A Post-Market Clinical Follow Up Study to Evaluate BD PureHub™ Disinfecting Cap Use on Needle-Free Connectors
Phase: NA
Conditions: Catheter Related Complication, Vascular Access Site Management, Disinfecting Cap
Sponsor: Becton, Dickinson and Company

Protocol Number: MDS-20PUREU001 
 
CONFIDENTIAL 
Version: 2.5 PMCF – AT01 
 
Date: 01DEC2022 
 
Page 1 of 39 
 
 
 
TITLE PAGE 
 
 
 
Protocol Title:  
A Post-Market Clinical Follow Up Study to Evaluate BD 
PureHub™ Disinfecting Cap Use on Needle-Free Connectors  
 
Protocol Number: 
 
MDS-20PUREU001 
 
Version Number: 
 
2.5 PMCF – AT01 
 
Study Device: 
 
BD PureHub™ Disinfecting Cap 
 
Study Type:  
 
Post-Market Clinical Follow-up Study 
 
Sponsor Name: 
 
Becton, Dickinson and Company – Medication Delivery Solutions 
 
Legal Registered Address: 1 Becton Drive, Franklin Lakes NJ 07417 
 
Sponsor Contact: 
Dr. Stephan Hofmann  
Senior Clinical Project Manager 
Global Clinical Affairs 
Wachhausstrasse 6 
76227 Karlsruhe, Germany 
T: +49 160 105 3421 
Stephan.Hofmann@bd.com 
 
 
Regulatory Agency Identifier Number(s): N/A 
 
 
 
 

Protocol Number: MDS-20PUREU001 
 
CONFIDENTIAL 
Version: 2.5 PMCF – AT01 
 
Date: 01DEC2022 
 
Page 2 of 39 
 
 
Version History 
Version 
Number 
Date 
Type 
Section 
Change 
1.0 
04-Jun-2021 
Initial release 
N/A 
N/A 
1.1 
30-Nov-2021 
Local amendment: 
Only applicable 
for UK 
N/A 
No change for V2.3 
1.2 
21-Jan-2022 
Local amendment: 
Only applicable 
for Spain 
N/A 
No change for V2.3 
2.0 
28-Feb-2022 
Local Amendment 
PMCF – provision 
of study devices: 
Changing study 
from Observational 
to Interventional; 
reduction minimum 
VAD Therapy 
period 
 
x Header Section 
 
 
x Sponsor Protocol 
Approval 
x Throughout the 
document 
x Synopsis – Participants 
 
 
x Synopsis 
 
x Section 2.3.1 Risk 
Assessment 
 
 
x Section 2.3.2 Benefit 
Assessment 
 
 
 
x Section 2.3.3 Overall 
Benefit: Risk Conclusion 
 
x Section 5.1 Inclusion 
Criteria 
 
 
x Protocol Title: Change from 
“Observation” to “Post-Market 
Clinical Follow Up” Study 
x Change of Statistician 
 
x Reference to “observational” 
changed  
 
x Inclusion criterion 2: Expected 
minimum VAD therapy 
reduced from 7 to 3 days 
x Addition of anticipated study 
timelines 
x Adjustment of risk section to 
PMCF with interventional 
element 
x Adjustment of risk section to 
PMCF with interventional 
element, addition of clinical 
benefits 
x Adjustment of risk section to 
PMCF with interventional 
element 
x Inclusion criterion 2: Expected 
minimum VAD therapy 
reduced from 7 to 3 days 
x Information added 
 
x Information added 

Protocol Number: MDS-20PUREU001 
 
CONFIDENTIAL 
Version: 2.5 PMCF – AT01 
 
Date: 01DEC2022 
 
Page 3 of 39 
 
 
Version 
Number 
Date 
Type 
Section 
Change 
x Section 6.4 Device 
Labeling 
 
x Section 6.5 Treatment 
Allocation and measures 
to minimize bias 
x Section 7.1 Study 
duration 
x Section 9.1.1. Adverse 
Events 
x Section 11.5 Device 
accountability 
x Section 12.1 Control of 
Study products 
 
 
 
 
x Updated timelines 
 
x “Procedure” added to AE 
definition 
x Information added 
 
x Clarification that Sponsor will 
provide marketed products as 
study devices 
V2.1 
15-Mar 2022 
Local amendment: 
Only applicable 
for BE 
x N/A 
x Local Amendment BE01 – Not 
applicable for this version 
V2.2 
30-May 2022 
Local amendment: 
Only applicable 
for ES01 
x N/A 
x Local Amendment ES01 – Not 
applicable for this version 
V2.3 
13JUL2022 
Local Amendment: 
Only applicable 
for ES02 
x Sponsor Protocol 
Approval 
 
 
x Synopsis & Section 5.2 – 
Exclusion Criteria 
x Change of medical monitor, 
medical affairs representative, 
and statistician 
 
x Change of exclusion criterion 
1 to allow for disinfecting cap 
placement within 12 hours 
prior to ICF signature 
V2.4 
11OCT2022 
Local Amendment: 
Only applicable 
for ES02 
x Sponsor Contact Details 
 
x Protocol 
x Section 7.1  
x Update of Clinical Project 
Manager  
x Update of Format 
x Updated timelines 

Protocol Number: MDS-20PUREU001 
 
CONFIDENTIAL 
Version: 2.5 PMCF – AT01 
 
Date: 01DEC2022 
 
Page 4 of 39 
 
 
Version 
Number 
Date 
Type 
Section 
Change 
V2.5 
01DEC2022 
Local Amendment: 
Only applicable 
for AT01 
x Abbreviations 
x Inclusion criteria 
(Synopsis & Section 5.1) 
x Synopsis 
x Update on Abbreviations  
x For AT01 LAR is not 
applicable 
x Update on Timelines & 
Investigational Sites  
 
 

Protocol Number: MDS-20PUREU001 
 
CONFIDENTIAL 
Version: 2.5 PMCF – AT01 
 
Date: 01DEC2022 
 
Page 5 of 39 
 
 
SPONSOR PROTOCOL APPROVAL 
 
 
Signature below indicates approval of the protocol as written. 
Individual or 
function 
Name 
Signature & Date 
Business Unit Medical 
Affairs 
Medical Monitor 
Klaus Hoerauf, MD, VP 
Medical Affairs, MDS 
 
Business Unit Medical 
Affairs 
Kyle De Boer 
Ass. Director, Medical 
Affair  
 
Business Unit 
Regulatory Affairs 
John Roberts 
Director, Regulatory 
Affairs, MDS 
 
Global Clinical 
Development 
Clinical Operations 
Stephan Hofmann 
Senior Clinical Project 
Manager, GCA 
 
Global Clinical 
Development 
Statistics 
Minyi Ji 
Principal Statistician 
Statistics & Clinical Data, 
GCA 
 
 
 
 
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Protocol Number: MDS-20PUREU001 
 
CONFIDENTIAL 
Version: 2.5 PMCF – AT01 
 
Date: 01DEC2022 
 
Page 6 of 39 
 
 
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 Institutional 
Review Board (IRB)/Ethics Committee (EC). 
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 IRB/EC, the signed CSA, the ethical 
principles of the Declaration of Helsinki, Good Clinical Practice (ICH E6) / ISO 14155, 
EU MDR (Council Regulation 2017/745 of 5 April 2017)), 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 IRB/EC 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 CSA, and Good Clinical Practice (GCP) as well as ISO regulations (e.g., ISO 
14155:2020). 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 
 
