NPWT Pre-registration Study: A Prospective, Multicentre Trial to Assess Performance, Safety and Efficacy of a Single-use NPWT Device
Phase: NA
Conditions: Wound Healing and Prevention
Sponsor: Smith & Nephew, Inc.

 
 
Clinical Protocol  
Study Number: CT1705POB 
 Pre-Registration Clinical Study  
Version: 9.0, 04Aug2021 
Page: 1 of 221   
 
 
CONFIDENTIAL AND PROPRIETARY 
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Nephew, Inc. and is intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or 
copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
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Sponsor Name and 
Address: 
 
T. J. Smith & Nephew Medical Ltd., 101 Hessle Rd, 
Hull, HU3 2BN, UK 
 
Investigational Product 
 
 NPWT system 
Single Identification 
Number of Clinical 
Investigation 
N/A 
Protocol Author(s): 
 
Sr Clinical Study Manager 
 
Sr Statistician II 

 
 
Clinical Protocol  
Study Number: CT1705POB 
 Pre-Registration Clinical Study  
Version: 9.0, 04Aug2021 
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CONFIDENTIAL AND PROPRIETARY 
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Nephew, Inc. and is intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or 
copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
Smith+Nephew, nor shall anyone make any use of it that is contrary to the expressed or implied wishes of 
Smith+Nephew. 
  
 
2 SYNOPSIS 
Title of Study: 
 Pre-Registration Study: Prospective, 
Multicentre Trial to assess performance and safety of 
 
  
Study Design: 
 
Prospective 
 
Multi-centre 
 
Non-randomised  
Study Type: 
Prospective Non-comparative 
Study Product:  
 
 NPWT system  
Comparison 
Group(s)*: 
(*if applicable) 
NA 
Study Purpose: 
Pre-Market clinical trial to demonstrate performance and 
safety of the 
 system. 
Primary Objective: 
To assess the functional clinical performance of 
 
 NPWT system over 7 days therapy through the 
verification of delivery of negative pressure, wound exudate 
management and dressing wear time. 
Secondary 
Objective(s): 
To assess clinical performance and safety of the 
 
 NPWT system within 30 days of surgery 
through the: 
 
 
Incidence of Surgical Site Infection (SSI)  
Superficial, deep organ space [CDC criteria] 
 
Incidence of Surgical site Complications (SSC) [as 
applicable: dehiscence (superficial/deep etc.), 
seroma, necrosis, hematoma, suture abscess] 
 
Condition of skin around the wound, and under the 
pump 
 
 
Any pain experienced by the subject in relation to the 
 system 
 

 
 
Clinical Protocol  
Study Number: CT1705POB 
 Pre-Registration Clinical Study  
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 Clinical Protocol - Device  Revision D; SOP-CD-05 Clinical Protocol 
Other Objective(s): 
To assess clinician acceptability of 
 dressing 
at 7 days 
To assess subject acceptability of 
 dressing 
at 7 days 
To assess ease of application & removal of the 
 
 dressing 
To assess subject comfort during wear 
Sample Size: 
It was planned to recruit a total of 88 subjects to allow for 
44 subjects to be recruited from each of the following 
specialties: orthopaedics (closed knee incisions e.g. after 
Total Knee Arthroplasty), and Abdominal surgery (closed 
abdominal surgical incisions of which at least 50% would be 
colorectal cases).  
An interim analysis was made after 44 subjects were 
recruited (22 from each indication). Based on the root cause 
analysis of seal loss, the study will continue on Abdominal 
surgical indications only at this time, whilst further 
investigative work continues into understanding the cause 
of seal loss in the orthopaedic surgery group.   
The 2nd phase of the study (post-interim analysis) will be 
powered according to previous sample size.  However, as no 
further subjects will be recruited for the orthopaedic surgery 
group, all 44 subjects recruited will be in the abdominal 
indication group. This will increase the total number of 
abdominal incisions to 66 (22 recruited following the 
protocol v7.0 and 44 following v8.0 of the protocol). This 
ensures that the primary endpoint is sufficiently powered for 
both the primary analysis of the abdominal data for all 
subjects as well as for a secondary analysis to be done on 
the data from those recruited according to protocol v8.0 
only. 
Number of Study 
Sites: 
There were 6 sites involved in the first phase of recruitment 
(three sites for each of the specialties). Based on the 
interim analysis, the study will continue on abdominal 
surgical indications only, with 6 sites for the second phase 
of recruitment. 

 
 
Clinical Protocol  
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copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
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Targeted Global 
Regions: 
UK   
Inclusion Criteria: 
 
The subject must provide written informed consent. 
 
Subjects eighteen (18) years of age or older. 
 
Willing and able to make all required study visits. 
 
Able to follow instructions. 
 
Subject is suitable to participate in the study in the 
opinion of the Investigator 
 
In Orthopaedic surgery (Phase 1 only): subject is 
scheduled for an elective primary knee replacement 
arthroplasty and ASA score of 2-3 
 
In Abdominal surgery: subject is scheduled for an 
elective open or laparoscopic gastrointestinal and/or 
gynaecological surgery with incision 5 cm and has 
an ASA score of 2-3.   
 
Immediately after the surgery, subject will have one 
suitable closed abdominal incision, (if there is more 
than one incision then the clinician should choose the 
one which in their opinion is most suited for 
 
therapy) that fits under the absorbent dressing area 
of the appropriate 
 dressing sizes 
(dressing sizes equivalent to 
 dressings
 
 
. 
 
Exclusion Criteria: 
 
Contraindications (per the 
 IB) or 
hypersensitivity to the use of the investigational 
product or their components (e.g. silicone adhesives 
and polyurethane films [direct contact with incision], 
acrylic adhesives [direct contact with skin], 
polyethylene fabrics and super-absorbent powders 
[polyacrylates]) within the dressing). 
 
Subjects with extremely fragile skin who require the 
use of SECURA non-sting barrier skin wipes and have 
hypersensitivity to the ingredients in the wipes 
 
Participation in the treatment period of another 
similar clinical trial (wound care related) within thirty 
(30) days of operative visit or during the study. 

 
 
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copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
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Subjects with skin features (e.g. tattoos, skin colour, 
pre-existing scarring) which in the opinion of the 
Investigator, will interfere with the study 
assessments. 
 
Subjects attending for an operation at the same 
surgery site (anatomical location) within the last 3 
months. 
 
Subjects undergoing a procedure as part of palliative 
care (to be confirmed during surgery). 
 
Subjects where the 
 area of the 
device would be placed on a load-bearing anatomical 
location (i.e. areas vulnerable to pressure damage). 
 
Subjects with incisions that are actively bleeding 
unless haemostasis has been achieved (to be 
confirmed during surgery). 
 
Subjects with infected skin lesions or incisions at the 
time of surgery (any area of the body). 
 
Subjects who have participated previously in this 
clinical trial  
 
Subjects with a history of poor compliance with 
medical treatment. 
 
 
 
Subjects with a medical or physical condition that, in 
the opinion of the Investigator, would preclude safe 
subject participation in the study. 
 
Subjects where the dressing cannot be fully applied 
without coming into contact with, or covering, tubes, 
drains, wires or other ancillary devices which may 
affect the seal, and/ or which will require removal 
before the end of the seven day period 
Study Duration: 
Prior to the interim analysis, it was estimated that the 
study duration will be eighteen months from when the first 
study site is initiated until last enrolled subject reaches 
last study assessment. This period included an estimated 
6-month period to prepare a mid-recruitment interim 
report, submit it and obtain feedback from MHRA. To 
reflect the much longer pause taken and time to secure 
approvals, the study duration is now expected to last 30 
months. 

 
 
Clinical Protocol  
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 Pre-Registration Clinical Study  
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copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
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Smith+Nephew. 
  
 
Other exploratory 
endpoint(s): 
 
Clinician acceptability of 
 system 
at discontinuation of therapy 
 
Subject acceptability of 
 system 
at discontinuation of therapy 
 
Ease of application & removal 
 
Subject comfort during wear  
 
Safety Data 
Safety, assessed through the incidence and severity of 
Adverse Events and Device Deficiencies. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Clinical Protocol  
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 Pre-Registration Clinical Study  
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copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
Smith+Nephew, nor shall anyone make any use of it that is contrary to the expressed or implied wishes of 
Smith+Nephew. 
  
 
3 CONTENTS  
3.1 Table of Contents 
1 SIGNATURES ..............................................................................................2 
1.1 Principal Investigator Signature Page ............................................... 2 
1.2 Coordinating Investigator Approval .................................................. 3 
1.3 Sponsor Approval ........................................................................... 4 
2 SYNOPSIS ..................................................................................................5 
3 CONTENTS ............................................................................................... 13 
3.1 Table of Contents ......................................................................... 13 
3.2 List of Tables ............................................................................... 16 
3.3 List of Figures .............................................................................. 16 
3.4 List of Abbreviations and Definitions ............................................... 17 
4 INTRODUCTION ........................................................................................ 19 
4.1 Background ................................................................................. 19 
4.2 Literature Summary ..................................................................... 22 
4.3 Study Purpose ............................................................................. 25 
4.4 Safety Consideration .................................................................... 26 
5 OBJECTIVE(S) ........................................................................................... 31 
5.1 Primary Objective ........................................................................ 31 
5.2 Secondary Objective(s)................................................................. 31 
5.3 Other Objective(s) ....................................................................... 32 
5.4 Claims ........................................................................................ 32 
6 INVESTIGATIONAL PRODUCT ...................................................................... 32 
6.1 Identification ............................................................................... 32 
6.2 Product Use ................................................................................. 38 
6.3 Packaging and Labelling ................................................................ 44 
6.4 Product Accountability Procedures .................................................. 46 
7 SUBJECT ENROLLMENT AND WITHDRAWAL .................................................. 47 

 
 
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copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
Smith+Nephew, nor shall anyone make any use of it that is contrary to the expressed or implied wishes of 
Smith+Nephew. 
  
 
7.1 Subject Population ....................................................................... 47 
7.2 Inclusion Criteria.......................................................................... 47 
7.3 Exclusion Criteria ......................................................................... 48 
7.4 Screening ................................................................................... 50 
7.5 Informed Consent ........................................................................ 51 
7.6 Enrolment ................................................................................... 52 
7.7 Lost to Follow-up ......................................................................... 52 
7.8 Withdrawal .................................................................................. 52 
8 STUDY DESIGN ......................................................................................... 54 
8.1 Study Design ............................................................................... 54 
8.2 Allocation and Blinding.................................................................. 57 
8.3 Data Management ........................................................................ 57 
8.4 Study Endpoints .......................................................................... 58 
8.5 Methods Used to Minimize Bias and Maximize Validity ....................... 60 
9 STUDY PROCEDURES ................................................................................. 62 
9.1 Visits and Examinations ................................................................ 62 
9.2 Study Methods and Measurements ................................................. 72 
9.3 Health Economics/Quality of Life .................................................... 81 
10 STATISTICAL DESIGN .............................................................................. 81 
10.1 General ..................................................................................... 81 
10.2 Analysis Populations ................................................................... 82 
10.3 Baseline Data ............................................................................ 82 
10.4 Efficacy Analysis ........................................................................ 83 
10.5 Safety Analyses ......................................................................... 87 
10.6 Interim Analyses ........................................................................ 88 
11 SAMPLE SIZE JUSTIFICATION ................................................................... 88 
11.1 Sample Size Justification Pre-Interim Analysis ............................... 88 
11.2 Changes to Sample Size Post-Interim Analysis ............................... 91 
12 ADVERSE EVENTS AND DEVICE DEFICIENCIES ........................................... 92 

 
 
Clinical Protocol  
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CONFIDENTIAL AND PROPRIETARY 
This document contains information that is confidential and proprietary to Smith & Nephew PLC and Smith & 
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copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
Smith+Nephew, nor shall anyone make any use of it that is contrary to the expressed or implied wishes of 
Smith+Nephew. 
  
 
12.1 Definitions (ISO/DIS 14155) ........................................................ 92 
12.2 AE Coding Dictionary .................................................................. 97 
12.3 Reporting procedures.................................................................. 97 
12.4 Unblinding of Investigational Product .......................................... 101 
12.5 Follow-up of Subjects with Adverse Events .................................. 101 
13 INVESTIGATOR OBLIGATIONS ................................................................ 102 
14 SPONSOR AND MONITOR RESPONSIBILITIES ........................................... 102 
14.1 Contract Research Organisation ................................................. 103 
14.2 Site Qualification Visit ............................................................... 103 
14.3 Site Initiation Visit .................................................................... 103 
14.4 Interim Monitoring Visit............................................................. 104 
14.5 Sponsor Audits and Regulatory Inspection ................................... 104 
14.6 Close-Out Visit ......................................................................... 104 
15 PROTOCOL DEVIATIONS ......................................................................... 104 
16 PROTOCOL AMENDMENTS....................................................................... 105 
17 CONFIDENTIALITY OF THE STUDY ........................................................... 105 
18 STATEMENTS OF COMPLIANCE ................................................................ 105 
19 END OF STUDY ...................................................................................... 106 
20 PUBLICATION POLICY ............................................................................ 107 
20.1 Publication of Study Data .......................................................... 107 
20.2 Data Sharing ........................................................................... 107 
21 REFERENCES ........................................................................................ 108 
22 APPENDICES ......................................................................................... 111 
22.1 Protocol Amendment 9 .............................................................. 111 
22.2 Protocol Amendment 8 .............................................................. 113 
8.3 
Data Management ................................................................. 121 
22.3 Protocol Amendment 7 .............................................................. 141 
22.4 Protocol Amendment 6 .............................................................. 151 
22.5 Protocol Amendment 5 .............................................................. 154 

 
 
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22.6 Protocol Amendment 4 .............................................................. 166 
22.7 Protocol Amendment 3 .............................................................. 185 
22.8 Protocol Amendment 2 .............................................................. 193 
22.9 Protocol Amendment 1 .............................................................. 201 
22.10 Instructions for Use ................................................................ 203 
22.11 Principal Investigator Obligations (ISO 14155:2020) ................... 210 
22.12 ASA Physical Status Classification System ................................. 216 
22.13 MHRA No Objection................................................................. 219 
 
3.2 List of Tables 
Table 1 Categories of Adverse Event.............................................................. .92 
 
3.3  List of Figures 
Figure 1 Diagrams and description of 
 device............................366 
Figure 2 Study Flowchart - Schedule of 
 follow-up for assessment of 
surgical site complications ............................................................................566 
Figure 3 Study Procedures by Visit ................................................................622 
Figure 4 VAS tool for assessment of closed surgical wounds evolution ...............744 
Figure 6 Evaluation and Reporting of AE ......................................................... 99 
Figure 7 Evaluation and Reporting of DD ........................................................100 
 
 
 
 
 
 

 
 
Clinical Protocol  
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HIPAA 
Health Information Portability Accountability Act 
IB 
 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation  
IEC 
Independent Ethics Committee 
IFU 
Instructions for Use 
Interventional 
study 
A type of clinical study in which participants are assigned to 
groups that receive one or more intervention/treatment so that 
researchers can evaluate the effects of the interventions on 
biomedical or health-related outcomes. 
IP 
Investigational Product  
IRB 
Institutional Review Board 
ISF 
Investigator Site File 
ITT 
Intention to Treat population 
LOCF 
Last Observation Carried Forward 
MedDRA 
Medical Dictionary for Regulatory Activities  
MHRA 
Medicines and Healthcare products Regulatory Agency 
NA or N/A 
Not Applicable 
N (or n) 
Total Sample Size (or subgroup sample size) 
NHS 
National Health Service  
Non-
interventional 
study 
A clinical study in which the investigational medical device of 
interest is used in accordance with the approved instructions 
for use. Assigning a subject/patient to a particular therapeutic 
arm is not decided in advance by a protocol but falls within 
current practice; use of the device is clearly separated from the 
decision to include the patient in the study. No additional 
diagnostic or monitoring procedures are used, and 
epidemiological methods are used to analyze the collected 
data. 
NPWT 
Negative Pressure Wound Therapy 

 
 
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PI 
Principal Investigator 
PMA 
Pre-Market Authorization 
PP 
Per-protocol Population 
RCT 
Randomized Controlled Trial 
RFID 
Radio Frequency Identification 
ROM 
Range of Motion 
S+N 
T. J. Smith & Nephew Medical Ltd. 
SADE 
Serious Adverse Device Effect(s) 
SAE 
Serious Adverse Event(s) 
SAF 
Safety population 
SAP 
Statistical Analysis Plan 
SSI 
Surgical Site Infection 
TGA 
Therapeutic Goods Administration 
TKA  
Total Knee Arthroplasty 
TÜV 
Technischer Überwachungsverein/ Technical Inspection 
Association 
Tx 
Treatment 
UK 
United Kingdom 
USADE 
Unanticipated Serious Adverse Device Effect(s) 
VAS 
Visual Analogue Scale 
4 INTRODUCTION 
4.1  Background 
4.1.1 The cost of wound healing failures and complications 
Facilitation of effective wound healing should be one of the primary therapeutic 
targets in any instance where injury to the skin tissue has occurred. Two surgical 
procedures that result in disruption to the skin tissue include closed abdominal 

 
 
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incisions and closed knee arthroplasty, each posing their own challenges in the 
healing process. Closed abdominal and closed knee arthroplasty incisions are alike in 
their characteristics with both involving primary closure of wounds following surgical 
procedures1. As a result, they encounter similar surgical site complications; however, 
the degree of risk of complications is likely to differ individually. Complications may 
consist of wound dehiscence, cellulitis, necrosis, superficial, deep and organ space 
surgical site infection, and delayed healing2,3. 
Due to their distinctive features the definition of success when treating each wound 
type can be reported differently within the literature, however ultimately the goal 
remains the same.  
For closed abdominal incisions and closed knee arthroplasty achievement of complete 
healing and avoidance of surgical site complications are common endpoints. Wound 
complications rates have been documented between 26-34%3,4,5 and 9-12%6,7,8 in 
closed abdominal and closed knee arthroplasty surgery respectively. A common 
factor that each wound type shares is the potential for failures to result in 
reoperation, re-hospitalisation, prolonged length of hospital stay and additional 
treatment resulting in increased costs3,9,10. In primary total knee arthroplasty the 
mean direct cost burden of 30 day readmissions has been shown as $13,008 and 
revision cases even higher at $29,89311. Although this figure encompasses all causes 
of readmissions it has been suggested that wound complications (including superficial 
infections, superficial dehiscence, and delayed healing) following total hip and knee 
arthroplasty may contribute heavily12. 
 
lives affecting physical, social, emotional and economic wellbeing3,13. Therefore it is 

 
 
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and high levels of wound fluid loss have been correlated with increased risk of post-
operative infection and dehiscence28. Xia et al (2014)29 demonstrated that in 20 
subjects with infected wounds NPWT significantly increased blood flow in the 
wounds when compared to pre application levels.  
Ultimately, the use of NPWT for closed abdominal incisions and closed knee 
arthroplasty has been linked to its clinical benefits, judged on the ability to 
minimise risk of surgical site complications. To enable NPWT to achieve this it must 
ensure compliance with the required negative pressure wound therapy protocols.  
A summary of known and potential risks and benefits to humans of each 
details of the full literature review, pre-clinical, clinical, safety data and a risk 
analysis refer to the IB. 
4.2  Literature Summary 
For each of the wound types a literature search was conducted to identify studies 
involving NPWT with particular focus on single-use portable systems where possible. 
Key studies relating to each area have been described below. 
Application as a post-operative dressing for closed surgically closed incision sites is a 
relatively new use of NPWT; despite this, it has still received reasonable attention 
30 published in 2017 the results of a randomised 
controlled trial comparing the effect of PICO versus standard dressings on 
postoperative surgical site infection in closed laparotomy wounds. In 50 subjects (25 
per cohort) it was shown that incidence of surgical site infection at 30 days 
postoperatively was significantly reduced within the group treated with PICO (8.3% 

 
 
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 Clinical Protocol - Device  Revision D; SOP-CD-05 Clinical Protocol 
NPWT; 32.0% control, p = 0.043). This advantage of treatment with PICO was also 
reflected in a significant reduction in the length of hospital stay (6.1 days NPWT; 14.7 
24 prospective study (2014), also using 
PICO, they assessed similar outcomes of surgical site events and compared results 
to a cohort using conventional dressings. Subjects enrolled in the study included 
those undergoing primary wound closure following breast or colorectal surgery. In 
the equally divided 50 subject colorectal surgery cohort, PICO resulted in significantly 
fewer instances of surgical site events (2 NPWT; 11 control, p = 0.008). It also 
resulted in nearly half the length of hospital stay compared to subjects treated with 
conventional dressings (7.1 days NPWT; 12 days control, p = 0.001). These findings 
have been further confirmed through a sub-group meta-analysis comparing PICO to 
standard care in abdominal surgery23. Selvaggi et al25 published in 2014 the results 
of a prospective, open-label, controlled study comparing PICO with standard dressing 
steroids and ASA score 2-3. 
Twenty-five people were treated with PICO and 25 with the standard dressing. 
Subjects were followed for 12 months postoperatively. The primary endpoint was the 
30-day rate of SSCs. Subjects treated with PICO had less SSC rates (OR 0.21, 95%CI 
0.15-0.5, p=0.001) resulting in shorter hospital stay. At last follow-up, readmission 
rates were lower with PICO.
In revision hip and knee surgery Cooper and Bas (2016)31 have previously compared 
the outcomes of closed incision NPWT and sterile antimicrobial dressing. In this 138 
subject (30 NPWT; 108 antimicrobial dressing) retrospective study they found the 
NPWT cohort developed significantly fewer overall wound complications (6.7% NPWT; 
26.9% antimicrobial dressing, p = 0.024). Total surgical site infections were also 
shown to be lessened (3.3% NPWT; 18.5% antimicrobial dressing, p = 0.045). 

 
 
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Furthermore, trends highlighted a lower number of superficial wound dehiscence and 
reoperations in the NPWT group; however these findings were non-significant. 
Karlakki et al (2016)17 evaluated the use of PICO in subjects undergoing elective 
primary total hip and knee arthroplasties. Within this non-blinded randomised control 
trial 220 subjects were recruited and assigned to be treated with either incisional 
NPWT or conventional dressings. Their findings revealed that NPWT resulted in a 4 
times lower number of surgical wound complications when compared to the 
conventional dressing group (2.0% NPWT; 8.4% control),however, in spite of the 
difference the results fell short close to statistical significance (p = 0.06). Results also 
showed a shorter hospital stay (3.8 days NPWT; 4.7 days control, p = 0.07). Further 
studies have suggested the same trend in reduced wound complication when PICO is 
applied to hip and knee revision arthroplasties32, however this is not unanimously 
agreed upon for all NPWT systems33. 
Hudson et al (2015)28 presented the results of a prospective, open label, non-
comparative study. They assessed the functionality and performance of PICO in 20 
subjects with closed surgical wounds (including knee implants and abdominal), 
traumatic wounds or meshed split thickness skin grafts. Results showed within 14 
days 55% of wounds had closed with a further 40% progressing to closure. In three 
case examples this study also demonstrated the ability for PICO system to achieve 
near continuous negative pressure within therapy limits. This study has highlighted 
the ability and potential for newer systems to successfully deliver therapeutic levels 
of negative pressure. 
Provided as a convenient, all-in-one, canister-free system, the current PICO versions 
support patients in maintaining their daily activities. Patients may be safely 
discharged with PICO in place25, 26, 34. The size and simplicity gives patients confidence 

 
 
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copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
Smith+Nephew, nor shall anyone make any use of it that is contrary to the expressed or implied wishes of 
Smith+Nephew. 
  
