3 Quantification of cell-free haemoglobin 
In accordance with previous research that has indicated the advantages and precision of the Harboe method 
for detection of cfHb 40-42, the study will measure cfHb via a direct spectrophotometric technique in 
conjunction with the Harboe assay which we have previously employed 43-45 and is an approved ISO test 
method for haemolysis (ISO 10993-4:2017).  The measurement of cfHB will be performed within 12 hours of 
sample collection.  To quantify cfHb via the Harboe assay, whole blood collected and anticoagulated with 
Ethylenediaminetetraacetic acid (EDTA), will be centrifuged at 1200 x g for 10 min.  The top half of the 
supernatant will be added to 0.01% Na2CO3 (1:6) and the absorbance of each sample will be measured at 380, 
415 and 450 nm using a spectrophotometer (MultiSkan GO, Thermo Fisher Scientific; MA, USA).  The cfHb 
will subsequently be calculated from these absorbances using the Harboe method 46 (Eq. 1). 
Equation 1. 
𝑐𝑓𝐻𝑏 (𝑚𝑔
𝑑𝐿) = (167.2𝐴𝑏𝑠415 −83.6𝐴𝑏𝑠450  −83.6𝐴𝑏𝑠380
10
) ×
1
𝑑𝑖𝑙𝑢𝑡𝑖𝑜𝑛 𝑖𝑛 𝑁𝑎2𝐶𝑂3
 
Additionally, an automated biochemistry analyzer (AU480, Beckman Coulter, USA) will be employed for a 
clinical measurement of haemolysis; however, the accuracy of the device is not sensitive to measurements 
below 50 mg/dL.  Lastly, visual assessment of haemolysis will be checked, and photographs taken of each 
sample. 
 
 
 
 
 
 
 
 
 
 
 
 

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16.4 Participant Instructions 
 
 
 
 
 

Protocol Number: BDT-19PIVCAU001 
 
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Date: 15 May 2020 
 
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