 

Protocol Number: MDS-20PUREU001 
 
CONFIDENTIAL 
Version: 2.5 PMCF – AT01 
 
Date: 01DEC2022 
 
Page 7 of 39 
 
 
SUB-INVESTIGATOR AGREEMENT PAGE 
 
Investigator Responsibilities 
 
1. The Sub-Investigator must receive study specific training prior to performing any data 
collection or study-related procedures.  
2. The Sub-Investigator shall conduct the study in accordance with the study protocol, any 
modifications as requested by the IRB/EC, the signed CSA, the ethical principles of the 
Declaration of Helsinki, Good Clinical Practice (ICH E6) / ISO 14155, EU MDR (Council 
Regulation 2017/745 of 5 April 2017)), and applicable national/regional regulations and 
laws. 
3. If applicable, ensure that written informed consent is obtained from each participant prior 
to the conduct of any study procedure, using the current IRB/EC 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 CSA, and Good Clinical Practice (GCP) as well as ISO regulations (e.g., ISO 
14155:2020). 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 
 
 
 

Protocol Number: MDS-20PUREU001 
 
CONFIDENTIAL 
Version: 2.5 PMCF – AT01 
 
Date: 01DEC2022 
 
Page 8 of 39 
 
 
TITLE PAGE .................................................................................................................................. 1 
Abbreviations ................................................................................................................................ 11 
1 
PROTOCOL SUMMARY .................................................................................................... 11 
1.1 
Synopsis ......................................................................................................................... 11 
2 
INTRODUCTION ................................................................................................................ 16 
2.1 
Background .................................................................................................................... 16 
2.2 
Rationale......................................................................................................................... 16 
2.3 
Risk/Benefit Assessment ................................................................................................ 16 
2.3.1 
Risk Assessment ..................................................................................................... 16 
2.3.2 
Benefit Assessment ................................................................................................. 18 
2.3.3 
Overall Benefit: Risk Conclusion ........................................................................... 19 
3 
OBJECTIVES AND ENDPOINTS ...................................................................................... 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 .................................................................................. 20 
4.3 
End of Study Definition ................................................................................................. 20 
5 
STUDY POPULATION ....................................................................................................... 21 
5.1 
Inclusion Criteria ............................................................................................................ 21 
5.2 
Exclusion Criteria ........................................................................................................... 21 
5.3 
Lifestyle Considerations ................................................................................................. 21 
5.4 
Screen Failures ............................................................................................................... 21 
5.5 
Vulnerable Population .................................................................................................... 21 
6 
STUDY INTERVENTION ................................................................................................... 22 
6.1 
Investigational/Test Device ............................................................................................ 22 
6.2 
Control Device/Standard of Care ................................................................................... 22 
6.3 
Ancillary Devices/Products ............................................................................................ 22 
6.4 
Device Labeling ............................................................................................................. 22 
6.5 
Treatment Allocation and Measures to Minimize Bias .................................................. 23 
7 
STUDY PROCEDURES AND ASSESSMENTS ................................................................ 23 
7.1 
Study duration ................................................................................................................ 23 
7.2 
Screening and Enrollment .............................................................................................. 23 
7.3 
Medical History / Baseline Assessments ....................................................................... 23 

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7.4 
Device Use ..................................................................................................................... 24 
7.5 
Efficacy (Performance) Assessment .............................................................................. 24 
7.6 
Safety Assessments ........................................................................................................ 25 
7.7 
Informational Assessments ............................................................................................ 25 
8 
PARTICIPANT DISCONTINUATION/WITHDRAWAL.................................................. 25 
8.1 
Discontinuation/Withdrawal .......................................................................................... 25 
8.2 
Lost to Follow-Up .......................................................................................................... 26 
9 
ADVERSE EVENTS AND DEVICE DEFICIENCIES ...................................................... 26 
9.1 
Definitions of Events ...................................................................................................... 26 
9.1.1 
Adverse Events (AEs) ............................................................................................. 26 
9.1.2 
Serious Adverse Events (SAEs).............................................................................. 26 
9.1.3 
Adverse Device Effect (ADE) / Serious Adverse Device Effect (SADE) .............. 27 
9.1.4 
Unanticipated (Serious) Adverse Device Effect (UADE/USADE) ........................ 27 
9.2 
Severity of Adverse Events ............................................................................................ 27 
9.3 
Relationship of Adverse Event to Device(s)/Procedure ................................................. 28 
9.4 
Reporting of Events ........................................................................................................ 28 
9.5 
Safety Committees ......................................................................................................... 29 
9.6 
Device Deficiencies........................................................................................................ 29 
9.7 
Serious Health Threat ..................................................................................................... 29 
10 STATISTICAL METHODS ................................................................................................. 30 
10.1 Overview of Study Design ............................................................................................. 30 
10.2 Sample Size Considerations ........................................................................................... 30 
10.3 Analysis Population........................................................................................................ 30 
10.4 Primary Performance Endpoints .................................................................................... 30 
10.5 Primary Safety Endpoint ................................................................................................ 30 
10.6 Informational Endpoint(s) .............................................................................................. 31 
10.7 Other Analyses ............................................................................................................... 31 
10.8 Interim Analysis ............................................................................................................. 31 
11 DATA COLLECTION AND RECORD MAINTENANCE ................................................ 31 
11.1 Case Report Forms ......................................................................................................... 31 
11.2 Source Documentation ................................................................................................... 31 
11.3 Data Management .......................................................................................................... 31 
11.4 Record Retention ............................................................................................................ 32 

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11.5 Device accountability ..................................................................................................... 32 
12 QUALITY CONTROL AND ASSURANCE ...................................................................... 32 
12.1 Control of Study Products .............................................................................................. 32 
12.2 Monitoring ...................................................................................................................... 32 
12.3 Audits and Inspections ................................................................................................... 33 
12.4 Protocol Deviations ........................................................................................................ 33 
13 ADMINISTRATIVE REQUIREMENTS ............................................................................ 34 
13.1 Investigator and Site Selection ....................................................................................... 34 
13.2 Training .......................................................................................................................... 34 
13.3 Required Documents ...................................................................................................... 34 
13.4 Insurance ........................................................................................................................ 34 
13.5 Publication Policy .......................................................................................................... 35 
13.6 Study Registration .......................................................................................................... 35 
13.7 Termination of Study ..................................................................................................... 35 
14 ETHICAL AND REGULATORY CONSIDERATIONS .................................................... 36 
14.1 IRB/EC Approval ........................................................................................................... 36 
14.2 Informed Consent and Confidentiality ........................................................................... 36 
14.2.1 Confidentiality ........................................................................................................ 37 
14.3 Regulatory Status ........................................................................................................... 37 
14.4 Statement of Compliance ............................................................................................... 37 
15 REFERENCES ..................................................................................................................... 38 
 
 
 