 
Contraindications 
The use of 
is contraindicated in the presence of: 
 
Malignancy in the wound bed or margins of the wound (Except palliative care 
to enhance quality of life) 
 
Previously confirmed and untreated osteomyelitis 
 
Non-enteric and unexplored fistulas 
 
Exposed arteries, veins, nerves or organs 
 
Exposed anastomotic sites 
 
Necrotic tissue with eschar present 
Storage 
The 
 system must be stored between 5 and 25oC and relative 
humidity between 10-75%. 
4.4.1 Benefits 
PICO systems maintain a nominal (80 mmHg) negative pressure wound therapy 
which may promote surgical site healing via removal of low to moderate levels of 
exudate and infectious materials.  
4.4.2 Anticipated Serious Adverse Device Effects 
Excessive bleeding is a serious risk associated with the application of suction to 
wounds which may result in death or serious injury. Careful subject selection, in view 
of the above stated contraindications, warnings and precautions is essential. Subjects 
with incisions that are actively bleeding are not eligible to participate in this study 

 
 
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copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
Smith+Nephew, nor shall anyone make any use of it that is contrary to the expressed or implied wishes of 
Smith+Nephew. 
  
 
unless haemostasis has been achieved (to be confirmed during surgery). The surgical 
site and dressing should be monitored for any evidence of a change in the blood loss 
status of the subject. 
4.4.3 OVERALL BENEFIT/RISK ANALYSIS 
The anticipated medical benefits are considered to outweigh the overall or individual 
residual risks associated with 
 system within the proposed indication. 
The risks associated with PICO NPWT are addressed with reference to the warnings 
and precautions in the IB. 
5 OBJECTIVE(S) 
5.1  Primary Objective 
To assess the functional clinical performance of 
 NPWT system over 
7 days therapy through the verification of delivery of negative pressure, wound 
exudate management and dressing wear time. 
5.2 Secondary Objective(s) 
To assess clinical performance and safety of the 
 NPWT system within 
30 days of surgery through the: 
 
Incidence of Surgical Site Infection (SSI)  Superficial, deep. [CDC criteria] 
 
Incidence of Surgical site Complications (SSC) [as applicable: dehiscence 
(superficial/deep, partial/total), seroma, necrosis, hematoma, suture abscess] 
 
Condition of skin around the wound, and under the pump 
 
 
Phase 1 only: Range of motion assessment (ROM) for the knee 
 
Any pain experienced by the subject in relation to the 
 system 

 
 
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copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
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Lot number 
 
Expiry Date 
 
Site number and address 
 
Place for the Subject number and Initials 
 
Place for Visit Date if applicable 
 
Exclusively for Clinical Investigation  
 
T. J. Smith & Nephew Medical Ltd., Hull, UK 
The labels on the IP secondary packaging contain the following information  
 
Study number 
 
Lot/batch number 
 
Expiry date 
 
Site number and contact details  
 
Place for the Subject number and Initials 
 
Place for Visit Date  
 
Storage conditions 
 
Exclusively for Clinical Investigation 
 
T. J. Smith & Nephew Medical Ltd, Hull, UK 
 
See IFU/IB 
 
Return all unused product at end of study 
6.3.2 Comparator Product 
This section is not applicable. 

 
 
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copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
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Smith+Nephew. 
  
 
6.3.3 Ancillary Product 
This section is not applicable as all ancillary product supplied is commercially available 
and used within its approved indications. 
 
6.4  Product Accountability Procedures 
The investigational site will maintain an inventory of the IP. Overall accountability is 
by the Investigator or designated individual maintaining an inventory, which will 
include details of receipt, use, waste, returns, and collection etc. by the Sponsor of 
the IP. Accountability records must document which products (batch, expiry, 
quantity) were used by which subjects. The Sponsor will provide log(s) to facilitate 
IP inventory control. All IP accountability logs must be retained in the Investigator 
Site File (ISF). These records must be available for inspection by the Sponsor, its 
designees, or by regulatory agencies at any time. 
The Study Monitor will ensure that the procedures and records are in place for 
appropriate reconciliation of all IP. As part of monitoring, the Study Monitor will check 
that the site personnel are following the proper procedures for accountability and 
completing all necessary documentation. 
During transit to the site and storage at the site, temperature loggers will be used 
to ensure that the IP does not fluctuate outside the recommended temperature for 
maintenance of the product components. 
 

 
 
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copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
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2. Subjects eighteen (18) years of age or older. 
3. Willing and able to make all required study visits. 
4. Able to follow instructions. 
5. Subject is suitable to participate in the study in the opinion of the Investigator 
6. (Phase 1 only): In Orthopaedic surgery: subject is scheduled for an elective prim
knee replacement arthroplasty and ASA* score of 2-3. 
7. In Abdominal surgery: subject is scheduled for an elective open or 
laparoscopic gastrointestinal and/or gynaecological surgery with incision 
5 
cm and has an ASA score of 2-3.  
8. Immediately after the surgery, subject will have one suitable closed abdominal 
or knee surgery incision(Phase 1 only), (if there is more than one incision, 
then the clinicians should choose the one which in their opinion is most suited 
to PICO therapy) that fits under the absorbent dressing area of the appropriate 
 dressing sizes 
 
  
*American Society of Anesthesiologists (ASA) Physical Status Classification System. See 
Appendix 22.11 
7.3 Exclusion Criteria 
Any one (1) of the following criteria will disqualify a potential subject from 
participation in the study: 

 
 
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copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
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1. 
Contraindications (per the 
 IB) or hypersensitivity to the use 
of the investigational product or their components (e.g. silicone adhesives 
and polyurethane films [direct contact with incision], acrylic adhesives [direct 
contact with skin], polyethylene fabrics and super-absorbent powders 
[polyacrylates]) within the dressing). 
2. 
Subjects with extremely fragile skin who require the use of SECURA non-sting 
barrier skin wipes and have hypersensitivity to the ingredients in the wipes 
3. 
Participation in the treatment period of another similar clinical trial (wound 
care related) within thirty (30) days of operative visit or during the study. 
4. 
Subjects with skin features (e.g. tattoos, skin colour, pre-existing scarring) 
which in the opinion of the Investigator, will interfere with the study 
assessments. 
5. 
Subjects attending for an operation at the same surgery site (anatomical 
location) within the last 3 months. 
6. 
Subjects undergoing a procedure as part of palliative care (to be confirmed 
during surgery). 
7. 
Subjects where the 
 area of the device would be placed 
on a load-bearing anatomical location (i.e. areas vulnerable to pressure 
damage). 
8. 
Subjects with incisions that are actively bleeding unless haemostasis has 
been achieved (to be confirmed during surgery). 
9.  
Subjects with infected skin lesions or incisions at the time of surgery (any 
area of the body). 

 
 
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copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
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10. 
Subjects who have participated previously in this clinical trial.  
11. 
Subjects with a history of poor compliance with medical treatment. 
12. 
 
13. 
Subjects with a medical or physical condition that, in the opinion of the 
Investigator, would preclude safe subject participation in the study. 
14. 
Subjects where the dressing cannot be fully applied without coming into 
contact with, or covering, tubes, drains, wires or other ancillary devices 
which may affect the seal, and/ or which will require removal before the end 
of the seven day period 
 
7.4 Screening 
Participating study sites are required to document all screened subjects considered 
for inclusion in this study. If a subject is excluded from the study, the reasons for 
exclusion will be documented in the subject's source documents and noted on the 
Screening and Enrolment Log. All screening activities which occur prior to consent 
shall be referred to as pre-screening.  
A screen failure is any subject who has signed a consent form and goes on to become 
ineligible for the study prior to the application of the study dressing (section 9.1.2 
and 9.1.3). Information must be captured in the appropriate CRFs up to the point of 
screen failure with the reason for screen failure specified. Screen failures will be 
documented in the subject's source documents and on the Trial Register. Any screen 
failures will be replaced. 

 
 
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copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
Smith+Nephew, nor shall anyone make any use of it that is contrary to the expressed or implied wishes of 
Smith+Nephew. 
  
 
7.5 Informed Consent 
Before conducting any study procedures or examinations, the purpose and nature of 
the study will be explained to the subject in their native language. The subject, or 
their legally authorized representative, will then read, sign, and personally date 
the IRB/IEC approved informed consent document(s) (see below for difficulties with 
reading and writing). Additionally, the individual who obtains consent from the 
subject will sign and date the informed consent document. A copy of the signed 
informed consent documentation will be provided to the subject, a copy will be placed 
 
If the subject is unable to read, the informed consent document and associated study 
information may be read aloud to the subject in the presence of an impartial witness. 
If possible, the subject shall sign and personally date the Informed Consent Form 
(ICF). Where this is not possible, due to difficulties in writing, the subject shall provide 
verbal consent to participate in the study. The witness shall then personally sign and 
date the informed consent form, attesting that the information was accurately 
explained and that the informed consent was freely given. 
All subjects will be given ample time (at least 24 hours) to consider participation 
following the explanation of the study/reading of the patient information sheet. If 
new information becomes available during the course of the study that can 
+ Nephew will 
ensure that information shall be provided to the subject(s) affected in written form 
and if relevant, all affected subjects shall be asked to confirm their continuing consent 
in writing. 

 
 
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copied in whole or in part, nor shall the contents be disclosed by any means without prior written permission from 
Smith+Nephew, nor shall anyone make any use of it that is contrary to the expressed or implied wishes of 
Smith+Nephew. 
  
 
7.6 Enrolment 
Enrolment in this study shall occur at the point the consent process has been 
completed and study number is allocated to the subject. 
7.7 Lost to Follow-up 
A subject will be considered lost to follow-up if he/she does not appear for the 7 day, 
14 day, or 30 day visit and study personnel are unable to contact the subject. 
Some actively enrolled subjects will not return for follow-up exams on time. Study 
personnel must make a reasonable effort to contact the subject and document the 
following contact attempts prior to declaring a subject to be lost to follow-up: the 
subject has been contacted according to the site's policies, but no fewer than 2 
documented phone contacts and 1 certified letter without response. Copies of all 
attempts to reach the subjects per regular mail or email and/or the attempts to 
contact the subject via other means should be documented and that documentation 
 
7.8 Withdrawal 
 
7.8.1 Withdrawal from Treatment 
Subjects may be withdrawn early from study treatment for the following reasons: 
 
Subject does not return following treatment (and pump is lost) 

 
 
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Treatment is prematurely ended for any reason (i.e. due to removal of the 
system by the subject or the investigator, failure of the pump, dressing falls 
off, seal can no longer be established) 
 
Treatment is disrupted for longer than 24 hours (i.e. airtight seal was disrupted 
and was not re-established with a 24-hour time period). 
 
At the discretion of the Investigator due to: 
o A change in treatment is clinically warranted (to include further 
treatment following 7-day therapy). 
o An adverse event or device deficiency 
o Any other significant reason identified by the Investigator 
 
7.8.2 Withdrawal from Study 
The Investigator may withdraw subjects from the study for many reasons, including 
but not limited to the following: 
 
subject lost to follow-up 
 
if the Investigator or the Sponsor stops the study for any reason and decides 
to withdraw subject(s) from the study 
 
any other significant reason identified by the Investigator 
For each case, information will be obtained in the source document and the Case 
Report Form (CRF), detailing circumstances leading to the withdrawal.  
Subjects who are withdrawn prior to the application of the study dressing will be 
replaced. 

 
 
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Subjects who are treated for bilateral knee surgery, and subjects who drop out, or 
are withdrawn, will not be re-entered into the study at a later date. 
 
7.8.3 
Study 
Study participation is voluntary and subjects may withdraw at any point during the 
study without giving their reason for doing so. Where subjects withdraw consent, the 
Investigator should make a reasonable effort to ascertain the reason(s), while fully 
ll be recorded in the 
CRF and in source documents.  
7.8.4 Use of Data Following Withdrawal 
In cases where the subject withdraws consent, the data collected up to the point of 
withdrawal may be used but no additional data for that subject may be collected.  
8 STUDY DESIGN 
8.1  Study Design 
This study is a prospective, multi-centre, non-randomised, non-blinded, single arm 
follow-up study to assess clinical performance and safety of 
 It is 
anticipated that up to 6 sites will participate within the UK. 
The treatment phase will be 7 days post-surgery with a study follow-up period up to 
30 days for assessment of complications. Seven days of therapy has been chosen as 
the length of time to assess device performance with use in real clinical conditions, 
since this is the length of time one system will operate and previous studies involving 

 
 
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8.2 Allocation and Blinding 
This study is non-randomised. 
8.3 Data Management 
This study utilizes a validated, 21 CFR Part 11 compliant, electronic data capture 
system. Access to the electronic data capture system is controlled through Smith 
and Nephew procedures.  
A Data Management Plan (DMP) is written according to Smith and Nephew 
procedures containing details of the data management process. The following is a 
brief description of the key points detailed in this plan.  
 
8.3.1 Data Review and Quality Assurance 
Data will be transcribed from the data source to an electronic Case Report Form 
(eCRF). All data requested on the eCRFs are considered required. Data points not 
collected and/or recorded will be considered deviations unless otherwise specified.  
Data collection is the responsibility of the clinical trial staff at the site under the 
supervision of the Principal Investigator. The Principal Investigator is responsible for 
ensuring the accuracy, completeness, legibility, and timeliness of the data reported. 
The Principal Investigator must provide his/her electronic signature on the 
appropriate eCRFs to be documented in compliance with local regulations. Changes 
to data previously submitted to the sponsor will require a new signature by the 
Investigator to acknowledge/approve the changes.  

 
 
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the borders observed during the dressing wearing period resulting or not, in 
an unplanned dressing change. 
 
8.4.2 Secondary Endpoints 
Clinical performance and safety of the 
 NPWT system over a 30 
day follow-up period to include:  
 
Incidence of Surgical Site Infection (SSI) 
 Superficial, deep, organ [CDC 
criteria] within 30 days of surgery 
 
Incidence of Surgical site Complications (SSC) [as applicable: dehiscence 
(superficial/deep, partial/total), seroma, necrosis, hematoma, suture abscess] 
within 30 days of surgery 
 
Condition of peri-wound skin and skin under the pump 
 assessed 
through visual inspection at 7, 14 and 30 days. 
 
Wound and Skin VAS score assessment at 7, 14 and 30 days 
 
Phase 1 only: Comparison of Wound and Skin VAS scores at days 7, 14 and 30 
as assessed by the treating clinicians versus scores provided by the 
independent assessor. 
 
Phase 1 only:Range of motion assessment (for knee subjects only) at pre-
operative, post-operative day 1, 7, 14 and 30 days 
 
Level of pain during wear of the 
 system, and at dressing 
removal assessed by VAS scale following 7-day therapy 
 

 
 
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8.4.3 Exploratory Endpoints 
 
Clinician acceptability of 
 system at discontinuation of therapy 
 
Subject acceptability of 
 system at discontinuation of therapy 
 
Ease of application & removal 
 
Subject comfort during wear.  
 
d 
perception of the device in general will be included in the analysis. 
8.4.4 Safety Endpoints 
Safety, assessed through the incidence and severity of Adverse Events and Device 
Deficiencies 
8.5  Methods Used to Minimize Bias and Maximize 
Validity 
 
8.5.1 Reduction of bias towards acceptability of IP system 
when compared with other manufacturers/models 
Smith & Nephew will ensure that reduction of bias towards acceptability of the 
 
 system against any others marketed, by being fully transparent with the 
aim of the study prior to commencing and through publishing the result of the primary 
endpoint following reporting on www.clintrials.gov and any other applicable trial 
registries. 

 
 
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8.5.2 Minimisation of bias due to low study numbers 
The statistical techniques for the study have attempted to account for bias brought 
about by low subject numbers. Subject attrition has been accounted for within the 
sample size calculation. This sample size was based on a previous PICO study data 
using similar data loggers. 
8.5.3 Attempt to retain ecological validity 
Phase 1 of the study included a single indication in two different surgical specialties 
and a range of contoured areas of the body where it may be difficult to obtain an 
effective negative pressure seal and where there may be a range of motion 
throughout therapy (i.e. knee). The inclusion/exclusion criteria are also not too 
restrictive with regard to subject demographic. This should mean that the results will 
be representative of a real clinical setting in hospital or at home, and for the proposed 
indication in the two specialties. 
 
8.5.4 Attempt to reduce ascertainment bias in data 
collection 
Subject and clinician will also be requested to verify any answer they give with some 
rationale for their answer where possible. 
 
 
 

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
9.1.2 Screening/Preoperative Visit (may be up to 6 weeks prior 
to operative visit) 
NOTE: Any subject who signs an informed consent but fails to meet the required entry criteria 
is considered to be a Screen Failure. Information must be captured in the appropriate CRFs 
up to the point of screen failure with the reason for screen failure specified (section 7.4). 
1.
Obtain written informed consent from the subject as detailed in Section 7.5 
----- Do not proceed until consent has been obtained ----- 
2.
Obtain demographic information and medical history (for current or chronic 
conditions as per the eCRF categories), including information on all 
concomitant medications/therapies.  
3.
Screen the subject for protocol inclusion/exclusion criteria. 
4.
Obtain range of motion measurements (for knee subjects only in Phase 1) 
5.
Subjects will be instructed to return to the treatment facility for the Operation 
Visit (within 6 weeks of consent). 
9.1.3 Baseline Operative Visit (Within 6 weeks of screening) 
NOTE: Any subject who has signed an informed consent but at this visit no longer meets the 
required eligibility criteria prior to the study dressing application is considered to be a Screen 
Failure. Information must be captured in the appropriate CRFs up to the point of screen failure 
with the reason for screen failure specified (section 7.4). 
1. 
Query subject regarding any changes in general health and the use of 
concomitant medications (if screening and surgery are not on the same 
date). 
2. 
Commence operation and collect surgery data [e.g. Type of surgery (closed 
surgical incision, (type of abdominal surgery, type of knee surgery, incision 
length, anatomical location and method of closure), 
3. 
Collect surgery risk factors (elective/emergency surgery, laparoscopic (y/n), 
incision length, use of prophylactic antibiotics, type (single/double/triple 

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
agent) and when administered (prior to start of surgery/after surgery 
began),  shaving of incision (yes/no/not needed), use of a wound protector 
(yes/no), surgical bioburden level(clean/clean-contaminated/ 
contaminated/dirty), intraoperative warming (yes/no)) 
4. 
Confirm eligibility following surgery details. NOTE: Subjects that no longer 
meet the eligibility criteria following surgery will be deemed a screen failure; 
operative information must be captured in the appropriate CRF with the 
reason for screen failure specified. These subjects will be replaced. 
5. 
Photograph incision using the camera (
 provided by the Sponsor. 
6. 
Assess the incision characteristics for likelihood of SSC (oedema, seroma, 
haematoma, skin necrosis. 
7. 
Assess the surrounding skin including the area under the pump (e.g., 
healthy, fragile, inflamed, erythema, bruising, eczematous, dry/flaky, 
macerated). 
8. 
Dispense study product. Record pump lot number, size of dressing used 
 
 and any ancillary 
products applied (SECURA No-Sting Skin prep, RENASYS Adhesive Gel 
Patch). Record also ancillaries in the vicinity (e.g. drains, stomas, lines, 
dressings). 
9. 
Assess ease of application, ease of establishing seal/negative pressure 
delivery, satisfaction of applying IP. 
10.
Take photograph of dressing in place. Take a photograph of the carton label 
to aid accountability checks (the label will contain the batch number). 
11.
If any adverse device effects or device deficiencies are observed or reported, 
they must be recorded as instructed in Section 12 - Adverse events and 
device deficiencies. 
12.
If there were failed attempts at applying the study product. Please record the 
device details and disposition of the device. 
9.1.4 Baseline Post-Operative Visit (within 24[±3 hours] if 
subject is well enough and coherent 
1.
Record the use of concomitant medications. 
2.
If any adverse device effects or device deficiencies are observed or reported, 
they must be recorded as instructed in Section 12 - Adverse events and 
device deficiencies. 

 
 
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intended for use only by Smith & Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
3.
Obtain range of motion measurements (for knee subjects only in Phase 1) 
4.
Instruct the subject on proper post treatment/postoperative care/procedures, 
including any contraindicated treatments/medication(s) and refer subject to 
the IFU. 
5.
Instruct the subject on follow-up procedures, including returning to the 
treatment facility for the Day 4 Follow-Up (FU) Visit in 4 days ±1 day post-
surgery. 
 
9.1.5 Day 4(± 1 day) Follow Up Dressing Inspection 
1.
Record date and treatment setting. If outpatient, record date of previous 
discharge. 
2.
If therapy is being discontinued prior to 4 days or dressing is no longer in 
place, complete the End of Therapy Assessment (9.1.6 below). 
3.
Record if therapy has been interrupted since the previous assessment and 
how long. 
4.
Record the use of concomitant medications. 
5.
Take photograph of dressing in place. 
6.
Assess subject comfort (yes, no) and pain level (VAS pain scale). 
7.
If any adverse device effects or device deficiencies are observed or reported, 
they must be recorded as instructed in Section 12 - Adverse events and 
device deficiencies. 
8.
Instruct the subject on follow-up procedures, including returning to the 
treatment facility for the End of Therapy Assessment Visit at 7  days post-
surgery. 
 
9.1.6 End of Therapy Assessment (7 days unless therapy is to be 
stopped sooner due to clinical need) 
1. 
Record date and treatment setting. If outpatient, and not previously 
recorded, record date of previous discharge. 
2. 
If therapy is being discontinued prior to 7 days, record reason (e.g. 
 
 NPWT system removed, treatment interrupted for 24 hours or 

 
 
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more, clinician recommends a change in treatment, at the discretion of the 
Investigator, adverse event, subjects own request, lost to follow up, other). 
3. 
Record the use of concomitant medications. 
4. 
Record reason if dressing is no longer in place (e.g. pain/discomfort from the 
dressing, subject removed, subjec
, adverse event, no vacuum, 
pump turned off, other). 
5. 
Record if therapy has been interrupted since the previous assessment and 
how long. 
6. 
Take photograph of dressing in place 
7. 
Obtain range of motion measurements (for knee subjects only in Phase 1) 
8. 
Assess subject satisfaction (overall performance of dressing, comfort, noise 
level, discreteness, portability, interference with daily living  showering, 
sleeping, socialising, working). 
9. 
Remove NPWT system as per procedure (section 9.2.4) for 
 
. Record the unique device identifier  
 
).  
10.
Assess ease of removal. 
11.
Record pain score (VAS) and subject comfort since last assessment and pain 
score on dressing removal. 
12.
A suitably qualified individual (as described in section 9.2.1) to complete CDC 
incision assessment and incision closure.  
13.
A suitably qualified individual (as described in section 9.2.1) to complete 
assessment of incision complications. If any complications have occurred, 
details of this and additional procedures to be collected (per section 9.1.9). 
14.
Assess the surrounding skin (e.g., healthy, fragile, inflamed, erythema, 
bruising, eczematous, dry/flaky,  macerated) 
15.
Assess the skin area under the pump (e.g., healthy, fragile, inflamed, 
erythema, bruising, eczematous, dry/flaky,  macerated) 
16 
Obtain range of motion measurements (for knee subjects only in Phase 1) 
17.
Photograph the incision using the camera (
 supplied by the 
Sponsor. The wound photographs and the resulting wound measures will be 
stored in a database. 
18.
Record 100mm VAS score for wound and skin assessment 

 
 
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19.
If any adverse device effects or device deficiencies are observed or reported, 
they must be recorded as instructed in Section 12 - Adverse events and 
device deficiencies. 
20.
Follow procedure for removal, appropriate labelling and storage of 
 
in IP. 
21.
Assess clinician acceptability of PICO NPWT system (Overall satisfaction, 
satisfaction with ability to manage incision, satisfaction regarding dressing 
retention, satisfaction as compared to other NPWT devices). 
22.
Instruct the subject on follow-up procedures, including returning to the 
treatment facility for the Day 14 FU Visit 3 at 14 (±3) days post-surgery. 
 
9.1.7 Day 14 Follow-Up (14[± 3] days 
1. 
Query subject regarding any changes in general health and the use of 
concomitant medications.  
2. 
A suitably qualified individual (as described in section 9.2.1) to complete CDC 
incision assessment and incision closure.  
3. 
A suitably qualified individual (as described in section 9.2.1) to complete 
assessment of incision complications. If any complications have occurred, 
details of this and further to be collected (as per 9.1.9).  
4. 
Assess the surrounding skin (e.g., healthy, fragile, inflamed, erythema, 
bruising, eczematous, dry/flaky, macerated).  
5. 
Assess the skin area under the pump (e.g., healthy, fragile, inflamed, 
erythema, bruising, eczematous, dry/flaky,  macerated) 
6 
Obtain range of motion measurements (for knee subjects only in Phase 1) 
7. 
Photograph the incision using the camera (
 supplied by the 
Sponsor. The wound photographs and the resulting wound measures will be 
stored in a database. 
8. 
Record 100mm VAS score for wound and skin assessment 
9. 
If any adverse device effects or device deficiencies are observed or reported, 
they must be recorded as instructed in Section 12 - Adverse events and 
device deficiencies.  
10.
Instruct the subject on follow-up procedures, including returning to the 
treatment facility for the Exit Visit at 30 (±3) day post-surgery.  