Protocol Number: MDS-20PUREU001 
 
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Version: 2.5 PMCF – AT01 
 
Date: 01DEC2022 
 
Page 11 of 39 
 
 
Abbreviations 
ADE 
Adverse Device Effect 
AE 
Adverse event 
BD 
Becton Dickinson and Company 
BSI 
Blood Stream Infection 
CE 
Certification Mark 
CI 
Confidence Interval 
CLABSI 
Central Line Associated Blood Stream Infection 
Defined as a primary BSI with use of a central vascular catheter in the 48 
hours (two days) before the onset of the infection 
CRBSI 
Catheter-related Bloodstream Infection 
Defined as the presence of bacteremia originating from an intravenous 
catheter1 
CSA 
Clinical Study Agreement 
CV 
Curriculum Vitae 
DEHP 
Diethylhexyl Phthalate 
DMP 
Data Management Plan 
eCRF 
Electronic Case Report/Record Form 
EEA 
European Economic Area 
EU 
European Union 
FDA 
Food and Drug Administration 
FDAAA 
FDA Amendments Act of 2007 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IFU 
Instructions for Use 
IPA 
Isopropyl Alcohol 
IRB/EC 
Institutional or Independent Review Board/Ethics Committee 
IV 
Intravenous  
LAR 
Legal Authorized Representative 
NDA 
Non-disclosure Agreement 
PI 
Principal Investigator 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SIV 
Site Initiation Visit 
TMF 
Trial Master File 
UADE 
Unexpected Adverse Device Effect 
USADE 
Unexpected Serious Adverse Device Effect 
VAD 
Vascular Access Device 
 
 

Protocol Number: MDS-20PUREU001 
 
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Date: 01DEC2022 
 
Page 12 of 39 
 
 
1 PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title 
A Post-Market Clinical Follow Up Study to Evaluate BD PureHub™ 
Disinfecting Cap Use on Needle-Free Connectors 
Rationale 
This study is designed to provide data utilizing the Becton Dickinson 
(BD) PureHub™ Disinfecting Cap for the purpose of providing clinical 
data required under European Union (EU) regulation 2017/745. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary Efficacy Objective 
To assess the rate of select 
performance measures of the BD 
PureHub™ Disinfecting Caps on 
swabbable needle-free connectors 
when 
used 
in 
a 
clinical 
environment. 
 Attachment success rate of the 
BD PureHub™ Disinfecting 
Caps to a needle-free connector 
(successful attachment/ total 
number of attachments) 
 Removal success rate of the 
BD PureHub™ Disinfecting 
Caps to a needle-free connector 
(successful 
removal/ 
total 
number of intended removals) 
Primary Safety Objective 
To assess the incidence of BD 
PureHub™ 
Disinfecting 
Cap 
device-related adverse events 
 Rate of device-related adverse 
events  
Informative Objectives 
To assess the frequency of BD 
PureHub™ Disinfecting Cap use 
 The number of BD PureHub™ 
Disinfecting Caps used per 
day/per study participant 
To summarize the purposes for 
removal of the BD PureHub™ 
Disinfecting Cap from the needle-
free connector 
 The purpose for each intended 
removal of the BD PureHub™ 
Disinfecting Cap from the 
needle-free connector 
To summarize the incidence of 
blood stream infection 
 Incidence 
of 
central 
line 
associated 
bloodstream 
infection (CLABSI) 
 Incidence 
of 
bloodstream 
infections 

Protocol Number: MDS-20PUREU001 
 
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Version: 2.5 PMCF – AT01 
 
Date: 01DEC2022 
 
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Protocol Title 
A Post-Market Clinical Follow Up Study to Evaluate BD PureHub™ 
Disinfecting Cap Use on Needle-Free Connectors 
Design and Overview 
A Post-Market Clinical Follow Up Study to Evaluate BD PureHub™ 
Disinfecting Cap Use on Needle-Free Connectors:  
This is a multi-center, prospective observational study of a minimum of 
150 study participants who have vascular access devices (VADs) with 
needle-free connectors as part of their routine medical care.  
Patients will be followed from the time of enrollment through the duration 
of one week post VAD therapy, department/ hospital discharge if VAD 
therapy has ended, or 45 days post enrollment date, whichever comes first. 
Study Device 
BD PureHub™ Disinfecting Cap is comprised of a threaded plastic cap 
containing a porous pad pre-saturated with 70% Isopropyl Alcohol (IPA) 
and sealed with a multilayer foil film. 
BD PureHub™ Disinfecting Caps are intended to be used as a disinfecting 
device for swabbable needle-free luer connectors prior to access and to 
act as a physical barrier between line accesses. 
Participants 
Inclusion Criteria: 
1. Has an eligible vascular access device with needle-free 
connectors in situ or will have one placed 
Note: This covers all needle-free devices, including central 
venous catheters, peripheral IV catheters and arterial VADs 
2. Is expected to receive VAD therapy for a minimum of 3 days 
3. Is expected to be available for regular observation from consent 
until end of study 
4. Able and willing to provide informed consent or legal authorized 
representative (LAR)* authorized to give consent on behalf of the 
participant  
*LAR not applicable for AT01 
Exclusion Criteria: 
1. BD PureHub™ Disinfecting Cap or any other disinfecting cap in 
place for more than twelve (12) hours (>12 hours) prior to study 
participation   
2. Presence of any infection, bacteremia, or septicemia is known or 
suspected 
3. Any condition which, in the opinion of the Investigator, precludes 
the participant from participation in this study 

Protocol Number: MDS-20PUREU001 
 
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Date: 01DEC2022 
 
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Protocol Title 
A Post-Market Clinical Follow Up Study to Evaluate BD PureHub™ 
Disinfecting Cap Use on Needle-Free Connectors 
Intervention(s)/Procedure(s) The BD PureHub™ Disinfecting Cap will be used for needle-free access 
of the vascular access device as necessary for each participant from 
enrollment through one week post VAD therapy, department/ hospital 
discharge if VAD therapy has ended, or 45 days post enrollment date, 
whichever comes first. During this time, attachment and removal success 
will be captured, as well as any device-related adverse events (AEs). 
Investigational Sites 
Up to 10 sites in the EU will participate in this study.  
Data Monitoring 
Committee 
A Data Monitoring Committee will not be used in this study. 
Regulatory Status 
The BD PureHub™ Disinfecting Cap is currently CE marked and 
marketed in the EEA under CE certificate 252.1127, CE mark #0050. 
Anticipated Study 
Timelines 
The enrollment of the study started on 31JAN2022. Last participant will 
leave the study approximately in Q2 2023. 
 
 

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Schema 
 
 
 
 
 
 
 
 
 
Participant with vascular access device in situ is 
screened against eligibility criteria 
Participant consent or assent (if under the age of 18 
years) is provided  
Demographic and medical history information is 
collected 
BD PureHub™ Disinfecting Cap is placed to each eligible 
needle-free connector by a clinician per the IFU 
BD PureHub™ Disinfecting Caps will be used at each 
vascular access at site through the course of the 
participant’s IV therapy  
Attachment/removal success will be collected at each 
access through discharge 
Participant will be followed until one week post VAD 
therapy, department/hospital discharge if VAD therapy has 
ended, or 45 days post enrollment, whichever comes first. 

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Date: 01DEC2022 
 
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Table 1 – Schedule of activities 
Procedure/Assessment 
Baseline 
Initial 
PureHub 
Placement1 
Day 0 
Each day 
during 
VAD 
Therapy2 
7-day 
Follow Up 
after VAD 
Therapy4 
End-of-study 
45-day FU or 
Department/ Hospital 
Discharge, whichever 
comes first5 
Informed consent process, incl. Informed 
consent signature date 
X 
  
  
  
  
Inclusion/Exclusion Criteria Check 
X 
 
 
 
 
Patient in-hospital location information 
X 
(X)7 
(X)7 
(X)7 
 
Demographics 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
VAD Information3 
X 
(X)6 
X 
 
 
BD PureHub™ Placement  
Record number of eligible needle-free 
connectors per VAD 
x Placement of PureHub™ Caps 
x Record number of new caps used and 
location catheter line per day incl. primary 
reason for cap replacement 
x Document Yes or No if able to successfully 
attach a PureHub™ Disinfecting Cap per 
needle-free connector for each attachment.  
x Document number of attachments 
x Document Yes or No if able to successfully 
remove the BD PureHub™ Disinfecting 
Cap from the needle-free connector 
x Document number of intended removals 
 
X 
X 
 
X 
Device related Adverse Events assessment 
 
X 
X 
X 
X 
Blood stream infection assessment 
 
X 
X 
X 
X 
Device deficiency assessment 
 
X 
X 
 
 
 
1) Initial PureHub™ Placement can be performed on same day as Baseline, provided ICF has been signed. 
2) Multiple Placements of PureHub™ Caps are possible per day 
3) VAD Information: At baseline -VAD type, number of VADs, number of lumens per catheter, location of VADs, 
date of VAD placement, type and number of needle-free connectors per VAD, type of dressing; subsequent visits; 
type of dressing in case of changes, dressing changes, needle-free connector changes,   
4) Only applicable for patients who continue to be hospitalized at the department/hospital and continue study 
participation 
5) End of study is also applicable if the patient is discharged from department and cannot be followed up by the 
clinical investigation team at another department/ward 
6) Baseline VAD Information at initial PureHub™ Placement day needs to be reconfirmed if the visit date is different 
to baseline date 
7) Only in case participant is transferred to another department/ward and continues in the study, or participant is 
discharged home in-between hospital visits but the VAD is still in place. 
 
 

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2 INTRODUCTION 
2.1 
Background 
Catheter-related blood stream infections (CRBSI) are bacterial infections that originate 
within a vascular access device (VAD). The International Society for Infectious Diseases 
report that CRBSIs account for 11% of all healthcare-associated infections and have an 
estimated attributable mortality rate between 12-25% (Lutwick and Bearman, 2019).   
 
Introduction of bacteria into the bloodstream via the VAD can come from several sources, 
including contamination of the device prior to insertion, skin organisms, contamination of 
the infusate, and contamination of the catheter hub (Gahlot, 2014). There are multiple 
recommendations for CRBSI prevention that targets each of these potential origin points. 
For needleless connectors, the guidelines for the Prevention of Intravascular CRBSIs 
considers scrubbing the access port of needleless connectors with an appropriate antiseptic 
(including 70% IPA) a Category 1A recommendation (O’Grady et al, 2017). Standards of 
clinical practice published by Society for Healthcare Epidemiology of America (SHEA) 
and Infusion Nurses Society (INS) have included disinfection caps in their 
recommendations (Marschall et al, 2014; Infusion Nurses Society, 2021).  
 
Alcohol-impregnated disinfectant caps were developed to simplify the disinfection process 
through passive disinfection. Furthermore, disinfectant caps act as a physical barrier 
between line accesses (Marschall 2014, Infusion Nurses Society, 2021). The BD 
PureHub™ disinfecting cap was designed for compatibility with market-leading needle-
free connectors prior to access and maintains a physical barrier to contamination for up to 
seven days. The BD PureHub™ disinfecting cap disinfects with a sterilized 70% IPA 
solution, providing a > 4-log (99.99%) reduction in bacteria within 1 minute of application. 
2.2 
Rationale 
This study is designed to provide data utilizing the BD PureHub™ Disinfecting Cap for 
the purpose of providing clinical data required under EU regulation 2017/745.   
2.3 
Risk/Benefit Assessment 
The BD PureHub™ Disinfecting Cap has been on the market in Europe since 2018 and as 
of July 2020, PureHub™ has been used in 122 institutions in EU and 131 institutions in 
US with more than 21.9 million units sold. 
 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of BD the PureHub™ Disinfecting Cap may be found in the 
Instructions for Use (IFU). 
2.3.1 
Risk Assessment 
Potential risks for the BD PureHub™ Disinfecting Cap devices are based on items noted 
in the Instructions for Use and are not unique to this study. 
 

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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Intervention (s) 
The 
BD 
PureHub™ 
Disinfecting Cap has a 
potential 
for 
trace 
amounts 
of 
IPA 
to 
ingress 
from 
the 
disinfecting cap into the 
fluid path of the infusion 
therapy system. 
A review of literature showed positive 
outcomes for the application as intended 
for the use of the BD PureHub™ 
Disinfecting Cap. A general patient 
benefit has been identified within the 
literature. However, one in-vitro study 
on another disinfecting cap found that 
use caused a change in the appearance of 
some E valves, and also allowed 
significant amounts of IPA to be 
injected. 
However, an assessment considering BD 
PureHub™ Disinfecting Cap found that 
the estimated ingress dose amount of BD 
PureHub™ 
disinfecting 
cap 
was 
determined to be below the BD derived 
acceptable exposure limit of IPA 
secondary to potential ingress. 
A caution statement “The safety of 
70% Isopropyl Alcohol caps has 
not yet been directly established in 
clinical 
use 
scenarios 
with 
neonates” has been added to the 
BD PureHub™ Disinfecting Caps 
IFU. A warning statement “Keep 
out of reach of children. In case of 
accidental ingestion, seek medical 
help or consult a poison control 
center immediately”, is included 
in the BD PureHub™ Disinfecting 
Caps IFU. 
Potential choking hazard 
for 
the 
pediatric 
population 
The literature also identified disinfectant 
caps as esophageal foreign bodies in 
pediatric patients, suggesting that they 
should be used with caution in this 
patient population given their potential to 
become ingested. One event like this was 
also identified in the database analysis of 
Clinical Experience. 
A potential for a choking hazard exists 
with a pediatric patient if the user does 
not apply the cap properly and the cap 
inadvertently 
falls 
off 
during 
unsupervised use or is not disposed of 
properly. Choking hazards are prevalent 
and always a risk with pediatric patients. 
The benefits of the disinfecting cap 
currently outweigh the risk of potential 
for choking. The risk has been assessed 
as mitigated and has been determined to 
be acceptable.  
The IFU instructs the user of 
proper 
application 
of 
the 
disinfecting cap, and to discard 
after use. A warning statement, 
“Potential choking hazard”, is 
included in the BD PureHub™ 
Disinfecting Cap IFU.  
 