 
 
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9.1.8 Exit Visit (30 (± 3) days) 
1. 
Query subject regarding any changes in general health and the use of 
concomitant medications. 
2. 
A suitably qualified individual (as described in section 9.2.1) to complete CDC 
incision assessment and incision closure. 
3. 
A suitably qualified individual (as described in section 9.2.1) to complete 
assessment of incision complications. If any complications have occurred, 
details of this and further to be collected (as per 9.1.9). 
4. 
Assess the surrounding skin (e.g., healthy, fragile, inflamed, erythema, 
bruising, eczematous, dry/flaky, macerated) 
5. 
Assess the skin area under the pump (e.g., healthy, fragile, inflamed, 
erythema, bruising, eczematous, dry/flaky,  macerated) 
6. 
Obtain range of motion measurements (for knee subjects only in Phase 1) 
7. 
Photograph the incision using the camera (
 supplied by the 
Sponsor. The wound photographs and the resulting wound measures will be 
stored in a database. 
8. 
Record 100mm VAS score for wound and skin assessment 
9. 
If any adverse device effects or device deficiencies are observed or reported, 
they must be recorded as instructed in Section 12 - Adverse events and 
device deficiencies. 
10.
Complete Exit Visit CRF 
 
 
9.1.9 Unscheduled Visits-SSC Assessment 
Unscheduled examinations may be conducted at the discretion of the Investigator with all 
obtained information recorded in the source documents and on the appropriate CRF. An 
unscheduled visit will be a visit that is not within the visit window for operative, post-
operative, end of therapy assessment, or 30 day exit, visits. 

 
 
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1.
Record the date that the complication occurred. 
2.
Record the complication type. Please provide as much detail as possible. 
3.
Record procedure (e.g. opening of wound, drainage of wound infection, 
antibiotics
oral, antibiotics
intravenous, re suture of wound, evacuation of 
hematoma, seroma aspiration, incision of an abscess, wound toilet, negative 
pressure wound dressing
cavity, change to antimicrobial or antibacterial 
treatment, other)/treatment changed to (e.g. a different NPWT system, simple 
foam dressing, antimicrobial dressing, other).  Photograph the incision using 
the camera (
 supplied by the Sponsor. The wound photographs and 
the resulting wound measures will be stored in a database. Record 100mm 
VAS score for wound and skin assessment. 
4.
Record any concomitant medications. 
5.
The complication and any device deficiencies must be recorded as instructed 
in Section 12 - Adverse events and device deficiencies. 
 
9.1.10 Concomitant Medications and Therapies 
A concomitant medication (e.g. drug, substance) and a concomitant therapy (e.g. physical 
therapy, TENS Unit, massage) are recorded at any time from enrolment into the study through 
 
 
Concomitant Medications 
Excluded Concomitant Medications 
The following concomitant medications are not permitted from the time of enrolment into the 
study until the exit visit has taken place: 
 No other ointments/gels/topical lotions/creams should be used with the PICO system as 
per the IB (other than the SECURA skin barrier wipes and RENASYS Adhesive Gel Patches 
provided as ancillary for the study). 

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
Recording Concomitant Medications in CRF 
All medications will be recorded in the CRF. Refer to the CRF Completion Guidelines for how 
medications are recorded.  
 
Concomitant Therapies 
Therapies Prohibited During the Study 
The use of the following concomitant therapies is not permitted during the study period: 
 No dressings (i.e. foam, gauze, ACTICOAT, wound contact layers) should be used under 
the IP during therapy. 
 No other NPWT devices (i.e. RENASYS, Vac) should be used following the 7 day therapy 
treatment period unless it becomes necessary on clinical grounds and this would be the 
routine clinical protocol provided by the site. 
Recording Concomitant Therapies in the CRF 
Only therapies related to (directly treating) the reference incision will be recorded on the 
CRF. Refer to the CRF Completion Guidelines for how concomitant therapies are recorded. 
9.1.11 Discontinued Subjects 
Discontinued subjects are those who voluntarily discontinue participation or who are lost to 
follow-up refer to section 7.8 for further details. Where possible, a full Exit Visit should be 
completed for all subjects who discontinue the study early. Where consent is withdrawn, the 
date and any reason given for discontinuation should be captured, at a minimum (see Section 
7.8.2). 

 
 
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Finally, if appropriate, the Investigator will also advise the subject of subsequent therapy 
and/or procedures necessary for their medical condition.  
Subjects who are withdrawn only from treatment will not automatically discontinue 
participation in the study, see Section 7.8. 
9.1.12 Subject Pregnancy 
Women of child-bearing potential are not excluded from the study. However, if a woman 
becomes pregnant during the study, S&N must be contacted immediately once the 
investigator is made aware of the pregnancy. Pregnancy is not reportable as an adverse 
event; however, complications related to the pregnancy may be reportable as determined 
on a case-by-case basis. Pregnancy-related information will be collected until the end of 
the pregnancy.  
9.2 Study Methods and Measurements 
 
9.2.1 Incision Closure, SSC and CDC-SSI Incision Assessment 
Incision closure is defined as 100% re-epithelisation without drainage or dressing 
requirements. Primary or first intention healing occurs when tissue is cleanly incised and re-
approximated and healing occurs without complications. The incisional defect re-epithelises 
rapidly and matrix deposition seals the defect. Incisional wounds are usually completely re-
epithelised in 24-48 hours, with continued healing of the underlying structures within 5-7 
days. Delayed wound healing 
unhealed, >7 days. 
Assessment of incision healing and potential complications will be completed by a suitably 
qualified individual at each of the specified time points. The assessment will be performed 
using the CDC definitions of surgical site infection. SSI are infections that occur within 30 

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
days of surgery or within a year if an implant is present. In addition, one of the following 
criteria must be met:  
(1) Purulent drainage from an incision (incisional infection) or from a drain below the fascia 
(deep infection);  
(2) A surgeon or attending physician diagnosing an SSI;  
(3) An infective organism being isolated from a culture of fluid or tissue obtained from the 
surgical wound (for incisional infections);  
(4) Spontaneous dehiscence or a surgeon deliberately re-opening the wound in the presence 
of fever or local pain, unless subsequent cultures were negative, or an abscess being 
detected during direct examinations (for deep infections). The grading of SSI is based on 
symptoms. 
In case of SSI, there may be also discharge (serous exudate, seropurulent, haemopurulent, 
pus), delayed healing, erythema, unexpected pain, tenderness, abnormal smell or wound 
breakdown. 
If dehiscence has occurred, the level of dehiscence will be defined as superficial (involve only 
separation at skin level) or deep (involve separation of tissues below the skin, may or may 
not include skin separation). Wound dehiscence will also be classified as partial or total. 
The wound size measurements will be performed directly from the wound photographs taken 
from the wound per each visit. The camera (
 will measure the lengths, the depth 
and the width of the wound automatically, if appropriate. The wound photographs and the 
resulting wound measures will be stored in a database.  
Assessment of the wound will also include the use of a validated 100 mm Visual Analogue 
Scale (VAS) as described by Keeney et al 35, where a very low score is associated to a wound 
with a major gapping, dehiscence, severe inflammation and/or infection; and a very high 
score correspond to a completely healed wound with no evidence for inflammation. VAS 

 
 
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In the case of local wound complications inducing local changes like periwound oedema, skin 
necrosis, dehiscence, 
 pictures will be used to assess the evolution of the event 
until the end of follow-up.  
® 
 Wound Assessment Device allows for a precise determination of surface 
areas, (depth and volume too if required) thus facilitate an objective follow up of the 
evolution of skin lesions (erythema, dehiscence). 
 
9.2.3 Assessment of Range of Motion (Phase 1 Only) 
Range of motion measurements are not routinely measured in PICO studies, and S&N is 
not expecting 
 to impact negatively the knee Range of Motion (ROM). ROM 
measurements are included as a requirement from MHRA as part of the safety assessment 
of the device when used over mobile anatomical regions, i.e. joints. Knee ROM will be 
assessed using a goniometer by a trained member of the study team (e.g. physiotherapist) 
at each of the specified time points. It is ideal that only one person is assigned this task for 
the duration of the study. The assessment will be performed using routine clinical practice 
to measure flexion and extension of the knee joint. 
Results from the ROM measurements were compared to published data from trials 
evaluating single use NPWT devices used in the postoperative management of similar 
closed surgical incisions in the knee population during the interim analysis.        
 
9.2.4 Photographs and Surgical Site Assessment 
Image
dressing application, at 7 days post operatively (or when dressing is removed), at 14 days 
and at 30 days postoperatively (or early exit visit) using a digital camera supplied by S&N.  

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
Photographic assessment will be performed with the 
® 
 
 
® 
 is a portable device that easily allows capture of high-resolution 
is then managed, analysed and 
stored in a central database. Information captured includes photographic images, 
quantitative measures, and other wound assessment data input by the assessing clinician, 
all obtained with no subject contact. 
® 
 builds that information into an 
clinical assessment or archiving. Information about performed wound measurements history 
is available on the system so that progression of the wound status can be calculated and 
presented. 
The images will be used to perform wound assessments by the treating investigator. 
Photograph should also be taken where appropriate of all DevD reported. Pictures will also 
constitute the pictorial record of the study reference incisions.  
The image should be framed such that the entire incision/dressing area nearly fills the frame. 
photograph. After obtaining the image, ensure that the image is clear (in focus) and that 
there is sufficient light to clearly see the wound/dressing. Instructions for capturing images 
will be supplied with the cameras. Training on the use of the 
® 
 camera will 
be given prior to start of the study.  
An image of the dressing in place will be taken after application, and before removal, to 
check the device compliance. All photographs should be linked to the relevant assessment 
on the CRF.  

 
 
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is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
TMP-
  
  
 
 
9.3 Health Economics/Quality of Life 
Specific validated Quality of Life questionnaires will not be collected for this study. However, 
assessment of acceptability of the therapies will be made by specific targeted questions to 
the clinician and subject as described in section 9.1.2 above. 
10 STATISTICAL DESIGN 
A Statistical Analysis Plan (SAP) will be written and finalized prior to database lock. The 
following is a brief description of the analyses to be described in this plan. The SAP will be 
more detailed and account for all analyses.  All analyses will be conducted with statistical 
software SAS Version 9.4 or later.   
10.1 General 
The subject data will be described and summarised using the baseline demographic and 
medical variables which include but are not limited to age, gender, ethnicity, medical and 
medication history, diagnostic factors as well as study process variables (e.g. AE and 
withdrawal(s). Summary statistics will be given according to the nature of the variable, 
continuous or categorical. For categorical variables, the number of observations, mean, 
standard deviation, median, minimum, and maximum will be presented, while for categorical 
variables the number of observations, frequency, and percentages will be reported. All 
summaries and analyses will be presented separately for each of the two cohorts of 
specialties recruited within the study: orthopaedics (closed knee incisions e.g. after Total 
Knee Arthroplasty), and Abdominal surgery (closed abdominal surgical incisions). No data 
will be combined between the two specialties. 
Primary, secondary, and exploratory outcome variables and derived variables will also be 
summarised accordingly separately by specialty. Parametric statistical tests will be used if 

 
 
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the data is normally distributed and corresponding non-parametric tests will be considered if 
the data is not. Where necessary, suitable regression techniques will be used to adjust for 
confounding since the study is non-randomised. The results will be reported at 5% 
significance level and where appropriate 95% confidence intervals (CI) will be given.  
10.2 Analysis Populations 
 
Safety Population (SAF), including all subjects who have received the study device. 
 
Full analysis set population (FAS), following ITT principle including all subjects recruited 
into the study. 
 
Per-Protocol Population 1 (PP), including all subjects in the full analysis set who have no 
significant protocol deviations and met the inclusion/exclusion criteria. 
Statistical analysis will be performed using each of the subject populations as follows. 
Analysis of the primary, secondary and exploratory performance objectives will be performed 
separately using both the Full Analysis Set and the Per Protocol Population. All safety analyses 
will utilize the Safety Population, separately for each specialty. 
Subsets of the above populations will be used for secondary analyses where appropriate to 
analyse only those subjects in the abdominal group who were recruited post-interim analysis 
and followed version 8.0 of the protocol. These subset populations will be labelled with the 
-
-FAS 
etc. 
10.3 Baseline Data 
The subjects will be described and summarised using the baseline demographic and medical 
variables which include but are not limited to age, gender, ethnicity, medical and medication 
history, diagnostic factors. Summary statistics will be given according to the nature of the 
variable, continuous or categorical. For categorical variables, the number of observations, 

 
 
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mean, standard deviation, median, minimum, and maximum will be presented, while for 
categorical variables the number of observations, frequency, and percentages will be 
reported.  
10.4 Efficacy Analysis 
The study is non-comparative and non-randomised, the impact of confounding on the 
measures of performance may be expected and will be evaluated through descriptive analysis 
of selected baseline and demographic variables and fitting of appropriate models on selected 
outcomes presented separately for each specialty.  
The primary analysis of the following endpoints will be done using FAS and PP analysis 
populations. However, an additional analysis will also be carried out on a subset of these 
populations (s-FAS and s-PP) which includes only subjects who were recruited post-interim 
analysis and followed protocol version 8.0. 
10.4.1 Analysis of Primary Endpoint(s) 
 Negative Pressure maintenance at nominal 80mmHg 
The following hypotheses will be tested to establish equivalence of the 
  
 compared to the internally derived value, with equivalence margin, 
1>0, for each specialty cohort:  
H0
- 
 0 
1 
Ha
- 
 0 | < 
1 
In the stated hypotheses,  represents the assumed mean operating pressure (80.2 mmHg) 
and  
 represents the mean 
 
 operating pressure.  The equivalence 
limit 1 = 7mmHg was chosen as a conservative non-clinically significant difference assuming 
that the difference is actually 0. The hypothesis will be tested by two-one-sided t-test (TOST) 

 
 
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CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith & Nephew PLC and Smith & Nephew, Inc. and is 
intended for use only by Smith & Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
at the alpha level of 0.025 (one-sided), separately for each specialty.  If the null hypothesis 
is rejected, equivalence will be confirmed. 
The corresponding 95% CI for each cohort will also be presented. 
 Dressing wear time in days as assessed through a combination of data from 
 
and CRF recorded data of any unplanned dressing change. 
The following hypotheses will be tested, for each specialty separately, to establish that the 
dressing wear time of the 
 
 pump system is strictly no worse 
(lower) than the literature derived value:  
H0
- 
 0  
 
Ha
- 
 0  >0 
In the stated hypothesis, µ represents the mean 
 dressing wear time in days 
and µ0 represents the literature derived value (4.6 days). A one sided (one sample) t-test 
with alpha = 0.025 will be used to evaluate the hypothesis for each specialty, the 
corresponding 95% CIs will also be presented. 
days will be reported as a percentage along with corresponding 95% confidence interval, for 
each specialty cohort. If necessary and if data allows, important associated factors will be 
adjusted for in a logistic model. 
 Exudate management assessed by no occurrence of exudate leaks as assessed by reported 
clinical data on any exudate leakage observed through a dressing or around the borders 
during the dressing wearing period resulting or not, in an unplanned dressing change. 
A binary variable for the non-leakage and leakage will be used and the proportion of 
reported/identified leaks will be presented as a frequency together with a percentage and a 

 
 
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intended for use only by Smith & Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
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95% CI separately for each specialty. For each specialty, the non-leakage proportion for the 
study will be tested using the Exact test to establish if it is different from the literature derived 
value of 85% projected. Further, the resulting lower limit of 95% CI for each specialty will 
be evaluated to establish if it excludes values of 65% and below. 
Composite Clinical Success (CCS) defined as a binary variable (1/0) (1 if all three of the 
following are true and 0 if at least one of the three is false): 
A. 
Average negative pressure within therapeutic range (-100mmHg to -60mmHg) 
B. 
Dressing wear time is 7 days 
C. 
No exudate leakage 
The Composite Clinical Success (CCS) will be reported as a count and percentage with a 95% 
CI separately for each specialty. 
A logistic model will be used to evaluate the adjusted and the un-adjusted models for the 
CCS primary outcome variable for each specialty, separately. The variables considered 
important and to be included in the final model are Age, Diabetic status and the presence of 
any other co-morbidity as a binary variable. All other baseline and medical factors collected 
at baseline will be evaluated for importance in adjusted models and only those statistically 
significant in an un-adjusted model will be considered in the final model.  
10.4.2 Analysis of Secondary Endpoint(s) 
Clinical performance and safety of the 
 NPWT system over a 30 day follow-
up period will be presented separately for each specialty, and will include:  
 Incidence of Surgical Site Infection (SSI)  Superficial, deep, organ [CDC criteria] within 
30 days of surgery 

 
 
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 Incidence 
of 
Surgical 
site 
Complications 
(SSC) 
[as 
applicable: 
dehiscence 
(superficial/deep, partial/total), seroma, necrosis, hematoma, suture abscess] within 30 
days of surgery 
 Wound and Skin VAS score assessment at 7, 14 and 30 days 
 Condition of peri-wound skin and skin under the pump 
 assessed through visual 
inspection at 7, 14 and 30 days. 
 Level of pain during wear of the 
 system, and at dressing removal assessed 
by VAS scale following 7-day therapy 
 Phase 1 only: Comparison of Wound and Skin VAS scores at days 7, 14 and 30 as assessed 
by the treating clinicians versus scores provided by the independent assessor. 
 Phase 1 only: Range of motion assessment (ROM) for the knee at pre-operative visit, 
post-operative visit, 7, 14 and 30 days.  
 Level of pain during dressing removal (VAS scale) - pain intensity as none, mild, moderate, 
or severe. 
For incidence of SSI and incidence of SSC binary variables indicating presence of/absence of 
will be defined and the frequencies together with percentages reported/identified outcomes 
will be reported separately for each specialty. A logistic model will be used to evaluate the 
adjusted and the un-adjusted models for the secondary variables, the incidence of surgical 
site infections, and incidence of surgical complications separately for each specialty. The 
variables considered important and to be included in the final model are Age, Diabetic status 
and the presence of any other co-morbidity as a binary variable. All other baseline and 
medical factors collected at baseline will be evaluated for importance in adjusted models and 
only those statistically significant in an un-adjusted model will be considered in the final 
model. 
Where the data is recorded both by the treating investigator, and by an independent 
medically qualified individual/assessor (for example, the wound and skin VAS score), the 
assessments will be presented separately for each assessor and results cross-tabulated 

 
 
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between assessors where appropriate. In each case analyses will be presented separately for 
each specialty. 
Summary statistics for all other secondary variables will be given, for each specialty 
separately, according to the nature of the variable, continuous or categorical. For categorical 
variables, the number of observations, mean, standard deviation, median, minimum, and 
maximum will be presented, while for categorical variables the number of observations, 
frequency, and percentages will be reported. 95% confidence intervals will be reported where 
appropriate. 
As range of motion is collected for subjects in the knee surgery group only there will be no 
summary of ROM in the s-FAS and s-PP analysis. 
 
10.4.3 Analysis of Exploratory Endpoints 
 
Acceptability (clinician/subject questionnaires)  
 
Subject comfort during wear (subject questionnaire) 
 
Ease of application & removal 
All exploratory end points will be summarised through descriptive statistics and tabulated 
accordingly, separately for each specialty. For categorical variables, the number of 
observations, mean, standard deviation, median, minimum, and maximum will be presented, 
while for categorical variables the number of observations, frequency, and percentages will 
be reported. 95% confidence intervals will be reported where appropriate. 
10.5 Safety Analyses 
 
Adverse Events and Device Deficiencies 

 
 
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All safety analyses and summaries will be conducted using the Safety Population. All safety 
summaries will be presented by specialty in conjunction with selected demographic variables 
e.g. gender. 
10.6 Interim Analyses 
As a condition for the MHRA No Objection decision, an interim analysis was required to be 
performed once the study has recruited 22 subjects in each specialty group who had 
completed the follow-up period. The study was paused while the MHRA assessed the results.  
There will be no further interim analysis performed as part of Phase 2 of this study. 
 
 
 
 
 
 
11 SAMPLE SIZE JUSTIFICATION 
 
11.1 Sample Size Justification Pre-Interim Analysis 
The sample size is justified based on the proposed three primary outcome variables of 
nominal pressure of 80mmHg, Dressing wear time in days and exudate management based 

 
 
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on incidence of exudate leakage. Each of the three hypotheses will be tested separately for 
each specialty cohort. 
For the nominal pressure the sample size is based on analysis to test equivalence of negative 
pressure delivery against the reference value of 80.2mmHg. Previous data extracted from 
the PICO 7 system were found to be distributed with a SD=14.8. For purposes of sample size 
calculation, the a priori assumption is that the 
 
 system will 
have a similar operating pressure to PICO 7, and therefore similar variability in pressure 
delivery is assumed.  The following hypotheses will be tested to establish the equivalence in 
mean operating pressure of 
  
 system  over 7 days compared 
to the reference value for PICO 7 (80.2 mmHg) with equivalence margin, 1:  
H0
- 
 0 
1 
Ha
- 
 0 | < 
1 
 
In the stated hypotheses,  represents the mean operating pressure of 
  
 system  and  
 represents , the reference value relating to the mean 
operating pressure of PICO 7 (=80.2mmHg, SD=14.8). The equivalence margin, 1 = 7 
mmHg was chosen as a conservative non-clinically significant difference for operating 
pressure assuming the difference is actually 0. The hypothesis will be tested, separately for 
each specialty cohort by a two-sided t-test  (TOST) at the alpha level of 0.025 (one-sided).  
If the null hypothesis is rejected, clinical equivalence in terms of pressure delivery will be 
confirmed. 
Based on the data used for sample size estimation, thirty eight (38) subjects are required to 
achieve 80% power to detect equivalence at the significance level of 
-sided) 
within 7mmHg using a two-sided t-test. Drawing from past experience, allowing that 15% of 
the subjects may be lost to follow up by the end of the study, a sample size of 44 subjects 

 
 
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per specialty are needed to achieve sufficient statistical power for each specialty to be 
analysed separately, within this study.  
Based on the above, a total of 88 subjects will be recruited, which will include 44 subjects 
with each of the following specialties: orthopaedics (closed surgical knee incisions, e.g. after 
total knee arthroplasty), and abdominal surgery (e.g. closed surgical abdominal incisions of 
which at least 50% would be colorectal cases).  
For the management of exudate, measured by incidence of exudate leakage, the sample size 
is evaluated for adequacy based on the non-leakage rate recorded by the NWPT system. 
According to internal data collected within Smith and Nephew surgical study involving Closed 
Abdominal and Orthopaedic subjects, 85% of the PICO NPWT systems had no exudate leaks. 
Therefore, assuming that 
 NWPT system will manage 85% of exudate 
effectively or better, demonstrated through no exudate leakage observed, a sample size of 
10 subjects for each specialty will be sufficient to exclude a response rate of 65% or less 
with 80% power by using a 2-sided 95% confidence interval for orthopaedics (closed knee 
incisions e.g. after Total Knee Arthroplasty), and Abdominal surgery (closed abdominal 
surgical incisions) separately.  With the planned 44 subjects per specialty, a response rate 
below 70% could be excluded for each specialty individually. 
For the dressing wear time (in days) the sample size is based on comparison of the 
 
 
 system compared to the literature derived value for each 
specialty separately. The mean dressing wear time derived from literature is 4.6 days and a 
standard deviation of 2.2539. It is projected that the 
 NWPT system will have 
a mean dressing wear time of 7 days with similar distribution to the literature value. 
The following hypotheses will be tested, for each specialty separately, to establish that the 
dressing wear time of the 
 
 system is strictly not worse 
(lower) than the literature derived value:  

 
 
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H0
- 
 0  
 
Ha
- 
 0  >0 
In the stated hypothesis, µ the mean 
 pump dressing wear time and µ0 
represents the literature derived value (4.6 days). A one-sided (one sample) t-test with alpha 
= 0.025 will be used to evaluate the hypothesis for each specialty. Based on the expected 
mean dressing wear time of 7 days, literature derived value of 4.6 days, and a standard 
deviation of 2.25 days, 80% power and 2.5% significance level, a sample size of 10 subjects 
per specialty is adequate to perform the above the hypothesis separately for each specialty 
cohort. Therefore, the planned forty-four subjects per specialty cohort are adequate to 
conclude that the 
 
 system is strictly not worse (lower) than 
the literature derived value for each speciality individually.  Further, with the planned 44 
subjects per specialty, a dressing wear time below 6.0 days could be excluded for each 
specialty individually for the 
 device, represented by the lower limit of the 
95% confidence interval lying above 6.0 days, based on assumptions previously listed; one-
sided t-test with 80% power, 2.5% significance level, with a standard deviation of 2.25 days 
and assumed 7 day wear time of the 
 device.  
No adjustment to the sample size calculations will be made to account for interim report 
related to safety review. The sample size was estimated using nQuery Advisor 4.0 and 
statistical software SAS Version 9.4. 
 
11.2 Changes to Sample Size Post-Interim Analysis 
An interim analysis was done after 44 subjects were recruited (22 from each indication). 
Based on the root cause analysis of seal loss, the study will continue on Abdominal surgical 
indications only at this time, whilst further investigative work continues into understanding 
the cause of seal loss in the orthopaedic surgery group. 

 
 
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is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
Note 1 to entry: This definition includes adverse events resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or operation, or any 
malfunction of the investigational medical device. 
Note 2 to entry: This definition includes any event resulting from use error or from 
intentional misuse of the investigational medical device. 
Note 3: This includes "comparator" if the comparator is a medical device. 
Not Related - An AE is considered to be not related to the use of an IP or the procedure 
when the effect is DEFINITELY UNRELATED to have any relationship to the use of the IP or 
the procedure; 
Related  An AE is considered to be related to the use of an IP or the procedure when 
there is a POSSIBLE, or DEFINITE relationship between the AE and the use of the IP or the 
procedure. 
An ADE is further categorized depending on whether the criteria in section 12.1.3 and 
12.1.4 are met. 
12.1.3 Related Serious Adverse Events and Serious Adverse 
Device Effects 
An AE or ADE is considered a Serious Adverse Event (SAE) or Serious Adverse Device 
Effects (SADE) if, it led to any of the following: 
a) death, 
b) serious deterioration in the health of the subject, users or other persons as defined by 
one or more of the following: 
1) a life-threatening illness or injury, or 

 
 
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2) a permanent impairment of a body structure or a body function including chronic 
disease, or 
3) in-patient or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function, 
c)  foetal distress, foetal death or a congenital abnormality or birth defect including 
physical or mental impairment 
Note 1: Planned hospitalization for a pre-existing condition, or a procedure required by the 
study protocol, without serious deterioration in health, is not considered a serious adverse 
event. 
12.1.4 Anticipated/Unanticipated Serious Adverse Device Effect 
An Unanticipated Serious Adverse Device Effect (USADE) is a serious ADE which by its 
nature, incidence, severity or outcome has not been identified in the current version of the 
risk assessment. 
Note 1: Anticipated serious adverse device effect (ASADE) is an effect which by its nature, 
incidence, severity or outcome has been identified in the risk assessment. 
  
12.1.5 Severity 
The severity of every AE will be assessed by the PI or medically qualified site staff to whom 
the responsibility has been delegated and documented on the delegation of authority log. AE 
should be classified as mild, moderate, or severe, regardless of whether or not the AE are 
considered to be serious or non-serious. The classification should be based on the following 
definitions: 

 
 
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Mild - An event is mild if the subject is aware of, but can easily tolerate the sign or 
symptom; 
Moderate - An event is moderate if the sign or symptom results in discomfort significant 
 
Severe - An event is severe if the sign or symptom is incapacitating and results in the 
 
12.1.6 Device Deficiency 
A Device Deficiency (DevD) is an inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, safety or performance. DD includes malfunctions, 
use errors and inadequate labeling. 
Note 1: DD includes malfunctions, use errors and inadequacy in the information supplied 
by the manufacturer including labelling.  
Note 2: This definition includes device deficiencies related to the investigational medical 
device or the comparator. 
Device deficiencies that did not lead to an adverse event but could have led to a medical 
occurrence  
a) if either suitable action had not been taken,  
b) if intervention had not been made, or  
c) if circumstances had been less fortunate,  
are considered Device Deficiencies with potential to cause SADE and shall be reported as 
specified in section 12.3. 

 
 
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12.2 AE Coding Dictionary 
The latest version of MedDRA will be used to code AEs.  
 
12.3 Reporting procedures 
AE of any kind and DevD will be recorded in the applicable CRF and source notes to include 
the date of occurrence, treatment and the details resolution. The Investigator will evaluate 
all AE for relationship to the device and procedure, seriousness, and severity (if applicable). 
DD will be evaluated for potential to cause SADE. The following timescales should be 
followed for the AE/DD information to be submitted/entered into the CRF and reported to 
the Sponsor or designee (see figure 6 and 7): 
 ADE and DD  without unreasonable delay 
 SAE, SADE and DD with potential to cause SADE  immediately (i.e. within 24 hours of 
the investigator being informed about the event) 
 All other events  according to usual timescales 
In addition to inputting SAE and SADE information within 24 hours of being aware of the 
event, the investigator should email Clinical.safety@Smith-nephew.com to alert the safety 
representative of the events existence and to clarify details if necessary. 
For ADE and DD, date of occurrence, and details of the product/procedure related to the 
event will be included and where applicable, pictures taken of the device. The deficient 
product should be retained for return to S&N unless it is contaminated (e.g. used dressings 
must not be retained). Updates to submitted information will be recorded in the CRF 
according to timescales above.  

 
 
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All AEs and DevDs will be reviewed by a medically qualified person appointed by the Sponsor 
to determine which, if any, meet criteria for expedited reporting to the regulatory authorities.  
The investigator will inform the regulatory agency and IRB/IEC of adverse events according 
to the IRB/IEC requirements.  
MHRA Reporting 
regulatory authorities within 10 working days. 
In addition to the reporting of individual serious adverse events as detailed above, a quarterly 
summary report of all serious adverse events will be provided to MHRA. 
 
 
 
Reporting to EC 
A SAE occurring to a research participant should be reported to the Committee where in 
the opinion of the Chief Investigator the event was related to administration of any of the 
research procedures, and was an unexpected occurrence.  
Reports of SAEs should be provided to the REC within 15 days of the Chief Investigator 
becoming aware of the event, in the format prescribed by the HRA and published on the 
website: 
All other events will be reported on a periodic/annual basis. 
Depending on the nature of the adverse event, S+
medical records, Imaging, operative notes, as well as results of any relevant laboratory tests 
performed or other documentation related to the AE. If the subject was hospitalized, a copy 

 
 
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of the discharge summary may be requested by S+N and should be forwarded as soon as it 
becomes available. In certain cases, S&N also may request a letter from the Investigator 
that summarizes the events related to the case. 
Refer to the ISF Sponsor Contact Information Sheet to report SAE, ADE and SADE, 
unanticipated SADE, and DD.   

 
 
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12.5.1 Ongoing Adverse Events at Study Discontinuation 
Adverse events which are related to a study procedure or S+N IP and are ongoing at end of 
event. 
Adverse events which are not related to a study procedure or S+N IP and are ongoing at 
study, or until the AE is resolved, whichever is sooner. 
At the time of data analysis (e.g. interim or final), an evaluation of ongoing events should 
take place and be listed as ongoing in the safety table. 
13 INVESTIGATOR OBLIGATIONS 
The Principal Investigator will comply with the commitments outlined in the in the Statement 
of Investigator, provided by the Sponsor/within the Clinical Trial Agreement, and with Good 
Clinical Practice (GCP), and all applicable regulatory requirements as outlined in Appendix 
22.11 of this protocol. 
In addition, the PI will ensure that the Financial Disclosure Statements will be completed by 
the PI and the Sub-Investigator upon entry into the study and as any changes that affect 
their financial disclosure status occur during the course of the study and up to one year after 
study completion. 
14 SPONSOR AND MONITOR RESPONSIBILITIES 
The Sponsor will designate a monitor to conduct the appropriate site visits at the appropriate 
intervals. The clinical investigation will be monitored to ensure that: the rights and wellbeing 
of the subjects are protected; the reported data are accurate, complete, and verifiable from 

 
 
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the source documents; and the study is conducted in compliance with the currently approved 
protocol and amendment(s), if applicable, with GCP regulations, and with applicable 
regulatory requirements. 
For this study there will be 100% source data verification on all variables which will be verified 
from the eCRF against subject medical records or source note worksheets or a combination 
of these documents. Detailed monitoring requirements will be documented within the Clinical 
Monitoring Plan for this study.  
14.1 Contract Research Organisation 
The sponsor has engaged Contract Research Organization (CRO) to assist in conducting 
agen
 
14.2 Site Qualification Visit 
A site qualification visit may be performed by the Sponsor prior to the execution of a clinical 
agreement to ensure that all Investigators have the appropriate training, staff, facilities, and 
resources to adequately conduct the study. 
14.3 Site Initiation Visit 
A site initiation visit to provide training on the specifics of the study, site obligations and 
expectations of study conduct will be performed by the Sponsor or qualified person 
designated by the Sponsor following the execution of the CTA and documented IRB/IEC 
approval.  

 
 
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CONFIDENTIAL AND PROPRIETARY 
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intended for use only by Smith & Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
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14.4 Interim Monitoring Visit 
Regular interim monitoring visits will be performed by the Sponsor or qualified person 
designated by the Sponsor. 
14.5 Sponsor Audits and Regulatory Inspection 
Quality Assurance auditors, whether an employee of the Sponsor or its designee, may 
evaluate study conduct at the study sites. These parties must have access to any and all 
study reports and source documentation, regardless of location and format.  
14.6 Close-Out Visit 
Study close-out visits will be performed by the Sponsor or designee to retrieve and account 
for all remaining clinical data and to resolve outstanding queries. During study close-out, 
the monitor will review investigator files to ensure required documents and records are on 
file, confirm the disposition of any other ancillary items used for the study, and review 
regulatory requirements regarding records retention and IRB/IEC reporting requirements. 
When no subjects have been included, a remove close-out visit may be conducted. 
15 PROTOCOL DEVIATIONS 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a subject in an emergency. Protocol deviations reported 
by the Investigator or discovered during monitoring visits will be compiled in a Protocol / 
GCP Deviation Log (TMP-CD-31-02 Protocol/GCP Deviation Log). Significant and/or 
recurrent protocol/GCP deviations will be documented on a protocol deviation form (TMP-
CD-31-01 Protocol/GCP Deviation) including identified root cause and, as necessary, 
appropriate corrective and preventive actions will be put in place and signed off by the 
study personnel. If it is deemed necessary full clinical CAPA will be initiated. 

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
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It is not allowed to use waivers to allow planned deviation of the study protocol.  
An investigator may be early terminated from the study upon identification of serious 
protocol deviations whereby there are concerns for patient safety or data quality (especially 
those not reported to the sponsor by the site). Early termination may also occur if there 
are repeated protocol deviations which have previously been addressed via corrective and 
preventative actions thereby suggesting an issue with site compliance. 
Give notification requirements and timeframes here for site staff and monitor to report to 
S+N and PI to report to IRB/IEC (which may be conducted by CSM). 
16 PROTOCOL AMENDMENTS 
Amendments should be made only in exceptional cases once the study has started. Protocol 
amendments must be approved by the protocol signatories prior to submission to the 
IRB/IEC. Protocol amendments need to be approved by the IRB/IEC and Regulatory 
Authority(ies), according to the applicable requirements prior to implementation at the site. 
 
17 CONFIDENTIALITY OF THE STUDY 
The confidentiality of this study and associated documents is governed by the terms of the 
Clinical Trial Agreement (CTA). 
18 STATEMENTS OF COMPLIANCE 
This clinical study will be performed in compliance with the ethical principles of the 
Declaration of Helsinki and ISO 14155: Clinical investigation of medical devices 
 Good 
Clinical Practice. 

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
This clinical study will not commence until the required approval/favourable opinion from the 
IRB/IEC and regulatory authority has been obtained. Any additional requirements imposed 
by the IRB/IEC or regulatory authority will be followed.  
Public Liability Insurance has been purchased by Smith & Nephew plc. Worldwide and 
incorporates coverage for personal injury in respect of clinical studies. The Sponsor agrees 
to operate in good faith and in accordance with ABHI (Association of British Healthcare 
Industries) guidelines regarding compensation for injury arising in the course of clinical 
studies. 
19 END OF STUDY 
The end of the study is defined as the last visit of the last subject undergoing treatment in 
the study. The expected duration of the study as defined from the first site initiated to the 
last subjects last visit is approximately 18 months. This includes an estimated six-month 
pause in enrolment while the interim analysis is reported to the MHRA. The length may be 
extended by the actual length of interim analysis review. Should any of the subjects suffer a 
complication during the course of the study, they will be analysed on an intention to treat 
basis and will be treated according to standard clinical care (that is considered to be the best 
care for the applicable complication). 
Should circumstances arise which require the termination of the entire study prior to its 
planned completion (e.g. safety concerns) or circumstances arise which mean the end of the 
participation of an individual site (e.g. departure of Investigator, non-compliance), then this 
will be undertaken according to the SOPs of the Sponsor.  

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
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20 PUBLICATION POLICY 
20.1 Publication of Study Data 
The preparation and submission for publication of manuscripts containing the study results 
shall be in accordance with a process determined by the Clinical Trial Agreements between 
the study Sponsor and participating institutions. The publication or presentation of any study 
results shall comply with all applicable privacy laws. 
20.2 Data Sharing 
Smith + Nephew is committed to upholding the highest ethical and legal standards involved 
in conducting clinical trials. Smith + Nephew therefore supports the data sharing 
requirements of The International Committee of Medical Journal Editors (ICMJE) published 
on the 6th June 2017. In accordance, Smith + Nephew will consider requests to share 
individual (de-identified) participant data that underlie the results of any interventional 
clinical trial, as presented from the 1st July 2018 within an ICMJE associated journal. 
Requests made by researchers who provide a methodologically sound proposal will be 
considered. Requests may include data that underlie results presented in text, tables, figures 
and appendices, together with data dictionaries. Availability of these data will begin 9 months 
and end 36 months after article publication. Data supplied may only be used by the 
researcher(s) named in the approved research proposal for the purposes of achieving the 
aims 
of 
the 
analyses 
specified 
therein. 
All 
proposals 
should 
be 
directed 
to 
datasharing.gcs@smith-nephew.com. To gain access, data requestors will need to sign a 
data access agreement. 
 
 
 

 
 
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21 REFERENCES 
 
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General Surgery in Neonates and Infants. Tokyo: Springer Japan; 2016:13-20. 
2. Galat DD, McGovern SC, Larson DR, Harrington JR, Hanssen AD, Clarke HD. Surgical treatment of 
early wound complications following primary total knee arthroplasty. The Journal of bone and joint 
surgery American volume. 2009;91(1):48-54. 
3. Lewis L, Convery P, Bolac C, Valea F, ... Cost of care using prophylactic negative pressure wound 
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4. Smith RL, Bohl JK, McElearney ST, et al. Wound infection after elective colorectal resection. Ann 
Surg. 2004;239(5):599-605; discussion 605-597. 
5. Nugent EK, Hoff JT, Gao F, et al. Wound complications after gynecologic cancer surgery. Gynecol 
Oncol. 2011;121(2):347-352. 
6. Carroll K, Dowsey M, Choong P, Peel T. Risk factors for superficial wound complications in hip and 
knee arthroplasty. Clin Microbiol Infect. 2014;20(2):130-135. 
7. Campbell AL, Patrick DA, Jr., Liabaud B, Geller JA. Superficial wound closure complications with 
barbed sutures following knee arthroplasty. J Arthroplasty. 2014;29(5):966-969. 
8. Pugely AJ, Martin CT, Gao Y, Mendoza-Lattes S, Callaghan JJ. Differences in short-term 
complications between spinal and general anesthesia for primary total knee arthroplasty. The 
Journal of bone and joint surgery American volume. 2013;95(3):193-199. 
9. Novakovic D, Patel RS, Goldstein DP, Gullane PJ. Salvage of failed free flaps used in head and neck 
reconstruction. Head Neck Oncol. 2009;1:33. 
10. Vince K, Chivas D, Droll KP. Wound complications after total knee arthroplasty. J Arthroplasty. 
2007;22(4 Suppl 1):39-44. 
11. Bosco JA, 3rd, Karkenny AJ, Hutzler LH, Slover JD, Iorio R. Cost burden of 30-day readmissions 
following Medicare total hip and knee arthroplasty. J Arthroplasty. 2014;29(5):903-905. 
12. Saucedo JM, Marecek GS, Wanke TR, Lee J, Stulberg SD, Puri L. Understanding Readmission After 
The Journal of Arthroplasty. 
2014;29(2):256-260. 
13. Andersson AE, Bergh I, Karlsson J, Nilsson K. Patients' experiences of acquiring a deep surgical site 
infection: an interview study. Am J Infect Control. 2010;38(9):711-717. 

 
 
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CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith & Nephew PLC and Smith & Nephew, Inc. and is 
intended for use only by Smith & Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
14. Armstrong DG, Lavery LA, Diabetic Foot Study C. Negative pressure wound therapy after partial 
diabetic 
foot 
amputation: 
a 
multicentre, 
randomised 
controlled 
trial. 
Lancet. 
2005;366(9498):1704-1710. 
15. Vuerstaek JDD, Vainas T, Wuite J, Nelemans P, Neumann MHA, Veraart JCJM. State-of-the-art 
treatment of chronic leg ulcers: A randomized controlled trial comparing vacuum-assisted closure 
(V.A.C.) with modern wound dressings. Journal of Vascular Surgery. 2006;44(5):1029-1037. 
16. Kugler NW, Carver TW, Paul JS. Negative pressure therapy is effective in abdominal incision closure. 
J Surg Res. 2016;203(2):491-494. 
17. Karlakki SL, Hamad AK, Whittall C, Graham NM, Banerjee RD, Kuiper JH. Incisional negative 
pressure wound therapy dressings (iNPWTd) in routine primary hip and knee arthroplasties: A 
randomised controlled trial. Bone & joint research. 2016;5(8):328-337. 
18. Bonds AM, Novick TK, Dietert JB, Araghizadeh FY, Olson CH. Incisional negative pressure wound 
therapy significantly reduces surgical site infection in open colorectal surgery. Dis Colon Rectum. 
2013;56(12):1403-1408. 
19. Blackham AU, Farrah JP, McCoy TP, Schmidt BS, Shen P. Prevention of surgical site infections in 
high-risk patients with laparotomy incisions using negative-pressure therapy. Am J Surg. 
2013;205(6):647-654. 
20. Stannard JP, Volgas DA, McGwin G, 3rd, et al. Incisional negative pressure wound therapy after 
high-risk lower extremity fractures. J Orthop Trauma. 2012;26(1):37-42. 
21. Brem MH, Bail HJ, Biber R. Value of incisional negative pressure wound therapy in orthopaedic 
surgery. Int Wound J. 2014;11 Suppl 1(s1):3-5. 
22. Gillespie BM, Rickard CM, Thalib L, et al. Use of Negative-Pressure Wound Dressings to Prevent 
Surgical Site Complications After Primary Hip Arthroplasty: A Pilot RCT. Surg Innov. 
2015;22(5):488-495. 
23. Strugala V, Martin R. Meta-Analysis of Comparative Trials Evaluating a Prophylactic Single-Use 
Negative Pressure Wound Therapy System for the Prevention of Surgical Site Complications. Surg 
Infect (Larchmt). 2017;18(7):810-819. 
24. Pellino G, Sciaudone G, Candilio G, et al. Preventive NPWT over closed incisions in general surgery: 
Does age matter? International Journal of Surgery. 2014;12(S2):S64-S68. 
25. Selvaggi F, Pellino G, Sciaudone G, et al. New advances in negative pressure wound therapy (NPWT) 
for surgical wounds of patients affected with Crohn's disease. Surg Technol Int. 2014;24:83-89. 
26. Malmsjo M, Huddleston E, Martin R. Biological effects of a disposable, canisterless negative pressure 
wound therapy system. Eplasty. 2014;14:e15. 
27. Hurd T. Evaluating the cost and benefits of innovations in chronic wound care products and 
practices. Ostomy Wound Management. 2013. 
28. Hudson DA, Adams KG, Van Huyssteen A, Martin R, Huddleston EM. Simplified negative pressure 
wound therapy: clinical evaluation of an ultraportable, no-canister system. Int Wound J. 
2015;12(2):195-201. 
29. Xia CY, Yu AX, Qi B, Zhou M, Li ZH, Wang WY. Analysis of blood flow and local expression of 
angiogenesisassociated growth factors in infected wounds treated with negative pressure wound 
therapy. Molecular medicine reports. 2014;9(5):1749-1754. 
30. O'Leary DP, Peirce C, Anglim B, et al. Prophylactic Negative Pressure Dressing Use in Closed 
Laparotomy Wounds Following Abdominal Operations: A Randomized, Controlled, Open-label Trial: 
The P.I.C.O. Trial. Ann Surg. 2017;265(6):1082-1086. 
31. Cooper HJ, Bas MA. Closed-Incision Negative-Pressure Therapy Versus Antimicrobial Dressings 
After Revision Hip and Knee Surgery: A Comparative Study. J Arthroplasty. 2016;31(5):1047-1052. 

 
 
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CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith & Nephew PLC and Smith & Nephew, Inc. and is 
intended for use only by Smith & Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
32. Hester T, Mahmood S, Moftah F. Is Single Use Portable Incisional Negative Pressure Wound Therapy 
System Suitable for Revision Arthroplasty? Advances in Orthopedic Surgery. 2015;2015. 
33. Manoharan V, Grant AL, Harris AC, Hazratwala K, Wilkinson MP, McEwen PJ. Closed Incision 
Negative Pressure Wound Therapy vs Conventional Dry Dressings After Primary Knee Arthroplasty: 
A Randomized Controlled Study. J Arthroplasty. 2016;31(11):2487-2494. 
34. Pellino G, et al Effects of a new pocket device for negative pressure wound therapy on surgical 
wounds of patients     affected with Crohn's disease: a pilot trial. Surg Innovation. 2013;21:204-
12. 
35. Keeney J, Cook J, Clawson s, Aggarwal A, Stannard J, Incisional negative pressure wound therapy 
devices improve short-term wound complications, but not long-term infection rate following hip and 
knee arthroplasty, J of Arthroplasty, 2019; https:doi.org/10.1016/j.arth.2018.12.008 
 
36. Hasanain M, Apostu D, Alrefaee A, Tarabichi S, Comparing the effect of tourniquet vs tourniquet-
less in  simultaneous bilateral total knee arthroplasties, J of Arthroplasty, 2019; doi: 
10.1016/j.arth.2018.02.013. Epub 2018 Feb 15 
37. Kayamori S, Tsukada S, Sato M, Komata K, Isida Y, Wakui M, Impact of postoperative 
compression dressing using polyethylene foam pad on the multimodal protocol for swelling 
control following total knee arthroplasty:a randomized controlled trial, Arthroplasty Today, 2016; 
doi: 10.1016/j.artd.2016.05.004 
38. Mutzuzaki H, Takeuchi R, Mataki Y, Wadano Y, Target range of motion for rehabilitation after total 
knee arthroplasty, Arthroplasty Today, 2016 Dec; 2(4): 199-204 
39. Flynn J, et al. Negative pressure dressings (PICOTM) on laparotomy wounds do not reduce risk of 
surgical site infection. Surg Infect 2019; doi: 0.1089/sur.2019.078.  
40. Helito CP, et al. The use of negative-pressure wound therapy after total knee arthroplasty is effective 
for reducing complications and the need for reintervention. BMC Musculoskeltal Disorders 2020; 
21: 1-8.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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22 APPENDICES 
 
22.1 Protocol Amendment 9 
22.1.1 General Purpose 
This amendment has been completed to document a clarification and update to 
Inclusion/Exclusion criteria, secondary endpoint and include the regulatory need being met by 
this study. 
22.1.2 Rationale 
Updates to the protocol were made to expand the inclusion criteria to include gynaecologic 
procedures, as this is a common abdominal surgery, which can occur alongside gastrointestinal 
surgical procedures and results in a closed surgical incisions; the indication under investigation 
within this study. The exclusion criteria for laparoscopic surgeries was also clarified to remove the 
focus on surgical incision technique and specify that the procedure requires an incision that must 
be greater than or equal to 5 cm to be eligible for study inclusion.  This is regardless of how the 
incision is created, which has been clarified and stated within the inclusion criteria, number 7.     
In addition, the changes agreed with MHRA for the continuation of this study which was missed in 
the last protocol version (retain only evaluation of VAS wound scores by treating clinician for 
phase 2) was added in this current version as well as wording to highlight the regulatory need 
being met by this study. A discussion on use of portable negative pressure in wound healing was 
deleted in error in the last version of this protocol and is being reinstated in this version.  
22.1.3 Effect on Study Procedures 
This amendment expands the patient population for the study to include gynaecologic procedures. 
This will be applied following amendment 9 approval. Amendment 9 also clarifies the definition for 
an appropriate/eligible incision in patients undergoing laparoscopic procedures (whereby an 
extended trocar port site of greater than or equal to 5cm has always been eligible in addition to a 
midline laparotomy) which should apply to the full study.  This simplified language, therefore, 
removes the double negative wording within the exclusion criteria (number 13) of Amendment 8 
and consolidates all procedural eligibility within the inclusion criteria, under inclusion number 7.  