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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Intervention (s) 
Process 
considerations 
that 
could 
lead 
to 
particulate within sponge 
assembly 
These are identified potential process 
considerations 
The IFU instructs clinicians that: 
“After removing the foil film, 
visually inspect the contents of the 
cap and do not use if it appears dry 
or contains particulate matter.” 
Process 
considerations 
that could lead to a dry 
sponge or insufficient 
IPA amount that may 
lead 
to 
ineffective 
disinfection. 
These are identified potential process 
considerations 
The IFU instructs clinicians that: 
“After removing the foil film, 
visually inspect the contents of the 
cap and do not use if it appears dry 
or contains particulate matter.” 
Study Procedures 
No study-specific risks 
identified  
 
 
Other 
Not applicable 
 
 
 
2.3.2 
Benefit Assessment 
There is no direct benefit for study participation for an individual patient, however the 
clinical benefits for the BD PureHub™ Disinfecting Cap are as follows:  
 
a. Easy to use disinfecting device for needle-free connectors.  
b. Easy to use device to act as a physical barrier on needle-free connectors between line 
accesses.  
c. Demonstrated in a laboratory a >4 log (99.99%) reduction on common causative agents 
in 
CRBSI 
including: 
Staphylococcus 
aureus, 
Staphylococcus 
epidermidis, 
Pseudomonas aeruginosa, Escherichia coli, Candida glabrata, Candida albicans, 
Acinetobacter baumannii.  
d. The BD PureHub™ Disinfecting Cap complies with the Infusion Nursing Society 
(2021) recommendation to perform passive disinfection on needle-free connectors by 
applying a cap or covering containing a disinfectant agent (e.g., 70% isopropyl alcohol, 
iodinated alcohol) to create a physical barrier to contamination between use. 
 
 

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2.3.3 
Overall Benefit: Risk Conclusion 
The BD PureHubTM Disinfecting Cap will be used by trained individuals as intended as 
part of this study on any patient population with consideration given to the procedure being 
performed and the disease state of the patient. There is no anticipated additional risk 
associated with the device use or any study procedure due to participation in this study 
compared to any BD PureHubTM Disinfecting Cap use as part of standard medical care. 
3 OBJECTIVES AND ENDPOINTS 
 
Objectives 
Endpoints 
Primary Performance Objective 
 
To assess the rate of select performance 
measures of the BD PureHub™ Disinfecting 
Caps on swabbable needle-free connectors 
when used in a clinical environment. 
x Attachment success rate of the BD PureHub™ 
Disinfecting Caps to a needle-free connector 
(successful 
attachment/total 
number 
of 
attachments) 
x Removal success rate of the BD PureHub™ 
Disinfecting Caps to a needle-free connector 
(successful removal/ total number of intended 
removals) 
Primary Safety Objective 
 
To assess the incidence of BD PureHub™ 
Disinfecting Cap device-related adverse events 
x Rate of device-related adverse events  
Informational Objective 
 
To assess the frequency of BD PureHub™ 
Disinfecting Cap use 
x The number of BD PureHub™ Disinfecting 
Caps used per day/per study participant 
To summarize the purposes for removal of the 
BD PureHub™ Disinfecting Cap from the 
needle-free connector 
x The purpose for each intended removal of the 
BD PureHub™ Disinfecting Cap from the 
needle-free connector 
To summarize the incidence of blood stream 
infection 
x Incidence 
of 
central 
line 
associated 
bloodstream infection (CLABSI)  
x Incidence of bloodstream infections 
 
 
 

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4 STUDY DESIGN 
4.1 
Overall Design 
This is a multi-center, single-arm, prospective post-market study that will enroll up to 175 
participants in order to have 150 evaluable participants who have vascular access devices 
as part of their routine medical care. Data related to the safety and performance of the BD 
PureHub™ Disinfecting Cap will be captured when used as intended. 
 
Participants will be screened against eligibility criteria and will be considered enrolled once 
the informed consent document is signed. Each study participant will have a BD 
PureHub™ Disinfecting Cap attached to each eligible needle-free connector to one or more 
VADs by a clinician. Clinicians will then be advised to place subsequent BD PureHub™ 
Disinfecting Caps as per the Instructions for Use through the course of the participant’s IV 
therapy. During this time, attachment and removal success will be captured, as well as any 
device-related adverse events (AEs). 
 
Participants will be followed from the time of enrollment until one week post VAD therapy, 
department/hospital discharge or 45 days post enrollment date, whichever comes first. 
Participants, with a VAD in place, who will be discharged from the hospital, but return 
regularly for catheter access to the site will remain in the study, either until the 45 days are 
reached or the VAD therapy is ended. If the catheter access will not be performed at the 
clinical trial site, the participant cannot continue in the study. 
4.2 
Scientific Rationale for Study Design 
This study is designed to collect clinical data on the performance of the BD PureHub™ 
Disinfecting Cap. The usage of the BD PureHub™ Disinfecting Cap according to its 
intended use will ensure that study activities have no direct impact on the endpoints being 
assessed and that they represent outcomes typically associated with intended medical use 
of the study device in clinical practice.  
4.2.1 
Participant Input into Design 
Not applicable. 
4.3 
End of Study Definition 
A participant is considered to have completed the study when one of the following 
conditions are met, whichever is the earliest.: 
- 
upon one week post VAD therapy (after the last VAD is removed),  
- 
at department discharge provided the clinical investigation team cannot follow-up the 
participant on another ward for study purposes,  
- 
at hospital discharge provided participant, if VAD is still placed, will not return for catheter 
access to the site or, 
- 
45 days from enrollment 
 
 

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If a participant has more than one (1) VAD with eligible needle-free connectors at study 
start, data will be collected on each VAD and the end of study time point occurs when the 
last VAD is removed. If an additional VAD is placed at a later time point, or if one of these 
VADs is replaced, then the new VAD is excluded from the study. 
 
The end of the study is defined as the date of the last study assessment of the last participant 
in the study. 
5 STUDY POPULATION 
5.1 
Inclusion Criteria 
In order to be eligible to participate in this study, an individual of any age or gender, must 
meet all of the following criteria: 
1. Has an eligible vascular access device in situ or will have one placed with needle-free 
connectors  
 
Note: This covers all needle-free devices, including central venous catheters, peripheral 
IV catheters and arterial VADs 
2. Is expected to receive VAD therapy for a minimum of 3 days 
3. Is expected to be available for regular observation from consent until end of study.   
4. Able and willing to provide informed consent or legal authorized representative 
(LAR)* authorized to give consent on behalf of the participant.  
*LAR not applicable for AT01 
5.2 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. BD PureHub™ Disinfecting Cap or any other disinfecting cap in place for more than 
twelve (12) hours (>12 hours) prior to study participation 
2. Presence of any infection, bacteremia, or septicemia is known or suspected 
3. Any condition which, in the opinion of the Investigator, precludes the participant from 
participation in this study 
5.3 
Lifestyle Considerations 
Not applicable. 
5.4 
Screen Failures 
Screen failures are not anticipated due to the non-investigational nature of the study.   
5.5 
Vulnerable Population 
As the instruction for use of the BD PureHub™ Disinfecting Caps does not foresee any 
limitations in terms of subject age or status and the study aims to collect data on clinical 
use, the study will also consider participants under 18 years of age, or participants requiring 
a LAR. In addition, pregnant and breastfeeding subjects are not excluded from study 
participation. As the study device will be used as intended, this population is considered to 
be not exposed to any additional risk due to study participation. 

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Some participating clinical sites may decide to not include vulnerable subjects as per their 
hospital policy or may not include minors as the participating department treats only adults. 
6 STUDY INTERVENTION 
6.1 
Investigational/Test Device 
BD PureHub™ Disinfecting Caps are intended to be used as a disinfecting device for 
swabbable needle-free luer connectors prior to access and to act as a physical barrier 
between line accesses. It is comprised of a threaded plastic cap containing a porous pad 
pre-saturated with 70% IPA, and sealed with a multilayer foil film. The BD PureHub™ 
Disinfecting Cap will disinfect the needle-free luer connector one (1) minute after 
application and act as a physical barrier for up to seven (7) days, if not removed. Proper 
application and removal of the device is detailed in the IFU. This product is not made with 
natural rubber latex or plasticizer Diethylhexyl Phthalate (DEHP). A picture of the device 
is provided below. 
 