 
 
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22.1.4 Details 
Section 
 
Revised Text 12/MAR/2021 
Version 8 
 
Revised Text 04/AUG/2021 
Version 9 
 
2 Synopsis 
Inclusion 
Criteria 
In Abdominal surgery: subject is 
scheduled for an 
elective open gastrointestinal surgery 
and has an 
ASA score of 2-3 
In Abdominal surgery: subject is 
scheduled for an elective open or 
laparoscopic gastrointestinal 
and/or gynaecological surgery with 
incision 5cm and has an ASA 
score of 2-3.  
2 Synopsis 
Exclusion 
Criteria 
Subjects undergoing exclusively 
abdominal 
laparoscopic surgery (except if the 
procedure is 
scheduled to include a laparotomy 
 
 
4.1.2 
The cost of wound healing failures and 
complications 
(duplicate of 4.1.1, copied in error 
when protocol v7 was moved to a new 
template deleting the discussion on 
use of portable negative pressure in 
wound healing) 
Use of portable negative pressure 
in wound healing 
 
(reinstated from v7.0) 
4.3 Study 
Purpose 
There is a need to generate clinical 
evidence for the 
 
NPWT system to 
demonstrate safety and performance 
of the device. 
The study results will be used to 
generate data to support 
regulatory submission for CE 
marking. There is a need to 
generate clinical evidence for the 
 
NPWT 
system to demonstrate safety and 
performance of the device. 
7.2 Inclusion 
Criteria 
In Abdominal surgery: subject is 
scheduled for an 
elective open gastrointestinal surgery 
and has an 
ASA score of 2-3 
In Abdominal surgery: subject is 
scheduled for an elective open or 
laparoscopic gastrointestinal 
and/or gynaecological surgery with 

 
 
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incision >/=5cm and has an ASA 
score of 2-3.   
 
7.3 Exclusion 
Criteria 
Subjects undergoing exclusively 
abdominal 
laparoscopic surgery (except if the 
procedure is 
scheduled to include a laparotomy 
 
 
8.4.2 
Secondary 
Endpoints 
 
Comparison of Wound and Skin VAS 
scores at days 7, 14 and 30 as 
assessed by the treating clinicians 
versus scores provided by the 
independent assessor. 
Phase 1 only: Comparison of 
Wound and Skin VAS scores at 
days 7, 14 and 30 as assessed by 
the treating clinicians versus 
scores provided by the 
independent assessor. 
10.4.2 Analysis 
of Secondary 
Endpoints 
Comparison of Wound and Skin VAS 
scores at days 7, 14 and 30 as 
assessed by the treating clinicians 
versus scores provided by the 
independent assessor. 
Phase 1 only: Comparison of 
Wound and Skin VAS scores at 
days 7, 14 and 30 as assessed by 
the treating clinicians versus 
scores provided by the 
independent assessor. 
 
22.1.5 Approvals/Notifications 
These updates are considered a substantial amendment and will be notified to MHRA and 
submitted for EC approval. The changes will only be implemented after MHRA/EC approval 
confirmation. 
22.2 Protocol Amendment 8 
22.2.1 General Purpose 
This amendment has been completed to document changes as agreed with MHRA following 
interim analysis discussion. 

 
 
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22.2.2 Rationale 
Updates to the protocol have been made to: 
 Reflect the changes agreed with MHRA to allow for Phase 2 recruitment to continue 
 Up-version to rebranded protocol template  
22.2.3 Effect on Study Status 
Not applicable; this amendment is to be in effect and implemented prior to subject 
enrollment for Phase 2. 
22.2.4 Details 
Section 
 
Current Text 10/APR/2019 
Version 7 
 
Revised Text 12/MAR/2021 
Version 8 
 
Header 
Old branding: 
New branding: 
 
Footer 
  
  
  
 
 
  
1 Signatures 
I have read the attached protocol 
 Pre-
Registration Clinical Study
7.0, dated 10APR2019 
I have read the attached protocol 
 Pre-
Registration Clinical Study
version 8.0, dated 12/MAR/2021 
 
Signature page updated with name 
of current approvers 
2 Synopsis 
Sample Size 
A total of 88 subjects will be 
recruited to allow for 44 subjects to 
be recruited from each of the 
following specialties: orthopaedics 
(closed knee incisions e.g. after Total 
Knee Arthroplasty), and Abdominal 
surgery (closed abdominal surgical 
It was planned to recruit a total of 
88 subjects to allow for 44 
subjects to be recruited from each 
of the following specialties: 
orthopaedics (closed knee incisions 
e.g. after Total Knee Arthroplasty), 
and Abdominal surgery (closed 

 
 
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incisions of which at least 50% would 
be colorectal cases).  
abdominal surgical incisions of 
which at least 50% would be 
colorectal cases).  
An interim analysis was made 
after 44 subjects were recruited 
(22 from each indication). Based 
on the root cause analysis of seal 
loss, the study will continue on 
Abdominal surgical indications only 
at this time, whilst further 
investigative work continues into 
understanding the cause of seal 
loss in the orthopaedic surgery 
group.   
The 2nd phase of the study (post-
interim analysis) will be powered 
according to previous sample size. 
However, as no further subjects 
will be recruited for the 
orthopaedic surgery group, all 44 
subjects recruited will be in the 
abdominal indication group. This 
will increase the total number of 
abdominal incisions to 66 (22 
recruited following the protocol 
v7.0 and 44 following v8.0 of the 
protocol). This ensures that the 
primary endpoint is sufficiently 
powered for both the primary 
analysis of the abdominal data for 
all subjects as well as for a 
secondary analysis to be done on 
the data from those recruited 
according to protocol v8.0 only. 
2 Synopsis 
Number of 
Study Sites 
Up to 6 total (three sites for 
each of the specialties) 
There were 6 sites involved in 
the first phase of recruitment 
(three sites for each of the 
specialties). Based on the interim 
analysis, the study will continue 
on abdominal surgical indications 

 
 
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only with 6 sites for the second 
phase of recruitment. 
2 Synopsis 
Targeted Global 
Regions 
UK and EU 
UK 
2 Synopsis 
Inclusion 
Criteria 
 In Orthopaedic surgery: 
subject is scheduled for an 
elective primary knee 
replacement arthroplasty and 
ASA score of 2-3 
 
 (Phase 1 only): In 
Orthopaedic surgery: subject is 
scheduled for an elective 
primary knee replacement 
arthroplasty and ASA* score of 
2-3. 
 
2 Synopsis 
Exclusion 
Criteria 
 
Added new exclusion criteria: 
15. Subjects where the dressing 
cannot be fully applied without 
coming into contact with, or 
covering, tubes, drains, wires or 
other ancillary devices which 
may affect the seal, and/ or 
which will require removal 
before the end of the seven day 
 
2 Synopsis 
Study Duration 
Eighteen months from when the 
first study site is initiated until 
last enrolled subject reaches 
last study assessment. This 
period includes an estimated 6 
month period to prepare a mid-
recruitment interim report, 
submit it and obtain feedback 
from MHRA. 
Prior to the interim analysis, it 
was estimated that the study 
duration will be eighteen months 
from when the first study site is 
initiated until last enrolled 
subject reaches last study 
assessment. This period included 
an estimated 6 month period to 
prepare a mid-recruitment 
interim report, submit it and 
obtain feedback from MHRA. To 
reflect the much longer pause 
taken and time to secure 
approvals, the study duration is 
now expected to last 30 months. 
2 Synopsis 
Exudate management assessed 
by no occurrence of exudate 
Exudate management assessed 
by no occurrence of exudate 

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
Primary 
Endpoint 
leaks as assessed through a 
combination of leakage alert 
data from device 
 
and/or clinical data on any 
leakage observed during the 
dressing wearing period 
resulting or not, in an 
unplanned dressing change 
leaks as assessed through 
clinical data on any leakage of 
exudate through a dressing or 
around the borders observed 
during the dressing wearing 
period resulting or not, in an 
unplanned dressing change 
2 Synopsis 
Secondary 
Endpoints 
 Range of motion assessment 
(ROM) for the knee at pre-
operative visit, post-operative 
visit, 1, 7, 14 and 30 days. 
 
 (Phase 1 only) Range of 
motion assessment (ROM) for 
the knee at pre-operative visit, 
post-operative visit, 1, 7, 14 and 
30 days. 
 
2 Synopsis 
Study Schedule
Study Window: End of Therapy 
Assessment 
7 (±1) day 
Study Window: End of Therapy 
Assessment 
7 days 
2 Synopsis 
Study 
Schematic 
Range of motion 
assessment*,** 
*Post dressing application 
**Pre and post-dressing 
removal 
(Phase 1 only) Range of motion 
assessment*,** 
*Post dressing application 
**Pre and post-dressing removal
Table of 
Contents 
 
Updated to reflect changes 
4.4 Safety 
Considerations 
Precautions: 
 
 may be used 
in conjunction with surgical 
drains provided the dressing is 
not placed over tubing where it 
exits the skin. Any surgical drain 
should be routed under the skin 
away from the edge of the 
dressing. RENASYS Gel patches 
can be employed in awkward 
areas as a means to achieve a 
seal. 
Precautions: 
 
 may be used in 
conjunction with ancillary devices 
such as surgical drains, PICC 
lines and other dressings, 
however these products should 
not be used under the 
 
dressing or dressing border as 
these products may cause air 
leaks into the dressing. RENASYS 
Gel patches can be employed in 
awkward areas as a means to 
achieve a seal. 

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
4.4 Safety 
Considerations 
Storage 
The 
 system 
must be stored between 5 and 
25oC. 
 
Storage 
The 
 system 
must be stored between 5 and 
25oC and relative humidity 
between 10-75%. 
5.2 Secondary 
Objectives 
Range of motion assessment 
(ROM) for the knee 
Phase 1 only: Range of motion 
assessment (ROM) for the knee 
6. 1.1 
Investigational 
Product 
For this study, 
 
system will be used to manage 
surgically closed incision sites 
(abdominal and knee). 
For this study, 
 
system will be used to manage 
surgically closed incision sites 
(abdominal and knee [phase 1 
only]). 
6.2.1 
Investigational 
Product 
 
 
1. Remove any excess hair. 
Flush out the wound with saline 
solution and pat dry any excess 
moisture. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4. Apply the absorbent part of 
the dressing centrally over the 
top of the wound.
 
Added instructions on Dressing 
Application: 
1. Remove any excess hair 
during surgical preparation. 
Clean the skin surrounding the 
incision with saline solution and 
pat dry any excess moisture. 
2. Plan the placement of the 
dressing over the surgical 
incision. Ensure there is enough 
clearance such that the edges of 
the dressing (including the 
adhesive strips once applied) 
would not overlap any ancillaries 
such as stomas, catheter lines, 
drains, dressings over smaller 
incisions etc. that will need to be 
adjusted or removed before the 
end of the treatment period of 7 
days. 
4. Apply the absorbent part of 
the dressing centrally over the 
top of the incision.
 

 
 
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 over the 
wound. 
 over the 
incision. 
6.2.1.3 
Securing 
 
in 
place 
6. Apply a fixation strip along 
each edge of 
 
using the same technique 
described in steps 11 to 15 to 
achieve a good seal. 
6. Apply a fixation strip along 
each edge of 
 
using the same technique 
described in steps 11 to 15 to 
achieve a good seal, ensuring 
that they do not overlap any 
ancillary devices such as drains, 
wires etc. 
6.3 packaging 
and Labelling 
Packaging and labelling will be 
prepared to meet regulatory 
requirements. 
 
 
Packaging and labelling will be 
prepared to meet regulatory 
requirements. 
Package integrity and labelling 
should be verified prior to use of 
the product and confirmed in the 
CRF. 
 
7.1 Subject 
Population 
Approximately 88 subjects 
scheduled for abdominal or knee 
surgery will be recruited to the 
study and will receive 
 
 The subjects will be 
recruited from up to 6 sites in 
the United Kingdom and EU. 
Sites failing to enrol may be 
replaced. There will 44 subjects 
recruited per surgical group 
(abdominal, knee) and 3 
research sites per surgical 
specialty. 
The original plan was to recruit a 
total of 88 subjects to allow for 
44 subjects to be recruited from 
each of the following specialties: 
orthopaedics (closed knee 
incisions e.g. after Total Knee 
Arthroplasty), and Abdominal 
surgery (closed abdominal 
surgical incisions of which at 
least 50% would be colorectal 
cases). There were 6 sites 
involved in the first phase of 
recruitment (three sites for each 
of the specialties). 
An interim analysis was made 
after 44 subjects were recruited 
(22 from each indication). Based 
on the root cause analysis of seal 
loss, Phase 2 of the study will 

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
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continue on Abdominal surgical 
indications only at this time, 
whilst further investigative work 
continues into understanding the 
cause of seal loss in the 
orthopaedic surgery group.   
The 2nd phase of the study 
(post-interim analysis) will be 
powered according to previous 
sample size. However, as no 
further subjects will be recruited 
for the orthopaedic surgery 
group, all 44 subjects recruited 
will be in the abdominal 
indication group. 
 
7.2 Inclusion 
Criteria 
 In Orthopaedic surgery: 
subject is scheduled for an 
elective primary knee 
replacement arthroplasty and 
ASA score of 2-3 
 
 (Phase 1 only): In 
Orthopaedic surgery: subject is 
scheduled for an elective 
primary knee replacement 
arthroplasty and ASA* score of 
2-3. 
 
7.3 Exclusion 
Criteria 
 
Added new exclusion criteria: 
Subjects where the dressing 
cannot be fully applied without 
coming into contact with, or 
covering, tubes, drains, wires or 
other ancillary devices which 
may affect the seal, and/ or 
which will require removal 
before the end of the seven day 
period 
7.5 Informed 
Consent 
All subjects will be given ample 
time (at least 24 hours) to 
consider participation following 
the explanation of the 
study/reading of the patient 
information sheet.  
All subjects will be given ample 
time (at least 24 hours) to 
consider participation following 
the explanation of the 
study/reading of the patient 
information sheet. 

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
If new information becomes 
available during the course of 
the study that can significantly 
and medical care, Smith + 
Nephew will ensure that 
information shall be provided to 
the subject(s) affected in written 
form and if relevant, all affected 
subjects shall be asked to 
confirm their continuing consent 
in writing. 
7.8.1 
Withdrawal 
from Treatment
 Treatment is prematurely 
ended for any reason (i.e. due 
to removal of the system by the 
subject, failure of the pump, 
dressing falls off, seal can no 
longer be established) 
 
 Treatment is prematurely 
ended for any reason (i.e. due to 
removal of the system by the 
subject or the investigator, 
failure of the pump, dressing 
falls off, seal can no longer be 
established) 
8.1 Study 
Design 
This study is a prospective, 
multi-centre, non-randomised, 
non-blinded, single arm follow-
up study to assess clinical 
performance and safety of 
 
 It is anticipated that 
up to 6 sites will participate 
within the UK and EU. 
This study is a prospective, 
multi-centre, non-randomised, 
non-blinded, single arm follow-
up study to assess clinical 
performance and safety of 
 
 It is anticipated that 
up to 6 sites will participate 
within the UK. 
8.3 Data 
Management 
V7.0 did not have a data 
management section 
8.3 Data Management 
This study utilizes a validated, 21 
CFR Part 11 compliant, electronic 
data capture system. Access to 
the electronic data capture 
system is controlled through 
Smith and Nephew procedures.  
A Data Management Plan (DMP) 
is written according to Smith and 
Nephew procedures containing 

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
details of the data management 
process. The following is a brief 
description of the key points 
detailed in this plan.  
 
8.3.1 Data Review and 
Quality Assurance 
Data will be transcribed from the 
data source to an electronic Case 
Report Form (eCRF). All data 
requested on the eCRFs are 
considered required. Data points 
not collected and/or recorded will 
be considered deviations unless 
otherwise specified.  
Data collection is the 
responsibility of the clinical trial 
staff at the site under the 
supervision of the Principal 
Investigator. The Principal 
Investigator is responsible for 
ensuring the accuracy, 
completeness, legibility, and 
timeliness of the data reported. 
The Principal Investigator must 
provide his/her electronic 
signature on the appropriate 
eCRFs to be documented in 
compliance with local 
regulations. Changes to data 
previously submitted to the 
sponsor will require a new 
signature by the Investigator to 
acknowledge/approve the 
changes.  

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
Visual and computer data review 
will be performed in line with 
Smith and Nephew procedures to 
identify possible data 
discrepancies. Manual and 
automatic queries will be created 
within the electronic data 
capture system, and will be 
issued by Smith and Nephew to 
the site for appropriate response. 
Site staff are responsible for 
resolving all queries in the 
electronic data capture system.  
8.3.2 Retention Period 
All eCRFs will be archived once 
the study is completed and will 
kept for a period of no less than 
five years after the later of the 
following dates: the date of 
which the study is terminated or 
completed or; the date that the 
records are no longer required 
supporting marketing 
applications. 
 
8.4.1 Primary 
Endpoint 
 Exudate management 
assessed by no occurrence of 
exudate leaks as assessed 
through a combination of 
leakage alert data from the 
device 
 and/or clinical 
data on any leakage observed 
during the dressing wearing 
period resulting or not, in an 
unplanned dressing change. 
 Exudate management 
assessed by no occurrence of 
exudate leaks as assessed 
through clinical data on any 
leakage of exudate through a 
dressing or around the borders 
observed during the dressing 
wearing period resulting or not, 
in an unplanned dressing 
change. 
 
8.4.2 
 Range of motion assessment 
(for knee subjects only) at pre-
 (Phase 1 only):Range of 
motion assessment (for knee 

 
 
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operative, post-operative day 1, 
7, 14 and 30 days 
subjects only) at pre-operative, 
post-operative day 1, 7, 14 and 
30 days 
 
8.5.3 
The study included a single 
indication in two different 
surgical specialties and a range 
of contoured areas of the body 
where it may be difficult to 
obtain an effective negative 
pressure seal and where there 
may be a range of motion 
throughout therapy (i.e. knee). 
The inclusion/exclusion criteria 
are also not too restrictive with 
regard to subject demographic. 
This should mean that the 
results will be representative of 
a real clinical setting in hospital 
or at home, and for the 
proposed indication in the two 
specialties. 
Phase 1 of the study included a 
single indication in two different 
surgical specialties and a range 
of contoured areas of the body 
where it may be difficult to 
obtain an effective negative 
pressure seal and where there 
may be a range of motion 
throughout therapy (i.e. knee). 
The inclusion/exclusion criteria 
are also not too restrictive with 
regard to subject demographic. 
This should mean that the results 
will be representative of a real 
clinical setting in hospital or at 
home, and for the proposed 
indication in the two specialties. 
 
9.1.1 Study 
Procedures by 
Visit 
Study Window: End of Therapy 
Assessment 
7 (±1) day 
Study Window: End of Therapy 
Assessment 
7 days 
9.1.1 Study 
Procedures by 
Visit 
Range of motion assessmentl 
Range of motion assessment 
(phase 1 only) 
 
9.1.2 
Screening/Preo
perative Visit 
4. Obtain range of motion 
measurements (knee subjects 
only) 
4.Obtain range of motion 
measurements (for knee 
subjects only in Phase 1) 
9.1.3 Baseline 
Operative Visit 
8. Dispense study product. 
Record pump lot number, size of 
dressing used (
 
 
 and any ancillary 
products applied (SECURA No-
8. Dispense study product. 
Record pump lot number, size of 
dressing used (
 
 
) and any ancillary 
products applied (SECURA No-
Sting Skin prep, RENASYS 

 
 
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Sting Skin prep, RENASYS 
Adhesive Gel Patch).  
Adhesive Gel Patch). Include also 
ancillaries in the vicinity (e.g. 
drains, stomas, lines, dressings).
9.1.3 Baseline 
Operative Visit 
10. Take photograph of dressing 
in place.  
10. Take photograph of dressing 
in place. Take a photograph of 
the carton label to aid 
accountability checks (the label 
will contain the batch number). 
9.1.4 Baseline 
Post-Operative 
visit 
3. Obtain range of motion 
measurements (knee subjects 
only) 
3. Obtain range of motion 
measurements (for knee 
subjects only in Phase 1) 
9.1.6 End of 
Therapy 
Assessment 
7. Obtain range of motion 
measurements (knee subjects 
only) 
7. Obtain range of motion 
measurements (for knee 
subjects only in Phase 1) 
9.1.6 End of 
Therapy 
Assessment 
14. Assess the surrounding skin 
including the area under the 
pump (e.g., healthy, fragile, 
inflamed, erythema, bruising, 
eczematous, dry/flaky,  
macerated) 
13. Assess the surrounding skin 
(e.g., healthy, fragile, inflamed, 
erythema, bruising, eczematous, 
dry/flaky,  macerated) 
 
14. Assess the skin area under 
the pump (e.g., healthy, fragile, 
inflamed, erythema, bruising, 
eczematous, dry/flaky,  
macerated) 
9.1.6 End of 
Therapy 
Assessment 
15. Obtain range of motion 
measurements (knee subjects 
only) 
Obtain range of motion 
measurements (for knee 
subjects only in Phase 1) 
9.1.7 Day 14 
4. Assess the surrounding skin 
including the area under the 
pump (e.g., healthy, fragile, 
inflamed, erythema, bruising, 
eczematous, dry/flaky,  
macerated) 
4. Assess the surrounding skin 
(e.g., healthy, fragile, inflamed, 
erythema, bruising, eczematous, 
dry/flaky,  macerated) 
 
5. Assess the skin area under the 
pump (e.g., healthy, fragile, 
inflamed, erythema, bruising, 
eczematous, dry/flaky,  
macerated) 

 
 
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9.1.7 Day 14 
5. Obtain range of motion 
measurements (knee subjects 
only) 
6. Obtain range of motion 
measurements (for knee 
subjects only in Phase 1) 
9.1.8 Day 30 
4. Assess the surrounding skin 
including the area under the 
pump (e.g., healthy, fragile, 
inflamed, erythema, bruising, 
eczematous, dry/flaky,  
macerated) 
4. Assess the surrounding skin 
(e.g., healthy, fragile, inflamed, 
erythema, bruising, eczematous, 
dry/flaky,  macerated) 
 
5. Assess the skin area under the 
pump (e.g., healthy, fragile, 
inflamed, erythema, bruising, 
eczematous, dry/flaky,  
macerated) 
9.1.8 Day 30 
5. Obtain range of motion 
measurements (knee subjects 
only) 
6. Obtain range of motion 
measurements (for knee 
subjects only in Phase 1) 
9.1.10 
Concomitant 
Therapies 
 No dressings (i.e. foam, 
gauze, ACTICOAT) should be 
used under the IP during 
therapy. 
 
 No dressings (i.e. foam, 
gauze, ACTICOAT, wound 
contact layers) should be used 
under the IP during therapy. 
9.2.1 Incision 
Closure, SSC 
and CDC-SSI 
incision 
assessment 
In addition, a medically qualified 
individual who is not deemed to 
have a vested interest in low 
reporting of complications and 
infections at an institutional 
level will complete a 
photographic incision 
assessment. This will include 1) 
assessment of whether the 
incision is fully 
closed/epithelialised, 2) 
assessment of infection, 
dehiscence or other 
complications. 3) Assessment of 
any potential AE on the skin 
under the dressing, and 
particularly the skin under the 
pump. 4) Wound assessment 
Deleted section  

 
 
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using the validated 100 mm 
VAS scoring tool. This 
assessment will use pictures 
captured with 
® 
 
The independent expert 
will be blinded to time points. 
9.2.1 Incision 
Closure, SSC 
and CDC-SSI 
incision 
assessment 
Results from secondary 
endpoint assessments (SSC, 
SSI rates, etc.) will be 
compared to published data 
from trials evaluating single use 
NPWT devices used in the 
postoperative management of 
similar closed surgical incisions 
in similar populations to comply 
with the conditions of MHRA 
Notice of No Objection 
(Appendix 23.12). To ensure 
closely approximate those of the 
similar research articles that it 
will be compared against, the 
Inclusion and Exclusion criteria 
have been updated. This allows 
the risk profile of the 
 
 population to be 
aligned with the review of 
literature. The additional 
published papers on similar 
populations will be identified 
prior to start inclusion.  Data 
comparison will be part of the 
interim analysis report, which is 
planned as described in section 
10.6. As this data comparison 
will be based on secondary 
endpoints, it will be intended 
mainly to explore the potential 
of 
 to safely 
promote clinical benefits.  
Results from secondary endpoint 
assessments (SSC, SSI rates, 
etc.) will be compared to 
published data from trials 
evaluating single use NPWT 
devices used in the postoperative 
management of similar closed 
surgical incisions in similar 
populations to comply with the 
conditions of MHRA Notice of No 
Objection (Appendix 23.12). To 
population will closely 
approximate those of the similar 
research articles that it will be 
compared against, the Inclusion 
and Exclusion criteria have been 
updated. This allows the risk 
profile of the 
 
population to be aligned with the 
review of literature.  
An internal analysis of previously 
reported level one studies 
showed the incidence of SSCs in 
abdominal surgery treated with 
PICO was 8.2%, (compared to 
23.4% in controls). 24,25,39 There 
is only one study reporting knees 
alone,40 with most studies 
combining both knee and hip 
arthroplasty, making analysis 
difficult, and S+N had previously 
agreed that such studies would 
not be included. In the study 

 
 
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Relevant published information 
for this purpose include so far 
the following: 
Karlakki et al [2016]17 reported 
a combined rate of SSC of 8.4% 
in 107 subjects treated with 
standard dressings (63 hips and 
44 knees). If taken separately, 
the rate of SSC was 13.6% after 
TKA and 4.7% after THA. 
Complications 
included:  superficial wound 
infections, haematoma, and 
prolonged wound discharge. 
  
Pellino et al. [2014]24 reported 
in a cohort of 25 colorectal 
subjects, after abdominal 
surgery, a length of stay of 7.1 
days, a rate of seroma of 40%, 
and a SSI rate of 44% 
according to CDC criteria. 
 
30 found a 
SSI rate of 32% after 30 days 
follow up in a cohort of 25 
subjects, whose closed 
abdominal incision was treated 
with standard dressings after 
undergoing open abdominal 
surgery. Length of stay for this 
group was 14.7 days. 
A summary of this relevant 
evidence for the surgical incision 
proposed in this protocol is 
presented in Table 9.2.1.1 
 
Table 9.2.1.1 Rates of surgical 
site complications as reported in 
relevant scientific papers 
which reported knees alone SSCs 
were reported in 34% of cases in 
the PICO group, compared to 
77% in the control group. 

 
 
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10.2 Analysis 
Populations 
(FAS), including all subjects 
recruited into the study. Safety 
Population (SAF), including all 
subjects who have received the 
study device.  
-Protocol Population (PP), 
including all subjects in the full 
analysis set who have no 
significant protocol deviations 
and met the inclusion/exclusion 
criteria. 
 
 Safety Population 
(SAF), including all 
subjects who have 
received the study 
device. 
 Full analysis set 
population (FAS), 
following ITT 
principle including 
all subjects 
recruited into the 
study. 
 Per-Protocol 
Population 1 (PP), 
including all 
subjects in the full 
analysis set who 
have no significant 
protocol deviations 
and met the 
inclusion/exclusion 
criteria. 
Statistical analysis will 
be performed using 
each of the subject 
populations as follows. 
Analysis of the 
primary, secondary 
and exploratory 
performance 
objectives will be 
performed separately 
using both the Full 
Analysis Set and the 
Per Protocol 
Population. All safety 
analyses will utilize 
the Safety Population, 
separately for each 
specialty. 

 
 
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Subsets of the above 
populations will be 
used for secondary 
analyses where 
appropriate to analyse 
only those subjects in 
the abdominal group 
who were recruited 
post-interim analysis 
and followed version 
8.0 of the protocol. 
These subset 
populations will be 
labelled with the 
-
clear, for example the 
subset of the full 
analysis set will be 
labelled s-FAS etc. 
 
10.4 Efficacy 
Analysis 
The study is non-comparative 
and non-randomised, the impact 
of confounding on the measures 
of performance may be 
expected and will be evaluated 
through descriptive analysis of 
selected baseline and 
demographic variables and 
fitting of appropriate models on 
selected outcomes presented 
separately for each specialty.  
The study is non-comparative 
and non-randomised, the impact 
of confounding on the measures 
of performance may be expected 
and will be evaluated through 
descriptive analysis of selected 
baseline and demographic 
variables and fitting of 
appropriate models on selected 
outcomes presented separately 
for each specialty.  
The primary analysis of the 
following endpoints will be done 
using FAS and PP analysis 
population. However, an 
additional analysis will also be 
carried out on a subset of these 
populations (s-FAS and s-PP) 
which includes only subjects who 
were recruited post-interim 

 
 
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analysis and followed protocol 
version 8.0. 
10.4.1 Analysis 
of Primary 
Endpoints 
Exudate management assessed 
by no occurrence of exudate 
leaks as assessed through a 
combination of leakage alert 
data from device 
 
and/or clinical data on any 
leakage observed during the 
dressing wearing period 
resulting or not, in an 
unplanned dressing change.  
 
Exudate management assessed 
by no occurrence of exudate 
leaks as assessed by reported 
clinical data on any exudate 
leakage observed through a 
dressing or around the borders 
during the dressing wearing 
period resulting or not, in an 
unplanned dressing change. 
10.4.1 Analysis 
of Primary 
Endpoints 
Composite Clinical Success 
(CCS) defined as a binary 
variable (1/0) (1 if all three of 
the following are true and 0 if at 
least one of the three is false):  
A. Nominal pressure is in the 
interval 80mmHg ± 7mmHg  
B. Dressing wear time is 7 days 
C. No leakage  
 
Composite Clinical Success 
(CCS) defined as a binary 
variable (1/0) (1 if all three of 
the following are true and 0 if at 
least one of the three is false): 
A. Average negative pressure 
within therapeutic range (-
100mmHg to -60mmHg) 
B. Dressing wear time is 7 days 
C. No exudate leakage 
 
10.4.2 Analysis 
of Secondary 
endpoints 
 
Range of motion assessment 
(ROM) for the knee at pre-
operative visit, post-
operative visit, 7, 14 and 30 
days.  
 
Range of motion assessment 
(ROM) for the knee at pre-
operative visit, post-
operative visit, 7, 14 and 30 
days. (Phase 1 only) 
 
10.4.2 Analysis 
of Secondary 
endpoints 
 
Added: 
As range of motion is collected 
for subjects in the knee surgery 
group only there will be no 

 
 
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summary of ROM in the s-FAS 
and s-PP analysis. 
10.6 Interim 
Analyses 
An interim analysis will be 
performed mainly for safety 
assessment purposes, once the 
study has recruited 22 subjects 
in specialty each group who 
have completed the follow-up 
period. The study will be paused 
while the MHRA assesses the 
results. 
As a condition for the MHRA No 
Objection decision, an interim 
analysis was required to be 
performed once the study has 
recruited 22 subjects in each 
specialty group who had 
completed the follow-up period. 
The study was paused while the 
MHRA assessed the results.  
There will be no further interim 
analysis performed as part of 
Phase 2 of this study. 
 
11 Sample Size 
Justification 
The sample size is justified 
based on the proposed three 
primary outcome variables of 
nominal pressure of 80mmHg, 
Dressing wear time in days and 
exudate management based on 
incidence of exudate leakage. 
Each of the three hypotheses 
will be tested separately for 
each specialty cohort.  
For the nominal pressure the 
sample size is based on analysis 
to test equivalence of negative 
pressure delivery against the 
reference value of 80.2mmHg. 
Previous data extracted from 
the PICO 7 system were found 
to be distributed with a 
SD=14.8. For purposes of 
sample size calculation, the a 
priori assumption is that the 
 
 
 system will have a similar 
operating pressure to PICO 7, 
and therefore similar variability 
An interim analysis was made 
after 44 subjects were recruited 
(22 from each indication). Based 
on the root cause analysis of seal 
loss, the study will continue on 
Abdominal surgical indications 
only at this time, whilst further 
investigative work continues into 
understanding the cause of seal 
loss in the orthopaedic surgery 
group.   
The 2nd phase of the study 
(post-interim analysis) will be 
powered according to previous 
sample size.  However, as no 
further subjects will be recruited 
for the orthopaedic surgery 
group, all 44 subjects recruited 
will be in the abdominal 
indication group. This will 
increase the total number of 
abdominal incisions to 66 (22 
recruited following the protocol 
v7.0 and 44 following v8.0 of the 

 
 
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in pressure delivery is assumed. 
The following hypotheses will be 
tested to establish the 
equivalence in mean operating 
pressure of 
 
 system over 7 
days compared to the reference 
value for PICO 7 (80.2 mmHg) 
 
- 
 
- 
 
represents the mean operating 
pressure of 
 
represents , the reference value 
relating to the mean operating 
pressure of PICO 7 
(=80.2mmHg, SD=14.8). The 
 7 
mmHg was chosen as a 
conservative non-clinically 
significant difference for 
operating pressure assuming 
the difference is actually 0. The 
hypothesis will be tested, 
separately for each specialty 
cohort by a two-sided t-test 
(TOST) at the alpha level of 
0.025 (one-sided). If the null 
hypothesis is rejected, clinical 
equivalence in terms of pressure 
delivery will be confirmed.  
Based on the data used for 
sample size estimation, thirty 
eight (38) subjects are required 
to achieve 80% power to detect 
equivalence at the significance 
-sided) 
within 7mmHg using a two-
sided t-test. Drawing from past 
experience, allowing that 15% 
protocol). This ensures that the 
primary endpoint is sufficiently 
powered for both the primary 
analysis of the abdominal data 
for all subjects as well as for a 
secondary analysis to be done on 
the data from those recruited 
according to protocol v8.0 only. 

 
 
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of the subjects may be lost to 
follow up by the end of the 
study, a sample size of 44 
subjects per specialty are 
needed to achieve sufficient 
statistical power for each 
specialty to be analysed 
separately, within this study.  
Based on the above, a total of 
88 subjects will be recruited, 
which will include 44 subjects 
with each of the following 
specialties: orthopaedics (closed 
surgical knee incisions, e.g. 
after total knee arthroplasty), 
and abdominal surgery (e.g. 
closed surgical abdominal 
incisions of which at least 50% 
would be colorectal cases).  
For the management of 
exudate, measured by incidence 
of exudate leakage, the sample 
size is evaluated for adequacy 
based on the non-leakage rate 
recorded by the NWPT system. 
According to internal data 
collected within Smith and 
Nephew surgical study involving 
Closed Abdominal and 
Orthopaedic subjects, 85% of 
the PICO NPWT systems had no 
exudate leaks. Therefore, 
assuming that 
 
NWPT system will manage 85% 
of exudate effectively or better, 
demonstrated through no 
exudate leakage observed, a 
sample size of 10 subjects for 
each specialty will be sufficient 
to exclude a response rate of 
65% or less with 80% power by 

 
 
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using a 2-sided 95% confidence 
interval for  
For the dressing wear time (in 
days) the sample size is based 
on comparison of the 
 
 
 
system compared to the 
literature derived value for each 
specialty separately. The mean 
dressing wear time derived from 
literature is 4.6 days and a 
standard deviation of 2.2539. It 
is projected that the 
 
 NWPT system will 
have a mean dressing wear time 
of 7 days with similar 
distribution to the literature 
value.  
The following hypotheses will be 
tested, for each specialty 
separately, to establish that the 
dressing wear time of the 
 
 
 
system is strictly not worse 
(lower) than the literature 
derived value:  
- 
 
- 
 
mean 
 pump 
represents the literature derived 
value (4.6 days). A one sided 
(one sample) t-test with alpha 
= 0.025 will be used to evaluate 
the hypothesis for each 
specialty. Based on the 
expected mean dressing wear 
time of 7 days, literature 
derived value of 4.6 days, and a 
standard deviation of 2.25 days, 
80% power and 2.5% 

 
 
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significance level, a sample size 
of 10 subjects per specialty is 
adequate to perform the above 
the hypothesis separately for 
each specialty cohort. 
Therefore, the planned forty-
four subjects per specialty 
cohort are adequate to conclude 
that the PICO  
orthopaedics (closed knee 
incisions e.g. after Total Knee 
Arthroplasty), and Abdominal 
surgery (closed abdominal 
surgical incisions) separately. 
With the planned 44 subjects 
per specialty, a response rate 
below 70% could be excluded 
for each specialty individually. 
 
system is strictly not worse 
(lower) than the literature 
derived value for each speciality 
individually. Further, with the 
planned 44 subjects per 
specialty, a dressing wear time 
below 6.0 days could be 
excluded for each specialty 
individually for the 
 
 device, represented 
by the lower limit of the 95% 
confidence interval lying above 
6.0 days, based on assumptions 
previously listed; one-sided t-
test with 80% power, 2.5% 
significance level, with a 
standard deviation of 2.25 days 
and assumed 7 day wear time 
of the 
 device.  
No adjustment to the sample 
size calculations will be made to 
account for interim report 
related to safety review. The 

 
 
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sample size was estimated 
using nQuery Advisor 4.0 and 
statistical software SAS Version 
9.4. 
12 Adverse 
Events and 
Device 
Deficiencies 
 
Updated definitions per 
ISO14155:2018 
Updated reporting requirements 
as per EC and MHRA approval 
letters 
15.1 CRO 
 
New section: 
The sponsor has engaged 
Contract Research Organization 
(CRO) to assist in conducting this 
study. When appropriate, the 
CRO is referred in study 
15.4 Interim 
Monitoring Visit
 
New section: 
Regular interim monitoring visits 
will be performed by the Sponsor 
or qualified person designated by 
the Sponsor. 
 
15.6 Close-out 
Visit 
Study close-out visits will be 
performed by the Sponsor or 
designee to retrieve and 
account for all remaining clinical 
data and to resolve outstanding 
queries. During study close-out, 
the monitor will review 
investigator files to ensure 
required documents and records 
are on file, confirm the 
disposition of any other ancillary
items used for the study, and 
review regulatory requirements 
Study close-out visits will be 
performed by the Sponsor or 
designee to retrieve and account 
for all remaining clinical data and 
to resolve outstanding queries. 
During study close-out, the 
monitor will review investigator 
files to ensure required 
documents and records are on 
file, confirm the disposition of 
any other ancillary items used 
for the study, and review 
regulatory requirements 
regarding records retention and 

 
 
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regarding records retention and 
IRB/IEC reporting requirements. 
 
IRB/IEC reporting requirements. 
When no subjects have been 
included, a remove close-out 
visit may be conducted. 
22 References 
 
Updated Pellino reference 
Added Flynn and Helito 
22.1 Protocol 
Amendment 8 
 
Added to Document these 
changes 
22.9 IFU 
 
Updated to new version 
22.10  
Principal Investigator 
Obligations (ISO14155:2011) 
Principal Investigator Obligations 
(ISO14155:2020) 
Text updated to reflect latest 
version 
22.11 ASA 
Physical Status 
Classification 
System 
Last Amended: October 15,2014 
(original approval: October 15, 
2014) 
Last Amended: December 13, 
2020 (original approval: October 
15, 2014) 
 
ASA IV Examples: 
Examples include (but not 
limited to): recent ( < 3 
months) MI, CVA, TIA, or 
CAD/stents, ongoing cardiac 
ischemia or severe valve 
dysfunction, severe reduction of 
ejection fraction, sepsis, DIC, 
ARD or ESRD not undergoing 
regularly scheduled dialysis 
ASA IV Examples: 
Examples include (but not 
limited to): recent ( < 3 months) 
MI, CVA, TIA, or CAD/stents, 
ongoing cardiac ischemia or 
severe valve dysfunction, severe 
reduction of ejection fraction, 
shock, sepsis, DIC, ARD or ESRD 
not undergoing regularly 
scheduled dialysis 
Tables and 
Figures 
 
Updated captions for automatic 
referencing 
 

 
 
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22.2.5 Approval/Notification 
These updates are considered a substantial amendment and will be notified to MHRA and 
submitted for EC approval. The changes will only be implemented after MHRA/EC approval 
confirmation. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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22.4 Protocol Amendment 6 
 
22.4.1 General Purpose 
This amendment has been completed following further discussion with MHRA. 
 
22.4.2 Rationale 
Updates to the protocol have been made to address a number of points raised by the MHRA 
during their review of the study.  
 
22.4.3 Effect on Study Status 
Not applicable. This amendment is to be in effect and implemented prior to subject enrollment. 
 
22.4.4 Details 
Section 
 
Revised Text 21/Jan/2019    
Version 5.0 
Revised Text 23/Jan/2019    
Version 6.0 
Synopsis 
A total of 88 subjects will be recruited 
to allow for 44 subjects to be recruited 
from each of the following specialties: 
orthopaedics (closed knee incisions 
A total of 88 subjects will be 
recruited to allow for 44 subjects to 
be recruited from each of the 
following specialties: orthopaedics 

 
 
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rate of SSC was 19%; to notice, in 
revision TKA patients (n=37) the rate 
of SSC with standard dressings was 
27%. Complications included SSI 
superficial and deep, persistent wound 
drainage, and need for revision 
surgery. 
 
Table 
9.2.1-1 
 
Removed reference to Keeney paper 
Qualified that Pellini paper is on 
colorectal patients only 
11 
Based on the above, a total of 88 
patients will be recruited, which will 
include 44 patients with each of the 
following specialties: orthopaedics 
(closed surgical knee incisions, e.g. 
after total knee arthroplasty), and 
abdominal surgery (e.g. closed 
surgical abdominal incisions).  
 
Based on the above, a total of 88 
patients will be recruited, which will 
include 44 patients with each of the 
following specialties: orthopaedics 
(closed surgical knee incisions, e.g. 
after total knee arthroplasty), and 
abdominal surgery (e.g. closed 
surgical abdominal incisions of which 
at least 50% would be colorectal 
cases).  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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22.5 Protocol Amendment 5 
22.5.1 General Purpose 
This amendment has been completed following further discussion with MHRA. 
 
22.5.2 Rationale 
Updates to the protocol have been made to address a number of points raised by the MHRA 
during their review of the study. Changes were made to provide details specialties under 
the closed surgical wound indication, to add language regarding comparison of the study 
results with existing evidence/literature for each of the secondary end points, to add details 
for the secondary end points wound assessment and to provide update to the statistics 
section. 
22.5.3 Effect on Study Status 
Not applicable. This amendment is to be in effect and implemented prior to subject 
enrolment. 
 
 
22.5.4 Details 
Section 
 
Revised Text 15/Jan/2019    
Version 4.0 
Revised Text 21/Jan/2019    
Version 5.0 
Synopsis 
8.3.2 
10.4.2 
Added secondary endpoint below: 
 
Wound and Skin VAS score assessment at 7, 14 and 30 days. 

 
 
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9.2.1 
Incision Closure and CDC 
Incision Assessment 
A medically qualified individual who 
is not deemed to have a vested 
interest in low reporting of 
complications and infections at an 
institutional level will complete 
incision assessment. This will 
include i) an assessment of whether 
the incision is fully 
closed/epithelialized , ii) an 
assessment of delayed healing, iii) 
an assessment of infection, 
dehiscence or other complications.  
Incision closure is defined as 100% 
re-epithelisation without drainage 
or dressing requirements. Primary 
or first intention healing occurs 
when tissue is cleanly incised and 
re-approximated and healing occurs 
without complications. The 
incisional defect re-epithelises 
rapidly and matrix deposition seals 
the defect. Incisional wounds are 
usually completely re-epithelised in 
24-48 hours, with continued healing 
of the underlying structures within 
5-7 days. Delayed wound healing 
would be defined as an incision that 
>7 days. 
Assessment of incision infection will 
be completed as specified per the 
CDC definitions of nosocomial 
surgical site infections at each of 
the specified time points to identify 
whether there is superficial, deep, 
or organ/space infection at the 
Incision Closure, SSC 
and CDC-SSI Incision 
Assessment 
Incision closure is defined as 
100% re-epithelisation without 
drainage or dressing 
requirements. Primary or first 
intention healing occurs when 
tissue is cleanly incised and re-
approximated and healing occurs 
without complications. The 
incisional defect re-epithelises 
rapidly and matrix deposition 
seals the defect. Incisional 
wounds are usually completely 
re-epithelised in 24-48 hours, 
with continued healing of the 
underlying structures within 5-7 
days. Delayed wound healing 
would be defined as an incision 
unhealed, >7 days. 
Assessment of incision healing 
and potential complications will 
be completed by the treating 
surgeon at each of the specified 
time points. The assessment will 
be performed using the CDC 
definitions of surgical site 
infection. SSI are infections that 
occur within 30 days of surgery 
or within a year if an implant is 
present. In addition, one of the 
following criteria must be met:  
(1) Purulent drainage from an 
incision (incisional infection) or 
from a drain below the fascia 
(deep infection);  

 
 
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incision site. Infection is defined as 
following criteria; abscess, 
cellulites, discharge, (serous 
exudate with inflammation, 
seropurulent, haemopurulent, pus) 
delayed healing, discoloration, 
unexpected 
pain/tenderness/bridging of the 
epithelium or soft tissue, abnormal 
can occur with or without the signs 
K F et al. 24, (2004). 
If dehiscence has occurred, the 
level of dehiscence will be defined 
as superficial (involve only 
separation at skin level) or deep 
(involve separation of tissues below 
the skin, may or may not include 
skin separation).  
A training session will be held for 
the individuals at each site to 
standardise how the assessments of 
complication, infection and 
dehiscence are made. 
(2) A surgeon or attending 
physician diagnosing an SSI;  
(3) An infective organism being 
isolated from a culture of fluid or 
tissue obtained from the surgical 
wound (for incisional infections);  
(4) Spontaneous dehiscence or a 
surgeon deliberately re-opening 
the wound in the presence of 
fever or local pain, unless 
subsequent cultures were 
negative, or an abscess being 
detected during direct 
examinations (for deep 
infections). The grading of SSI is 
based on symptoms. 
 
In case of SSI, there may be also 
discharge (serous exudate, 
seropurulent, haemopurulent, 
pus), delayed healing, erythema, 
unexpected pain,  tenderness, 
abnormal smell or wound 
breakdown. 
If dehiscence has occurred, the 
level of dehiscence will be 
defined as superficial (involve 
only separation at skin level) or 
deep (involve separation of 
tissues below the skin, may or 
may not include skin separation). 
Wound dehiscence will also be 
classified as partial or total. 
The wound size measurements 
will be performed directly from 
the wound photographs taken 
from the wound per each visit. 
The camera 
 will 
measure the lengths, the depth 

 
 
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and the width of the wound 
automatically, if appropriate. The 
wound photographs and the 
resulting wound measures will be 
stored in a database.  
Assessment of the wound will 
also include the use of a 
validated 100 mm Visual 
Analogue Scale (VAS) as 
described by Keeney et al 35, 
where a very low score is 
associated to a wound with a 
major gapping, dehiscence, 
severe inflammation and/or 
infection; and a very high score 
correspond to a completely 
healed wound with no evidence 
for inflammation. VAS 
assessment for wound evolution 
will be performed by the treating 
investigator.  
In addition, a medically qualified 
individual who is not deemed to 
have a vested interest in low 
reporting of complications and 
infections at an institutional level 
will complete a photographic 
incision assessment. This will 
include 1) assessment of whether 
the incision is fully 
closed/epithelialised, 2) 
assessment of delayed healing, 
3) assessment of infection, 
dehiscence or other 
complications. 4) Assessment of 
any potential AE on the skin 
under the dressing, and 
particularly the skin under the 
pump. 5) Wound assessment 
using the validated 100 mm VAS 

 
 
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scoring tool. This assessment will 
use pictures captured with 
® 
 
The 
independent expert will be 
blinded to time points. 
Representative images for 
guidance on the use of the 
validated 100 mm VAS scale are 
presented here below. 
 