 
Figure 1 Example of disinfecting cap (BD PureHub™ disinfecting cap) 
6.2 
Control Device/Standard of Care 
Not applicable; this is a single-arm study. 
6.3 
Ancillary Devices/Products 
Ancillary devices will include the participant’s VAD, eligible needle-free luer connectors, 
intravenous tubing, and dressings, or any other material associated with the participant 
venous access. These products will be used as part of the standard of care of each site. 
Selected information regarding these devices will be collected (See Section 7.7). The use 
of other disinfecting caps than the PureHubTM disinfecting cap is not allowed. 
6.4 
Device Labeling 
This study will utilize marketed product. As such, no special labelling is required. 
However, to ensure that the BD PureHubTM disinfecting cap will be used at the study sites 
only on behalf of the study, the device packaging will be labeled as “For clinical trial use 
only”. 

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6.5 
Treatment Allocation and Measures to Minimize Bias 
This is a post-market clinical follow up study in which the BD PureHubTM disinfecting cap 
is used as intended. The choice of using the cap is left to the discretion of the clinician. 
7 STUDY PROCEDURES AND ASSESSMENTS 
x Study activities and their timing are summarized in the Schedule of Activities (Table 
1) 
x Adherence to the study design requirements, is essential and required for study conduct. 
x All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log 
to record details of all participants screened and to confirm eligibility or record reasons 
for screening failure, as applicable. 
7.1 
Study duration 
The study participation per participant will last 45 days at maximum, the overall conduct 
of the study is expected to last approximately 14-15 months from first participant enrolled 
up to last participant having last visit, which is projected for ~ Q2 2023. The anticipated 
enrollment period is 13 months. 
7.2 
Screening and Enrollment 
After screening against inclusion/exclusion criteria, potential participants will be provided 
with detailed information about the study. For details on the Informed Consent process, 
please refer to section 14.2. A participant will be considered enrolled once informed 
consent (or assent as applicable) is signed. Enrolled patients will be assigned a unique 
participant number. 
7.3 
Medical History / Baseline Assessments 
Participant baseline and demographic information will be documented, including, but not 
limited to age, sex assigned at birth, primary diagnosis, and medical history. Information 
on the participants vascular access device, including but not limited to:  
 
x Type of VADs to be assessed per study participant 
x Per VAD the following information will also be collected: 
o Date of insertion 
o Date of removal 
o VAD placement site location  
o Number of lumens 
o Type of dressing/securement 
o Type and number of needle-free connector(s),  
o Type and number of intravenous tubing/ extension set(s) 
o Type and number of other add-on devices i.e. valves, stop cocks  

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7.4 
Device Use 
Each study participant will have a BD PureHub™ Disinfecting Cap attached to each 
eligible needle-free connector by a clinician. “Eligible” needle-free connector will be 
defined as a swabbable needle-free connector not already in use and is reasonably able to 
be accessed by a clinician. 
 
Clinicians should place subsequent BD PureHub™ Disinfecting Caps as per the 
Instructions for Use. Lot numbers of the PureHub™ devices will be documented in the 
eCRF. 
 
Clinicians will be advised to follow the respective unit protocol for disinfection of needle-
free luer connectors prior to initial access. 
7.5 
Efficacy (Performance) Assessment 
Clinicians will be requested to document the following with each use of the BD PureHub™ 
Disinfecting Cap: 
x Attachment success: The clinician will document if able to successfully attach the BD 
PureHub™ Disinfecting Cap to each of the applicable needle-free connectors securely. 
(Documenting either “Yes” or “No”).  
 An attachment is defined as the process of placing a PureHub™ Disinfecting Cap 
on an eligible needle-free connector. 
 If the clinician can successfully attach the first BD PureHub™ Disinfecting Cap, 
they should document “Yes” as this would be an attachment success. Attachment 
success means the cap is securely attached to the needle-free connector and that the 
needle-free luer is connected. 
 If the clinician is unable to successfully attach the cap to the needle-free connector, 
they should use a new subsequent BD PureHub™ Disinfecting Cap. The answer to 
attachment success would be “No” as more than one cap was needed to reach 
attachment success. The number of subsequent caps needed to achieve a successful 
attachment during this procedure need to be documented.  
 
If the clinician is unable to attach the cap to the needle-free connector with any subsequent 
caps, they should document the number of subsequent caps used and document “Unable to 
attach.” 
x Removal success: The clinician will document if able to successfully remove the BD 
PureHub™ Disinfecting Cap from the needle-free connector (Yes/No).  
 An intended removal is defined as the process of removing a successfully attached 
PureHub™ Disinfecting Cap from an eligible needle-free connector for the purpose 
of access to the needle-free connector or to replace with a new PureHub™ 
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If the clinician can remove the PureHub™ Disinfecting Cap from the needle-free 
connector, they should document “Yes” as this would be a removal success. 
If the clinician cannot remove the PureHub™ Disinfecting Cap from the needle-free 
connector, they should document “No”. 
7.6 
Safety Assessments 
Device-related AEs and device deficiencies will be captured as they occur until the 
participant concluded his/her participation to the study. Details about AEs are provided in 
Section 9. 
7.7 
Informational Assessments  
The following data may also be collected for informational purposes only: 
x Participant in-hospital location: Main department/ward, date of hospitalization, if 
applicable: any participant transfer in the hospital provided participant is still followed 
up by the clinical investigation team: date of move to another department/ward, name 
of new department/ward 
x Vascular access device details used in conjunction with the BD PureHub™ 
Disinfecting Cap. In addition to the VAD information to be collected as referenced in 
section 7.3 , the following information will be documented throughout the study:  
o Per catheter: 
 Type of dressing  
 Dressing changes  
 Needle-free connecter changes  
 Daily assessment of any change to type and number of intravenous tubing/ 
extension set(s) 
 Daily assessment of any change to type and number of other add-on devices i.e. 
valves, stop cocks  
o Current catheter care practice 
x The number of BD PureHub™ Disinfecting Caps used per day/per study participant 
x The primary reason for each intended removal of the BD PureHub™ Disinfecting Cap 
removal. 
x Incidence of bloodstream infection, including CLABSIs will be documented. 
8 PARTICIPANT DISCONTINUATION/WITHDRAWAL  
8.1 
Discontinuation/Withdrawal 
x 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. 
x At the time of discontinuing from the study, no further data will be collected for the 
participant. 

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x 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. 
x Participants who withdraw or discontinue the study early may be replaced. 
8.2 
Lost to Follow-Up 
Not applicable; these participants will be in the department/hospital for the duration of the 
study.  
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 or procedure and whether anticipated 
or unanticipated [ISO14155:2020].   
 
In this study, AE collection will be limited to those events judged to be related or likely 
related to the BD PureHub™ Disinfecting Cap and any events of bloodstream infection, 
including CLABSIs (as defined in the List of Abbreviations).  
 
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. Likewise, 
planned hospital visits and/or hospital stays should not be considered as adverse events. 
Exacerbation of an existing condition should be reported as an AE if the event meets the 
protocol definition of an AE. 
 