VAS tool for assessment of closed 
surgical wounds evolution 
Results from secondary endpoint 
assessments (SSC, SSI rates, 
etc.) will be compared to 
published data from trials 
evaluating single use NPWT 
devices used in the postoperative 
management of similar closed 
surgical incisions in similar 
populations. As this data 
comparison will be based on 
secondary endpoints, it will be 
intended only to explore the 
potential of 
 to 
safely promote clinical benefits. 
 
Relevant published information 
for this purpose include the 
following: 

 
 
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Karlakki et al [2016]17 reported a 
combined rate of SSC of 8.4% in 
107 patients treated with 
standard dressings (63 hips and 
44 knees). If taken separately, 
the rate of SSC was 13.6% after 
TKA and 4.7% after THA. 
Complications 
included:  superficial wound 
infections, haematoma, and 
prolonged wound discharge. 
 
Keeney el al [2019]35 reported a 
rate of 12.7% SSC (particularly 
persistent wound drainage) in a 
population of orthopaedic 
patients (n=213] treated with 
standard dressings after THA and 
TKA. This included primary and 
revision surgery as well as 
patients bearing or not 
associated surgical risk factors 
such as BMI >35, diabetes or 
smoking. In primary TKA 
(n=126) the rate of SSC was 
19%; to notice, in revision TKA 
patients (n=37) the rate of SSC 
with standard dressings was 
27%. Complications included SSI 
superficial and deep, persistent 
wound drainage, and need for 
revision surgery. 
 
Pellino et al. [2014]24 reported in 
a cohort of 25 colorectal patients, 
after abdominal surgery, a length 
of stay of 7.1 days, a rate of 
seroma of 40%, and a SSI rate 
of 44% according to CDC criteria. 
 
30 found a 
SSI rate of 32% after 30 days 

 
 
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follow up in a cohort of 25 
patients, whose closed abdominal 
incision was treated with 
standard dressings after 
undergoing open abdominal 
surgery. Length of stay for this 
group was 14.7 days. 
 
A summary of this relevant 
evidence for the surgical incision 
proposed in this protocol is 
presented in Table 9.2.1.1 
Reference 
Incision 
type 
Reported 
rate of 
SSC, (size 
of cohort) 
with 
Standard 
Dressings 
Karlakki et 
al 17 
Closed 
surgical 
knee 
incision 
13.6% 
(n=44) 
Keeney et al 
35 
Closed 
surgical 
knee 
incision 
Primary TKA 
19% 
(n=126) 
Revision 
TKA 27% 
(n=37) 
Pellino et al 
24 
Closed 
surgical 
abdominal 
incision 
SSI at 30 
days 44% 
(n=25) 
30 
Closed 
surgical 
abdominal 
incision 
SSI at 30 
days 32% 
(n=25) 
 
Results from this trial will be also 
compared to actually reported 
rates of SSC in each one of the 
research centres (where 
available) for the concerned 
specialty and types of surgery.  
 
This assessment will be intended 
to ensure that 
 is 

 
 
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to assess the evolution of the 
event until the end of follow-up.  
® 
 Wound 
Assessment Device allows for a 
precise determination of surface 
areas, (depth and volume too if 
required) thus facilitate an 
objective follow up of the 
evolution of skin lesions 
(erythema, dehiscence). 
9.2.3 
Surgical Site and 
Dressing 
Photographs 
postsurgical incision will be 
captured prior to initial dressing 
application, at 7 days post 
operatively (or when dressing is 
removed) and at 30 days 
postoperatively (or early exit visit) 
using a digital camera supplied by 
S&N. The images will be used as a 
pictorial record of the study 
reference incisions.  
A photo ruler labelled with the 
the date will be supplied by S&N 
and will be placed in the field of the 
photograph. The image should be 
framed such that the entire 
incision/dressing nearly fills the 
frame. Ensure that identifying 
face, are not visible in the 
photograph. After obtaining the 
image, ensure that the image is 
clear (in focus) and that there is 
sufficient light to clearly see the 
Photographs and 
Surgical Site 
Assessment  
postsurgical incision (and wound 
zone) will be captured prior to 
initial dressing application, at 7 
days post operatively (or when 
dressing is removed), at 14 days 
and at 30 days postoperatively 
(or early exit visit) using a digital 
camera supplied by S&N.  
Photographic assessment will be 
performed with the 
® 
 
 
® 
 is a 
portable device that easily allows 
capture of high-resolution 
graphic information about a 
then managed, analysed and 
stored in a central database. 
Information captured includes 
photographic images, 
quantitative measures, and other 
wound assessment data input by 
the assessing clinician, all 
obtained with no subject contact. 

 
 
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incision/dressing. Instructions for 
capturing images will be supplied 
with the cameras. Training on the 
use of the camera will be given 
during the site initiation visit. 
An image of the dressing in place 
will be taken after application, and 
before removal, to check the device 
compliance. 
 
® 
 builds that 
information into an electronic 
record for either printing, 
database, further clinical 
assessment or archiving. 
Information about performed 
wound measurements history is 
available on the system so that 
progression of the wound status 
can be calculated and presented. 
The images will be used to 
perform wound assessments by 
the treating investigator, and by 
an independent expert. 
Photograph should also be taken 
where appropriate of all DevD 
reported. Pictures will also 
constitute the pictorial record of 
the study reference incisions.  
The image should be framed such 
that the entire incision/dressing 
area nearly fills the frame. 
Ensure that identifying 
face, are not visible in the 
photograph. After obtaining the 
image, ensure that the image is 
clear (in focus) and that there is 
sufficient light to clearly see the 
wound/dressing. Instructions for 
capturing images will be supplied 
with the cameras. Training on the 
use of the 
® 
 
camera will be given prior to 
start of the study.  
An image of the dressing in place 
will be taken after application, 
and before removal, to check the 

 
 
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21.2.4 
Revised Text 14/Jan/2019    Version 
4.0 
Revised Text 15/Jan/2019    
Version 4.0 
 
 
 
 
 
 
22.6 Protocol Amendment 4 
22.6.1 General Purpose 
This amendment has been completed following discussions with MHRA following the 
November 2018 resubmission. 
 
22.6.2 Rationale 
Updates to the protocol have been made to address a number of points raised by the 
MHRA during their review of the study. Changes include updates to the specialties 
included in the study, sample size, number of sites, length of study and stats section. 
 
 
22.6.3 Effect on Study Status 
Not applicable. This amendment is to be in effect and implemented prior to subject 
enrolment. 
 
 

 
 
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22.6.4 Details 
Section 
 
Revised Text 6/Nov/2018    
Version 3.1 
Revised Text 15/Jan/2019    
Version 4.0 
Throughout 
All references to skin graft and split thickness skin grafts were 
removed.      
Throughout 
Standardisation of formatting 
Synopsis 
Secondary Objectives: 
 
To assess clinical performance 
and safety of the 
 
 
NPWT system within 30 days of 
surgery through the: 
 Incidence of Surgical Site 
Infection (SSI)  Superficial, 
deep. [CDC criteria] 
 Incidence of Surgical site 
Complications (SSC) [as 
applicable:dehiscence 
(superficial/deep etc.), 
seroma, necrosis, 
hematoma, suture abscess] 
 Percentage of successful skin 
graft take at Days 7, 14 and 
30 
 Condition of surrounding skin 
around the wound bed, and 
under the pump 
 
 Any pain experienced by the 
subject in relation to the 
 system 
Secondary Objectives: 
To assess clinical performance 
and safety of the 
 
 NPWT system 
within 30 days of surgery 
through the: 
 
Incidence of 
Surgical Site 
Infection (SSI)  
Superficial, deep 
organ space [CDC 
criteria] 
 
Incidence of Surgical 
site Complications 
(SSC) [as applicable: 
dehiscence 
(superficial/deep etc.), 
seroma, necrosis, 
hematoma, suture 
abscess] 
 
Condition of skin 
around the wound, 
and under the 
 
 
 
Any pain 
experienced by the 
subject in relation to 
the 
 
system 

 
 
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surgery (except for those with 
perforated bowel or peritonitis). 
perforated bowel or 
peritonitis). 
7.3 
12. Subjects with split thickness 
skin grafts to correct venous 
ulcers where compression 
therapy is needed for healing 
(based on clinicians expertise). 
Removed Exclusion criteria 
#12 
8.1 
It is anticipated that up to 9 
sites will participate within the 
UK and EU. 
It is anticipated that up to 6 
sites will participate within the 
UK and EU. 
8.3.2 
Secondary Endpoints 
 
Clinical performance and 
safety of the 
 
NPWT system over a 30 day 
follow-up period to include: 
 
 Incidence of Surgical Site 
Infection (SSI)  Superficial, 
deep, organ [CDC criteria] 
within 30 days of surgery 
 
Incidence of Surgical site 
Complications (SSC) [as 
applicable: dehiscence 
(superficial/deep/organ.), 
seroma, necrosis, 
hematoma, suture abscess] 
within 30 days of surgery 
 
Percentage of skin graft take 
at Days 7, 14 and 30 as 
assessed by clinician visual 
assessment 
 
Condition of peri-wound skin 
and skin under the 
 
 assessed through 
visual inspection at 7, 14 and 
30 days. 
 
Level of pain during wear of 
the 
 system, 
and at dressing removal 
assessed by VAS scale 
following 7 day therapy 
Secondary Endpoints 
Clinical performance and 
safety of the 
 
NPWT system over a 30 day 
follow-up period to include:  
 
Incidence of Surgical Site 
Infection (SSI)  
Superficial, deep, organ 
[CDC criteria] within 30 
days of surgery.  
 
Incidence of Surgical site 
Complications (SSC) [as 
applicable: dehiscence 
(superficial/deep, 
partial/total), seroma, 
necrosis, hematoma, suture 
abscess] within 30 days of 
surgery 
 
Condition of peri-wound 
skin and skin under the 
 assessed 
through visual inspection at 
7, 14 and 30 days. 
 
Level of pain during wear of 
the 
 system, 
and at dressing removal 
assessed by VAS scale 
following 7 day therapy 

 
 
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8.4.3 
The study includes a single 
indication in three different 
surgical specialties and a range 
of contoured areas of the body 
where it may be difficult to 
obtain an effective negative 
pressure seal and where there 
may be a range of motion 
throughout therapy (i.e knee).  
The study includes a single 
indication in two different 
surgical specialties and a 
range of contoured areas of 
the body where it may be 
difficult to obtain an effective 
negative pressure seal and 
where there may be a range of 
motion throughout therapy 
(i.e. knee).  
9.1.1 
 
Removed skin graft and skin 
graft complications 
assessments in schedule of 
assessments table 
9.1.3 
2. Commence operation and 
collect surgery data [e.g. Type 
of surgery (closed surgical 
incision, (type of abdominal 
surgery (type of knee surgery, 
method of closure), STSG 
(meshed / unmeshed) and 
reference wound type)]. 
2. Commence operation and 
collect surgery data [e.g. Type 
of surgery (closed surgical 
incision, (type of abdominal 
surgery, type of knee surgery, 
incision length, anatomical 
location and method of 
closure)]. 
9.1.3 
3. Collect surgery risk factors 
(elective/emergency surgery, 
laparoscopic (y/n), incision 
length, use of prophylactic 
antibiotics, type 
(single/double/triple agent) and 
when administered (prior to 
start of surgery/after surgery 
began), shaving of incision 
(yes/no/not needed), use of a 
wound protector (yes/no), 
clean/contaminated surgery 
(clean/clean-contaminated/ 
contaminated/dirty), 
intraoperative warming 
(yes/no)) 
3.Collect surgery risk factors 
(elective/emergency surgery, 
laparoscopic (y/n), incision 
length, use of prophylactic 
antibiotics, type 
(single/double/triple agent) 
and when administered (prior 
to start of surgery/after 
surgery began),  shaving of 
incision (yes/no/not needed), 
use of a wound protector 
(yes/no), surgical bioburden 
level (clean/clean-
contaminated/ 
contaminated/dirty), 
intraoperative warming 
(yes/no)) 

 
 
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9.1.3 
5. Photograph incision/skin 
graft using the camera provided 
by the Sponsor. 
5. Photograph incision using 
the camera provided by the 
Sponsor. 
9.1.3 
6. Assess the incision/skin graft 
characteristics for likelihood of 
SSC (oedema, seroma, 
haematoma, skin necrosis, graft 
loss). 
6. Assess the incision 
characteristics for likelihood of 
SSC (oedema, seroma, 
haematoma, skin necrosis). 
9.1.6, 
9.1.7 
9.1.8 
9.1.10.2 
9.2.1. 
9.2.2 
9.2.3 
Deleted references to skin graft  
9.1.9 
2.Record the complication type 
(e.g. superficial infection i.e. 
cellulitis, deep infection, 
organ/space infection, 
oedematous, seroma, 
haematoma, abscess, discharge 
(serous exudate with 
inflammation, seropurulent, 
haemopurulent, pus), delayed 
healing, discoloration, 
unexpected 
pain/tenderness/bridging of the 
epithelium or soft tissue, 
abnormal smell, wound 
breakdown, severe bruising, 
superficial dehiscence, deep 
dehiscence, other). 
2.Record the complication type 
(e.g. superficial infection i.e. 
cellulitis, deep infection, 
organ/space infection, 
oedematous, seroma, 
haematoma, abscess, 
discharge (serous exudate with 
inflammation, seropurulent, 
haemopurulent, pus), delayed 
healing, discoloration, 
unexpected 
pain/tenderness/bridging of 
the epithelium or soft tissue, 
abnormal smell, wound 
breakdown, severe bruising, 
superficial dehiscence, deep 

 
 
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dehiscence, partial dehiscence, 
total dehiscence). 
10.1 
 
New text: 
All summaries and analyses 
will be presented separately 
for each of the two cohorts of 
specialties recruited within the 
study: orthopaedics (closed 
knee incisions e.g. after Total 
Knee Arthroplasty), and 
Abdominal surgery (closed 
abdominal surgical incisions). 
No data will be combined 
between the two specialties. 
10.1 
Primary, secondary, and 
exploratory outcome variables 
and derived variables will also 
be summarised accordingly. 
Primary, secondary, and 
exploratory outcome variables 
and derived variables will also 
be summarised accordingly 
separately by specialty. 
10.2 
Statistical analysis will be 
performed using each of the 
patient populations as follows. 
Analysis of the primary, 
secondary and exploratory 
performance objectives will be 
performed separately using 
both the Full Analysis Set and 
the Per Protocol Population. All 
safety analyses will utilize the 
Safety Population. 
Statistical analysis will be 
performed using each of the 
patient populations as follows. 
Analysis of the primary, 
secondary and exploratory 
performance objectives will be 
performed separately using 
both the Full Analysis Set and 
the Per Protocol Population, for 
each specialty. All safety 
analyses will utilize the Safety 
Population, separately for each 
specialty. 
10.4 
The study is non-comparative 
and non-randomised, the 
impact of confounding on the 
measures of performance may 
be expected and will be 
evaluated through descriptive 
analysis of selected baseline 
and demographic variables and 
The study is non-comparative 
and non-randomised, the 
impact of confounding on the 
measures of performance may 
be expected and will be 
evaluated through descriptive 
analysis of selected baseline 
and demographic variables and 
fitting of appropriate models 

 
 
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recorded data of any 
unplanned dressing change. 
 
The following hypotheses will 
be tested to establish 
equivalence of the 
 
 
 
system compared to the 
literature derived value, with 
equivalence margin, 1>0: 
- 
1 
- 
1 
represents the assumed mean 
dressing wear time in days 
 pump 
dressing wear time. The 
equivalence margin is 2.4 
days. A two-one sided t-test 
with alpha = 0.05 will be used 
to 
evaluate the hypothesis. A 
binary variable accounting for 
below 7 days wear off time 
will also be used and the 
proportion wearing of before 7 
days will be reported as a 
percentage along with 
corresponding confidence 
interval. If necessary and if 
data allows, 
important associated factors 
will be adjusted for in a 
logistic model. 
 
 Exudate management 
assessed by no occurrence of 
exudate leaks as assessed 
through a combination of 
leakage alert data from device 
recorded data of any 
unplanned dressing change. 
The following hypotheses will 
be tested, for each specialty 
separately, to establish that 
the dressing wear time of the 
 
 
 system is strictly no 
worse (lower) than the 
literature derived value:  
H0
- 
 0  
 
Ha
- 
 0  >0 
In the stated hypothesis, µ 
represents the mean 
 
 dressing wear 
time in days and µ0 
represents the literature 
derived value (4.6 days). A 
one sided (one sample) t-test 
with alpha = 0.025 will be 
used to evaluate the 
hypothesis for each specialty, 
the corresponding 95% CIs 
will also be presented. 
A binary variable indicating 
(denoted by 0/1) will also be 
used and the proportion of 
dressings with a wear time 
percentage along with 
corresponding 95% 
confidence interval, for each 
specialty cohort. If necessary 
and if data allows, important 
associated factors will be 

 
 
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intended for use only by Smith & Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
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 and/or clinical data 
on any leakage observed 
during the dressing wearing 
period resulting or not, in an 
unplanned dressing change.  
 
A binary variable for the non-
leakage and leakage will be 
used and the proportion of 
reported/identified leaks will 
be presented as a frequency 
together with a percentage 
and a 95% CI. The non-
leakage proportion for the 
study will be tested using the 
Exact test to establish if it is 
different from the literature 
derived value of 85% 
projected. The lower limit of 
95% CI will be evaluated to 
establish if it excludes values 
of 65% and below. 
 
The logistic model will be used 
to evaluate the adjusted and 
the un-adjusted models for 
the CCS primary outcome 
variable. The variables 
considered important and to 
be included in the final model 
are Age, Diabetic status and 
the presence of any other 
comorbidity as a binary 
variable. All other baseline 
and medical factors collected 
at baseline will be evaluated 
for importance in adjusted 
models and only those 
statistically significant in an 
un-adjusted model will be 
considered in the final model.  
 
adjusted for in a logistic 
model. 
 Exudate management 
assessed by no occurrence of 
exudate leaks as assessed 
through a combination of 
leakage alert data from 
device 
and/or 
clinical data on any leakage 
observed during the dressing 
wearing period resulting or 
not, in an unplanned dressing 
change. 
A binary variable for the non-
leakage and leakage will be 
used and the proportion of 
reported/identified leaks will 
be presented as a frequency 
together with a percentage 
and a 95% CI separately for 
each specialty. For each 
specialty, the non-leakage 
proportion for the study will 
be tested using the Exact 
test to establish if it is 
different from the literature 
derived value of 85% 
projected. Further, the 
resulting lower limit of 95% 
CI for each specialty will be 
evaluated to establish if it 
excludes values of 65% and 
below. 
Composite Clinical Success 
(CCS) defined as a binary 
variable (1/0) (1 if all three of 
the following are true and 0 if 

 
 
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Composite Clinical Success 
(CCS) defined as a binary 
variable (1/0) (1 if all three of 
the following are true 
and 0 if at least one of the 
three is false): 
A. Nominal pressure is in the 
interval 80mmHg ± 7mmHg 
B. Dressing wear time is 7 days 
C. No leakage 
The Composite Clinical Success 
(CCS) will be reported as a 
count and percentage with a 
95% CI. 
at least one of the three is 
false): 
A.Nominal pressure is in 
the interval 80mmHg ± 
7mmHg 
B.Dressing wear time is 7 
days 
C.No leakage 
The Composite Clinical 
Success (CCS) will be reported 
as a count and percentage 
with a 95% CI separately for 
each specialty. 
A logistic model will be used to 
evaluate the adjusted and the 
un-adjusted models for the 
CCS primary outcome variable 
for each specialty, separately. 
The variables considered 
important and to be included 
in the final model are Age, 
Diabetic status and the 
presence of any other co-
morbidity as a binary variable. 
All other baseline and medical 
factors collected at baseline 
will be evaluated for 
importance in adjusted models 
and only those statistically 
significant in an un-adjusted 
model will be considered in the 
final model. 
10.4.2 
 Incidence of Surgical site 
Complications (SSC) [as 
applicable: dehiscence 
(superficial/deep/organ.), 
seroma, necrosis, hematoma, 
suture abscess] within 30 
days of surgery 
 Incidence of Surgical site 
Complications (SSC) [as 
applicable: dehiscence 
(superficial/deep 
partial/total), seroma, 
necrosis, hematoma, suture 

 
 
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reference value for PICO 7 
(80.2 mmHg) with equivalence 
margin, 1: 
H0
- 
0 
1 
Ha
- 
0 | < 
1 
In the stated hypotheses, 
 
represents the mean operating 
pressure of 
 
 system and 
0 
represents , the reference value 
relating to the mean operating 
pressure of PICO 7 
(=80.2mmHg, SD=14.8). The 
equivalence margin, 1 = 7 
mmHg was chosen as a 
conservative non-clinically 
significant difference for 
operating pressure assuming 
the difference is actually 0. The 
hypothesis will be tested by 
two-sided t-test at the alpha 
level of 0.05. 
If the null hypothesis is 
rejected, clinical equivalence in 
terms of pressure delivery will 
be 
confirmed. 
 
Based on the data used for 
sample size estimation, thirty 
eight (38) subjects are required 
to achieve 80% power to detect 
equivalence at the significance 
25 within 
7mmHg using a two-sided t-
test. Drawing from past 
experience, allowing that 15% 
of the subjects may be lost to 
follow up by the end of the 
study, a sample size of 
establish the equivalence in 
mean operating pressure of 
  
 
 system  over 7 days 
compared to the reference 
value for PICO 7 (80.2 mmHg) 
with equivalence margin, 1:  
H0
- 
 0 
1 
Ha
- 
 0 | < 
1 
 
In the stated hypotheses,  
represents the mean operating 
pressure of 
  
 system  and  
 represents , the reference 
value relating to the mean 
operating pressure of PICO 7 
(=80.2mmHg, SD=14.8). The 
equivalence margin, 1 = 7 
mmHg was chosen as a 
conservative non-clinically 
significant difference for 
operating pressure assuming 
the difference is actually 0. 
The hypothesis will be tested, 
separately for each specialty 
cohort by a two-sided t-test  
(TOST) at the alpha level of 
0.025 (one-sided).  If the null 
hypothesis is rejected, clinical 
equivalence in terms of 
pressure delivery will be 
confirmed. 
Based on the data used for 
sample size estimation, thirty 
eight (38) subjects are 
required to achieve 80% 
power to detect equivalence at 

 
 
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approximately 44 subjects are 
needed in this study. A total of 
44 patients will be recruited to 
allow a minimum of 10 patients 
with each of 
the following indications to be 
recruited: grafts, closed knee, 
and closed abdomen. The 
remainder 
of the sample will be made up 
from any of the three permitted 
indications included in the 
study. 
 
For the management of 
exudate, measured by incidence 
of exudate leakage, the sample 
size is 
evaluated for adequacy based 
on the non-leakage rate 
recorded by the NWPT system. 
According to internal data 
collected within Smith and 
Nephew surgical study involving 
Cardiothoracic, Cardiovascular 
and Orthopaedic subjects, 85% 
of the PICO NPWT systems had 
no exudate leaks. Therefore, 
assuming that 
 
NWPT system will manage 85% 
of exudate 
effectively or better, 
demonstrated through no 
exudate leakage observed, a 
sample size of 30 
subjects will be sufficient to 
exclude a response rate of 65% 
or less with 80% power by 
using a 2-sided 95% confidence 
interval. With the full 44 
subjects a response rate below 
70% could be 
0.025 (one-sided) within 
7mmHg using a two-sided t-
test. Drawing from past 
experience, allowing that 15% 
of the subjects may be lost to 
follow up by the end of the 
study, a sample size of 44 
subjects per specialty are 
needed to achieve sufficient 
statistical power for each 
specialty to be analysed 
separately, within this study.  
Based on the above, a total of 
88 patients will be recruited, 
which will include 44 patients 
with each of the following 
specialties: orthopaedics 
(closed surgical knee incisions, 
e.g. after total knee 
arthroplasty), and abdominal 
surgery (e.g. closed surgical 
abdominal incisions).  
For the management of 
exudate, measured by 
incidence of exudate leakage, 
the sample size is evaluated 
for adequacy based on the 
non-leakage rate recorded by 
the NWPT system. According 
to internal data collected 
within Smith and Nephew 
surgical study involving Closed 
Abdominal and Orthopaedic 
subjects, 85% of the PICO 
NPWT systems had no exudate 
leaks. Therefore, assuming 
that 
 NWPT 
system will manage 85% of 
exudate effectively or better, 
demonstrated through no 

 
 
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excluded. 
 