The clinical course of the 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. The Investigator must supply the Sponsor with 
information concerning the follow up and/or resolution of the AE. 
9.1.2 
Serious Adverse Events (SAEs) 
A serious adverse event is defined by ISO14155:2020 as an adverse event that led to:  
a. death,  
b. serious deterioration in the health of the participant, users, or other persons as defined 
by one or more of the following: 
a. a life-threatening illness or injury, or 
b. a permanent impairment of a body structure or a body function including chronic 
diseases, or 
c. in-patient or prolonged hospitalization, or 
d. medical or surgical intervention to prevent life-threatening illness or injury, or 
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e. fetal distress, fetal death, a congenital abnormality, or birth defect including 
physical or mental impairment 
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, 
installation 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 the appropriate governing body per ISO 14155:2020. 
9.2 
Severity of Adverse Events 
Each AE shall be assessed for its severity, or the intensity of an event, experienced by the 
participant according to the criteria below. 
 
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 
 
 

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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, that is, AEs directly attributable to 
the study device (BD PureHub™ Disinfecting Cap) used. 
 
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 
For all adverse events, all sections of the appropriate electronic Case Report Form (eCRF) 
must be completed. 
 
x All SAEs, SADEs, and/or UADEs/USADEs must be reported to the Sponsor via the 
eCRF without unjustified delay and within three (3) working days of the 
site/investigator becoming aware of the event.   
 
x De-identified copies of all requested relevant documentation should be submitted to the 
Sponsor within 72 hours of knowledge, as appropriate.  
 
x Safety related correspondence or questions can be addressed to following contact: 
CROMSOURCE Safety Unit: 
Email: pharmacovigilance@cromsource.com 
Fax: +39 045 825 0574 
 

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It is the responsibility of the Investigator or their designee to report adverse events to 
individual Institutional Review Boards (IRBs)/Ethics Committees (ECs). The Sponsor or 
their designee is responsible for reporting AEs to regulatory authorities according to the 
local regulations in each participating country. 
9.5 
Safety Committees 
A safety committee will not be used for this study. 
9.6 
Device Deficiencies 
The Investigator will record a device deficiency if a device used in the study, which 
appeared to be inadequate with respect to its identity, quality, durability, reliability, 
usability, safety or performance,  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 will be recorded on the appropriate Case Report Form and will be promptly 
reported to the Sponsor. The device(s) should be returned to the Sponsor if requested. 
 
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 by the Sponsor under 21 CFR part 
803 Medical Device Reporting if necessary, or as required by appropriate national laws 
and regulations. 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 IRB/EC of such device deficiencies 
in accordance with the IRB/EC and/or local regulations. 
9.7 
Serious Health Threat 
During the course of the study, device deficiencies or adverse events will be assessed if 
they constitute a serious health threat. The serious health threat is a signal from any adverse 
event or device deficiency that indicates an imminent risk of death or a serious deterioration 
in the health in subjects, users or other persons, and that requires prompt remedial action 
for other subjects, users or other persons. Serious health threat includes the possibility of 
multiple deaths occurring at short intervals, or other significant and unexpected serious 
adverse events that can be regarded as a potential serious health hazard in subjects, users 
or other persons and which are possibly related to the investigation device use. 
 
 

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10 STATISTICAL METHODS 
The statistical analysis plan will be finalized prior to the database lock and will include a 
more technical and detailed description of the statistical analyses described in the following 
sections. This section includes a summary of the planned statistical analyses of the most 
important endpoints including primary and exploratory endpoints. 
10.1 
Overview of Study Design 
This is a multi-center, single-arm, prospective study to assess the overall safety and 
performance of the BD PureHub™ Disinfecting Cap. 
10.2 
Sample Size Considerations 
Assuming the primary endpoints of successful insertion rate and successful removal rate 
are each 90%, a sample size of 150 participants with only 1 insertion/removal observed per 
participant would result in a 4.8% precision for each point estimate (i.e. the 95% confidence 
interval (CI) is the point estimate ±4.8%, using a simple asymptotic approach for CI of one 
proportion). The precision margin will tighten as the number of line access per participant 
increases, for example, with an average of 4 insertions/removals per participant, the 
precision would be ±2.4%.   
 
Additionally, with a sample size of 150, the probability of observing at least one rare 
AE/complication with a 1% rate (per participant) is 78% and the probability of observing 
at least one rare AE/complication with a 2% rate (per participant) is 95%. 
10.3 
Analysis Population 
The following populations are defined: 
 
Population 
Description 
Enrolled  
All participants who sign the ICF 
Evaluable 
All enrolled participants who have at least 1 BD PureHub™ 
Disinfecting Cap applied. 
10.4 
Primary Performance Endpoints 
The attachment (removal) success rate will be calculated by dividing the number of 
successful attachment (removal) by the total number of attachments (removals); 95% CI 
will be calculated using a score method. 
10.5 
Primary Safety Endpoint 
The rate of device-related adverse events will be calculated as the number of participants 
with adverse events related to device divided by the total number of participants; 95% CI 
will be calculated using a score method.  
 
 

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10.6 
Informational Endpoint(s) 
Descriptive statistics for the informational endpoints defined in Section 3 will be provided. 
Summary statistics for categorical variables will include frequency counts and percentages 
and for continuous variables will include mean, standard deviation, minimum, median, and 
maximum. 
10.7 
Other Analyses 
Not applicable. 
10.8 
Interim Analysis 
No interim analysis is planned for this study.   
11 DATA COLLECTION AND RECORD MAINTENANCE 
11.1 
Electronic Case Report Forms 
The Investigator is responsible for ensuring the completeness and accuracy of all study 
documentation. 
 
All required clinical data will be collected/documented in sponsor-provided electronic 
Case Report Forms (eCRFs). Applicable national and local regulations are followed on the 
handling of electronic data. Modification of the eCRFs will only be made if deemed 
necessary by the Sponsor and/or the appropriate regulatory body. 
 
Site numbers and participant numbers will be used to track participant information 
throughout the study. Participant personal information will be pseudonymized/de-
identified. 
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 file of each enrolled participant.   
11.3 
Data Management 
Data management is the responsibility of the Sponsor or their designee. Data from 
completed eCRFs will be managed in a secured, controlled database. A Data Management 
Plan (DMP) will be developed that outlines the procedures used for recording, data 
tracking, data review, database cleaning, issuing/resolving data queries and database lock. 
Procedures for rectifying errors and omissions, verification, validations and securing of the 
electronic data system as well as data storage will also be contained within the DMP. The 
procedure to maintain and protect the participants data privacy and information on data 
storage upon completion of the study will be detailed in the DMP too.   
A data snapshot is planned to be performed after 50% of the participants have completed 
the study. The data will be used for monitoring purposes only and will not impact the design 
or conduct of the study. Further details on the data snapshot process will be addressed in 
the DMP. 

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11.4 
Record Retention 
The Investigator shall retain all study records for a minimum of ten (10) years after the 
study has ended. Study records may be stored longer if required by national law or other 
local rules. The data for some of these records may be available in computerized form but 
the final responsibility for maintaining study records remains with the Investigator. 
 
The Investigator may withdraw from the responsibility to maintain records for the period 
required by transferring custody of the records to any other person who will accept 
responsibility for retaining them. Notice of a transfer shall be given to the Sponsor not later 
than ten (10) working days after the transfer occurs. 
11.5 
Device accountability 
If a study site is provided with PureHub™ Disinfecting Caps by the Sponsor, device 
accountability between Sponsor and the site will be performed (Number of devices 
shipped, number of devices used at trial site, number of devices shipped back/discarded at 
end of study). In this case, Principal Investigator needs to ensure that the caps are only used 
for study purposes. 
12 QUALITY CONTROL AND ASSURANCE 
12.1 
Control of Study Products 
In this post-market study, marketed devices will be used, provided by the Sponsor. No 
special controls are required in this study.  
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 
Investigator(s) and 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 IRB/EC 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 IRB/EC, 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 visits 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 between Sponsor and the site, 

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continued maintenance and calibration of study-specific equipment (if applicable), and 
continued IRB/EC acceptance of the study. 
 
At the completion of the study, the Sponsor-Monitor will conduct a final close-out visit 
(COV). The purpose of this visit may include but is not limited to collecting all outstanding 
study data documents, confirming that the Investigator’s files are accurate and complete, 
reviewing the record retention requirements with the Investigator, and ensuring that all 
applicable requirements for closure of the study are met.  
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 Investigator and his team will make themselves available during 
the visit. The Investigator 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 eCRFs. 
The participant’s anonymity must be ensured, and data checked during the audit must 
remain confidential. 
 
As soon as the Investigator is aware of an upcoming inspection/audit by the Health 
Authorities, he/she will promptly inform the Sponsor. As agreed with the Investigator, 
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 IRB/EC 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 IRB/EC’s requirement.   
 
It is the Investigator’s responsibility to ensure that there are no deviations from the 
Protocol. Except in an emergency, when a protocol deviation is planned or anticipated, the 
Sponsor should be contacted for approval. All deviations must be recorded on the 
appropriate eCRF 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. 

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13 ADMINISTRATIVE REQUIREMENTS 
13.1 
Investigator and Site Selection 
The Investigator 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 
Investigator(s), Sub-Investigator(s) and Study Coordinator(s) will be maintained in the 
Sponsor’s files as documentation of qualification by training and experience. 
 
The Principal Investigator will sign the Investigator Agreement page of this protocol, 
agreeing to comply with all applicable regulations and the requirements of this study as per 
the CSA.   
 
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 
Each Investigator and appropriate site personnel will be trained on this protocol and study 
requirements during the SIV and on the study device, if needed. All training will be 
documented and filed at the investigational site and with the Sponsor. 
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: 
x Fully executed Non-disclosure Agreement (NDA) between PI/site and Sponsor; 
x CVs, signed and dated within 2 years of study start for the PI and Sub-Investigator(s); 
x CVs for Study Coordinator(s); 
x Signed CSA by PI/site (or designee); 
x Signed Investigator Agreement Page by PI and Sub-Investigator(s); 
x Signed Financial Disclosure Statement by PI and Sub-Investigator(s); 
x Completed and Signed Training Log by PI and Sub-Investigator(s); 
x Study Personnel Identification list; 
x Written approval from the IRB/EC of both the protocol and ICF, and any other 
applicable protocol specific material; and 
x IRB/EC Membership List, Assurance of Compliance Form, or equivalent. 
13.4 
 Insurance 
Where required by local regulation, insurance coverage will be provided by BD for study 
participants. 

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13.5 
 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. Formal presentation(s) or 
publication(s) of data collected from this study will 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 publication of the principal results from any single-center experience within the study 
is not allowed until the preparation and publication of the multicenter results. Exceptions 
to this rule require the prior approval of the Sponsor. 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. 
13.6 
Study Registration 
While this is a not an Applicable Clinical Trial and does not meet the FDA Amendments 
Act of 2007 (FDAAA) criteria for clinical study registration, the study will be registered 
on www.clinicaltrials.gov to ensure transparency. The study will also be registered on 
additional local registries, if applicable. The content of the publicly accessible database(s) 
will be updated throughout the conduct of the clinical study and the results will be entered 
after study completion. 
13.7 
Termination of Study 
The Sponsor reserves the right to suspend enrollment or terminate the study at any time for 
any reason. If suspicion of an unacceptable risk, including serious health threat to subjects, 
arises during the study, the Sponsor may suspend the study while the risk is assessed. The 
sponsor shall terminate the clinical investigation if an unacceptable risk which cannot be 
controlled is confirmed. 
  
Additionally, 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 IRB/EC and/or non-compliance with this protocol or other clinical research 
requirements. Written notice will be submitted to the Investigator in advance of such 
termination.  
 
In the event of study suspension or termination, the Sponsor will send a report outlining 
the circumstances to the IRB/EC, and all Investigators and Regulatory Authorities as 
required by regulation.  

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14 ETHICAL AND REGULATORY CONSIDERATIONS 
14.1 
IRB/EC Approval 
Investigators or designees must submit the study protocol, Informed Consent Forms (if 
applicable), and all other locally required documentation to an appropriate IRB/EC 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 IRB/EC must 
give written renewal of the original approval at least annually to continue the study, if 
applicable per local regulation. In this case, a copy of the written renewal must be provided 
to the Sponsor. 
 
The IRB/EC 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 Investigator or designee is responsible for fulfilling any conditions of approval 
imposed by the IRB/EC, such as regular safety reporting, study timing, etc. The 
Investigator or designee will provide the Sponsor with copies of such reports. 
14.2 
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. For participants under the age of 18, participants’ 
parent(s)/guardian must provide their informed consent and the child must provide assent, 
depending on local EC requirements, by personally signing and dating the respective 
consent form prior to begin of this study. For adult participants, where the participant is 
not able to or not capable to give informed consent, the legal representative will be asked 
to give consent on behalf of the participant. However, the participant will also be informed 
about the study within his/her ability to understand. 
 
The Informed Consent process has to be documented in the participant’s medical records. 
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 privacy laws (e.g., General Data Protection Regulation [GDPR] requirements in 
the EU) 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 by signing and dating the form 
personally in accordance with ISO 14155: 2020(E). The participant will receive a copy of 

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his/her signed ICF. If new information becomes available that may significantly affect the 
subject’s health status, then this information will be provided in written form. Re-consent 
will be obtained if this is considered as necessary. 
 
The above requirements also apply with respect to informed consent obtained from 
participant’s legally designated representative. 
14.2.1 
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, documentation, or clinical samples submitted to the Sponsor. 
 
Any data collected meeting the definition of protected/confidential health information or 
personal identifying information will be collected and maintained using the designated 
authorizations and following privacy procedures as specified in the applicable regulatory 
authority regulations including the EU GDPR.   
 
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.  
14.3 
Regulatory Status 
The study device is CE marked and will be studied in a post-market fashion in Europe. 
14.4 
Statement of Compliance 
This clinical investigation will be conducted in compliance with the protocol and following 
regulatory requirements: 
x ISO14155:2020 (Good Clinical Practice); 
x EU MDR (Council Regulation 2017/745 of 5 April 2017); 
x Ethical principles of the Declaration of Helsinki, in its current revision; and 
x Applicable sections of the national laws and regulations. 
 
The clinical investigation will not commence at a clinical site until approval (favorable 
opinion) from the respective IRB/EC has been received. All additional requirements 
imposed by the IRB/EC(s) will be followed. Involvement of the national competent 
authorities (e.g. by notification, seeking authorization) will be accomplished as required by 
national laws and regulations. 
 
 

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