For the dressing wear time the 
sample size is based on non-
inferiority of the 
 
 
system 
compared to the literature 
derived value. The mean 
dressing wear time derived 
from literature is 4.6 days and a 
standard deviation of 2.2539. It 
is projected that the 
 
 NWPT system will 
have a mean dressing wear 
time of 7 days, therefore 
assuming a non-inferiority limit 
of 2.4 days is logical, assuming 
the acceptable value will lie 
above 4.6 days. 
 
The following hypotheses will be 
tested to establish non-
inferiority of the 
 
 
 
system compared to the 
literature derived value, non-
inferiority margin, 1>0: 
H0
- 
0 
1 
Ha
- 
0 | < 
1 
represents the assumed mean 
dressing wear time in days and 
 
represents the mean 
 
 pump dressing wear 
time. The non-inferiority margin 
is 
2.4 days. A two-one sided 
sample t-test with alpha = 
exudate leakage observed, a 
sample size of 30 subjects for 
each specialty will be sufficient 
to exclude a response rate of 
65% or less with 80% power 
by using a 2-sided 95% 
confidence interval for 
orthopaedics (closed knee 
incisions e.g. after Total Knee 
Arthroplasty), and Abdominal 
surgery (closed abdominal 
surgical incisions) separately.  
With the planned  44 subjects 
per specialty, a response rate 
below 70% could be excluded 
for each specialty individually. 
For the dressing wear time (in 
days) the sample size is based 
on comparison of the 
 
 
 
system compared to the 
literature derived value for 
each specialty separately. The 
mean dressing wear time 
derived from literature is 4.6 
days and a standard deviation 
of 2.2539. It is projected that 
the 
 NWPT 
system will have a mean 
dressing wear time of 7 days 
with similar distribution to the 
literature value. 
The following hypotheses will 
be tested, for each specialty 
separately, to establish that 
the dressing wear time of the 
 
 
system is strictly not 

 
 
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0.025 will be used to evaluate 
the hypothesis. 
Based on the mean dressing 
wear time of 7 days and a 
standard deviation of 2.25, an 
noninferiority 
margin of 2.4 days, 80% power 
and 5% significance level, a 
sample size of 33 subjects is 
adequate to test for non-
inferiority. Therefore, forty-four 
subjects are adequate to 
conclude noninferiority. 
 
The sample size was estimated 
using nQuery Advisor 4.0 and 
statistical software SAS Version 
9.4. 
worse (lower) than the 
literature derived value:  
H0
- 
 0 
1 
Ha
- 
 0 | < 
1 
In the stated hypothesis, µ the 
mean 
 pump 
dressing wear time and µ0 
represents the literature 
derived value (4.6 days). A 
one sided (one sample) t-test 
with alpha = 0.025 will be 
used to evaluate the 
hypothesis for each specialty. 
Based on the expected mean 
dressing wear time of 7 days, 
literature derived value of 4.6 
days, and a standard deviation 
of 2.25 days, 80% power and 
2.5% significance level, a 
sample size of 33 subjects per 
specialty is adequate to 
perform the above hypothesis 
separately for each specialty 
cohort. Therefore, the planned 
forty-four subjects per 
specialty cohort are adequate 
to conclude that the 
 
 
 
system is strictly not worse 
(lower) than the literature 
derived value for each 
speciality individually.  Further, 
with the planned 44 subjects 
per specialty, a dressing wear 
time below 6.0 days could be 
excluded for each specialty 
individually for the 
 
 device, represented 
by the lower limit of the 95% 
confidence interval lying above 

 
 
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Section 
 
Current Text 26/Jun/2018 
Version 2.0 
Revised Text 10/Oct/2018    
Version 3.0 
manufacturers 
and 
notified 
bodies 
under 
Directives 
order to confirm the clinical 
safety and clinical performance 
of 
 
 
for 
CE 
marking. 
S&N 
will use 
the 
results of the proposed clinical 
study on 
 
 in 
combination with results from 
extensive published clinical data 
on 
PICO 
Single Use 
NPWT 
System for CE marking together 
with a comprehensive design 
verification 
and 
validation 
package of evidence for 
 
 
 
 
 
22.7.4 Additional Modifications 
The following modifications are required to correct some aspects of amendment 3 (synopsis 
not updated in line with change to sample size and error in table header). In addition an error 
in eligibility criteria no 12 has been corrected. 
This amendment is to be in effect and implemented prior to any subject enrolment. 
Section 
 
Current Text 10/Oct/2018 
Version 3.0 
Revised Text 06/Nov/2018    
Version 3.1 
Study Synopsis: 
sample size 
Forty four (44) subjects will be 
recruited to allow for 10 patients 
for each of the four selected 
indications of grafts, closed knee, 
A total of 44 patients will be 
recruited to allow a minimum of 
10 patients with each of the 
following indications to be 
recruited: grafts, closed knee, 

 
 
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22.8 Protocol Amendment 2 
22.8.1 General Purpose 
This amendment was completed following initial MHRA review of the protocol. 
 
22.8.2 Rationale 
Updates to the protocol were made to address a number of points raised by the MHRA during 
their review of the study. Namely updates and corrections to referencing throughout, an 
increase to the length of time for any potential participants since surgery at the same 
anatomical site, a decrease in the number of sites due to concerns of heterogenecity, 
additional information added to the statistical section. 
 
22.8.3 Effect on Study Status 
Not applicable; this amendment is to be in effect and implemented prior to subject 
enrollment. 
 
22.8.4 Details 
This amendment specifically revised the protocol as follows: 
Throughout  Updates made to correct referencing  
Sample size increased from 40 to 44  
Introduction Section 4.1.1  
The following text has been added 
 
-risk population. Indications for surgery were multiple 
(cancer (86%), trauma and chronic wounds), in patients relatively old and having multiple 

 
 
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comorbidities. From all the factors assessed, only three showed statistical significance, BMI 
>30, peripheral vascular disease (PVD) and the concomitant use of immuno-suppressants. 
On the contrary, in burn patients, who have a good tissue vascularity, the rate of skin graft 
success when using NPWT has been reported to be high
 
and later in the same section: 
 
wound complications (including superficial infections, superficial dehiscence, and delayed 
healing) following total hip and knee arthroplasty may contribute heavily. 
Subject Population Section 7.1  
ngdom 
 
Exclusion criteria Section 7.3  
same surgery site (anatom
 
Statistical Section 10.4.1  
Old text:   
 Pressure maintenance at nominal 80mmHg  
The following hypotheses will be tested to establish equivalence of the 
 
 system compared to the internally derived value, with equivalence margin, 
1>0:  
H0
- 
0  
1 
Ha
- 
0  < 1 
 

 
 
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In the stated hypotheses, µ represents the assumed mean operating pressure (80.2 mmHg) 
and µ  represents the mean 
 pump operating pressure. The equivalence limit 
1 = 7mmHg was chosen as a conservative non-clinically significant difference assuming that 
the difference is actually 0. The hypothesis will be tested by two-sided t-test at the alpha 
level of 0.05. If the null hypothesis is rejected, equivalence will be confirmed.  
A one sample t-test and corresponding CI will be used to evaluate this hypothesis. 
 Dressing wear time (7 days) as assessed through a combination of; data from device 
 and CRF recorded data of any unplanned dressing change.  
The mean dressing wear time will be reported together with the standard deviation. A binary 
variable accounting for below 7 days wear off time will also be used and the proportion 
wearing of before 7 days will be reported as a percentage along with corresponding 
confidence interval. If necessary and if data allows, important associated factors will be 
adjusted for in a logistic model. 
 Exudate management assessed by no occurrence of exudate leaks as assessed through a 
combination of leakage alert data from device 
 and/or clinical data on any leakage 
observed during the dressing wearing period resulting or not, in an unplanned dressing 
change  
A binary variable also for the leakage will also be used and the proportion of 
reported/identified leaks will be presented as a frequency together with a percentage and a 
95% CI. 
Composite Clinical Success (CCS) defined as a binary variable (1/0) (1 if all three of the 
following are true and 0 if at least one of the three is false): 
A Nominal pressure is in the interval 80mmHg ± 7mmHg  
B Dressing wear time is 7 days  
C No leakage  

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
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The Composite Clinical Success (CCS) will be reported as a count and percentage with a 
95% CI. 
New text:  
 Pressure maintenance at nominal 80mmHg  
The following hypotheses will be tested to establish equivalence of the 
 
 system compared to the internally derived value, with equivalence margin, 
1>0:  
H0
- 
0  
1 
Ha
- 
0  < 1 
 
In the stated hypotheses, µ represents the assumed mean operating pressure (80.2 mmHg) 
and µ  represents the mean 
 pump operating pressure. The equivalence limit 
1 = 7mmHg was chosen as a conservative non-clinically significant difference assuming that 
the difference is actually 0. The hypothesis will be tested by two-one-sided t-test (TOST) at 
the alpha level of 0.05. If the null hypothesis is rejected, equivalence will be confirmed. A 
two-one sided t-test and corresponding CI will be used to evaluate this hypothesis.  
 Dressing wear time (7 days) as assessed through a combination of; data from device 
 and CRF recorded data of any unplanned dressing change. 
The following hypotheses will be tested to establish equivalence of the 
 
 system compared to the literature derived value, with equivalence margin, 
d1>0: 
H0
- 
0  
1 
Ha
- 
0  < 1 
 
In the stated hypothesis, µ represents the assumed mean dressing wear time in days and 
µ  represents the mean 
 pump dressing wear time. The equivalence margin 
is 2.4 days. A two-one sided t-test with alpha = 0.05 will be used to evaluate the hypothesis. 
A binary variable accounting for below 7 days wear off time will also be used and the 

 
 
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proportion wearing of before 7 days will be reported as a percentage along with 
corresponding confidence interval. If necessary and if data allows, important associated 
factors will be adjusted for in a logistic model. 
 Exudate management assessed by no occurrence of exudate leaks as assessed through a 
combination of leakage alert data from device
 and/or clinical data on any leakage 
observed during the dressing wearing period resulting or not, in an unplanned dressing 
change  
The following hypothesis will be tested to establish the non-inferiority of the 
 
 system exudate management to the literature derived value of 85% with 
non-inferiority margin, d1>0:  
H0
- 
0  
1 
Ha
- 
0  < 1 
tin 
managed through evaporation. The non-inferiority margin is 10%. An Exact test for non-
inferiority of the study proportion to the literature derived 85% assuming a non-inferiority 
limit of -10%. A binary variable also for the leakage will also be used and the proportion of 
reported/identified leaks will be presented as a frequency together with a percentage and a 
95% CI.  
The logistic model will be used to evaluate the adjusted and the un-adjusted models for the 
CCS primary outcome variable. The variables considered important and to be included in the 
final model are Age, Diabetic status and the presence of any other co-morbidity as a binary 
variable. All other baseline and medical factors collected at baseline will be evaluated for 
importance in adjusted models and only those statistically significant in an un-adjusted 
model will be considered in the final model. Composite Clinical Success (CCS) defined as a 
binary variable (1/0) (1 if all three of the following are true and 0 if at least one of the three 
is false):  

 
 
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A Nominal pressure is in the interval 80mmHg ± 7mmHg  
B Dressing wear time is 7 days  
C No leakage  
The Composite Clinical Success (CCS) will be reported as a count and percentage with a 
95% CI. 
Analysis of Secondary Endpoints Section 10.4.2  
Old text: 
Clinical efficacy and safety of the 
 NPWT system over a 30 day follow-up 
period to include:  
o 
Incidence of Surgical Site Infection (SSI)  Superficial, deep, organ [CDC criteria] within 
30 days of surgery  
o 
Incidence 
of 
Surgical 
site 
Complications 
(SSC) 
[as 
applicable: 
dehiscence 
(superficial/deep/organ.), seroma, necrosis, hematoma, suture abscess] within 30 days 
of surgery 
o 
Percentage of skin graft take at Days 7, 14 and 30 as assessed by clinician visual 
assessment  
o 
Condition of peri-wound skin and skin under the 
 assessed through visual 
inspection at 7, 14 and 30 days.  
o 
Level of pain during wear of the 
 system, and at dressing removal 
assessed by VAS scale following 7 day therapy  
o 
Level of pain during dressing removal (VAS scale) - pain intensity as none, mild, 
moderate, or severe.  
For incidence of SSI and incidence of SSC binary variables indicating presence of/absence of 
will be defined and the frequencies together with percentages reported/identified outcomes 
will be reported. Logistic models will be fitted and important associated factors adjusted for 
if there is adequate data. 

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith & Nephew.  
  
  
 
Summary statistics for all other secondary variables will be given according to the nature of 
the variable, continuous or categorical. For categorical variables, the number of 
observations, mean, standard deviation, median, minimum, and maximum will be 
presented, while for categorical variables the number of observations, frequency, and 
percentages will be reported. 95% confidence intervals will be reported where appropriate.  
New text  
Clinical performance and safety of the 
 NPWT system over a 30 day follow-
up period to include: 
o Incidence of Surgical Site Infection (SSI)  Superficial, deep, organ [CDC criteria] within 
30 days of surgery  
o Incidence 
of 
Surgical 
site 
Complications 
(SSC) 
[as 
applicable: 
dehiscence 
(superficial/deep/organ.), seroma, necrosis, hematoma, suture abscess] within 30 days 
of surgery 
o Percentage of skin graft take at Days 7, 14 and 30 as assessed by clinician visual 
assessment 
o Condition of peri-wound skin and skin under the pump 
 assessed through visual 
inspection at 7, 14 and 30 days. 
o Level of pain during wear of the 
 system, and at dressing removal 
assessed by VAS scale following 7 day therapy 
o Level of pain during dressing removal (VAS scale) - pain intensity as none, mild, 
moderate, or severe.  
For incidence of SSI and incidence of SSC binary variables indicating presence of/absence of 
will be defined and the frequencies together with percentages reported/identified outcomes 
will be reported. The logistic model will be used to evaluate the adjusted and the un-adjusted 
models for the secondary variables, the incidence of surgical site infections, incidence of 
surgical complications and skin graft take. The variables considered important and to be 
included in the final model are Age, Diabetic status and the presence of any other co-

 
 
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morbidity as a binary variable. All other baseline and medical factors collected at baseline 
will be evaluated for importance in adjusted models and only those statistically significant in 
an un-adjusted model will be considered in the final model. 
Summary statistics for all other secondary variables will be given according to the natture 
of the variable, continuous or categorical. For categorical variables, the number of 
observations, mean, standard deviation, median, minimum, and maximum will be 
presented, while for categorical variables the number of observations, frequency, and 
percentages will be reported. 95% confidence intervals will be reported where appropriate. 
Study Design Section 8.1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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22.9 Protocol Amendment 1 
22.9.1 General Purpose 
This minor amendment was completed following initial ethical review of the protocol. 
 
22.9.2 Rationale 
The ethics committee stipulated that adults with reduced capacity and emergency cases are 
not needed for valid study data in this study. Therefore a minimum of 24 hours consideration 
should be given for informed consent and the reference to 2 hours consideration time must 
be removed. 
 
22.9.3 Effect on Study Status 
Not applicable; this amendment is to be in effect and implemented prior to subject 
enrollment. 
 
22.9.4 Details 
This amendment specifically revised the protocol as follows: 
Informed consent 
The text,  
associated study 
information may be read aloud to the subject in the presence of an impartial witness. If 
possible the subject shall sign and personally date the Informed Consent Form (ICF). Where 
this is not possible, due to difficulties in writing, the subject shall provide verbal consent to 

 
 
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participate in the study. The witness shall then personally sign and date the informed consent 
form, attesting that the information was accurately explained and that the informed consent 
was freely given. 
In the case 
legally authorized representative (parent or legal guardian). If the legally authorized 
representative is unable to read/write a witness signature is required as described 
previously. 
All subjects will be given time to consider participation following the explanation of the 
study/reading of the patient information sheet. If the surgery is not considered emergency 
then at least 24 hours is preferred. If less than 24 hours is needed due to an emergency 
then the subject may be consented a few hours after explanation of the study is given. No 
true emergency cases (where the subject is unconscious or does not have time to consider 
 
was changed to, 
information may be read aloud to the subject in the presence of an impartial witness. If 
possible the subject shall sign and personally date the Informed Consent Form (ICF). Where 
this is not possible, due to difficulties in writing, the subject shall provide verbal consent to 
participate in the study. The witness shall then personally sign and date the informed consent 
form, attesting that the information was accurately explained and that the informed consent 
was freely given. 
All subjects will be given ample time (at least 24 hours) to consider participation following 
 
 

 
 
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22.10 Instructions for Use 

 
 
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contents be disclosed by any means without prior written permission from Smith & Nephew, nor shall anyone make any use of it that 
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22.11 Principal Investigator Obligations (ISO 
14155:2020) 
1. General:  
The role of the principal investigator is to implement, oversee the management of the 
day-to-day conduct of the clinical investigation as well as ensure data integrity and the 
rights, safety, and well- being of the subjects involved in the clinical investigation. The 
principal investigator is responsible for ensuring adequate training and qualification of 
the investigation site team and for maintaining oversight of their activities. The principal 
investigator may delegate tasks to qualified members of the investigation site team but 
retains responsibility for the clinical investigation (see also 7.6 of ISO14155:2020). This 
also applies when activities are outsourced to an external organization by the principal 
investigator in which case he/she shall implement procedures to ensure the integrity of 
all tasks performed and any data generated by this external organization.   
2. Qualification of the PI.  
The PI shall: 
a. be qualified by education, training, and experience to assume responsibility for the 
proper conduct of the clinical investigation in accordance with this document; 
evidence of such qualifications of the principal investigator shall be provided to the 
sponsor through up-to-date CVs or other relevant documentation,  
NOTE National regulations can also apply.  
b. be experienced in the field of application and trained in the use of the investigational 
device under consideration,  
c. disclose potential conflicts of interest, including financial, that can interfere with the 
conduct of the clinical investigation or interpretation of results, and  
d. be knowledgeable with the method of obtaining informed consent.  
3. Qualification of investigation site. The PI shall be able to demonstrate that the proposed 
investigation site: 

 
 
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a. has the required number of eligible subjects needed within the agreed recruitment 
period,  
b. has an investigation site team that is: qualified by education, training, and 
experience to assume responsibility for the proper conduct of the clinical 
investigation in accordance with this document; evidence of such qualifications for 
members of the investigation site team shall be documented through up-to-date 
CVs or other relevant documentation,  
NOTE National regulations can also apply.  
c. has adequate facilities. 
 
4. Communication with the IEC.  
The PI shall:  
a. provide 
the 
Sponsor 
with 
copies 
of 
any 
clinical-investigation-related 
communications between the PI and the EC, 
b. comply with the requirements described in 5.6 of ISO 14155: 
c. obtain the written and dated approval/favourable opinion of the EC for the clinical 
investigation, and ensure that regulatory authority approval is provided by the 
sponsor and communicated to the EC where required, before recruiting subjects and 
implementing all subsequent amendments, if required,  
d.  perform safety reporting as specified in 10.8 (for adverse event categorization, see 
Annex F),  
e.  promptly report any deviations from the CIP that affect the rights, safety or well-
being of the subject or the scientific integrity of the clinical investigation, including 
those which occur under emergency circumstances, if required by the EC or the CIP, 
NOTE National regulations can also apply.  
f. 
notify suspension, premature termination, or routine close-out of the clinical 
investigation as described in Clause 8.  

 
 
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In particular circumstances, the communication with the EC can be performed by 
the sponsor, partly or in full, in which case the sponsor shall keep the principal 
investigator informed. 
5. Informed consent process.  
The principal investigator shall  
a. comply with the requirements specified in 5.8,  
b. ensure compliance with ethical principles for the process of obtaining informed 
consent, and  
c. ensure and document appropriate training if an authorized designee is appointed 
to conduct the informed consent process.  
NOTE Regulatory requirements can apply. 
6. Compliance with the protocol.  
The principal investigator shall: 
a.  indicate his/her acceptance of the CIP in writing, 
b. conduct the clinical investigation in compliance with the CIP,  
c. create and maintain source documents throughout the clinical investigation and 
make them available as requested during monitoring visits or audits as well as 
maintain documentation of the type and location of these source documents, 
d. ensure that the investigational device is used solely by authorized users as 
specified in 7.2, and in accordance with the CIP and instructions for use,  
e. propose to the sponsor any appropriate modification(s) of the CIP or 
investigational device or of the use of the investigational device,  
f. 
refrain from implementing any modifications to the CIP without agreement from 
the sponsor, EC and regulatory authorities, if required,  
g. document and explain any deviation from the approved CIP that occurred during 
the course of the clinical investigation,  
h. ensure that an adequate investigation site team and facilities exist and are 
maintained and documented during the clinical investigation,  

 
 
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i. 
ensure that maintenance and calibration of the equipment relevant for the 
assessment of the clinical investigation is appropriately performed and 
documented, where applicable, 
j. 
ensure the accuracy, completeness, legibility and timeliness of the data reported 
to the sponsor in the CRFs and in all required reports,  
k. maintain the device accountability records,  
l. 
 comply with the procedure for the safe return of investigational devices including 
potentially hazardous devices, and in case of reported device deficiencies, 
collaborate with the sponsor to provide the necessary information allowing an 
accurate analysis where appropriate,  
m. allow and support the sponsor to perform monitoring and auditing activities,  
n. be accessible to the monitor and respond to questions during monitoring visits,  
o. determine the cause and implement appropriate corrective and preventive actions 
to address significant noncompliance, 
p. allow and support regulatory authorities and the EC when performing auditing 
activities, 
q. ensure that all clinical investigation-related records are retained as specified in 
8.3,  
r. 
sign the clinical investigation report, as specified in 8.4.  
 
7. Medical care of subjects. The Principal Investigator shall 
a.  provide adequate medical care to a subject during and after a subject's 
participation in a clinical investigation in the case of adverse events, as described 
in the informed consent,  
b. inform the subject of the nature and possible cause of any adverse events 
experienced,  

 
 
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c. provide the subject with the necessary instructions on proper use, handling, 
storage and return of the investigational device, when it is used or operated by 
the subject, 
d.  inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that can be required, 
e. provide the subject with well-defined procedures for possible emergency situations 
related to the clinical investigation, and make the necessary arrangements for 
emergency treatment, including decoding procedures for blinded/masked clinical 
investigations, as needed, 
f. 
ensure that clinical records are clearly marked to indicate that the subject is 
enrolled in a particular clinical investigation, 
g. if appropriate, provide subjects enrolled in the clinical investigation with some 
means of showing their participation, together with identification and compliance 
information for concomitant treatment measures (contact address and telephone 
numbers shall be provided),  
h. inform, with the subject's approval the subject's personal physician about the 
subject's participation in the clinical investigation,  
NOTE National regulations can apply.  
i. 
make all reasonable efforts to ascertain the reason(s) for a subject's premature 
withdrawal from the clinical investigation while fully respecting the subject's 
rights.  
8. Safety reporting. The Principal Investigator shall: 
a. record every adverse event and observed device deficiency, together with an 
assessment (adverse event categorization, see Annex F),  
b. report to the sponsor, without unjustified delay, all serious adverse events and 
device deficiencies that could have led to a serious adverse device effect; this 
information shall be promptly followed by detailed written reports, as specified in 
the CIP,  

 
 
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c. report to the EC serious adverse events and device deficiencies that could have 
led to a serious adverse device effect, if required by the CIP or by the EC,  
NOTE 1 National regulations can also apply.  
d. report to regulatory authorities serious adverse events and device deficiencies that 
could have led to a serious adverse device effect,  
NOTE 2 National regulations can apply.  
e. supply the sponsor, upon sponsor's request, with any additional information 
related to the safety reporting of a particular event.  

 
 
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7 
 
 
 
 
22.12 ASA Physical Status Classification System 
Developed By: ASA House of Delegates/Executive Committee 
Last Amended: December 13, 2020 (original approval: October 15, 2014) 
 
ASA PS Classification 
Definition 
Examples, including, but 
not limited to: 

 
 
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face of significant cardiac 
pathology or multiple 
organ/system dysfunction 
ASA VI 
A declared brain-dead 
patient whose organs are 
being removed for donor 
purposes 
  
* The addition of E denotes emergency surgery: (an emergency is defined as existing when delay in 
treatment of the patient would lead to a significant increase in the threat to life or body part) 
 
 
 
 

 
 
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22.13 MHRA No Objection 
 

 
 
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